Determination of orthodontic tooth movement and tissue reaction following demineralized freeze-dried bone allograft grafting intervention

PubMed Central

Seifi, Massoud; Ghoraishian, Seyed Ahmad

2012-01-01

Background: Socket preservation after tooth extraction is one of the indications of bone grafting to enhance preorthodontic condition. The aim of this study is to determine the effects of socket preservation on the immediate tooth movement, alveolar ridge height preservation and orthodontic root resorption. Materials and Methods: In a split-mouth technique, twelve sites in three dogs were investigated as an experimental study. Crushed demineralized freeze-dried bone allograft (DFDBA) (CenoBone®) was used as the graft material. The defects were made by the extraction of 3rd premolar. On one side of each jaw, the defects were preserved by DFDBA and defects of the other side left opened as the control group. Simultaneously the teeth adjacent to the defects were pulled together by a NiTi coil spring. After eight weeks, the amount of (OTM), alveolar height, and root resorption were measured. Analysis of variance was used for purpose of comparison. Results: There was a slight increase in OTM at grafted sites as they were compared to the control sites (P<0.05). Also a significant bone resorption in control site and successful socket preservation in experimental site were observed. Reduction of root resorption at the augmented site was significant compared to the normal healing site (P<0.05). Conclusion: Using socket preservation, tooth movement can be immediately started without waiting for the healing of the recipient site. This can provide some advantages like enhanced rate of OTM, its approved effects on ridge preservation that reduces the chance of dehiscence and the reduction of root resorption. PMID:22623939

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

PubMed Central

Cottrell, Jessica A.; Vales, Francis M.; Schachter, Deborah; Wadsworth, Scott; Gundlapalli, Rama; Kapadia, Rasesh; O'Connor, J. Patrick

2010-01-01

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. PMID:20625499

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

PubMed

Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endochondral vs. intramembranous demineralized bone matrices as implants for osseous defects.

PubMed

Nidoli, M C; Nielsen, F F; Melsen, B

1999-05-01

This study focuses on the difference in regenerative capacity between endochondral and intramembranous demineralized bone matrices (DBMs) when implanted into bony defects. It also focuses on the possible influence of the type of skeletal recipient site (orthotopic or heterotopic). Of 34 Wistar rats, 10 served as a source of DBM, and 24 were divided into two groups of 12 animals. In group A identical defects were produced in the parietal bones, whereas in group B the defects were produced in each radius. The right defects were implanted with endochondral DBM and the left defects were implanted with intramembranous DBM. Descriptive and/or histomorphometric analyses were performed by means of light and polarized microscopy, and radiography (group B). Right and left data were compared to disclose differences in bone-healing capacity. The quantitative results demonstrated that endochondral DBM displays a greater regenerative capacity than intramembranous DBM when implanted heterotopically. The different clinical performances of endochondral and intramembranous bone grafts might be explained on the basis of the mechanical rather than the osteoinductive principle. The qualitative results suggest that the type of bone deposition induced by the DBMs is not related to the type of implanted DBM. Recipient site characteristics and/or environmental factors seem decisive in the occurrence of either types of ossification.

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways

PubMed Central

Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A.; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague–Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases. PMID:26657206

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways.

PubMed

Dixit, Manisha; Raghuvanshi, Ashutosh; Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague-Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases.

Repair of segmental radial defect with autologous bone marrow aspirate and hydroxyapatite in rabbit radius: A clinical and radiographic evaluation

PubMed Central

Yassine, Kalbaza Ahmed; Mokhtar, Benchohra; Houari, Hemida; Karim, Amara; Mohamed, Melizi

2017-01-01

Aim: Finding an ideal bone substitute to treat large bone defects, delayed union and nonunions remain a challenge for orthopedic surgeons and researchers. Several studies have been conducted on bone regeneration; each has its own advantages and disadvantages. The aim of this study was to evaluate the effect of a combination of hydroxyapatite (HA) powder with autologous bone marrow (BM) aspirate on the repair of segmental radial defect in a rabbit model. Materials and Methods: A total of 36 male and adult New Zealand rabbit with a mean weight of 2.25 kg were used in this study. Approximately, 5 mm defect was created in the mid-shaft of the radius to be filled with HA powder in the control group “HA” (n=18) and with a combination of HA powder and autologous BM aspirate in the test group “HA+BM” (n=18). Animals were observed daily for healing by inspection of the surgical site, and six rabbits of each group were sacrificed at 30, 60, and 90 post-operative days to perform a radiographic evaluation of defect site. Results: Obtained results revealed a better and more rapid bone regeneration in the test group: Since the defect was rapidly and completely filled with mature bone tissue after 90 days. Conclusion: Based on these findings, we could infer that adding a BM aspirate to HA is responsible of a better regeneration process leading to a complete filling of the defect. PMID:28831217

A novel bone scraper for intraoral harvesting: a device for filling small bone defects.

PubMed

Zaffe, Davide; D'Avenia, Ferdinando

2007-08-01

To evaluate histologically the morphology and characteristics of bone chips harvested intraorally by Safescraper, a specially designed cortical bone collector. Bone chips harvested near a bone defect or in other intraoral sites were grafted into a post-extractive socket or applied in procedures for maxillary sinus floor augmentation or guided bone regeneration. Core biopsies were performed at implant insertion. Undecalcified specimens embedded in PMMA were studied by histology, histochemistry and SEM. Intraoral harvesting by Safescraper provided a simple, clinically effective regenerative procedure with low morbidity for collecting cortical bone chips (0.9-1.7 mm in length, roughly 100 microm thick). Chips had an oblong or quadrangular shape and contained live osteocytes (mean viability: 45-72%). Bone chip grafting produced newly formed bone tissue suitable for implant insertion. Trabecular bone volume measured on biopsies decreased with time (from 45-55% to 23%). Grafted chips made up 50% or less of the calcified tissue in biopsies. Biopsies presented remodeling activities, new bone formation by apposition and live osteocytes (35% or higher). In conclusion, Safescraper is capable of collecting adequate amounts of cortical bone chips from different intraoral sites. The procedure is effective for treating alveolar defects for endosseous implant insertion and provides good healing of small bone defects after grafting with bone chips. The study indicates that Safescraper is a very useful device for in-office bone harvesting procedures in routine peri-implant bone regeneration.

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

[Osteostimulating effect of bone xenograft on bone tissue regeneration].

PubMed

Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

2015-01-01

The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

Poly(trimethylene carbonate)-based composite materials for reconstruction of critical-sized cranial bone defects in sheep.

PubMed

Zeng, Ni; van Leeuwen, Anne C; Grijpma, Dirk W; Bos, Ruud R M; Kuijer, Roel

2017-02-01

The use of ceramic materials in repair of bone defects is limited to non-load-bearing sites. We tested poly(trimethylene carbonate) (PTMC) combined with β-tricalcium phosphate or biphasic calcium phosphate particles for reconstruction of cranial defects. PTMC-calcium phosphate composite matrices were implanted in cranial defects in sheep for 3 and 9 months. Micro-computed tomography quantification and histological observation were performed for analysis. No differences were found in new bone formation among the defects left unfilled, filled with PTMC scaffolds, or filled with either kind of PTMC-calcium phosphate composite scaffolds. Porous β-TCP scaffolds as control led to a larger amount of newly formed bone in the defects than all other materials. Histology revealed abundant new bone formation in the defects filled with porous β-TCP scaffolds. New bone formation was limited in defects filled with PTMC scaffolds or different PTMC-calcium phosphate matrices. PTMC matrices were degraded uneventfully. New bone formation within the defects followed an orderly pattern. PTMC did not interfere with bone regeneration in sheep cranial defects and is suitable as a polymer matrix for incorporating calcium phosphate particles. Increasing the content of calcium phosphate particles in the composite matrices may enhance the beneficial effects of the particles on new bone formation. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Periodontal healing in one-wall intra-bony defects in dogs following implantation of autogenous bone or a coral-derived biomaterial.

PubMed

Kim, Chang-Sung; Choi, Seong-Ho; Cho, Kyoo-Sung; Chai, Jung-Kiu; Wikesjö, Ulf M E; Kim, Chong-Kwan

2005-06-01

Autogenous bone grafts and bone biomaterials are being used as part of protocols aiming at reconstruction of periodontal defects. There is a limited biologic information on the effect of such materials on periodontal healing, in particular aberrant healing events that may prevent their general use. The objective of this study was, using histological techniques, to evaluate periodontal healing with focus on root resorption and ankylosis following implantation of autogenous bone and a coral-derived biomaterial into intra-bony defects in dogs. One-wall intra-bony periodontal defects were surgically created at the distal aspect of the second and the mesial aspect of the fourth mandibular premolars in either right or left jaw quadrants in four Beagle dogs. Each animal received particulated autogenous bone and the resorbable calcium carbonate biomaterial into discrete one-wall intra-bony defects. The mucoperiosteal flaps were positioned and sutured to their pre-surgery position. The animals were euthanized 8 weeks post-surgery when block sections of the defect sites were collected and prepared for qualitative histological analysis. There were no significant differences in periodontal healing between sites receiving autograft bone and the coral-derived biomaterial. A well-organized periodontal ligament bridging new bone and cementum regeneration was observed extending coronal to a notch prepared to delineate the apical extent of the defect. Osteoid and bone with enclosed osteocytes were formed onto the surface of both autograft and coral particles. Although small resorption pits were evident in most teeth, importantly none of the biomaterials provoked marked root resorption. Ankylosis was not observed. Particulated autogenous bone and the coral-derived biomaterial may be implanted into periodontal defects without significant healing aberrations such as root resorption and ankylosis. The histopathological evaluation suggests that the autogenous bone graft has a limited osteogenic potential as demonstrated in this study model.

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

PubMed Central

Agarwal, Rachit; García, Andrés J.

2015-01-01

Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

Mimix hydroxyapatite cement use in the reconstruction of the craniofacial skeleton.

PubMed

Mann, Robert J; Blount, Andrew L; Neaman, Keith C; Korepta, Lindsey

2011-11-01

Reconstruction of the craniofacial skeleton has undergone a significant evolution during the past century. Initially, the use of autogenous bone grafts from various sites was the criterion standard. However, owing to donor site morbidity and lack of sufficient bone for large defects, surgeons have relied on various bone substitutes. Hydroxyapatite (HA) has served as an alternative to autogenous grafts, but questions regarding biocompatibility, risk of infection, and slow set times have hampered its acceptance. This article serves as a review of a single surgeon's experience using HA in the craniofacial skeleton. Eighteen patients receiving HA between March 2000 and November 2006 were observed. Sixteen underwent recontouring of skull-based bone defects, and 2 underwent recontouring for nasal and alveolar defects. The mean amount of HA used in each patient was 30.2 g. For large contour irregularities, the maximum thickness of HA used was 8 mm. The size of bone defects ameliorated averaged 4.8 cm(2). Complications occurred in 3 (16.7%) of 18 patients and included scalp hematoma and superficial cellulitis. In addition, 1 patient developed a facial abscess after placement along the alveolar floor, which necessitated removal. Hydroxyapatite represents a viable alternative to autogenous bone grafts when used in the correct manner. Hydroxyapatite should be used only for smaller defects or used in conjunction with absorbable plates when attempting to fill larger defects. Use of HA for nasal piriform augmentation or alveolar bone grafting should not be considered owing to problems with late infections.

Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model.

PubMed

Luangphakdy, V; Shinohara, K; Pan, H; Boehm, C; Samaranska, A; Muschler, G F

2015-01-12

Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP-2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 %±1.2 and 11.2 %±1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

Superficial Circumflex Iliac Artery-Based Iliac Bone Flap Transfer for Reconstruction of Bony Defects.

PubMed

Yoshimatsu, Hidehiko; Iida, Takuya; Yamamoto, Takumi; Hayashi, Akitatsu

2018-05-12

 The superficial circumflex iliac artery (SCIA)-based iliac bone flap has yet to be widely used. The purpose of this article is to validate the feasibility of SCIA-based iliac bone flap transfers for reconstruction of small to moderate-sized bony defects. Retrospective outcome comparisons between SCIA-based iliac bone flaps and fibula flaps were made.  Twenty-six patients with bony tissue defects underwent reconstructions using either free SCIA-based iliac bone flaps (13) or fibula flaps (13). Outcomes were evaluated 9 months after the reconstruction on the following basis: bone length, pedicle length, skin paddle area, bone union, donor-site complications, skin paddle survival, and complications at the reconstructed site.  There was no statistically significant difference in pedicle length (iliac bone vs. fibula; 5.5 ± 1.8 vs. 4.1 ± 1.5 cm; p  = 0.181), in bone union rate (iliac bone vs. fibula; 100 vs 92.3%; p  = 0.308), in donor-site complication rate (iliac bone vs. fibula; 0 vs. 7.7%; p  = 0.308), or in skin paddle complete survival rate (iliac bone vs. fibula; 100 vs. 83.3%; p  = 0.125). Statistically significant differences were observed in bone flap length (iliac bone vs. fibula; 4.8 ± 2.2 vs. 11.1 ± 4.8 cm; p  = 0.0005), in skin paddle area (superficial circumflex iliac artery perforator flap vs. peroneal artery perforator flap; 58.8 ± 35.6 vs. 27.7 ± 17.5 cm 2 ; p  = 0.0343), and in reconstructed site complication rate (iliac bone vs. fibula; 0 vs. 30.8%; p  = 0.030).  In our series of SCIA-based iliac bone flap transfers, up to 8 × 3 cm could be procured along the iliac crest. When compared with fibula flap transfers, there were no significant statistical differences in pedicle length or in bone union rate; the SCIA-based iliac bone flap may be a feasible option for bony defects of small to moderate size. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Histological and Histometrical Evaluation of two Synthetic Hydroxyapatite Based Biomaterials in the Experimental Periodontal Defects in Dogs.

PubMed

D'lima, Johnson Prakash; Paul, Jose; Palathingal, Plato; Varma, Brr; Bhat, Mahalinga; Mohanty, Mira

2014-09-01

The present study was to evaluate histologically and histometrically the efficacy of Chitra granules in the regeneration of alveolar bone and to compare it with that of OsteoGenR (HA Resorb)(TM) in iatrogenically created alveolar bone defects in mongrel dogs. Four dogs (16 sites) were used for this split-mouth study. The animals were divided randomly into two groups of two animals. Same animals were used as control and test. Each dog had four implantation sites. The periodontal defects were prepared by acute defect model. Animals were sacrificed at 3 months (n=2), 6 months (n=2) and histologic and histometric evaluation was carried out. The data was analysed using statistical package Graph pad Software. Comparison of the hard and soft tissue parameters in the two groups was done using the Wilcoxan (Man Whitney), two tailed t-test. A p-value less than 0.05 were considered significant. Maturing bone with immature periodontal ligament fibers were observed at three months and advanced osteogenesis at six months with both the types of bone graft materials. The mean values showed that amount of new bone formed with OsteoGenR (HA Resorb)(TM) was slightly more than that obtained by Chitra granules in histometric evaluation. Histological study showed similar healing pattern with both the types of bone graft materials with maturing bone at 3 months and advanced osteogenesis at six months in experimental intraosseous periodontal defects in dogs. However, histological evaluation for longer period is necessary to determine the time taken for complete replacement of the bone graft materials with new bone.

Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

PubMed

Huang, Guofeng; Liu, Guojun; Zhang, Feng; Gao, Jianting; Wang, Jiangze; Chen, Qi; Wu, Benwen; Ding, Zhenqi; Cai, Taoyi

2017-01-01

Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 ( p <0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group ( p <0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

Biodegradable hybrid tissue engineering scaffolds for reconstruction of large bone defects

NASA Astrophysics Data System (ADS)

Barati, Danial

Complex skeletal injuries and large bone fractures are still a significant clinical problem in US. Approximately 1.5 million Americans (veterans, their families, and civilians) every year suffer from bone loss due to traumatic skeletal injuries, infection, and resection of primary tumors that require extensive grafting to bridge the gap. The US bone graft market is over $2.2 billion a year. Due to insufficient mechanical stability, lack of vascularity, and inadequate resorption of the graft, patients with traumatic large skeletal injuries undergo multiple costly operations followed by extensive recovery steps to maintain proper bone alignment and length. Current strategies for repairing damaged or diseased bones include autologous or allograft bone transplantations. However, limited availability of autografts and risk of disease transmission associated with allografts have necessitated the search for the development of new bone graft options and strategies. The overall goal of this project is to develop a much-needed bone-mimetic engineered graft as a substitute for current strategies providing required bone grafts for reconstruction of large bone defects. This project will use the structure of natural cortical bone as a guide to produce an engineered bone graft with balanced strength, osteogenesis, vascularization, and resorption. The outcome of this project will be a biodegradable hybrid scaffold system (similar to natural cortical bone) including a mechanically strong scaffold allowing for mechanical stability of the load-bearing defect site and a soft and highly porous structure such as a hydrogel phase which will allow for efficient cell and growth factor delivery into the defect implantation site, cell niche establishment and promotion of mineralization. Successful completion of this project will transform bone graft technology for regeneration of complex bone defects from a frozen or freeze-dried allograft to a safe, infection-free, mechanically-stable, osteoinductive, and vasculogenic graft that is ultimately displaced by the patient's own tissue.

Association Between Peri-implant Bone Morphology and Marginal Bone Loss: A Retrospective Study on Implant-Supported Mandibular Overdentures.

PubMed

Ding, Qian; Zhang, Lei; Geraets, Wil; Wu, Wuqing; Zhou, Yongsheng; Wismeijer, Daniel; Xie, Qiufei

The present study aimed to explore the association between marginal bone loss and type of peri-implant bony defect determined using a new peri-implant bony defect classification system. A total of 110 patients with implant-supported mandibular overdentures were involved. Clinical information was collected, including gender, age, smoking habit, and the overdenture attachment system used. Peri-implant bony defect types and marginal distances (ie, distance between the marginal bone level and the top of the implant shoulder) of all sites were identified on panoramic radiographs by a single experienced observer. The associations between marginal distance and peri-implant bony defect type, gender, age, smoking habit, attachment system, and time after implantation were investigated using marginal generalized linear models and regression analysis. A total of 83 participants were included in the final sample with a total of 224 implants involving 3,124 implant sites. The mean observation time was 10.7 years. All peri-implant bony defect types except Type 5 (slit-like) were significantly related to marginal distance in all models (P < .01). Smoking and time after implantation were significantly related to marginal distance while gender, age, and the overdenture attachment system used were not. The peri-implant bony defect type, determined using the new classification system, is associated with the extent of marginal bone loss.

Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute material.

PubMed

Kruse, A; Jung, R E; Nicholls, F; Zwahlen, R A; Hämmerle, C H F; Weber, F E

2011-05-01

A comparison of synthetic hydroxyapatite/silica oxide, xenogenic hydroxyapatite-based bone substitute materials with empty control sites in terms of bone regeneration enhancement in a rabbit calvarial four non-critical-sized defect model. In each of six rabbits, four bicortical calvarial bone defects were generated. The following four treatment modalities were randomly allocated: (1) empty control site, (2) synthetic hydroxyapatite/silica oxide-based (HA/SiO) test granules, (3) xenogenic hydroxyapatite -based granules, (4) synthetic hydroxyapatite/silica oxide -based (HA/SiO) test two granules. The results of the latter granules have not been reported due to their size being three times bigger than the other two granule types. After 4 weeks, the animals were sacrificed and un-decalcified sections were obtained for histological analyses. For statistical analysis, the Kruskal-Wallis test was applied (P<0.05). Histomorphometric analysis showed an average area fraction of newly formed bone of 12.32±10.36% for the empty control, 17.47±6.42% for the xenogenic hydroxyapatite -based granules group, and 21.2±5.32% for the group treated with synthetic hydroxyapatite/silica oxide -based granules. Based on the middle section, newly formed bone bridged the defect to 38.33±37.55% in the empty control group, 54.33±22.12% in the xenogenic hydroxyapatite -based granules group, and to 79±13.31% in the synthetic hydroxyapatite/silica oxide -based granules group. The bone-to-bone substitute contact was 46.38±18.98% for the xenogenic and 59.86±14.92% for the synthetic hydroxyapatite/silica oxide-based granules group. No significant difference in terms of bone formation and defect bridging could be detected between the two bone substitute materials or the empty defect. There is evidence that the synthetic hydroxyapatite/silica oxide granules provide comparable results with a standard xenogenic bovine mineral in terms of bone formation and defect bridging in non-critical size defects. © 2010 John Wiley & Sons A/S.

Clinical and histologic evaluation of calcium-phosphate bone cement in interproximal osseous defects in humans: a report in four patients.

PubMed

Mellonig, James T; Valderrama, Pilar; Cochran, David L

2010-04-01

This study evaluated the clinical and histologic results of a calcium phosphate bone cement in the treatment of human periodontal intraosseous defects. Four patients with chronic advanced periodontitis in whom treatment with complete dentures was planned were recruited. The cement was implanted in one defect per subject with a presurgical probing depth of at least 7 mm and a radiographic bone defect of 4 mm or more. Patients were seen every 2 weeks for periodontal maintenance. At 6 months, clinical measurements were repeated and the tooth was removed en bloc for histologic processing. Results demonstrated that all defects resulted in probing depth reduction and, at three of the four defects, in clinical attachment level gain. However, no site showed periodontal regeneration. There was no new bone formation. New cementum and connective tissue were limited to 0.2 mm or less. Large deposits of the bone cement were noted encapsulated in connective tissue.

A clinical investigation of demineralized bone matrix putty for treatment of periodontal bony defects in humans.

PubMed

Banjar, Arwa Ahmed; Mealey, Brian L

2013-01-01

The goal of this study was to evaluate the effectiveness of demineralized bone matrix (DBM) putty, consisting of demineralized human bone allograft matrix in a carrier of bovine collagen and alginate, for the treatment of periodontal defects in humans. Twenty subjects with at least one site having a probing depth ≥ 6 mm and radiographic evidence of bony defect depth > 3 mm were included. The infrabony defects were grafted with DBM putty bone graft. The following clinical parameters were assessed at baseline and 6 months posttreatment: probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). Bone fill was evaluated using transgingival probing and standardized radiographs taken at baseline and 6 months posttreatment. The 6-month evaluation showed a significant PD reduction of 3.27 ± 1.67 mm and clinical attachment gain of 2.27 ± 1.74 mm. Bone sounding measurements showed a mean clinical bone defect fill of 2.93 ± 1.87 mm and a mean radiographic bone fill of 2.55 ± 2.31 mm. The use of DBM putty was effective for treatment of periodontal bony defects in humans. Significant improvement in CAL, PD, and bone fill was observed at 6 months compared to baseline.

Bone Regeneration in Rat Cranium Critical-Size Defects Induced by Cementum Protein 1 (CEMP1)

PubMed Central

Serrano, Janeth; Romo, Enrique; Bermúdez, Mercedes; Narayanan, A. Sampath; Zeichner-David, Margarita; Santos, Leticia; Arzate, Higinio

2013-01-01

Gene therapy approaches to bone and periodontal tissue engineering are being widely explored. While localized delivery of osteogenic factors like BMPs is attractive for promotion of bone regeneration; method of delivery, dosage and side effects could limit this approach. A novel protein, Cementum Protein 1 (CEMP1), has recently been shown to promote regeneration of periodontal tissues. In order to address the possibility that CEMP1 can be used to regenerate other types of bone, experiments were designed to test the effect of hrCEMP1 in the repair/regeneration of a rat calvaria critical-size defect. Histological and microcomputed tomography (µCT) analyses of the calvaria defect sites treated with CEMP1 showed that after 16 weeks, hrCEMP1 is able to induce 97% regeneration of the defect. Furthermore, the density and characteristics of the new mineralized tissues were normal for bone. This study demonstrates that hrCEMP1 stimulates bone formation and regeneration and has therapeutic potential for the treatment of bone defects and regeneration of mineralized tissues. PMID:24265720

Periodontal tissue reaction to customized nano-hydroxyapatite block scaffold in one-wall intrabony defect: a histologic study in dogs

PubMed Central

Lee, Jung-Seok; Park, Weon-Yeong; Cha, Jae-Kook; Jung, Ui-Won; Kim, Chang-Sung; Lee, Yong-Keun

2012-01-01

Purpose This study evaluated histologically the tissue responses to and the effects of a customized nano-hydroxyapatite (n-HA) block bone graft on periodontal regeneration in a one-wall periodontal-defect model. Methods A customized block bone for filling in the standardized periodontal defect was fabricated from prefabricated n-HA powders and a polymeric sponge. Bilateral 4×4×5 mm (buccolingual width×mesiodistal width×depth), one-wall, critical-size intrabony periodontal defects were surgically created at the mandibular second and fourth premolars of five Beagle dogs. In each dog, one defect was filled with block-type HA and the other served as a sham-surgery control. The animals were sacrificed following an 8-week healing interval for clinical and histological evaluations. Results Although the sites that received an n-HA block showed minimal bone formation, the n-HA block was maintained within the defect with its original hexahedral shape. In addition, only a limited inflammatory reaction was observed at sites that received an n-HA block, which might have been due to the high stability of the customized block bone. Conclusions In the limitation of this study, customized n-HA block could provide a space for periodontal tissue engineering, with minimal inflammation. PMID:22586523

Periodontal tissue reaction to customized nano-hydroxyapatite block scaffold in one-wall intrabony defect: a histologic study in dogs.

PubMed

Lee, Jung-Seok; Park, Weon-Yeong; Cha, Jae-Kook; Jung, Ui-Won; Kim, Chang-Sung; Lee, Yong-Keun; Choi, Seong-Ho

2012-04-01

This study evaluated histologically the tissue responses to and the effects of a customized nano-hydroxyapatite (n-HA) block bone graft on periodontal regeneration in a one-wall periodontal-defect model. A customized block bone for filling in the standardized periodontal defect was fabricated from prefabricated n-HA powders and a polymeric sponge. Bilateral 4×4×5 mm (buccolingual width×mesiodistal width×depth), one-wall, critical-size intrabony periodontal defects were surgically created at the mandibular second and fourth premolars of five Beagle dogs. In each dog, one defect was filled with block-type HA and the other served as a sham-surgery control. The animals were sacrificed following an 8-week healing interval for clinical and histological evaluations. Although the sites that received an n-HA block showed minimal bone formation, the n-HA block was maintained within the defect with its original hexahedral shape. In addition, only a limited inflammatory reaction was observed at sites that received an n-HA block, which might have been due to the high stability of the customized block bone. In the limitation of this study, customized n-HA block could provide a space for periodontal tissue engineering, with minimal inflammation.

Pre-augmentation soft tissue expansion improves scaffold-based vertical bone regeneration - a randomized study in dogs.

PubMed

Kaner, Doğan; Zhao, Han; Arnold, Wolfgang; Terheyden, Hendrik; Friedmann, Anton

2017-06-01

Soft tissue (ST) dehiscence with graft exposure is a frequent complication of vertical augmentation. Flap dehiscence is caused by failure to achieve tension-free primary wound closure and by the impairment of flap microcirculation due to surgical trauma. Soft tissue expansion (STE) increases ST quality and quantity prior to reconstructive surgery. We hypothesized that flap preconditioning using STE would reduce the incidence of ST complications after bone augmentation and that optimized ST healing would improve the outcome of bone regeneration. Self-filling tissue expanders were implanted in mandibular bone defects in ten beagle dogs. After expansion, alloplastic scaffolds were placed for vertical bone augmentation in STE sites and in control sites without STE pre-treatment. ST flap microcirculation was analysed using laser Doppler flowmetry. The incidence of graft exposures was evaluated after 2 weeks. Bone formation was assessed after 2 months, using histomorphometry and immunohistochemistry. Test sites showed significantly less impairment of perfusion and faster recovery of microcirculation after bone augmentation. Furthermore, no flap dehiscences occurred in STE sites. Bone regeneration was found in both groups; however, significantly greater formation of new bone was detected in test sites with preceding STE. Preconditioning using STE improved ST healing and bone formation after vertical augmentation. The combination of STE and the subsequent placement of alloplastic scaffolds may facilitate the reconstruction of severe bone defects. © 2016 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

Histological and Histometrical Evaluation of two Synthetic Hydroxyapatite Based Biomaterials in the Experimental Periodontal Defects in Dogs

PubMed Central

Paul, Jose; Palathingal, Plato; Varma, BRR; Bhat, Mahalinga; Mohanty, Mira

2014-01-01

Aim: The present study was to evaluate histologically and histometrically the efficacy of Chitra granules in the regeneration of alveolar bone and to compare it with that of OsteoGenR (HA Resorb)TM in iatrogenically created alveolar bone defects in mongrel dogs. Materials and Methods: Four dogs (16 sites) were used for this split-mouth study. The animals were divided randomly into two groups of two animals. Same animals were used as control and test. Each dog had four implantation sites. The periodontal defects were prepared by acute defect model. Animals were sacrificed at 3 months (n=2), 6 months (n=2) and histologic and histometric evaluation was carried out. Statistical Analysis: The data was analysed using statistical package Graph pad Software. Comparison of the hard and soft tissue parameters in the two groups was done using the Wilcoxan (Man Whitney), two tailed t-test. A p-value less than 0.05 were considered significant. Results: Maturing bone with immature periodontal ligament fibers were observed at three months and advanced osteogenesis at six months with both the types of bone graft materials. The mean values showed that amount of new bone formed with OsteoGenR (HA Resorb)TM was slightly more than that obtained by Chitra granules in histometric evaluation. Conclusion: Histological study showed similar healing pattern with both the types of bone graft materials with maturing bone at 3 months and advanced osteogenesis at six months in experimental intraosseous periodontal defects in dogs. However, histological evaluation for longer period is necessary to determine the time taken for complete replacement of the bone graft materials with new bone. PMID:25386523

Direct current stimulation of bone production in the horse: preliminary study with a "gap healing" model.

PubMed

Collier, M A; Brighton, C T; Norrdin, R; Twardock, A R; Rendano, V T

1985-03-01

The effect of a 20-microA direct-current implantable bone growth stimulator (BGS) on bone production with a "gap healing" model in the horse was evaluated. The right and left 4th metatarsal bones (Mt-4) were used in 7 adult horses to create the "gap healing" model. A 4-mm section of the Mt-4 bone was resected bilaterally in each horse. The BGS was surgically placed into the 7 left Mt-4 defects. The 7 right Mt-4 defects served as controls. Six horses survived the 16-week experimental period. Signs of pain, decreased range of limb motion, or lameness was not observed in any animal during the 16 weeks. None of the animals showed complete healing radiographically. Four stimulated sites showed less periosteal reaction and 2 showed greater reaction than the 6 controls. The greatest amount of periosteal reaction or bone resorption was seen around the screws and plates in both groups. Uptakes of 99mTc-MDP in counts/pixel for control sites and stimulated sites were 7.90 and 8.25 in the "gap defect" and 5.19 and 5.06 in the areas adjacent to the gap defect. The ratio of uptake between the gap defect and adjacent area was 1.5 and 1.58 respectively. Biocompatability of the BGS was excellent; however, 1 horse had a broken cathode wire 5 cm from the generator capsule at 6 weeks. All polyethylene cathode sheaths were fluid filled at 16 weeks. The average mineralization rates were 1.57 +/- 0.34, 1.71 +/- 0.28 mm/day and bone formation activity was 0.0182 +/- 0.171, and 0.0168 +/- 0.0149 mm2/day for control limbs and stimulated limbs, respectively. There was no significant difference between groups in any of the histomorphometric values measured. Direct current (20 microA) did not increase bone production in this experiment. Methods to objectively evaluate electrically induced osteogenesis and a "gap defect" model for BGS research on the horse are discussed. The results provide a basis for additional research on electrical stimulation of fractures in the horse and for dose-response studies.

Radiographical and clinical evaluation of critical size defects in rabbit calvaria filled with allograft and autograft: a pilot study

PubMed Central

Oporto V, Gonzalo H; Fuentes, Ramón; Borie, Eduardo; del Sol, Mariano; Orsi, Iara Augusta; Engelke, Wilfried

2014-01-01

Regeneration of resorbed edentulous sites can be induced by bone grafts from the subject himself and/or by the use of biomaterials. At present, there has been an extensive search for biomaterials that are evaluated by artificially creating one or more critical defects. The aim of this work was to clinically and radiographically analyze bone formation by the use of some biomaterials in artificially created defects in the parietal bone of rabbits. Six rabbits were used, creating defects of 8 mm in diameter in parietal bones. One defect was maintained with coagulum only, and in others, freeze-dried bone allograft (FDBA), autologous bone, and a combination of autologous bone with FDBA respectively, were added. Animals were sacrificed at 15-90 days with 2 weeks interval each, and calvaria were analyzed macroscopically, measuring by digital caliper the lack of filling at the surface of defects, identifying limits at anteroposterior and coronal view, realizing a digital photograph register of their external surfaces. This was subsequently evaluated radiographically by occlusal film radiography used to quantify its density through software. In conclusion, autologous bone showed the best behavior, clinically as well as radiographically. However, FDBA is a good option as an alternative to autologous bone as its behavior was slightly lower over time. The combination of autologous bone and FDBA in the same defect showed results considerably inferior to grafts used separately. Low radiopacity and clear limits were observed through time for the control coagulum filled defect. PMID:25126163

An oxidized implant surface may improve bone-to-implant contact in pristine bone and bone defects treated with guided bone regeneration: an experimental study in dogs.

PubMed

Gurgel, Bruno César de Vasconcelos; Gonçalves, Patrícia Furtado; Pimentel, Suzana Peres; Nociti, Francisco Humberto; Sallum, Enilson Antonio; Sallum, Antonio Wilson; Casati, Marcio Zaffalon

2008-07-01

The aim of the present study was to histometrically evaluate bone healing in the absence of bone defects and in the presence of surgically created bone defects treated by guided bone regeneration at oxidized and turned implant surfaces. Three months after dental extractions, standardized buccal dehiscence defects (height: 5 mm; width: 4 mm) were surgically created following implant site preparation in the mandible of 10 dogs. Oxidized-surface implants (OSI) and turned-surface implants (TSI) were inserted bilaterally, and the bone defects were treated by guided bone regeneration. After 3 months of healing, the animals were sacrificed, blocks were dissected, and undecalcified sections were obtained and processed for histometric analysis. The percentage of bone-to-implant contact (BIC) and bone density (BD) was evaluated inside the threads on the buccal (regenerated bone) and lingual sides (pristine bone) of the implants. Data were evaluated using two-way analysis of variance (P <0.05). New bone formation could be observed in OSI and TSI in the region of the defect creation. The BIC values observed in OSI for pristine and regenerated bone were 57.03% +/- 21.86% and 40.86% +/- 22.73%, respectively. TSI showed lower values of BIC in pristine bone (37.39% +/- 23.33%) and regenerated bone (3.52% +/- 4.87%). The differences between OSI and TSI were statistically significant. BD evaluation showed no statistically significant differences between OSI and TSI in pristine and regenerated bone. The oxidized implant surface promoted a higher level of BIC than the turned implant surface at pristine and regenerated bone.

Bone Healing in Extraction Sockets Covered With Collagen Membrane Alone or Associated With Porcine-Derived Bone Graft: a Comparative Histological and Histomorphometric Analysis.

PubMed

Guarnieri, Renzo; Testarelli, Luca; Stefanelli, Luigi; De Angelis, Francesca; Mencio, Francesca; Pompa, Giorgio; Di Carlo, Stefano

2017-01-01

The present paper reports data of a randomized study aimed to analyse and compare the histologic and histomorphometric aspects of bone healing in extraction sites covered with collagen membrane alone or associated with porcine-derived bone graft. Thirty patients, with single extraction sockets without severe bone wall defects in the premolar/molar region, were included. Ten extraction sockets were grafted with porcine-derived bone and covered with collagen membrane (group 1), 10 sites were covered with collagen membrane alone (group 2), and 10 sites healed spontaneously (group 3). After 4 months of healing, 26 (8 in group 1, 9 in group 2, and 9 in group 3) bone core specimens were harvested for histologic evaluation, then dental implants were placed. Sites in the group 1 and in the group 2 showed similar histologic and histomorphometric results without significantly differences in the percentage of vital bone (57.43% [SD 4.8] vs. 60.01% [SD 3.2]), and non-mineralized connective tissue 22.99% (SD 5.3) vs. 18.53% (SD 6.2). In group 1 a 16.57% (SD 3.8) of residual material was found. Results showed that the use of collagen membrane alone or associated to porcine-derived bone improves the healing bone process compared to that of extraction sites spontaneously healed. Moreover, histomorphometric data related to bone quality, indicated that extraction sites without severe walls defects and with a vestibular bone thickness > 1.5 mm, treated with a low resorbtion rate collagen membrane alone, do not need more than 4 months for dental implant insertion.

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

PubMed Central

Maisani, Mathieu; Pezzoli, Daniele; Chassande, Olivier; Mantovani, Diego

2017-01-01

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels. PMID:28634532

Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs.

PubMed

Boix, Damien; Gauthier, Olivier; Guicheux, Jérôme; Pilet, Paul; Weiss, Pierre; Grimandi, Gaël; Daculsi, Guy

2004-05-01

The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. Third and fourth mandibular premolars were extracted from three beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, titanium implants were immediately placed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and biphasic calcium phosphate ceramic granules. The right defects were left unfilled as controls. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. No post-surgical complications were observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (P<0.05) increase in terms of the number of threads in contact with bone, bone-to-implant contact, and peri-implant bone density of approximately 8.6%, 11.0%, and 14.7%, respectively. In addition, no significant difference was observed when number of threads, bone-to-implant contact, and bone density in the filled defects were compared to the no-defect sites. It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increases bone regeneration around immediately placed implants.

Papineau debridement, Ilizarov bone transport, and negative-pressure wound closure for septic bone defects of the tibia.

PubMed

Karargyris, Orestis; Polyzois, Vasilios D; Karabinas, Panayiotis; Mavrogenis, Andreas F; Pneumaticos, Spyros G

2014-08-01

Ilizarov pioneered bone transport using a circular external fixator. Papineau described a staged technique for the treatment for infected pseudarthrosis of the long bones. This article presents a single-stage Papineau technique and Ilizarov bone transport, and postoperative negative-pressure wound dressing changes for septic bone defects of the tibia. We studied the files of seven patients (mean age, 32 years) with septic bone defects of the tibia treated with a Papineau technique and Ilizarov bone transport in a single stage, followed by postoperative negative-pressure wound dressing changes. All patients had septic pseudarthrosis and skin necrosis of the tibia. The technique included a single-stage extensive surgical debridement of necrotic bone, open bone grafting with cancellous bone autograft and bone transport, and postoperative negative-pressure wound dressing changes for wound closure. The mean time from the initial injury was 6 months (range, 4-8 months). The mean follow-up was 14 months (range, 10-17 months). All patients experienced successful wound healing at a mean of 29 days. Six patients experienced successful bone regeneration and union at the docking side at a mean of 6 months. One patient experienced delayed union at the docking site, which was treated with autologous cancellous bone grafting. Two patients experienced pin track infection, which was successfully treated with antibiotics and pin site dressing changes. All patients were able to return to their work and previous levels of activity, except one patient who had a stiff ankle joint and had to change his job. No patient experienced recurrence of infection, or fracture of the regenerated or transported bone segment until the period of this study. The combined Papineau and Ilizarov bone transport technique with negative-pressure wound closure provides for successful eradication of the infection, reconstruction of the bone defect, and soft-tissue closure. A single-stage surgical treatment is feasible, without any complications.

Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

PubMed

Reyes, Ricardo; Rodríguez, Jose Antonio; Orbe, Josune; Arnau, María Rosa; Évora, Carmen; Delgado, Araceli

2018-11-01

The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eight weeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600 ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.

Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination.

PubMed

McGuire, Michael K; Scheyer, Todd; Nevins, Myron; Schupbach, Peter

2009-02-01

The current study examined the histologic and microcomputed tomographic (micro CT) outcomes of the treatment of gingival recession defects with either a subepithelial connective tissue graft (CTG) or 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) on a beta tricalcium phosphate (beta-TCP) matrix. Gingival recession defects were surgically created in six premolar teeth with no more than 3 mm of keratinized marginal tissue, an osseous crest 2 to 3 mm apical to the newly created gingival margin, and recession depth of at least 3 mm. The defects were left untouched for 2 months; then, four defects were grafted with rhPDGF-BB + beta-TCP + a wound healing dressing, and two defects received CTGs. A coronally advanced flap covered each grafted site. Nine months later, sections were obtained for examination. All four sites treated with rhPDGF-BB + beta-TCP showed connective tissue fibers (Sharpey fibers) perpendicularly inserting into newly formed cementum and alveolar bone. In the two sites treated with CTGs, a long junctional epithelium was seen coronal to the osseous crest and connective tissue fibers ran parallel to the adjacent root surfaces, with no evidence of insertion into cementum or bone. There was no evidence of regeneration of cementum, inserting connective tissue fibers, or supporting alveolar bone. Regeneration of the periodontium in gingival recession defects is possible through growth factor-mediated therapy.

Deproteinized bovine bone mineral particles and osseointegration of implants without primary bone contact: an experimental study in dogs.

PubMed

Sivolella, Stefano; Bressan, Eriberto; Salata, Luiz A; Quiñones, Maria E; Lang, Niklaus P; Botticelli, Daniele

2014-03-01

To evaluate the influence on osseointegration of Deproteinized bovine bone mineral (DBBM) particles used to fill defects of at least 1 mm around implants having no primary contact with bone. Premolars and first molars were extracted bilaterally from the mandible of six Labrador dogs. After 3 months of healing, mucoperiosteal full-thickness flaps were elevated, and one recipient site was prepared in the molar region of each hemi-mandible to place implants. These were installed with a deliberate circumferential and periapical space to the bone walls of 1.2 mm. All implants were stabilized with passive fixation plates to maintain the implants in situ and without any contact with the implant bed. The control sites were left to be filled with coagulum, while at the test sites, the residual gap was filled with DBBM. After 3 months of submerged healing, the animals were sacrificed. Ground sections were prepared and analyzed histomorphometrically. Mineralized bone-to-implant contact was 4.0% and 3.9% for control and test sites, respectively. The width of the residual defects was 0.48 mm and 0.88 mm at the control and test sites, respectively. The percentage of implant surface covered by a layer of dense connective tissue of 0.12 mm of width on average was 84.9% and 88.5% at the control and test sites, respectively. A minor and not predictable degree of contact or distance osteogenesis was obtained on the implant surface when primary contact of the implant surface with the implant bed had deliberately been avoided. DBBM grafting of the artificial gap did not favor osseointegration. Neither did it enhance the ability to bridge the gap with newly formed bone in an artificial defect wider than 1 mm. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Evaluation of moxifloxacin-hydroxyapatite composite graft in the regeneration of intrabony defects: A clinical, radiographic, and microbiological study

PubMed Central

Nagarjuna Reddy, Y. V.; Deepika, P. C.; Venkatesh, M. P.; Rajeshwari, K. G.

2016-01-01

Background: The formation of new connective periodontal attachment is contingent upon the elimination or marked reduction of pathogens at the treated periodontal site. An anti-microbial agent, i.e. moxifloxacin has been incorporated into the bone graft to control infection and facilitate healing during and after periodontal therapy. Materials and Methods: By purposive sampling, 15 patients with at least two contralateral vertical defect sites were selected. The selected sites in each individual were divided randomly into test and control sites according to split-mouth design. Test site received moxifloxacin-hydroxyapatite composite graft and control site received hydroxyapatite-placebo gel composite graft. Probing depth (PD) and Clinical attachment level (CAL) were assessed at baseline, 3, 6, 9, and 12 months. Bone probing depth (BPD) and hard tissue parameters such as amount of defect fill, percentage of defect fill, and changes in alveolar crest were assessed at baseline, 6, and 12 months. Changes in subgingival microflora were also assessed by culturing the subgingival plaque samples at baseline and at 3-month follow-up. The clinical, radiographic, and microbiological data obtained were subjected to statistical analysis using descriptive statistics, paired sample t-test, independent t-test, and contingency test. Results: On intragroup comparison at test and control sites, there was a significant improvement in all clinical and radiographic parameters. However, on intergroup comparison of the same, there was no statistically significant difference between test and control sites at any interval. Although test sites showed slightly higher amount of bone fill, it was not statistically significant. There was a significant reduction in the counts of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis at both sites from baseline to 3 months. In addition, there was a significant reduction at test sites as compared to control sites at 3-month follow-up (P = 0.003 and P = 0.013). Conclusion: The reduction in microbial counts found in test sites at 3-month follow-up could not bring similar significant improvements in the clinical and radiographic parameters though the test sites showed slightly higher bone fill. PMID:27630501

Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect.

PubMed

Singh, Krishna Bhan; Dixit, Manisha; Dev, Kapil; Maurya, Rakesh; Singh, Divya

2017-06-01

The bone regeneration and healing effect of formononetin was evaluated in a cortical bone defect model that predominantly heals by intramembranous ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a drill-hole injury was generated in the midfemoral bones of all animals. Treatment with formononetin commenced the day after and continued for 21 d. Parathyroid hormone (PTH1-34) was used as a reference standard. Animals were killed at days 10 and 21. Femur bones were collected at the injury site for histomorphometry studies using microcomputed tomography (μCT) and confocal microscopy. RNA and protein were harvested from the region surrounding the drill-hole injury. For immunohistochemistry, 5 µm sections of decalcified femur bone adjoining the drill-hole site were cut. μCT analysis showed that formononetin promoted bone healing at days 10 and 21 and the healing effect observed was significantly better than in Ovx mice and equal to PTH treatment in many aspects. Formononetin also significantly enhanced bone regeneration as assessed by calcein-labelling studies. In addition, formononetin enhanced the expression of osteogenic markers at the injury site in a manner similar to PTH. Formononetin treatment also led to predominant runt-related transcription factor 2 and osteocalcin localisation at the injury site. These results support the potential of formononetin to be a bone-healing agent and are suggestive of its promising role in the fracture-repair process.

Biomimetic materials for controlling bone cell responses.

PubMed

Drevelle, Olivier; Faucheux, Nathalie

2013-01-01

Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks, such as pain and morbidity at both donor and acceptor sites, the limited quantity of material available, and frequently its inappropriate shape. Researchers have therefore developed alternative strategies that involve biomaterials to fill bone defects. These biomaterials must be biocompatible and interact with the surrounding bone tissue to allow their colonization by bone cells and blood vessels. The latest generation biomaterials are not inert; they control cell responses like adhesion, proliferation and differentiation. These biomaterials are called biomimetic materials. This review focuses on the development of third generation materials. We first briefly describe the bone tissue with its cells and matrix, and then how bone cells interact with the extracellular matrix. The next section covers the materials currently used to repair bone defects. Finally, we describe the strategies employed to modify the surface of materials, such as coating with hydroxyapatite and grafting biomolecules.

Effect of Implanting a Soft Tissue Autograft in a Central-Third Patellar Tendon Defect: Biomechanical and Histological Comparisons

PubMed Central

Kinneberg, Kirsten R. C.; Galloway, Marc T.; Butler, David L.; Shearn, Jason T.

2011-01-01

Previous studies by our laboratory have demonstrated that implanting a stiffer tissue engineered construct at surgery is positively correlated with repair tissue stiffness at 12 weeks. The objective of this study was to test this correlation by implanting a construct that matches normal tissue biomechanical properties. To do this, we utilized a soft tissue patellar tendon autograft to repair a central-third patellar tendon defect. Patellar tendon auto-graft repairs were contrasted against an unfilled defect repaired by natural healing (NH). We hypothesized that after 12 weeks, patellar tendon autograft repairs would have biomechanical properties superior to NH. Bilateral defects were established in the central-third patellar tendon of skeletally mature (one year old), female New Zealand White rabbits (n = 10). In one limb, the excised tissue, the patellar tendon autograft, was sutured into the defect site. In the contralateral limb, the defect was left empty (natural healing). After 12 weeks of recovery, the animals were euthanized and their limbs were dedicated to bio-mechanical (n = 7) or histological (n = 3) evaluations. Only stiffness was improved by treatment with patellar tendon autograft relative to natural healing (p = 0.009). Additionally, neither the patellar tendon autograft nor natural healing repairs regenerated a normal zonal insertion site between the tendon and bone. Immunohistochemical staining for collagen type II demonstrated that fibrocartilage-like tissue was regenerated at the tendon-bone interface for both repairs. However, the tissue was disorganized. Insufficient tissue integration at the tendon-to-bone junction led to repair tissue failure at the insertion site during testing. It is important to re-establish the tendon-to-bone insertion site because it provides joint stability and enables force transmission from muscle to tendon and subsequent loading of the tendon. Without loading, tendon mechanical properties deteriorate. Future studies by our laboratory will investigate potential strategies to improve patellar tendon autograft integration into bone using this model. [DOI: 10.1115/1.4004948] PMID:22010737

Use of the Er:YAG laser for improved plating in maxillofacial surgery: comparison of bone healing in laser and drill osteotomies.

PubMed

Lewandrowski, K U; Lorente, C; Schomacker, K T; Flotte, T J; Wilkes, J W; Deutsch, T F

1996-01-01

Surgical reconstruction of bony defects in the maxillofacial region involves fixation of bony fragments with mini and micro plates. Bone stabilization during hole drilling is often challenging due to the need to apply pressure when using a conventional mechanical Hall drill. In addition, fragmentation of the fragile bones may occur and complicate the reconstruction. The pulsed Er:YAG laser offers an attractive alternative drilling modality because it does not require physical contact with the bone in order to drill holes, cuts bone with minimal thermal damage, and allows precise control of bone cutting. The objective of this study was to investigate the pulsed Er:YAG laser as an alternative to the mechanical bur by comparing bone healing using both modalities. Bone healing in an inferior border defect of the rat mandible was examined using either an Er:YAG laser or a mechanical bur for drilling. The healing of osteotomies in facial bones and of screw holes for plate stabilization of free bone fragments was studied. All defects healed by 4 weeks postoperatively. Histologic evaluation demonstrated no difference in the amount of newly formed woven bone at the osteotomy site or screw holes made by either the laser or the drill. The extent of thermal damage at the osteotomy sites was comparable in laser and mechanically cut bone fragments. On the basis of this study we suggest that the Er: YAG laser can be used clinically in thin, fragile bones in the maxillofacial region.

Comparison of different grafting materials for treatment of bone defect distal to the molar in canine.

PubMed

Ge, Jing; Yang, Chi; Wang, Yong; Zheng, Jiawei; Hua, Hongfei; Zhu, Jun

2018-03-25

The extraction of impacted mandibular 3rd molar is highly related to bone defect distal to the adjacent 2nd molar. The aim of this study was to evaluate the effect of different grafting materials for the treatment of bone defect distal to the mandibular molar in canine model. In 12 beagle dogs, bilateral mandibular 2nd and 3rd molars were extracted and entire mesial bone of the 2nd molar extracted socket was surgically removed. Twenty-four bone defects (4 mm width and 8 mm depth) were randomly assigned to 4 groups, and grafted using 1 of the following protocols: (1) group C: no graft; (2) group Ta: autogenous bone (AB); (3) group Tb: deproteinized bovine bone mineral (DBBM) with a collagen membrane (CM); and (4) group Tab: an equal mixture of AB/DBBM + CM. Quantitative imageology analyses using micro-CT and fluorescence microscopy, as well as qualitative analyses using histological and histomorphometric evaluations, were characterized at postoperative 12 weeks. Significant differences of all variables were tested by multivariate analysis (P < .05). The defect depth was significantly lower in groups Ta, Tb, and Tab (1.70, 1.97, and 1.61 mm, respectively; mean) than in the group C (3.66 mm, P < .01, all). Compared to the sites received DBBM/CM, sites grafted with AB or AB/DBBM exhibited significant greater and faster new bone formation (P < .01). The percentage of DBBM remnants area (%) was significantly higher in group Tb than in group Tab (10.43% and 1.13%, P < .01; mean). Our data suggested grafting AB alone, DBBM/CM, or AB/DBBM/CM resulted in similar periodontal parameters in canine. Furthermore, the AB could accelerate new bone regeneration and mineralization, and promote the biodegradation of DBBM. © 2018 Wiley Periodicals, Inc.

The influence of platelet-rich fibrin on angiogenesis in guided bone regeneration using xenogenic bone substitutes: a study of rabbit cranial defects.

PubMed

Yoon, Jong-Suk; Lee, Sang-Hwa; Yoon, Hyun-Joong

2014-10-01

The purpose of this study was to investigate the influence of platelet-rich fibrin (PRF) on angiogenesis and osteogenesis in guided bone regeneration (GBR) using xenogenic bone in rabbit cranial defects. In each rabbit, 2 circular bone defects, one on either side of the midline, were prepared using a reamer drill. Each of the experimental sites received bovine bone with PRF, and each of the control sites received bovine bone alone. The animals were sacrificed at 1 week (n = 4), 2 weeks (n = 3) and 4 weeks (n = 3). Biopsy samples were examined histomorphometrically by light microscopy, and expression of vascular endothelial growth factor (VEGF) was determined by immunohistochemical staining. At all experimental time points, immunostaining intensity for VEGF was consistently higher in the experimental group than in the control group. However, the differences between the control group and the experimental group were not statistically significant in the histomorphometrical and immunohistochemical examinations. The results of this study suggest that PRF may increase the number of marrow cells. However, PRF along with xenogenic bone substitutes does not show a significant effect on bony regeneration. Further large-scale studies are needed to confirm our results. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Effect of Semelil, an Herbal Selenium-Based Medicine, on New Bone Formation in Calvarium of Rabbits

PubMed Central

Rasouli-Ghahroudi, Amir Alireza; Rokn, Amirreza; Mashhadi-Abbas, Fatemeh

2018-01-01

Background This study aims to analyze the effect of Semelil, an herbal selenium-based medicine, on osteogenesis in rabbit calvarium defects. Methods Four identical bony defects (8 mm) were created in the calvarium of 16 New Zealand male rabbits and filled randomly with xenogenic bone substitute material (Bio-Oss®) and semelil herbal drug (ANGIPARS™). One site was filled with Bio-Oss (B); the second site was treated with ANGIPARS (A); the third site was treated with ANGIPARS + Bio-Oss (AB); and the fourth site was left as untreated control (C) and defects were left unfilled. Rabbits were randomly divided into two groups (n = 8) and sacrificed at four and eight weeks. Percentage of new bone formation, type of the newly formed bone, percentage of the remaining xenograft biomaterial, and foreign body reaction (FBR) were evaluated via histological and histomorphometric analyses. Results The percentage of new bone formation was significantly different among four groups. The highest effect was observed in AB, followed by A, B, and C groups, respectively. The difference in the mean percentage of new bone formation between four and eight weeks was significant for all four groups (P < 0.001). Regarding bone formation, the interaction effect of A and B was significant at four (P < 0.001) and eight weeks (P = 0.002). ANGIPARS alone and in presence of Bio-Oss enhanced new bone formation at both four and eight weeks (P < 0.001). The mean amount of new bone formation was significantly different at four and eight weeks in groups C (P = 0.008), A (P < 0.001), B (P < 0.001), and AB (P = 0.003). FBR was not observed in any group. Conclusion Semelil may be useful as an adjunct to conventional osteoconductive materials in order to enhance osteogenesis. PMID:29682529

Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients.

PubMed

Alonso, Nivaldo; Tanikawa, Daniela Yukie Sakai; Freitas, Renato da Silva; Canan, Lady; Ozawa, Terumi Okada; Rocha, Diógenes Laércio

2010-10-01

A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting.

BoneCeramic graft regenerates alveolar defects but slows orthodontic tooth movement with less root resorption.

PubMed

Ru, Nan; Liu, Sean Shih-Yao; Bai, Yuxing; Li, Song; Liu, Yunfeng; Wei, Xiaoxia

2016-04-01

BoneCeramic (Straumann, Basel, Switzerland) can regenerate bone in alveolar defects after tooth extraction, but it is unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate 3-dimensional real-time root resorption and bone responses in grafted sites during orthodontic tooth movement. Sixty 5-week-old rats were randomly assigned to 3 groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss; Geistlich Pharma, Wolhusen, Switzerland), or no graft, after the extraction of the maxillary left first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures and root resorption were evaluated using in-vivo microcomputed tomography. Stress distribution and corresponding tissue responses were examined by the finite element method and histology. Mixed model analysis of variance was performed to compare the differences among time points with Bonferroni post-hoc tests at the significance level of P <0.05. The BoneCeramic group had the least amount of tooth movement and root resorption volumes and craters, and the highest bone volume fraction, trabecular number, and mean trabecular thickness, followed by the Bio-Oss and the control groups. The highest stress accumulated in the cervical region of the mesial roots. BoneCeramic has better osteoconductive potential and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction sites. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model

PubMed Central

Anzai, Jun; Nagayasu-Tanaka, Toshie; Terashima, Akio; Asano, Taiji; Yamada, Satoru; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

2016-01-01

The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT). After FGF-2 (0.3%) or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC) were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological healing process. PMID:27391131

Reconstruction of mandibular defects with autogenous bone grafts: a review of 30 cases.

PubMed

Sajid, Malik Ali Hassan; Warraich, Riaz Ahmed; Abid, Hina; Ehsan-ul-Haq, Muhammad; Shah, Khurram Latif; Khan, Zafar

2011-01-01

Multitudes of options are available for reconstruction of functional and cosmetic defects of the mandible, caused by various ailments. At the present time, autogenous bone grafting is the gold standard by which all other techniques of reconstruction of the mandible can be judged. The purpose of this study was to evaluate the outcome of different osseous reconstruction options using autogenous bone grafts for mandibular reconstruction. This Interventional study was conducted at Department of Oral and Maxillofacial Surgery, King Edward Medical University/Mayo Hospital Lahore, from January 2008 to July 2009 including one year follow-up. The study was carried out on thirty patients having bony mandibular defects. They were reconstructed with the autogenous bone grafts from different graft donor sites. On post-operative visits they were evaluated for outcome variables. Success rate of autogenous bone grafts in this study was 90%. Only 10% of the cases showed poor results regarding infection, resorption and graft failure. Autogenous bone grafts, non-vascularised or vascularised, are a reliable treatment modality for the reconstruction of the bony mandibular defects with predictable functional and aesthetic outcome.

Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits.

PubMed

Mohseni, Mahmoud; Jahandideh, Alireza; Abedi, Gholamreza; Akbarzadeh, Abolfazl; Hesaraki, Saeed

2018-03-01

Bone regeneration is an important objective in clinical practice and has been used for different applications. The aim of this study was to evaluate the effectiveness of nanocomposite tricalcium phosphate (TCP)/collagen scaffolds combined with hydroxyapatite scaffold for bone healing in surgery of femoral defects in rabbits. In this study, 45 mature male New Zealand white rabbits between 6 and 8 months old and weighting between 3 and 3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were performed after intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg) and Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter-5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were coloured and randomly divided into three experimental groups of 15 animals each. Group 1 received pure medical nanocomposite TCP/collagen granules, group 2 received hydroxyapatite, and third group was a control group which received no treatment. Histopathological evaluation was performed on days 15, 30, and 45 after surgery. On days 15, 30, and 45 after surgery, the quantity and the velocity of stages of bone formation at the healing site in nanocomposite TCP/collagen group were better than HA and control groups and the quantity of newly formed lamellar bone at the healing site in nanocomposite TCP/collagen group were better than onward compared with HA and control groups. In conclusion, it seems that TCP/collagen nanocomposite has a significant role in the reconstruction of bone defects and can be used as scaffold in bone fractures.

Recent Developments of Functional Scaffolds for Craniomaxillofacial Bone Tissue Engineering Applications

PubMed Central

Kinoshita, Yukihiko; Maeda, Hatsuhiko

2013-01-01

Autogenous bone grafting remains a gold standard for the reconstruction critical-sized bone defects in the craniomaxillofacial region. Nevertheless, this graft procedure has several disadvantages such as restricted availability, donor-site morbidity, and limitations in regard to fully restoring the complicated three-dimensional structures in the craniomaxillofacial bone. The ultimate goal of craniomaxillofacial bone reconstruction is the regeneration of the physiological bone that simultaneously fulfills both morphological and functional restorations. Developments of tissue engineering in the last two decades have brought such a goal closer to reality. In bone tissue engineering, the scaffolds are fundamental, elemental and mesenchymal stem cells/osteoprogenitor cells and bioactive factors. A variety of scaffolds have been developed and used as spacemakers, biodegradable bone substitutes for transplanting to the new bone, matrices of drug delivery system, or supporting structures enhancing adhesion, proliferation, and matrix production of seeded cells according to the circumstances of the bone defects. However, scaffolds to be clinically completely satisfied have not been developed yet. Development of more functional scaffolds is required to be applied widely to cranio-maxillofacial bone defects. This paper reviews recent trends of scaffolds for crania-maxillofacial bone tissue engineering, including our studies. PMID:24163634

Preliminary in vivo report on the osteocompatibility of poly(anhydride-co-imides) evaluated in a tibial model.

PubMed

Ibim, S E; Uhrich, K E; Attawia, M; Shastri, V R; El-Amin, S F; Bronson, R; Langer, R; Laurencin, C T

1998-01-01

A novel class of polymers with mechanical properties similar to cancellous bone are being investigated for their ability to be used in weight-bearing areas for orthopedic applications. The poly(anhydride-co-imide) polymers based on poly[trimellitylimidoglycine-co-1,6-bis(carboxyphenoxy)hexan e] (TMA-Gly:CPH) and poly[pyromellitylimidoalanine-co-1,6-bis(carboxyphenoxy)hexa ne] (PMA-Ala:CPH) in molar ratios of 30:70 were investigated for osteocompatibility, with effects on the healing of unicortical 3-mm defects in rat tibias examined over a 30-day period. Defects were made with surgical drill bits (3-mm diameter) and sites were filled with poly(anhydride-co-imide) matrices and compared to the control poly(lactic acid-glycolic acid) (PLAGA) (50:50), a well-characterized matrix frequently used in bone regeneration studies, and defects without polymeric implants. At predetermined time intervals (3, 6, 9, 12, 20, and 30 days), animals were sacrificed and tissue histology was examined for bone formation, polymer-tissue interaction, and local tissue response by light microscopy. The studies revealed that matrices of TMA-Gly:CPH and PMA-Ala:CPH produced responses similar to the control PLAGA with tissue compatibility characterized by a mild response involving neutrophils, macrophages, and giant cells throughout the experiment for all matrices studied. Matrices of PLAGA were nearly completely degraded by 21 days in contrast to matrices of TMA-Gly:CPH and PMA-Ala:CPH that displayed slow erosion characteristics and maintenance of shape. Defects in control rats without polymer healed by day 12, defects containing PLAGA healed after 20 days, and defects containing poly(anhydride-co-imide) matrices produced endosteal bone growth as early as day 3 and formed bridges of cortical bone around matrices by 30 days. In addition, there was marrow reconstitution at the defect site for all matrices studied along with matured bone-forming cells. This study suggests that novel poly(anhydride-co-imides) are promising polymers that may be suitable for use as implants in bone surgery, especially in weight-bearing areas.

Vertical bone growth following autotransplantation of the developing maxillary third molar to replace a retained mandibular permanent molar: a case report.

PubMed

Plakwicz, Paweł; Czochrowska, Ewa Monika; Milczarek, Anna; Zadurska, Malgorzata

2014-01-01

A retained permanent mandibular first molar caused arrested development and a defect of the alveolar bone in a 16-year-old girl. Extraction of the ankylosed tooth was immediately followed by autotransplantation of the developing maxillary third molar. At the 3-year follow-up examination the interproximal bone level at the autotransplanted molar was equal to that of the neighboring teeth. Cone beam computed tomography showed bone at the labial aspect of the transplant. The eruption of the autotransplanted tooth stimulated vertical alveolar bone development and repaired the bone defect. Additionally, there was closure of the posterior open bite that was initially present at the ankylosed molar site.

Effects of Recombinant Human Bone Morphogenetic Protein-2 on Vertical Bone Augmentation in a Canine Model.

PubMed

Hsu, Yung-Ting; Al-Hezaimi, Khalid; Galindo-Moreno, Pablo; O'Valle, Francisco; Al-Rasheed, Abdulaziz; Wang, Hom-Lay

2017-09-01

Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)-2, under space-making titanium mesh in a canine model. Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP-2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4-month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro-CT) assessment and histologic analysis. Membrane exposure was found on five of 11 (45.5%) rhBMP-2-treated sites, whereas it was found on nine of 11 (81.8%) non-rhBMP-2-treated sites. Within 4 months of healing, rhBMP-2-treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P <0.05) than controls. Experimental hemimandibles exhibited lower rates of membrane exposure and a noteworthy, ectopic bone formation above the mesh in 72% of sites. Results from micro-CT also suggested a trend of less vertical bone gain and bone mineral density in controls (P >0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP-2 sites. With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP-2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non-rhBMP-2 sites.

Reconstruction of Extensive Soft-Tissue Defects with Concomitant Bone Defects in the Lower Extremity with the Latissimus Dorsi-Serratus Anterior-Rib Free Flap.

PubMed

Sia, Wei Tee; Xu, Germaine Guiqin; Puhaindran, Mark Edward; Tan, Bien Keem; Cheng, Mathew Hern Wang; Chew, Winston Yoon Chong

2015-07-01

The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction. Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients. All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap. The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Ridge preservation at implants installed immediately after molar extraction. An experimental study in the dog.

PubMed

Favero, Giacomo; Lang, Niklaus P; De Santis, Enzo; Gonzalez, Brismayda Garcia; Schweikert, Michael T; Botticelli, Daniele

2013-03-01

To evaluate the influence of deproteinized bovine bone mineral (DBBM), in conjunction with a collagen membrane, on bone resorption at implants installed in a lingual position immediately into extraction sockets with horizontal residual buccal defects >2.0 mm. The pulp tissue of the mesial roots of (1) M(1) was removed in six Labrador dogs, and the root canals were filled with gutta-percha and cement. Flaps were elevated. The molars were hemi-sectioned and the distal roots removed. Implants were installed in a lingual position and with the shoulder flush with the buccal bony crest. After installation, defects of about 2.5 and 2.7 mm in width resulted at the buccal aspects of the test and control sites, respectively. Only in the left site (test), deproteinized bovine bone mineral (DBBM) particles were placed into the defect concomitantly with the placement of a collagen membrane. On the control sites, no biomaterials were applied. A non-submerged healing was allowed. After 3 months of healing, one control implant was not integrated and was excluded from the analysis, together with the contralateral test implant. All remaining implants were integrated into mature bone. The buccal alveolar bony crest was resorbed more at the test compared with the control sites, 2.2 ± 0.9 mm and 1.5 ± 1.3 mm, respectively. The vertical resorption of the lingual plate was 1.6 ± 1.5 mm and 1.5 ± 1.1 mm at the test and control sites, respectively. Only small residual DBBM particles were found at the test sites (1.4%). The use of DBBM particles to fill buccal defects of ≥2.5 mm at implants installed immediately into alveolar extraction sockets did not preserve the buccal bony wall. © 2012 John Wiley & Sons A/S.

Reconstruction of large diaphyseal bone defect by simplified bone transport over nail technique: A 7-case series.

PubMed

Ferchaud, F; Rony, L; Ducellier, F; Cronier, P; Steiger, V; Hubert, L

2017-11-01

Reconstruction of large diaphyseal bone defect is complex and the complications rate is high. This study aimed to assess a simplified technique of segmental bone transport by monorail external fixator over an intramedullary nail.A prospective study included 7 patients: 2 femoral and 5 tibial defects. Mean age was 31years (range: 16-61years). Mean follow-up was 62 months (range: 46-84months). Defects were post-traumatic, with a mean length of 7.2cm (range: 4 to 9.5cm). For 3 patients, reconstruction followed primary failure. In 4 cases, a covering flap was necessary. Transport used an external fixator guided by an intramedullary nail, at a rate of 1mm per day. One pin was implanted on either side of the distraction zone. The external fixator was removed 1 month after bone contact at the docking site. Mean bone transport time was 11 weeks (range: 7-15 weeks). Mean external fixation time was 5.1months (range: 3.5 to 8months). Full weight-bearing was allowed 5.7months (range: 3.5-13months) after initiation of transport. In one patient, a pin had to be repositioned. In 3 patients, the transported segment re-ascended after external fixatorablation, requiring repeat external fixation and resumption of transport. There was just 1 case of superficial pin infection. Reconstruction quality was considered "excellent" on the Paley-Marr criteria in 6 cases. The present technique provided excellent reconstruction quality in 6 of the 7 cases. External fixation time was shorter and resumption of weight-bearing earlier than with other reconstruction techniques, notably including bone autograft, vascularized bone graft or the induced membrane technique. Nailing facilitated control of limb axis and length. The complications rate was 50%, comparable to other techniques. This study raises the question of systematic internal fixation of the docking site, to avoid any mobilization of the transported segment. The bone quality, axial control and rapidity shown by the present technique make it well-adapted to reconstruction of diaphyseal bone defect. Four-case series. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Changes in bone microstructure and toughness during the healing process of long bones

NASA Astrophysics Data System (ADS)

Ishimoto, T.; Nakano, T.; Umakoshi, Y.; Tabata, Y.

2009-05-01

It is of great importance to understand how bone defects regain the microstructure and mechanical function of bone and how the microstructure affects the mechanical function during the bone healing process. In the present study on long bone defects, we investigated the relationship between the recovery process of fracture toughness and biological apatite (BAp)/collagen (Col) alignment as an index of the bone microstructure to clarify the bone toughening mechanisms. A 5-mm defect introduced in the rabbit ulna was allowed to heal naturally and a three-point bending test was conducted on the regenerated site to assess bone toughness. The bone toughness was quite low at the early stage of bone regeneration but increased during the postoperative period. The change in toughness agreed well with the characteristics of the fracture surface morphology, which reflected the history of the crack propagation. SEM and microbeam X-ray diffraction analyses indicated that the toughness was dominated by the degree and orientation of the preferred BAp/Col alignment, i.e. bundles aligned perpendicular to the crack propagation clearly contributed to the bone toughening owing to extra energy consumption for resistance to crack propagation. In conclusion, regenerated bone improves fracture toughness by reconstructing the preferred BAp/Col alignment along the bone longitudinal axis during the healing process of long bones.

Biphasic β-TCP mixed with silicon increases bone formation in critical site defects in rabbit calvaria.

PubMed

Calvo-Guirado, José Luis; Garces, Miguel; Delgado-Ruiz, Rafael Arcesio; Ramirez Fernandez, Maria P; Ferres-Amat, Eduard; Romanos, Georgios E

2015-08-01

The aim of this study was to assess the bone regeneration of critical size defects in rabbit calvarias filled with β-TCP doped with silicon. Twenty-one New Zealand rabbits were used in this study. Two critical size defects were created in the parietal bones. Three experimental groups were evaluated: Test A (HA/β-TCP granules alone), Test B (HA/β-TCP granules plus 3% silicon), Control (empty defect). The animals were sacrificed at 8 and 12 weeks. Evaluation was performed by μCT analysis and histomorphometry. μCT evaluation showed higher volume reduction in Test A group compared with Test B (P < 0.05). The Test B group showed the highest values for cortical closure and bone formation around the particles, followed by Test A and controls (P < 0.05). Within the limitations of this animal study, it can be concluded that HA/β-TCP plus 3% silicon increases bone formation in critical size defects in rabbit calvarias, and the incorporation of 3% silicon reduces the resorption rate of the HA/β-TCP granules. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

PubMed

Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M

1999-03-01

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.

Bone allografting in children

NASA Astrophysics Data System (ADS)

Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

2017-09-01

A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

Treatment of intrabony defects with resorbable materials, non-resorbable materials and flap debridement.

PubMed

Zybutz, M D; Laurell, L; Rapoport, D A; Persson, G R

2000-03-01

Different types of barriers are used in guided tissue regenerative procedures. This prospective study compared resorbable citric acid ester softened polylactic acid membranes (RM) and non-resorbable expanded polytetrafluoroethylene (ePTFE) barriers (NRM) in GTR treatment of intrabony defects. 29 subjects were randomly assigned to the RM group or NRM group. Each patient received one GTR procedure. An open flap debridement (FD) was performed at another site 2 weeks later to evaluate healing potential. Clinical treatment outcomes were finally evaluated 12 months after surgery for changes of pocket depth PD, probing attachment level PAL, and probing bone level PBL, and radiographically for bone change using standardised radiographs. No differences in healing patters after surgery were found between patients in the 2 study groups as evaluated from the FD surgical procedures. NRM treated sites showed less signs of post-surgical inflammation during the 1st 4 weeks of healing than did RM treated sites (p<0.05). GTR-treated defects in the RM group, initially 7.0+/-2.2 mm deep, showed PD reduction of 3.3+/-2.2 mm, PAL gain of 2.4+/-1.8 mm, PBL gain of 2.4+/-3.7 mm (28%) and a radiographic bone fill of 2.3+/-2.4 mm. Defects treated with the NRM exhibited PD reduction of 3.1+/-2.1 mm, PAL gain of 2.4+/-0.8 mm, PBL gain of 2.2+/-1.7 mm (25%) and a radiographic bone fill of 3.3+/-2.2 mm. All improvements were statistically significant (p<0.01) but there was no difference between RM and NRM treatments for any of the efficacy variables. The results of this study indicated that there was no clinically significant difference in treatment outcomes following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes as compared to ePTFE barriers. The overall mean inter-proximal vertical bone defect fill at 12 months as assessed from intra-oral radiographs was 44% of the original mean defect depth. Thus, no clinically significant difference in treatment outcomes was observed following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes or ePTFE barriers.

PTH promotes allograft integration in a calvarial bone defect.

PubMed

Sheyn, Dmitriy; Cohn Yakubovich, Doron; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M; Gazit, Dan; Gazit, Zulma

2013-12-02

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.

The Results of the Surgical Treatment of Spontaneous Rhinorrhea via Craniotomy and the Contribution of CT Cisternography to the Detection of Exact Leakage Side of CSF.

PubMed

Tumturk, Abdulfettah; Ulutabanca, Halil; Gokoglu, Abdulkerim; Oral, Sukru; Menku, Ahmet; Kurtsoy, Ali

2016-01-01

To share the results of conventional surgery in rhinorrhea and the contribution of computerized tomography (CT) cisternography to determination of the site of cerebrospinal fluid (CSF) leak. Twelve cases treated for spontaneous rhinorrhea were included in this study. All the cases underwent cranial CT and magnetic resonance imaging (MRI). CT cisternography was performed in four patients whose bone defect or leakage site could not be detected by CT and MRI. In order to repair the defect, either the galea or galea together with collagen matrix was used and the procedure was supported with fibrin glue. In the cases, postoperative rhinorrhea was seen in neither the early nor the late follow up period. We observed no complications related to CT cisternography or craniotomy. The leakage area was successfully detected with CT cisternography when the other methods failed. Bone defect can usually be shown by means of CT. However, when bone-defect cannot be shown or the dura in the defective area is intact, CT cisternography is useful to show the CSF leak. Conventional surgery was very succesful in the treatment of spontaneous rhinorrhea but it was cosmetically problematic. In the patients both treated with galea and galea together with collagen matrix, the repair of the defect was successful.

Secondary closure of alveolar cleft with resorbable collagen membrane and a combination of intraoral autogenous bone graft and deproteinized anorganic bovine bone

PubMed Central

Aly, Lobna Abdel Aziz; Hammouda, Nelly

2016-01-01

Objects: Secondary alveolar bone grafting is a method that enables an excellent oral rehabilitation of the patients having alveolar cleft. The aim of this work is to report the closure of the alveolar cleft with the use of harvested autogenous bone graft combined with deproteinized anorganic bovine bone (Bio-Oss) under local anesthesia. Settings and Sample Population: Nine patients with age range, 8–11 years were consulted for their unilateral alveolar cleft. Materials and Methods: A combination of symphyseal bone and deproteinized bovine bone mineral (DBBM) was placed into the alveolar cleft defect. Clinical and radiographical assessments were performed at 1, 3, and 6 months postoperatively. Results: The healing period was uneventful in all cases, and no complications, such as membrane exposure, infection, or harvest site morbidity, were observed. All treated defect sites exhibited excellent bone formation, with an average of 5.45 mm (range, 2–9 mm; standard deviation 1.93 mm) of augmentation achieved overall. Conclusion: The treatment of vertically deficient alveolar ridges with guided bone regeneration using a mixture of autogenous bone and DBBM and resorbable collagen membrane can be considered successful, using this technique in an out-patient office setting. PMID:28299252

Apatite-coated Silk Fibroin Scaffolds to Healing Mandibular Border Defects in Canines

PubMed Central

Zhao, Jun; Zhang, Zhiyuan; Wang, Shaoyi; Sun, Xiaojuan; Zhang, Xiuli; Chen, Jake; Kaplan, David L.; Jiang, Xinquan

2010-01-01

Tissue engineering has become a new approach for repairing bony defects. Highly porous osteoconductive scaffolds perform the important role for the success of bone regeneration. By biomimetic strategy, apatite-coated porous biomaterial based on silk fibroin scaffolds (SS) might provide an enhanced osteogenic environment for bone-related outcomes. To assess the effects of apatite-coated silk fibroin (mSS) biomaterials for bone healing as a tissue engineered bony scaffold, we explored a tissue engineered bony graft using mSS seeded with osteogenically induced autologous bone marrow stromal cells (bMSCs) to repair inferior mandibular border defects in a canine model. The results were compared with those treated with bMSCs/SS constructs, mSS alone, SS alone, autologous mandibular grafts and untreated blank defects. According to radiographic and histological examination, new bone formation was observed from 4 weeks post-operation, and the defect site was completely repaired after 12 months for the bMSCs/mSS group. In the bMSCs/SS group, new bone formation was observed with more residual silk scaffold remaining at the center of the defect compared with the bMSCs/mSS group. The engineered bone with bMSCs/mSS achieved satisfactory bone mineral densities (BMD) at 12 months post-operation close to those of normal mandible (p>0.05). The quantities of newly formed bone area for the bMSCs/mSS group was higher than the bMSCs/SS group (p<0.01), but no significant differences were found when compared with the autograft group (p>0.05). In contrast, bony defects remained in the center with undegraded silk fibroin scaffold and fibrous connective tissue, and new bone only formed at the periphery in the groups treated with mSS or SS alone. The results suggested apatite-coated silk fibroin scaffolds combined with bMSCs could be successfully used to repair mandibular critical size border defects and the premineralization of these porous silk fibroin protein scaffolds provided an increased osteoconductive environment for bMSCs to regenerate sufficient new bone tissue. PMID:19505603

Effect of membrane exposure on guided bone regeneration: A systematic review and meta-analysis.

PubMed

Garcia, Jeffrey; Dodge, Austin; Luepke, Paul; Wang, Hom-Lay; Kapila, Yvonne; Lin, Guo-Hao

2018-03-01

This review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at peri-implant sites and edentulous ridges. Electronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A random-effects meta-analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported. Overall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was -76.24% (95% CI = -137.52% to -14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at peri-implant sites was -27.27% (95% CI of -45.87% to -8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure. Based on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For peri-implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A randomized controlled clinical trial comparing small buccal dehiscence defects around dental implants treated with guided bone regeneration or left for spontaneous healing.

PubMed

Jung, Ronald E; Herzog, Milan; Wolleb, Karin; Ramel, Christian F; Thoma, Daniel S; Hämmerle, Christoph H F

2017-03-01

The aim of the present randomized controlled clinical study was to test whether small bony dehiscence defects (≤5 mm) left to heal spontaneously result in the same clinical and radiological outcome as defects treated with guided bone regeneration (GBR). Twenty-two patients who received at least one implant with a small bony dehiscence defect were enrolled in the study. If the defect height was ≤5 mm, the site was randomly assigned to either the spontaneous healing (SH) group or the GBR group. In the SH group, the defect was left without any treatment. In the GBR group, the defects around the implants were grafted with deproteinized bovine bone mineral (DBBM) and covered with a native collagen membrane. Clinical and radiographic measurements were performed 6 months after implant placement with a reentry surgery and at the time of crown insertion and the subsequent follow-up appointments at 3, 6, 12 and 18 months after loading. For statistical analyses, the mixed linear model was applied for the clinical and radiographic measurements observed around the implants. Simple comparisons of the location of the measurements in the two independent groups are performed with the Mann-Whitney U-test. In addition, the mixed model assumptions were checked. The implant and crown survival rate 18 months after loading was 100%, revealing no serious biologic or prosthetic complication. The mean changes of the buccal vertical bone height between implant placement and reentry surgery after 6 months revealed a small bone loss of -0.17 ± 1.79 mm (minimum -4 mm and maximum 2.5 mm) for the SH group and a bone gain of 1.79 ± 2.24 mm (minimum of -2.5 mm and maximum of 5 mm) for the GBR group, respectively (P = 0.017). Radiographic measurements demonstrated a slight bone loss of -0.39 ± 0.49 mm for the SH group and a stable bone level of 0.02 ± 0.48 mm for GBR group after 18 months. All peri-implant soft tissue parameters revealed healthy tissues with no difference between the two groups. Small bony dehiscence defects left for spontaneous healing demonstrated high implant survival rates with healthy and stable soft tissues. However, they revealed more vertical bone loss at the buccal aspect 6 months after implant insertion and also more marginal bone loss between crown insertion and 18 months after loading compared to sites treated with GBR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alcohol intake may impair bone density and new cementum formation after enamel matrix derivative treatment: histometric study in rats.

PubMed

Corrêa, M G; Gomes Campos, M L; Marques, M R; Ambrosano, G M B; Casati, M Z; Nociti, F H; Sallum, E A

2016-02-01

Alcohol intake may interfere with bone metabolism; however, there is a lack of information about the outcomes of regenerative approaches in the presence of alcohol intake. Enamel matrix derivative (EMD) has been used in periodontal regenerative procedures resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of alcohol intake. Twenty Wistar rats were randomly assigned to two groups: G1 = alcohol intake (n = 10) and G2 = non-exposed to alcohol intake (n = 10). Thirty days after initiation of alcohol intake, fenestration defects were created at the buccal aspect of the first mandibular molar of all animals from both groups. After the surgeries, the defects of each animal were randomly assigned to two subgroups: non-treated control and treated with EMD. The animals were killed 21 d later. G1 showed less defect fill for non-treated controls. Bone density (BD) and new cementum formation were lower for G1 when compared to G2, for EMD-treated and non-treated sites. EMD treatment resulted in greater BD and new cementum formation in both groups and defect fill was not significantly different between groups in the EMD-treated sites. The number of tartrate-resistant acid phosphatase-positive osteoclasts was significantly higher in G1 when compared to G2 and in EMD-treated sites of both groups. Alcohol intake may produce a significant detrimental effect on BD and new cementum formation, even in sites treated with EMD. A limited positive effect may be expected after EMD treatment under this condition. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of cranial bone transport distraction with and without adipose grafting.

PubMed

Koch, Felix P; Yuhasz, Mikell M; Travieso, Rob; Wong, Kenneth; Clune, James; Zhuang, Zhen W; Van Houten, Joshua; Steinbacher, Derek M

2014-05-01

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

Effect of intermittent administration of teriparatide on the mechanical and histological changes in bone grafted with β-tricalcium phosphate using a rabbit bone defect model

PubMed Central

Komatsu, Jun; Nagura, Nana; Iwase, Hideaki; Igarashi, Mamoru; Ohbayashi, Osamu; Nagaoka, Isao; Kaneko, Kazuo

2018-01-01

Grafting β-tricalcium phosphate (TCP) is a well-established method for restoring bone defects; however, there is concern that the mechanical stability of the grafted β-TCP is not maintained during bone translation. Teriparatide has an anabolic effect, stimulating bone formation and increasing bone mineral density for the treatment of osteoporosis. The aim of the present study was to evaluate the effect of intermittent teriparatide treatment on changes in bone grafted with β-TCP using a rabbit bone defect model. Bone defects (5×15 mm) were created in the distal femoral condyle of Japanese white rabbits, and β-TCP granules of two different total porosities were manually grafted. Teriparatide (40 µg/kg) or 0.2% rabbit serum albumin solution as a vehicle control was subcutaneously injected three times per week following the surgery. At 4 or 8 weeks post-surgery, serum samples were obtained and the levels of γ-carboxylated osteocalcin (Gla-OC) were quantified using ELISA. Histomorphometry was also performed using sections of graft sites following staining for tartrate resistant acid phosphatase. Activity and mechanical strength (maximum shear strength, maximum shear stiffness and total energy absorption) were evaluated using an axial push-out load to failure test. Teriparatide treatment significantly increased (P<0.05) the serum levels of Gla-OC, a specific marker for bone formation, suggesting that teriparatide enhances bone formation in β-TCP-grafted rabbits. Furthermore teriparatide increased the degradation of β-TCP by bone remodeling (P<0.05) and promoted the formation of new bone following application of the graft compared with the control group (P<0.01). Furthermore, teriparatide suppressed the reduction in mechanical strength (P<0.05) during bone translation in bone defects grafted with β-TCP. The results of the present study demonstrate that teriparatide is effective in maintaining the mechanical stability of grafted β-TCP, possibly by promoting new bone formation. PMID:29387179

Strontium enhances osseointegration of calcium phosphate cement: a histomorphometric pilot study in ovariectomized rats.

PubMed

Baier, Martin; Staudt, Patric; Klein, Roman; Sommer, Ulrike; Wenz, Robert; Grafe, Ingo; Meeder, Peter Jürgen; Nawroth, Peter P; Kasperk, Christian

2013-06-07

Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone. Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine. Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups. The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.

Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.

PubMed

Marini, Joan C; Reich, Adi; Smith, Simone M

2014-08-01

Osteogenesis imperfecta or 'brittle bone disease' has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for osteogenesis imperfecta as a collagen-related disorder, where most cases are due to autosomal dominant type I collagen defects, while rare, mostly recessive, forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development, and future of this paradigm shift in the understanding of osteogenesis imperfecta. Bone-restricted interferon-induced transmembrane (IFITM)-like protein (BRIL) and pigment epithelium-derived factor (PEDF) defects cause types V and VI osteogenesis imperfecta via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational modification. Heat shock protein 47 (HSP47) and FK506-binding protein-65 (FKBP65) defects cause types X and XI osteogenesis imperfecta via aberrant collagen crosslinking, folding, and chaperoning, while defects in SP7 transcription factor, wingless-type MMTV integration site family member 1 (WNT1), trimeric intracellular cation channel type b (TRIC-B), and old astrocyte specifically induced substance (OASIS) disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase bone morphogenetic protein 1 (BMP1) causes type XII osteogenesis imperfecta due to altered collagen maturation/processing. Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of osteogenesis imperfecta types by shared mechanism to simplify current nosology, and has prodded investigations into common pathways in osteogenesis imperfecta. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

PubMed Central

Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

2016-01-01

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

Middle cranial fossa approach to repair tegmen defects assisted by three-dimensionally printed temporal bone models.

PubMed

Ahmed, Sameer; VanKoevering, Kyle K; Kline, Stephanie; Green, Glenn E; Arts, H Alexander

2017-10-01

To explore the perioperative utility of three-dimensionally (3D)-printed temporal bone models of patients undergoing repair of lateral skull base defects and spontaneous cerebrospinal fluid leaks with the middle cranial fossa approach. Case series. 3D-printed temporal bone models-based on patient-specific, high-resolution computed tomographic imaging-were constructed using inexpensive polymer materials. Preoperatively, the models demonstrated the extent of temporal lobe retraction necessary to visualize the proposed defects in the lateral skull base. Also preoperatively, Silastic sheeting was arranged across the modeled tegmen, marked, and cut to cover all of the proposed defect sites. The Silastic sheeting was then sterilized and subsequently served as a precise intraoperative template for a synthetic dural replacement graft. Of note, these grafts were customized without needing to retract the temporal lobe. Five patients underwent the middle cranial fossa approach assisted by 3D-printed temporal bone models to repair tegmen defects and spontaneous cerebrospinal fluid leaks. No complications were encountered. The prefabricated dural repair grafts were easily placed and fit precisely onto the middle fossa floor without any additional modifications. All defects were covered as predicted by the 3D temporal bone models. At their postoperative visits, all five patients maintained resolution of their spontaneous cerebrospinal fluid leaks. Inexpensive 3D-printed temporal bone models of tegmen defects can serve as beneficial adjuncts during lateral skull base repair. The models provide a panoramic preoperative view of all tegmen defects and allow for custom templating of dural grafts without temporal lobe retraction. 4 Laryngoscope, 127:2347-2351, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Focal cartilage defect compromises fluid-pressure dependent load support in the knee joint.

PubMed

Dabiri, Yaghoub; Li, LePing

2015-06-01

A focal cartilage defect involves tissue loss or rupture. Altered mechanics in the affected joint may play an essential role in the onset and progression of osteoarthritis. The objective of the present study was to determine the compromised load support in the human knee joint during defect progression from the cartilage surface to the cartilage-bone interface. Ten normal and defect cases were simulated with a previously tested 3D finite element model of the knee. The focal defects were considered in both condyles within high load-bearing regions. Fluid pressurization, anisotropic fibril-reinforcement, and depth-dependent mechanical properties were considered for the articular cartilages and menisci. The results showed that a small cartilage defect could cause 25% reduction in the load support of the knee joint due to a reduced capacity of fluid pressurization in the defect cartilage. A partial-thickness defect could cause a fluid pressure decrease or increase in the remaining underlying cartilage depending on the defect depth. A cartilage defect also increased the shear strain at the cartilage-bone interface, which was more significant with a full-thickness defect. The effect of cartilage defect on the fluid pressurization also depended on the defect sites and contact conditions. In conclusion, a focal cartilage defect causes a fluid-pressure dependent load reallocation and a compromised load support in the joint, which depend on the defect depth, site, and contact condition. Copyright © 2015 John Wiley & Sons, Ltd.

Regenerative Medicine for Periodontal and Peri-implant Diseases

PubMed Central

Larsson, L.; Decker, A.M.; Nibali, L.; Pilipchuk, S.P.; Berglundh, T.; Giannobile, W.V.

2015-01-01

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. PMID:26608580

Sclerostin-neutralizing Antibody Enhances Bone Regeneration around Oral Implants.

PubMed

Yu, Shan Huey; Hao, Jie; Fretwurst, Tobias; Liu, Min; Kostenuik, Paul; Giannobile, William V; Jin, Qiming

2018-06-19

Dental implants have been an important option for the replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. Monoclonal antibody against sclerostin (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model. To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after the extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1x2 mm custom titanium implants were pressed-fitted into the osteotomies. Coincident with initial implant placement, Scl-Ab or vehicle was administered subcutaneously twice weekly at a dose of 25 mg/kg for 10-28 days and compared to a vehicle control. Rats were sacrificed 10, 14 and 28d after surgery, and maxillae were harvested and analyzed by micro-computed tomography (microCT), histology and histomorphometry. MicroCT analysis demonstrated that maxillary bone volume fraction was approximately 2 to 2.5-fold greater in Scl-Ab treated animals as compared to vehicle alone at days 14 and 28. Consistent with those findings, 2-D bone fill percentage within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28d. In addition, bone-implant contact at 28d was approximately 2-fold greater in the Scl-Ab group compared to vehicle controls. These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects, and to enhance dental implant osseointegration.

Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta-tricalcium phosphate ({beta}-TCP) on the beagle dog 1-wall periodontal defect model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anzai, Jun, E-mail: anzai_jun@kaken.co.jp; Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871; Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp

Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontalmore » tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal regeneration following severe destruction by progressive periodontitis.« less

PTH promotes allograft integration in a calvarial bone defect

PubMed Central

Sheyn, Dmitriy; Yakubovich, Doron Cohn; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M.; Gazit, Dan; Gazit, Zulma

2013-01-01

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and micro–computed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in Allograft + PTH–treated mice comparing to Allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the Allograft + PTH–treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment. PMID:24131143

3D-Printed Atsttrin-Incorporated Alginate/Hydroxyapatite Scaffold Promotes Bone Defect Regeneration with TNF/TNFR Signaling Involvement.

PubMed

Wang, Quan; Xia, Qingqing; Wu, Yan; Zhang, Xiaolei; Wen, Feiqiu; Chen, Xiaowen; Zhang, Shufang; Heng, Boon Chin; He, Yong; Ouyang, Hong-Wei

2015-08-05

High expression levels of pro-inflammatory tumor necrosis factor (TNF)-α within bone defects can decelerate and impair bone regeneration. However, there are few available bone scaffolds with anti-inflammatory function. The progranulin (PGRN)-derived engineered protein, Atsttrin, is known to exert antagonistic effects on the TNF-α function. Hence, this study investigates whether 3D-printed Atsttrin-incorporated alginate(Alg)/hydroxyapatite(nHAp) scaffolds can facilitate bone healing through affecting the TNF/TNFR signaling. A 3D bioprinting system is used to fabricate Atsttrin-Alg/nHAp composite scaffolds, and the Atsttrin release from this scaffold is characterized, followed by evaluation of its efficacy on bone regeneration both in vitro and in vivo. The 3D-printed Atsttrin-Alg/nHAp scaffold exhibits a precisely defined structure, can sustain Atsttrin release for at least 5 days, has negligible cytotoxicity, and supports cell adhesion. Atsttrin can also attenuate the suppressive effects of TNF-α on BMP-2-induced osteoblastic differentiation in vitro. The 3D-printed Atsttrin-Alg/nHAp scaffold significantly reduces the number of TNF-α positive cells within wound sites, 7 days after post-calvarial defect surgery. Additionally, histological staining and X-ray scanning results also show that the 3D-printed Atsttrin-Alg/nHAp scaffold enhances the regeneration of mice calvarial bone defects. These findings thus demonstrate that the precise structure and anti-inflammatory properties of 3D-printed Atsttrin-Alg/nHAp scaffolds may promote bone defect repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

PubMed

Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

PubMed Central

Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects.

PubMed

Poudel, Sher Bahadur; Bhattarai, Govinda; Kook, Sung-Ho; Shin, Yun-Ji; Kwon, Tae-Ho; Lee, Seung-Youp; Lee, Jeong-Chae

2017-10-01

Transgenic plant cell suspension culture systems have been utilized extensively as convenient and efficient expression systems for the production of recombinant human growth factors. We produced insulin-like growth factor-1 using a plant suspension culture system (p-IGF-1) and explored its effect on new bone formation in calvarial defects. We also compared the bone regenerating potential of p-IGF-1 with commercial IGF-1 derived from Escherichia coli (e-IGF-1). Male C57BL/6 mice underwent calvarial defect surgery, and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 13μg of p-IGF-1 (p-IGF-1 group) or e-IGF-1 (e-IGF-1 group). The sham group did not receive any treatment with ACS or IGFs after surgery. Live μCT and histological analyses showed critical-sized bone defects in the sham group, whereas greater bone formation was observed in the p-IGF-1 and e-IGF-1 groups than the ACS group both 5 and 10weeks after surgery. Bone mineral density, bone volume, and bone surface values were also higher in the IGF groups than in the ACS group. Local delivery of p-IGF-1 or e-IGF-1 more greatly enhanced the expression of osteoblast-specific markers, but inhibited osteoclast formation, in newly formed bone compared with ACS control group. Specifically, p-IGF-1 treatment induced higher expression of alkaline phosphatase, osteocalcin, and osteopontin in the defect site than did e-IGF-1. Furthermore, treatment with p-IGF-1, but not e-IGF-1, increased mineralization of MC3T3-E1 cells, with the attendant upregulation of osteogenic marker genes. Collectively, our findings suggest the potential of p-IGF-1 in promoting the processes required for bone regeneration. Copyright © 2017. Published by Elsevier Ltd.

Improving bone repair of femoral and radial defects in rabbit by incorporating PRP into PLGA/CPC composite scaffold with unidirectional pore structure.

PubMed

He, Fupo; Chen, Yan; Li, Jiyan; Lin, Bomiao; Ouyang, Yi; Yu, Bo; Xia, Yuanyou; Yu, Bo; Ye, Jiandong

2015-04-01

In this study, a platelet-rich plasma poly(lactic-co-glycolic acid) (PRP-PLGA)/calcium phosphate cement (CPC) composite scaffold was prepared by incorporating PRP into PLGA/CPC scaffold with unidirectional pore structure, which was fabricated by the unidirectional freeze casting of CPC slurry and the following infiltration of PLGA. The results from in vitro cell experiments and in vivo implantation in femoral defects manifested that incorporation of PRP into PLGA/CPC scaffold improved in vitro cell response (cell attachment, proliferation, and differentiation), and markedly boosted bone formation, angiogenesis and material degradation. The incorporation of PRP into scaffold showed more outstanding improvement in osteogenesis as the scaffolds were used to repair the segmental radial defects, especially at the early stage. The new bone tissues grew along the unidirectional lamellar pores of scaffold. At 12 weeks postimplantation, the segmental radial defects treated with PRP-PLGA/CPC scaffold had almost recuperated, whereas treated with the scaffold without PRP was far from healed. Taken together, the PRP-PLGA/CPC scaffold with unidirectional pore structure is a promising candidate to repair bone defects at various sites. © 2014 Wiley Periodicals, Inc.

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.

PubMed

Lee, Jung-Seok; Wikesjö, Ulf M E; Jung, Ui-Won; Choi, Seong-Ho; Pippig, Susanne; Siedler, Michael; Kim, Chong-Kwan

2010-04-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model. Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow. rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.

Influence of Autologus Adipose Derived Stem Cells and PRP on Regeneration of Dehiscence-Type Defects in Alveolar Bone: A Comparative Histochemical and Histomorphometric Study in Dogs

PubMed Central

Aziz Aly, Lobna Abdel; El- Menoufy, Hala; Hassan, Amal; Ragae, Alyaa; Atta, Hazem Mahmoud; Roshdy, Nagwa Kamal; Rashed, Laila Ahmed; Sabry, Dina

2011-01-01

Background and Objectives: Autogenous bone grafts is considered to be the best choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs) represents a promising tool for new clinical concepts in supporting cellular therapy. The goal of our study was to investigate bone regeneration following application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at dehiscence-type defects in alveolar bone in dogs. Methods and Results: Standardized buccal dehiscence defects (4× 3×3 mm) were surgically created in eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or without grafting material. Three months later; a bone core was harvested from grafted and non grafted sites for histological, histochemical and histomorphometric assessment. There was no evidence of inflammation or adverse tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a significantly higher result (p≤ 0.05), with a mean area % of spongy bone and compact bone of (64.96±5.37 and 837.62±24.95), compared to ASCs alone (47.65±1.43 and 661.92±12.65) and without grafting (33.55± 1.74 and 290.85±7.27) respectively. The area % of lamellated bone increased significantly reaching its highest level in group A followed by group B. Also a significant increase in area % of neutral mucopolysaccharides and calcified reactivity of Masson|s Trichrome stain in groups A and B compared to group C was obtained. Conclusions: Our results suggest that, the addition of PRP to ASCs enhances bone formation after 3 months and may be clinically effective in accelerating postsurgical healing in both periodontal and maxillofacial surgical applications. PMID:24298335

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

PubMed Central

Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

2017-01-01

The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

Reconstruction of large cranial defect with alloplastic material (bone cement-cold cure polymethyl-methacrylate resin).

PubMed

Hallur, Neelakamal; Goudar, Gayatri; Sikkerimath, Basavaraj; Gudi, Santosh S; Patil, Ravi S

2010-06-01

A 40-years-old male patient reported to our department with a chief complaint of persistent palatal fluid discharge and large depressed forehead defect. He gave a history of trauma 20 months back due to head on collision to electric pole and underwent surgery twice for open reduction and fixation of facial skeletal fractures. After 9 months of surgery again a third surgery was performed for the removal of frontal bone due to infection and osteomyelitis at the same site. Extra-oral examination revealed a large fronto-cranial defect extending from superior border of frontal bone to supra-orbital margins bilaterally in length, and from frontal right lateral to frontal left lateral side in width, measuring 8.0 cm in length, 10.5 cm in width and 1.5 to 2.0 cm in depth. Intra-oral sinus fluid discharge was from left posterior palatal region. Preoperative CT was taken and reconstruction of fronto-cranial defect was successfully performed with bone cement. Alloplastic implant reconstruction achieved an excellent esthetic result without any complications.

Flow-Through Free Fibula Osteocutaneous Flap in Reconstruction of Tibial Bone, Soft Tissue, and Main Artery Segmental Defects.

PubMed

Li, Zonghuan; Yu, Aixi; Qi, Baiwen; Pan, Zhenyu; Ding, Junhui

2017-08-01

The aim of this report was to present the use of flow-through free fibula osteocutaneous flap for the repair of complex tibial bone, soft tissue, and main artery segmental defects. Five patients with bone, soft tissue, and segmental anterior tibial artery defects were included. The lengths of injured tibial bones ranged from 4 to 7 cm. The sizes of impaired soft tissues were between 9 × 4 and 15 × 6 cm. The lengths of defect of anterior tibial artery segments ranged from 6 to 10 cm. Two patients had distal limb perfusion problems. Flow-through free fibula osteocutaneous flap was performed for all 5 patients. Patients were followed for 12 to 18 months. All wounds healed after 1-stage operation, and all flow-through flaps survived. The distal perfusion after vascular repair was normal in all patients. Superficial necrosis of flap edge was noted in 1 case. After the local debridement and partial thickness skin graft, the flap healed uneventfully, and the surgical operation did not increase injury to the donor site. Satisfactory bone union was achieved in all patients in 2 to 4 months postoperation. Enlargement of fibula graft was observed during follow-up from 12 to 18 months. The functions of adjacent joints were recovered, and all patients were able to walk normally. Flow-through free fibula osteocutaneous flap was shown to be an effective and efficient technique for repairing composite tibial bone, soft tissue, and main artery segmental defects. This 1-stage operation should be useful in clinical practice for the treatment of complex bone, soft tissue, and vessel defects.

Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heterotopic ossification

USDA-ARS?s Scientific Manuscript database

Heterotopic ossification (HO), or endochondral bone formation at nonskeletal sites, often results from traumatic injury and can lead to devastating consequences. Alternatively, the ability to harness this phenomenon would greatly enhance current orthopedic tools for treating segmental bone defects. ...

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates.

PubMed

Nevins, Myron; Al Hezaimi, Khalid; Schupbach, Peter; Karimbux, Nadeem; Kim, David M

2012-07-01

This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet-derived growth factor-BB (rhPDGF-BB), to augment localized posterior mandibular defects in non-human primates (Papio hamadryas). Bilateral critical-sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non-human primate. All sites exhibited vertical ridge augmentation, with physiologic hard- and soft-tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non-significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF-BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical-sized defects. This investigation supplies additional evidence that eHAC blocks infused with rhPDGF-BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.

Maxillary anterior ridge augmentation with recombinant human bone morphogenetic protein 2.

PubMed

Edmunds, Ryan K; Mealey, Brian L; Mills, Michael P; Thoma, Daniel S; Schoolfield, John; Cochran, David L; Mellonig, Jim

2014-01-01

No human studies exist on the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an absorbable collagen sponge (ACS) as a sole graft material for lateral ridge augmentation in large ridge defect sites. This series evaluates the treatment outcome of maxillary anterior lateral ridge augmentation with rhBMP-2/ACS. Twenty patients were treated with rhBMP-2/ACS and fixation screws for space maintenance. Cone beam volumetric tomography measurements were used to determine gain in ridge width, and a bone core biopsy was obtained. The mean horizontal ridge gain was 1.2 mm across sites, and every site gained width.

Platelet-Rich Plasma Gel Combined with Bovine-Derived Xenograft for the Treatment of Dehiscence Around Immediately Placed Conventionally Loaded Dental Implants in Humans: Cone Beam Computed Tomography and Three-Dimensional Image Evaluation.

PubMed

ArRejaie, Aws; Al-Harbi, Fahad; Alagl, Adel S; Hassan, Khalid S

2016-01-01

This study clinically and radiographically investigated the potential of platelet-rich plasma (PRP) gel combined with bovine-derived xenograft to treat dehiscence defects around immediate dental implants. This study was performed on 32 sites from 16 patients who each received an immediate implant for a single tooth replacement at a maxillary anterior or premolar site. Patients were divided into two groups according to the augmented materials used. One group received an immediate implant and filling of defects using a PRP gel plus bovine-derived xenograft. The other group received an immediate implant and filling of defects with a bovine-derived xenograft without PRP gel. Cone beam computed tomography (CBCT) was taken before placement, and at 6 and 12 months postsurgery. Both treatment procedures resulted in significant improvements for the primary outcome regarding bone fill, as well as the marginal bone level. In addition, statistically significant differences were found in the bone density for the combined therapy compared with sites treated with bovine-derived xenografts alone (P ≤ .01). Autogenous PRP gel combined with bovine-derived xenograft demonstrated superiority to the bovine-derived xenograft alone, which suggested that it could be successfully applicable for the treatment of dehiscence around an immediate dental implant. Moreover, CBCT can be used to measure dehiscence and to assess bone thickness along the implant.

The indications and donor-site morbidity of tibial cortical strut autografts in the management of defects in long bones.

PubMed

Lauthe, O; Soubeyrand, M; Babinet, A; Dumaine, V; Anract, P; Biau, D J

2018-05-01

Aims The primary aim of this study was to determine the morbidity of a tibial strut autograft and characterize the rate of bony union following its use. Patients and Methods We retrospectively assessed a series of 104 patients from a single centre who were treated with a tibial strut autograft of > 5 cm in length. A total of 30 had a segmental reconstruction with continuity of bone, 27 had a segmental reconstruction without continuity of bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity was defined as any event that required a modification of the postoperative management. Union was assessed clinically and radiologically at a median of 36 months (IQR, 14 to 74). Results Donor-site morbidity occurred in four patients (4%; 95% confidence interval (CI) 1 to 10). One patient had a stress fracture of the tibia, which healed with a varus deformity, requiring an osteotomy. Two patients required evacuation of a haematoma and one developed anterior compartment syndrome which required fasciotomies. The cumulative probability of union was 90% (95% CI 80 to 96) at five years. The type of reconstruction (p = 0.018), continuity of bone (p = 0.006) and length of tibial graft (p = 0.037) were associated with the time to union. Conclusion The tibial strut autograft has a low risk of morbidity and provides adequate bone stock for treating various defects of long bones. Cite this article: Bone Joint J 2018;100-B:667-74.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

PubMed Central

Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia.

PubMed

Boukpessi, Tchilalo; Hoac, Betty; Coyac, Benjamin R; Leger, Thibaut; Garcia, Camille; Wicart, Philippe; Whyte, Michael P; Glorieux, Francis H; Linglart, Agnès; Chaussain, Catherine; McKee, Marc D

2017-02-01

Seven young patients with X-linked hypophosphatemia (XLH, having inactivating PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of defective bone mineralization near osteocytes - the so-called hallmark periosteocytic (lacunar) "halos" of XLH. OPN was also localized in the pericanalicular matrix extending beyond the osteocyte lacunae, as well as in the hypomineralized matrix of tooth dentin. OPN, a potent inhibitor of mineralization normally degraded by PHEX, is a member of a family of acidic, phosphorylated, calcium-binding, extracellular matrix proteins known to regulate dental, skeletal, and pathologic mineralization. Associated with the increased amount of OPN (along with inhibitory OPN peptide fragments) in XLH bone matrix, we found an enlarged, hypomineralized, lacuno-canalicular network - a defective pattern of skeletal mineralization that decreases stiffness locally at: i) the cell-matrix interface in the pericellular environment of the mechanosensing osteocyte, and ii) the osteocyte's dendritic network of cell processes extending throughout the bone. Our findings of an excess of inhibitory OPN near osteocytes and their cell processes, and in dentin, spatially correlates with the defective mineralization observed at these sites in the skeleton and teeth of XLH patients. These changes likely contribute to the dento-osseous pathobiology of XLH, and participate in the aberrant bone adaptation and remodeling seen in XLH. Copyright © 2016 Elsevier Inc. All rights reserved.

Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects.

PubMed

Giannobile, W V; Ryan, S; Shih, M S; Su, D L; Kaplan, P L; Chan, T C

1998-02-01

Osteogenic protein-1 (OP-1) is a member of the transforming growth factor beta superfamily and is a potent modulator of osteogenesis and bone cell differentiation. This preclinical study in dogs sought to assess the effects of OP-1 on periodontal wound healing in surgically created critical size Class III furcation defects. Eighteen male beagle dogs were subjected to the creation of bilateral mandibular 5 mm osseous defects. A split-mouth design was utilized which randomly assigned opposing quadrants to control therapy (surgery alone or collagen vehicle) or 1 of 3 ascending concentrations of OP-1 in a collagen vehicle (0.75 mg OP-1/g collagen, 2.5 mg/g, or 7.5 mg/g). Thus, 9 quadrants per test group received OP-1, 9 quadrants per control group received surgery alone, and 9 quadrants received collagen vehicle alone. Test articles were delivered by a surgeon masked to the treatment, and fluorogenic bone labels were injected at specified intervals post-treatment. Eight weeks after defect creation and OP-1 delivery, tissue blocks of the mandibulae were taken for masked histomorphometric analysis to assess parameters of periodontal regeneration (e.g., bone height, bone area, new attachment formation, and percent of defect filled with new bone). Histomorphometry revealed limited evidence of osteogenesis, cementogenesis, and new attachment formation in either vehicle or surgery-alone sites. In contrast, sites treated with all 3 concentrations of OP-1 showed pronounced stimulation of osteogenesis, regenerative cementum, and new attachment formation. Lesions treated with 7.5 mg/g of OP-1 in collagen regenerated 3.9+/-1.7 mm and 6.1+/-3.4 mm2 (mean +/-S.D.) of linear bone height and bone area, respectively. Furthermore, these differences were statistically different from both control therapies for all wound healing parameters (P < 0.0001). No significant increase in tooth root ankylosis was found among the treatment groups when compared to the surgery-alone group. We conclude that OP-1 offers promise as an attractive candidate for treating severe periodontal lesions.

Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials

PubMed Central

Kim, Hak-Jun; Park, Kyeongsoon; Kim, Sung Eun; Song, Hae-Ryong

2014-01-01

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5 mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1 mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5 mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1 mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5 mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1 mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects. PMID:24804202

Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2

PubMed Central

Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn

2015-01-01

Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation. PMID:25813520

Regenerative Medicine for Periodontal and Peri-implant Diseases.

PubMed

Larsson, L; Decker, A M; Nibali, L; Pilipchuk, S P; Berglundh, T; Giannobile, W V

2016-03-01

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. © International & American Associations for Dental Research 2015.

Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

2015-01-01

The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were detected for chair-time (P = 0.3524), for VAS pain immediately after surgery (P = 0.5644), VAS pain after 1 week (P = 0.5074) and VAS pain after 2 weeks (P = 0.6950). A slight difference (0.24 mm, 95%CI from 0.0004 to 0.47, P = 0.0464) was detected in radiographic peri-implant bone loss favouring the CJ group. No significant differences, except for radiographic bone loss, were observed in this randomised controlled trial comparing anorganic bovine bone with collagen porcine membranes versus synthetic resorbable bone made of pure β-tricalcium phosphate with pericardium collagen membranes for horizontal augmentation.

Comparative finite element analysis of skull mechanical properties following parietal bone graft harvesting in adults.

PubMed

Haen, Pierre; Dubois, Guillaume; Goudot, Patrick; Schouman, Thomas

2018-02-01

Parietal bone grafts are commonly used in cranio-maxillo-facial surgery. Both the outer and the internal layer of the calvarium can be harvested. The bone defect created by this harvesting may induce significant weakening of the skull that has not been extensively evaluated. Our aim was to evaluate the consequences of parietal bone graft harvesting on mechanical properties of the skull using a finite element analysis. Finite elements models of the skull of 3 adult patients were created from CT scans. Parietal external and internal layer harvest models were created. Frontal, lateral, and parietal loading were modeled and von Mises stress distributions were compared. The maximal von Mises stress was higher for models of bone harvesting, both on the whole skull and at the harvested site. Maximal von Mises stress was even higher for models with internal layer defect. Harvesting parietal bone modifies the skull's mechanical strength and can increase the risk of skull fracture, mainly on the harvested site. Outer layer parietal graft harvesting is indicated. Graft harvesting located in the upper part of the parietal bone, close to the sagittal suture and with smooth internal edges and corners should limit the risk of fracture. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Current Approaches to Bone Tissue Engineering: The Interface between Biology and Engineering.

PubMed

Li, Jiao Jiao; Ebied, Mohamed; Xu, Jen; Zreiqat, Hala

2018-03-01

The successful regeneration of bone tissue to replace areas of bone loss in large defects or at load-bearing sites remains a significant clinical challenge. Over the past few decades, major progress is achieved in the field of bone tissue engineering to provide alternative therapies, particularly through approaches that are at the interface of biology and engineering. To satisfy the diverse regenerative requirements of bone tissue, the field moves toward highly integrated approaches incorporating the knowledge and techniques from multiple disciplines, and typically involves the use of biomaterials as an essential element for supporting or inducing bone regeneration. This review summarizes the types of approaches currently used in bone tissue engineering, beginning with those primarily based on biology or engineering, and moving into integrated approaches in the areas of biomaterial developments, biomimetic design, and scalable methods for treating large or load-bearing bone defects, while highlighting potential areas for collaboration and providing an outlook on future developments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee.

PubMed

Bhattacharjee, Atanu; McCarthy, Helen S; Tins, Bernhard; Roberts, Sally; Kuiper, J H; Harrison, Paul E; Richardson, James B

2016-05-01

Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Case series; Level of evidence, 4. Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)-12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)-had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. The mean defect size was 4.5 ± 2.6 cm(2) (range, 1-9 cm(2)), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A total of 3 patients had treatment failure, with 1 requiring total knee replacement at 5 years (Lysholm score of 33 at failure) and the other 2 requiring further surgical intervention because of persistent symptoms at 2 and 4 years, respectively (both had Lysholm score of 45 at failure). The Lysholm score in these patients before failure were still noted to be higher than at the preoperative level. The OsPlug technique shows significant improvement of functional outcome for up to 5 years in patients with high-grade osteochondritis dissecans or osteochondral defect. This is the first report describing association of bone graft integration with functional outcome after such a procedure. It also demonstrates histologic evidence of integration of the repair cartilage with the underlying bone graft. © 2016 The Author(s).

Computer-assisted selection of donor sites for autologous grafts

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Zeilhofer, Hans-Florian U.; Sader, Robert; Hoffmann, Karl-Heinz; Gerhardt, Paul; Horch, Hans-Henning

1997-05-01

A new method is proposed for a precise planning of autologous bone grafts in cranio- and maxillofacial surgery. In patients with defects of the facial skeleton, autologous bone transplants can be harvested from various donor sites in the body. The preselection of a donor site depends i.a. on the morphological fit of the available bone mass and the shape of the part that is to be transplanted. A thorough planning and simulation of the surgical intervention based on 3D CT studies leads to a geometrical description and the volumetric characterization of the bone part to be resected and transplanted. Both, an optimal fit and a minimal lesion of the donor site are guidelines in this process. We use surface similarity and voxel similarity measures in order to select the optimal donor region for an individually designed transplant.

Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix.

PubMed

Vidyadharan, Arun Kumar; Ravindran, Anjana

2014-01-01

Patient wanted to restore her lost teeth with implants in the lower left first molar and second premolar region. Cone beam computerized tomography (CBCT) revealed inadequate bone width and height around future implant sites. The extraction socket of second premolar area revealed inadequate socket healing with sparse bone fill after 4 months of extraction. To evaluate the clinical feasibility of using a collagen physical resorbable barrier made of human pericardium (HP) to augment localized alveolar ridge defects for the subsequent placement of dental implants. Ridge augmentation was done in the compromised area using Puros® demineralized bone matrix (DBM) Putty with chips and an HP allograft membrane. Horizontal (width) and vertical hard tissue measurements with CBCT were recorded on the day of ridge augmentation surgery, 4 month and 7 months follow-up. Intra oral periapical taken 1 year after implant installation showed minimal crestal bone loss. Bone volume achieved through guided bone regeneration was a gain of 4.8 mm horizontally (width) and 6.8 mm vertically in the deficient ridge within a period of 7 months following the procedure. The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

Computer-based planning of optimal donor sites for autologous osseous grafts

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Chlebiej, Michal; Zerfass, Peter; Zeilhofer, Hans-Florian U.; Sader, Robert; Mikolajczak, Pawel; Keeve, Erwin

2002-05-01

Bone graft surgery is often necessary for reconstruction of craniofacial defects after trauma, tumor, infection or congenital malformation. In this operative technique the removed or missing bone segment is filled with a bone graft. The mainstay of the craniofacial reconstruction rests with the replacement of the defected bone by autogeneous bone grafts. To achieve sufficient incorporation of the autograft into the host bone, precise planning and simulation of the surgical intervention is required. The major problem is to determine as accurately as possible the donor site where the graft should be dissected from and to define the shape of the desired transplant. A computer-aided method for semi-automatic selection of optimal donor sites for autografts in craniofacial reconstructive surgery has been developed. The non-automatic step of graft design and constraint setting is followed by a fully automatic procedure to find the best fitting position. In extension to preceding work, a new optimization approach based on the Levenberg-Marquardt method has been implemented and embedded into our computer-based surgical planning system. This new technique enables, once the pre-processing step has been performed, selection of the optimal donor site in time less than one minute. The method has been applied during surgery planning step in more than 20 cases. The postoperative observations have shown that functional results, such as speech and chewing ability as well as restoration of bony continuity were clearly better compared to conventionally planned operations. Moreover, in most cases the duration of the surgical interventions has been distinctly reduced.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

PubMed Central

Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures. PMID:26451104

Alveolar bony crest preservation at implants installed immediately after tooth extraction: an experimental study in the dog.

PubMed

Favero, Giacomo; Botticelli, Daniele; Favero, Giovanni; García, Brismayda; Mainetti, Tomaso; Lang, Niklaus P

2013-01-01

To evaluate the influence of deproteinized bovine bone mineral in conjunction with a collagen membrane, at implants installed into sockets in a lingual position immediately after tooth extraction, and presenting initial horizontal residual buccal defects <2 mm. The pulp tissue of the mesial roots of (4)P(4) was removed in six Labrador dogs, and the root canals were filled with gutta-percha and cement. Flaps were elevated, and the buccal and lingual alveolar bony plates were exposed. The premolars were hemi-sectioned, and the distal roots were removed. Implants were installed in a lingual position and with the margin flush with the buccal bony crest. After installation, defects resulted at about 1.7 mm in width at the buccal aspects, both at the test and control sites. Only in the left site (test), deproteinized bovine bone mineral (DBBM) particles were placed into the defect concomitantly with the placement of a collagen membrane. A non-submerged healing was allowed. After 3 months of healing, one implant was found not integrated and was excluded from the analysis together with the contralateral control implant. All remaining implants were integrated into mature bone. The bony crest was located at the same level of the implant shoulder, both at the test and control sites. At the buccal aspect, the most coronal bone-to-implant contact was located at a similar distance from the implant margin at the test (1.7 ± 1.0 mm) and control (1.6 ± 0.8 mm) sites, respectively. Only small residual DBBM particles were found at the test sites. The placement of an implant in a lingual position into a socket immediately after tooth extraction may favor a low exposure of the buccal implant surface. The use of DBBM particles, concomitantly with a collagen membrane, did not additionally improve the outcome obtained at the control sites. © 2011 John Wiley & Sons A/S.

Effectiveness of Platelet Rich Plasma and Bone Graft in the Treatment of Intrabony Defects: A Clinico-radiographic Study

PubMed Central

Jalaluddin, Mohammad; Mahesh, Jayachandran; Mahesh, Rethi; Jayanti, Ipsita; Faizuddin, Mohamed; Kripal, Krishna; Nazeer, Nazia

2018-01-01

Background & Objectives: Periodontal disease is characterized by the presence of gingival inflammation, periodontal pocket formation, loss of connective tissue attachment and alveolar bone around the affected tooth. Different modalities have been employed in the treatment and regeneration of periodontal defects which include the use of bone grafts, PRP and other growth factors.The purpose of this prospective, randomized controlled study was to compare the regenerative efficacy of PRP and bonegraft in intrabony periodontal defects. Methodology: This randomized control trial was carried out in the Department of Periodontics & Oral Implantology, Kalinga Institute of Dental Sciences and Hospital, KIIT University, Bhubaneswar. The study sample included 20 periodontal infrabony defects in 20 patients, 12 males and 8 females. The patients were aged between 25 -45 years(with mean age of 35 years). The 20 sites selected for the study were was randomly divided into 2 groups of 10 sites each. Group A: PRP alone, Group B: Bone Graft. Statistical Anaysis & Results: Statistical Analysis Was Done Using SPSS (Version 18.0): Statistical analysis was done usingpaired ‘t’ tests and ANOVA that revealed a significant reduction ingingival index, plaque index, probing pocket depth and gain in clinical attachment level at various time intervalswithin both the groups. Radiographic evaluation revealed statistically significant defect fill (p<0.001) at the end of 6months within both the groups. However, there was astatistically significant difference seen in group B radiographically, when compared to group A. Conclusion: Both the groups showed promising results in enhancing periodontal regeneration; however the resultswith bonegraftwere comparatively better, although not statistically significant when compared to PRP alone. PMID:29682091

Interactions between bone cells and biomaterials: An update.

PubMed

Beauvais, Sabrina; Drevelle, Olivier; Jann, Jessica; Lauzon, Marc-Antoine; Foruzanmehr, Mohammadreza; Grenier, Guillaume; Roux, Sophie; Faucheux, Nathalie

2016-06-01

As the populations of the Western world become older, they will suffer more and more from bone defects related to osteoporosis (non-union fractures, vertebral damages), cancers (malignant osteolysis) and infections (osteomyelitis). Autografts are usually used to fill these defects, but they have several drawbacks such as morbidity at the donor site and the amount and quality of bone that can be harvested. Recent scientific milestones made in biomaterials development were shown to be promising to overcome these limitations. Cell interactions with biomaterials can be improved by adding at their surface functional groups such as adhesive peptides and/or growth factors. The development of such biomimetic materials able to control bone cell responses can only proceed if it is based on a sound understanding of bone cell behavior and regulation. This review focuses on bone physiology and the regulation of bone cell differentiation and function, and how the latest advances in biomimetic materials can be translated within promising clinical outcomes.

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.

PubMed

Ho, Steve S; Vollmer, Nina L; Refaat, Motasem I; Jeon, Oju; Alsberg, Eben; Lee, Mark A; Leach, J Kent

2016-10-01

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autotransplantation of Immature Third Molars and Orthodontic Treatment After En Bloc Resection of Conventional Ameloblastoma.

PubMed

Osterne, Rafael Lima Verde; Moreira Neto, José Jeová Siebra; de Araújo Lima, Augusto Darwin Moreira; Nogueira, Renato Luiz Maia

2015-09-01

Ameloblastoma treatment can lead to significant bone defects; consequently, oral rehabilitation can be challenging. We present the case of a 14-year-old girl diagnosed with a conventional ameloblastoma in the mandible who was treated using en bloc resection and rehabilitated with autotransplantation of the immature third molars and orthodontic treatment. The lesion was in the region of the lower left canine and premolars, and en bloc resection resulted in a significant alveolar bone defect. Autotransplantation of the lower third molars to the site of the lower left premolars was performed. After 2 years, the upper left third molar was transplanted to the site of the lower left canine. During the orthodontic treatment period, considerable alveolar bone formation was observed in the region of the transplanted teeth, and roots developed. To the best of our knowledge, this is the first reported case of alveolar bone formation induction caused by tooth transplantation after ameloblastoma treatment. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating β-tricalcium phosphate: a preclinical study in dogs.

PubMed

Hoshi, S; Akizuki, T; Matsuura, T; Ikawa, T; Kinoshita, A; Oda, S; Tabata, Y; Matsui, M; Izumi, Y

2016-02-01

Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating β-tricalcium phosphate (β-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/β-TCP sponge on ridge augmentation in dogs. Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/β-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/β-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). The combined use of rhFGF-2 and gelatin/β-TCP sponge promotes ridge augmentation in canine saddle-type bone defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant: 1-Day, 3-Week, and 3-Month Repair.

PubMed

Bell, Angela D; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W; Hurtig, Mark B; Hoemann, Caroline D

2013-04-01

Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro-computed tomography. Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Bone plate-induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant.

Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant

PubMed Central

Bell, Angela D.; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W.; Hurtig, Mark B.

2013-01-01

Objective: Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. Design: In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro–computed tomography. Results: Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Conclusion: Bone plate–induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant. PMID:26069656

Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells.

PubMed

Shi, Jiajia; Sun, Jie; Zhang, Wen; Liang, Hui; Shi, Qin; Li, Xiaoran; Chen, Yanyan; Zhuang, Yan; Dai, Jianwu

2016-10-07

The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34 + and c-kit + endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

Short-term implantation effects of a DCPD-based calcium phosphate cement.

PubMed

Frayssinet, P; Gineste, L; Conte, P; Fages, J; Rouquet, N

1998-06-01

Calcium phosphate cements can be handled in paste form and set in a wet medium after precipitation of calcium phosphate crystals in the implantation site. Depending on the products entering into the chemical reaction leading to the precipitation of calcium phosphates, different phases can be obtained with different mechanical properties, setting times and injectability. We tested a cement composed of a powder, containing beta-tricalcium phosphate (beta-TCP) and sodium pyrophosphate mixed with a solution of phosphoric and sulphuric acids. The cement set under a dicalcium phosphate dihydrate (DCPD)-based matrix containing beta-TCP particles. This was injected with a syringe into a defect drilled in rabbit condyles, the control being an identical defect left empty in the opposite condyle. The condyles were analysed histologically 2, 6 and 18 weeks after implantation. After injection into the bone defect the cement set and formed a porous calcium phosphate structure. Two different calcium phosphate phases with different solubility rates could be identified by scanning electron microscopy (SEM) observation. The less-soluble fragments could be degraded by cell phagocytosis in cell compartments of low pH or integrated in the newly formed bone matrix. The degradation rate of the material was relatively high but compatible with the ingrowth of bone trabeculae within the resorbing material. The ossification process was different from the creeping substitution occurring at the ceramic contact. Bone did not form directly at the cement surface following the differentiation of osteoblasts at the material surface. The trabeculae came to the material surface from the edges of the implantation site. Bone formation in the implantation site was significantly higher than in the control region during the first week of implantation. In conclusion, this material set in situ was well tolerated, inducing a mild foreign-body reaction, which did not impair its replacement by newly formed bone within a few weeks.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

PubMed

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P < 0.05). Tissue-engineered bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

Host responses to a strontium releasing high boron glass using a rabbit bilateral femoral defect model.

PubMed

O'Connell, Kathleen; Pierlot, Caitlin; O'Shea, Helen; Beaudry, Diane; Chagnon, Madeleine; Assad, Michel; Boyd, Daniel

2017-10-01

Borate glasses have shown promising potential as bioactive materials. With recent research demonstrating that glass properties may be modulated by appropriate compositional design. This may provide for indication specific material characteristics and controlled release of therapeutic inorganic ions (i.e., strontium); controlling such release is critical in order to harness the therapeutic potential. Within this sub-chronic pilot study, a rabbit long-bone model was utilized to explore the safety and efficacy of a high borate glass (LB102: 70B 2 O 3 -20SrO-6Na 2 O-4La 2 O 3 ) particulate (90 - 710 μm) for bone regeneration. Six bilateral full-thickness defects (Ø = 3.5 mm; L = 8 mm) were created in three white New Zealand rabbits. Longitudinal non-decalcified sections of each defect site were produced and stained with Goldner's Trichrome. Histopathological examination revealed that LB102 demonstrated osteoconductive and osseointegrative properties with greater new bone being formed within and surrounding LB102 particles, when compared to the sham control. The inflammatory cell infiltration was observed to be slightly higher in the control when compared to LB102 defect sites, while no significant difference in fibrosis and neovascularization was determined, indicating that healing was occurring in a normal fashion. These data further suggest the possible utility of high borate glasses with appropriate compositional design for medical applications, such as bone augmentation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1818-1827, 2017. © 2016 Wiley Periodicals, Inc.

Bioactive scaffold for bone tissue engineering: An in vivo study

NASA Astrophysics Data System (ADS)

Livingston, Treena Lynne

Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment with cells seeded at the time of surgery. Porous, surface modified bioactive ceramic is a promising scaffold material for tissue-engineered bone repair. Bone formation and scaffold resorption act in concert for maintenance and improvement of the structural properties of the long bones over time. As determined histomorphometrically and mechanically, the rate of incorporation of the scaffold was enhanced with the tissue-engineered constructs.

Bone transport osteogenesis for reconstruction of a bone defect in the tibiotarsus of a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata).

PubMed

Johnston, Matthew S; Thode, Henry P; Ehrhart, Nicole P

2008-03-01

A yellow-naped Amazon parrot (Amazona ochrocephala auropalliata) was presented 5 months after a traumatic fracture of its left tibiotarsus. Fixation of the simple, closed, mid-diaphyseal fracture was originally with an intramedullary pin and external coaptation with a modified Robert-Jones bandage. During the subsequent 5 months, the bone became osteopenic, and the middle third of the tibiotarsus exhibited probable avascular necrosis. After various fixation attempts failed, the parrot was fitted with a ring fixator device, and bone transport osteogenesis was attempted. Within 7 weeks, the left tibiotarsus had regrown to full length, but the docking site at the proximal fracture line had not healed. After 2 more surgeries to debride bone ends to stimulate healing, the leg in this parrot became functional. This is the first reported clinical use of bone transport osteogenesis in a pet bird. Materials and techniques were applied successfully to this parrot, which suggests that bone transport osteogenesis deserves further study for the repair of large bone defects in birds.

Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

PubMed

Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

2016-05-01

The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term.

Effect of Intraoperative Platelet-Rich Plasma Treatment on Postoperative Donor Site Knee Pain in Patellar Tendon Autograft Anterior Cruciate Ligament Reconstruction: A Double-Blind Randomized Controlled Trial.

PubMed

Walters, Brian L; Porter, David A; Hobart, Sarah J; Bedford, Benjamin B; Hogan, Daniel E; McHugh, Malachy M; Klein, Devon A; Harousseau, Kendall; Nicholas, Stephen J

2018-05-01

Donor site morbidity in the form of anterior knee pain is a frequent complication after bone-patellar tendon-bone (BPTB) autograft anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to examine the effect of the intraoperative administration of platelet-rich plasma (PRP) on postoperative kneeling pain. It was hypothesized that PRP treatment would reduce knee pain. Randomized controlled trial; Level of evidence, 2. Fifty patients (mean ± SD age, 30 ± 12 years) undergoing BPTB ACL autograft reconstruction were randomized to the PRP (n = 27) or sham (n = 23) treatment. In either case, 10 mL of venous blood was drawn before the induction of anesthesia and either discarded (sham) or processed (PRP) for preparation of a PRP gel to be later mixed with donor site bone chips and inserted into the patellar defect. At 12 weeks, 6 months, 1 year, and 2 years after surgery, patients completed International Knee Documentation Committee (IKDC) forms and visual analog scale pain scores for activities of daily living and kneeling. Healing indices at the donor site were assessed by routine noncontrast magnetic resonance imaging (MRI) at 6 months. Mixed-model analysis of variance was used to assess the effect of PRP on patient symptoms and MRI indices of donor site healing, as measured by the width of the donor site defect. Kneeling pain, pain with activities of daily living, and IKDC scores were not different between treatment groups at any of the time intervals ( P = .08-.83). Kneeling pain improved from 12 weeks to 6 months and from 1 to 2 years ( P < .05). IKDC scores improved substantially from 12 weeks to 6 months ( P < .001) and continued to improve to 2 years (PRP, 86 ± 19; sham, 89 ± 10). MRI indices of donor site healing were not different between treatment groups ( P = .53-.90). Whether randomized to receive PRP in their patellar defect or not, patients continued to have similar levels of kneeling pain and patellar defect sizes after autograft BPTB ACL reconstruction. Registration: NCT01765712 ( ClinicalTrials.gov identifier).

[The effect of noncoherent infrared radiation on the bone tissue reparation of the mandible in an experiment].

PubMed

Deriabin, E I

1997-01-01

Exposure of rabbits with mandibular bone defects to coherent infrared radiation (IR) at a wavelength of 890 nm decreased the intensity of inflammation by accelerating the repair. The results of exposure of the injured site to noncoherent IR radiation are compatible with those of IR laser exposure.

Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect.

PubMed

Mantripragada, Venkata P; Jayasuriya, Ambalangodage C

2016-06-01

Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which include two groups for BMP-7 incorporated microparticles (by two techniques), microparticles without BMP-7, and defect itself (negative control). Healthy bone formation was observed around the microparticles, which were only confined to the defect site and did not disperse. Histology indicated minor inflammatory response around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT analysis of bone surface density and porosity was found to be significantly more (p<0.05) for microparticles containing groups, in comparison with controls, which suggests that the new bone formed in the presence of microparticles is more interconnected and porous. Collagen fibrils analysis conducted using multiphoton microscopy showed significant improvement in the formation of bundled collagen area (%) in microparticles containing groups in comparison with controls, indicating higher cross-linking between the fibrils. Microparticles were biocompatible and did not degrade in the 12 week implant period. Copyright © 2016 Elsevier B.V. All rights reserved.

Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

PubMed

Taiani, J T; Buie, H R; Campbell, G M; Manske, S L; Krawetz, R J; Rancourt, D E; Boyd, S K; Matyas, J R

2014-07-01

In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (μCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

Is bone transplantation the gold standard for repair of alveolar bone defects?

PubMed

Raposo-Amaral, Cassio Eduardo; Bueno, Daniela Franco; Almeida, Ana Beatriz; Jorgetti, Vanda; Costa, Cristiane Cabral; Gouveia, Cecília Helena; Vulcano, Luiz Carlos; Fanganiello, Roberto D; Passos-Bueno, Maria Rita; Alonso, Nivaldo

2014-01-01

New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate), compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7) defects were repaired with autogenous bone grafts; Group 2 (n = 5) defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5) defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5) defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6) defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2-5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01) and 38.35% ± 19.59% (p = 0.06) of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30) and 61.80% ± 2.14% (p = 0.88) of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

A lateral ridge augmentation study to evaluate a synthetic membrane for guided bone regeneration: an experiment in the canine mandible.

PubMed

Vierra, Matthew; Mau, Lian Ping; Huynh-Ba, Guy; Schoolfield, John; Cochran, David L

2016-01-01

To evaluate guided bone regeneration outcomes in defects protected with an in situ formed polyethylene glycol (PEG) hydrogel membrane as compared to a non-cross-linked collagen membrane (CM). Four mandibular alveolar ridge defects were created in eight hound dogs. Regenerative procedures were randomly allocated to one of four groups consisting of freeze-dried bone allograft, which is referred to in this study as freeze-dried bone xenograft (FDBX) + PEG, autogenous bone (AB) + PEG, AB + CM, and AB alone. After 8 weeks, titanium dental implants were placed into augmented sites. After 8 weeks of allowed time for osseointegration, the animals were sacrificed to harvest block specimens for bone-to-implant contact (BIC) and ridge width histomorphometric analysis. Polyethylene glycol membranes had an exposure rate of 50% as compared to 12.5% for sites grafted with CM. Regenerative outcomes with respect to implant placement were least favorable for FDBX + PEG which had implants placed in 37.5% of augmented sites compared to 100% implant placement for all other groups. No statistically significant differences were noted between groups for ridge width measurements in implant and non-implant histologic sections (P > 0.05). Buccal BIC (%) values between treatment groups also failed to reach statistical significant difference (FDBX + PEG [60.2 ± 9.4]; AB + PEG [58.8 ± 8.5]; AB + CM [57.9 ± 12.8]; AB [61.0 ± 10.2]). When used in conjunction with FDBX, PEG had unpredictable bone formation and in most cases negatively impacted future implant placement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model.

PubMed

Ge, Zigang; Tian, Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo, Jin Fei; Cao, Tong

2009-04-01

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models.

Digital subtraction radiographic analysis of the combination of bioabsorbable membrane and bovine morphogenetic protein pool in human periodontal infrabony defects

PubMed Central

GUIMARÃES, Maria do Carmo Machado; PASSANEZI, Euloir; SANT’ANA, Adriana Campos Passanezi; GREGHI, Sebastião Luiz Aguiar; TABA JUNIOR, Mario

2010-01-01

Objectives This study assessed the bone density gain and its relationship with the periodontal clinical parameters in a case series of a regenerative therapy procedure. Material and Methods Using a split-mouth study design, 10 pairs of infrabony defects from 15 patients were treated with a pool of bovine bone morphogenetic proteins associated with collagen membrane (test sites) or collagen membrane only (control sites). The periodontal healing was clinically and radiographically monitored for six months. Standardized presurgical and 6-month postoperative radiographs were digitized for digital subtraction analysis, which showed relative bone density gain in both groups of 0.034 ± 0.423 and 0.105 ± 0.423 in the test and control group, respectively (p>0.05). Results As regards the area size of bone density change, the influence of the therapy was detected in 2.5 mm2 in the test group and 2 mm2 in the control group (p>0.05). Additionally, no correlation was observed between the favorable clinical results and the bone density gain measured by digital subtraction radiography (p>0.05). Conclusions The findings of this study suggest that the clinical benefit of the regenerative therapy observed did not come with significant bone density gains. Long-term evaluation may lead to a different conclusions. PMID:20835573

In vivo study of microarc oxidation coated biodegradable magnesium plate to heal bone fracture defect of 3mm width.

PubMed

Wu, Y F; Wang, Y M; Jing, Y B; Zhuang, J P; Yan, J L; Shao, Z K; Jin, M S; Wu, C J; Zhou, Y

2017-10-01

Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance appeal increasing interests as a revolutionary biodegradable metal for fractured bone fixing implants application. However, the in vivo corrosion degradation of the implants and bone healing response are not well understood, which is highly required in clinic. In the present work, 10μm and 20μm thick biocompatible MAO coatings mainly composed of MgO, Mg 2 SiO 4 , CaSiO 3 and Mg 3 (PO 4 ) 2 phases were fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an improved corrosion resistance of magnesium by the MAO coatings. The 10μm and 20μm coated and uncoated magnesium plates were separately implanted into the radius bone fracture site of adult New Zealand white rabbits using a 3mm width bone fracture defect model to investigate the magnesium implants degradation and uninhibited bone healing. Taking advantage of the good biocompatibility of the MAO coatings, no adverse effects were detected through the blood test and histological examination. The implantation groups of coated and uncoated magnesium plates were both observed the promoting effect of bone fracture healing compared with the simple fracture group without implant. The releasing Mg 2+ by the degradation of implants into the fracture site improved the bone fracture healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic differentiation. Mg degradation and bone fracture healing promoting must be tailored by microarc oxidation coating with different thickness for potential clinic application. Copyright © 2017. Published by Elsevier B.V.

In-situ tissue regeneration through SDF-1α driven cell recruitment and stiffness-mediated bone regeneration in a critical-sized segmental femoral defect.

PubMed

Cipitria, Amaia; Boettcher, Kathrin; Schoenhals, Sophia; Garske, Daniela S; Schmidt-Bleek, Katharina; Ellinghaus, Agnes; Dienelt, Anke; Peters, Anja; Mehta, Manav; Madl, Christopher M; Huebsch, Nathaniel; Mooney, David J; Duda, Georg N

2017-09-15

In-situ tissue regeneration aims to utilize the body's endogenous healing capacity through the recruitment of host stem or progenitor cells to an injury site. Stromal cell-derived factor-1α (SDF-1α) is widely discussed as a potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i) deliver SDF-1α for the recruitment of endogenous bone marrow-derived stromal cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii) induce hydrogel stiffness-mediated osteogenic differentiation in-vivo. Ionically crosslinked alginate hydrogels with a stiffness optimized for osteogenic differentiation were used. Fast-degrading porogens were incorporated to impart a macroporous architecture that facilitates host cell invasion. Endogenous cell recruitment to the defect site was successfully triggered through the controlled release of SDF-1α. A trend for increased bone volume fraction (BV/TV) and a significantly higher bone mineral density (BMD) were observed for gels loaded with SDF-1α, compared to empty gels at two weeks. A trend was also observed, albeit not statistically significant, towards matrix stiffness influencing BV/TV and BMD at two weeks. However, over a six week time-frame, these effects were insufficient for bone bridging of a segmental femoral defect. While mechanical cues combined with ex-vivo cell encapsulation have been shown to have an effect in the regeneration of less demanding in-vivo models, such as cranial defects of nude rats, they are not sufficient for a SDF-1α mediated in-situ regeneration approach in segmental femoral defects of immunocompetent rats, suggesting that additional osteogenic cues may also be required. Stromal cell-derived factor-1α (SDF-1α) is a chemoattractant used to recruit host cells for tissue regeneration. The concept that matrix stiffness can direct mesenchymal stromal cell (MSC) differentiation into various lineages was described a decade ago using in-vitro experiments. Recently, alginate hydrogels with an optimized stiffness and ex-vivo encapsulated MSCs were shown to have an effect in the regeneration of skull defects of nude rats. Here, we apply this material system, loaded with SDF-1α and without encapsulated MSCs, to (i) recruit endogenous cells and (ii) induce stiffness-mediated osteogenic differentiation in-vivo, using as model system a load-bearing femoral defect in immunocompetent rats. While a cell-free approach is of great interest from a translational perspective, the current limitations are described. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison of ossification of demineralized bone, hydroxyapatite, Gelfoam, and bone wax in cranial defect repair.

PubMed

Papay, F A; Morales, L; Ahmed, O F; Neth, D; Reger, S; Zins, J

1996-09-01

Demineralized bone allografts in the repair of calvarial defects are compared with other common bone fillers. This study uses a video-digitizing radiographic analysis of calvarial defect ossification to determine calcification of bone defects and its relation to postoperative clinical examination and regional controls. The postoperative clinical results at 3 months demonstrated that bony healing was greatest in bur holes filled with demineralized bone and hydroxyapatite. Radiographic analysis demonstrated calcification of demineralized bone-filled defects compared to bone wax- and Gelfoam-filled regions. Hydroxyapatite granules are radiographically dense, thus not allowing accurate measurement of true bone healing. The results suggest that demineralized bone and hydroxyapatite provide better structural support via bone healing to defined calvarial defects than do Gelfoam and bone wax.

Evaluation of the Parietal Bones in the Rat as a Specific Site for the Testing of Osteogenic Materials. A Simple Animal Model to Study Bone Implant Material.

DTIC Science & Technology

1981-10-01

Intraosseous Appliance in the Treatment of Mandibular Fractures . J Oral Surg 30:344-348, 1977. 6. MELCHER, A.H. and IRVING, J.T.: The Healing...on the observed results. Investigators have prepared osseous defects in monkeys, sheep, and dogs in an attempt to study the effects of bone inducing...occur in the control animals. Sufficient bone must also be available so that the risk of fracture is mitigated. 3. The animal should allow for

Cellular Sites of Immunologic Unresponsiveness*

PubMed Central

Chiller, Jacques M.; Habicht, Gail S.; Weigle, William O.

1970-01-01

The reconstitution of the immune response of lethally irradiated mice to human γ-globulin is dependent on the synergistic action of bone marrow with thymus cells. Immunologic unresponsiveness appears to involve a functional defect at each of these cellular levels, inasmuch as neither bone marrow nor thymus cells from unresponsive donors are capable of demonstrating synergism in combination with their normal counterpart. PMID:4192271

A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

PubMed

Gao, Jianting; Huang, Guofeng; Liu, Guojun; Liu, Yan; Chen, Qi; Ren, Lei; Chen, Changqing; Ding, Zhenqi

2016-08-01

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects. © The Author(s) 2016.

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

PubMed Central

Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Stanley, Alexandra; Albertson, Craig; Simonet, Jacqueline; Fisher, Shannon

2017-01-01

During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID:26992365

[Revision hip arthroplasty by Waldemar Link custom-made total hip prosthesis].

PubMed

Medenica, Ivica; Luković, Milan; Radoicić, Dragan

2010-02-01

The number of patients undergoing hip arthroplasty revision is constantly growing. Especially, complex problem is extensive loss of bone stock and pelvic discontinuity that requires reconstruction. The paper presented a 50-year old patient, who ten years ago underwent a total cement artrhroplasty of the left hip. A year after the primary operation the patient had difficulties in walking without crutches. Problems intensified in the last five years, the patient had severe pain, totally limited movement in the left hip and could not walk at all. Radiographically, we found loose femoral component, massive loss of bone stock of proximal femur, acetabular protrusion and a consequent pelvic discontinuity. Clinically, a completely disfunctional left hip joint was registered (Harris hip score--7.1). We performed total rearthroplasty by a custom-made Waldemar Link total hip prosthesis with acetabular antiprotrusio cage and compensation of bone defects with a graft from the bone bank. A year after the operation, we found clinically an extreme improvement in Harris hip score--87.8. Radiographically, we found stability of implanted components, a complete graft integration and bone bridging across the site of pelvic discontinuity. Pelvic discontinuity and massive loss of proximal femoral bone stock is a challenging and complex entity. Conventional prostheses cannot provide an adequate fixation and stability of the hip. Application of custom-made prosthesis (measured specificaly for a patient) and additional alografting bone defects is a good method in revision surgery after unsuccessful hip arthroplasty with extensive bone defects.

Mastoid cortex plasty using bone pate.

PubMed

Yanagihara, Naoaki; Hinohira, Yasuyuki; Sato, Hidemitu

2002-07-01

To describe the surgical technique of mastoid cortex plasty using bone pate and its clinical significance. Retrospective. Tertiary medical center. Bone pate collected while drilling the mastoid cortex was mixed with fibrin glue to make a pate plate. The mastoid cortex defect was closed with a pate plate cut to the desired shape and size. Mastoid cortex plasty was included in the first-stage operation in 49 patients who underwent staged tympanoplasty. The second-stage operation was an inspection to see whether the mastoid cortex was reconstructed and the ingrowth of fibrous soft tissue was prevented. In 35 patients, the mastoid cortex was reconstructed completely, and soft tissue ingrowth into the mastoid cavity was blocked completely. In the remaining 14 patients, a defect of varying size occurred at the site of drainage-tube insertion. This defect was small enough to prevent soft tissue ingrowth into the mastoid cavity. Mastoid cortex plasty is a simple and rapid procedure for preventing postoperative deformity of the mastoid process and is valuable for restoring mastoid cavity function.

Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

PubMed

Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

2014-10-01

Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

Does grafting of third molar extraction sockets enhance periodontal measures in 30- to 35-year-old patients?

PubMed

Hassan, Khalid S; Marei, Hesham F; Alagl, Adel S

2012-04-01

This study was designed to evaluate the use of xenograft plus a membrane as grafting material for periodontal osseous defects distal to the mandibular second molar compared with nongrafted extraction sites after removal of impacted mandibular third molars. We performed a single-blind, randomized, controlled clinical trial, and the sample comprised of subjects at high risk for the development of periodontal osseous defects distal to the second molar after third molar extraction (aged 30-35 years), pre-existing osseous defects distal to the second molar, and horizontal third molar impaction. The predictor variable was the treatment status of the second molar osseous defects. The third molar extraction sites were grafted with an anorganic xenograft plus a membrane. The other sites received a full-thickness flap and extraction of the third molar without placement of the grafting materials. The outcome variables were the change in gingival index, pocket probing depth, and clinical attachment level on the distobuccal aspect of the second molar preoperatively and at 3, 6, 9, and 12 months after surgery. Data were statistically analyzed by multivariate analysis of variance, and the statistical significance was set at P < .05. The study was composed of 28 sites that were selected by use of a split-mouth design for each patient, and this was randomly determined through a biased coin randomization. Twelve months after third molar removal, there was a statistically significant gain in the clinical attachment level and a reduction in the probing pocket depth in the grafted sites compared with the nongrafted sites (P < .001). Moreover, there was a significant difference in the alveolar bone height during the monitoring periods for the grafted sites compared with the nongrafted sites (P < .001). Grafting of osseous defects distal to mandibular second molars with an anorganic xenograft plus a membrane predictably resulted in a significant reduction in the probing pocket depth, clinical attachment level gain, and bone fill, which suggests that grafting the extraction sites with an anorganic xenograft plus a membrane could prevent periodontal disease in the future. Published by Elsevier Inc.

The treatment of infected nonunion of the tibia following intramedullary nailing by the Ilizarov method.

PubMed

Megas, Panagiotis; Saridis, Alkis; Kouzelis, Antonis; Kallivokas, Alkiviadis; Mylonas, Spyros; Tyllianakis, Minos

2010-03-01

The purpose of this study was to demonstrate the effectiveness of the Ilizarov method and circular external fixator in order to eradicate the infection and restore bone union, limb anatomy and functionality in cases with infected nonunion of the tibia following intramedullary nailing. During 7 years nine patients suffering from infected nonunion of the tibia after intramedullary nailing were treated in our department. The series comprised seven men and two women with an average age of 39.7 years (range 21-75 years). The patients had previously undergone an average of 4.8 operations (range 3-6 operations). Active purulent bone infection occurred in all nine patients. Bone defect was present in all patients with a mean size of 5 cm (range 2-12 cm). In three cases with bone defect less than 2 cm, monofocal compression osteosynthesis technique was used. In the rest cases where bone defect exceeded 2 cm, bifocal consecutive distraction-compression osteosynthesis technique was applied. Three patients required a local gastrocnemius flap. The mean follow-up period was 26.6 months (range 13-42 months). Results were evaluated using Paley's functional and radiological scoring system. Bone union was achieved in all nine patients without recurrence of infection during the follow-up period. Bone results were graded as excellent in five cases and good in the rest four cases. Functional results were graded as excellent in three cases, good in four and fare in two cases. Mean external fixation time was 187.4 days (range 89-412 days) and mean lengthening index was 32 days/cm (range 27-39 days/cm). Complications observed included eight grade II pin tract infections, axial deformity at the lengthening site in two cases and at the nonunion site in another two cases. Ankle joint stiffness was detected in five cases. The Ilizarov method may be an effective method in infected nonunions of the tibia following intramedullary nailing. Copyright 2009 Elsevier Ltd. All rights reserved.

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages

PubMed Central

Das, Anusuya; Segar, Claire E; Hughley, Brian B; Bowers, Daniel T; Botchwey, Edward A

2013-01-01

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. PMID:24064148

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages.

PubMed

Das, Anusuya; Segar, Claire E; Hughley, Brian B; Bowers, Daniel T; Botchwey, Edward A

2013-12-01

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis

PubMed Central

Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

2015-01-01

Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs’ potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs’ homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs’ involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair. PMID:26722424

Management of Distal Tibial Metaphyseal Bone Defects With an Intramedullary Nitinol Scaffold: A Novel Technique.

PubMed

Ford, Samuel E; Ellington, J Kent

2017-08-01

Difficult problems that are faced when reconstructing severe pilon fractures include filling metaphyseal defects and supporting an impacted, multifragmented articular surface. Supplements to plate fixation currently available in a surgeon's armamentarium include cancellous bone autograft, structural bone allograft, demineralized bone matrix, and calcium-based cements. Cancellous autograft possesses limited inherent mechanical stability and is associated with graft site morbidity. Structural allografts incorporate inconsistently and are plagued by late resorption. Demineralized bone matrix also lacks inherent structural stability. Calcium phosphate cements are not rigidly fixed to bone unless fixation is applied from cortical bone or through a plate, which must be taken into consideration when planning fixation. The Conventus DRS (Conventus Orthopaedics, Maple Grove, MN) implant is an expandable nitinol scaffold that takes advantage of the elasticity and shape memory of nitinol alloy. Once deployed and locked, it serves as a stable intramedullary base for fragment-specific periarticular fracture fixation, even in the face of metaphyseal bone loss. Two cases of successful implant use are presented. In both cases, the implant is used to fill a metaphyseal void and provide stable articular support to the distal tibial plafond. Therapeutic Level V: Case Report, Expert Opinion.

Healing bone lesion defects using injectable CaSO4 /CaPO4 -TCP bone graft substitute compared to cancellous allograft bone chips in a canine model.

PubMed

Hall, Deborah J; Turner, Thomas M; Urban, Robert M

2018-04-16

CaSO 4 /CaPO 4 -TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical-size axial defect created bilaterally into the proximal humerus. CaSO 4 /CaPO 4 -TCP bone graft substitute (PRO-DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze-dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann-Whitney tests. There was more bone in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO 4 /CaPO 4 -TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO 4 /CaPO 4 -TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze-dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model

PubMed Central

Lopez, Maria de Almeida; Olate, Sergio; Lanata-Flores, Antonio; Pozzer, Leandro; Cavalieri-Pereira, Lucas; Cantín, Mario; Vásquez, Bélgica; de Albergaria-Barbosa, José

2013-01-01

The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non-absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey’s test, considering statistical significance when p<0.1. Adequate bone repair was observed in the membrane-covered defects. At 3 weeks, organization of the tissue, bone formation from the periphery of the defect and the absence of inflammatory infiltrate were observed in both experimental groups, but the defect covered with absorbable membrane presented statistically greater bone formation. At 8 weeks, both membrane-covered defects showed adequate bone formation without significant differences, although they did in fact present differences with the control defect in both periods (p>0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects. PMID:24228090

Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model.

PubMed

Xie, Huanxin; Ji, Ye; Tian, Qi; Wang, Xintao; Zhang, Nan; Zhang, Yicai; Xu, Jun; Wang, Nanxiang; Yan, Jinglong

2017-11-01

To explore the effects of autogenous bone particle/titanium fiber composites on repairing segmental bone defects in rabbits. A model of bilateral radial bone defect was established in 36 New Zealand white rabbits which were randomly divided into 3 groups according to filling materials used for bilaterally defect treatment: in group C, 9 animal bone defect areas were prepared into simple bilateral radius bone defect (empty sham) as the control group; 27 rabbits were used in groups ABP and ABP-Ti. In group ABP, left defects were simply implanted with autogenous bone particles; meanwhile, group ABP-Ti animals had right defects implanted with autogenous bone particle/titanium fiber composites. Animals were sacrificed at 4, 8, and 12 weeks, respectively, after operation. Micro-CT showed that group C could not complete bone regeneration. Bone volume to tissue volume values in group ABP-Ti were better than group ABP. From histology and histomorphometry Groups ABP and ABP-Ti achieved bone repair, the bone formation of group ABP-Ti was better. The mechanical strength of group ABP-Ti was superior to that of other groups. These results confirmed the effectiveness of autologous bone particle/titanium fiber composites for promoting bone regeneration and mechanical strength.

Effect of 1% sodium alendronate in the non-surgical treatment of periodontal intraosseous defects: a 6-month clinical trial

PubMed Central

DUTRA, Bernardo Carvalho; OLIVEIRA, Alcione Maria Soares Dutra; OLIVEIRA, Peterson Antônio Dutra; MANZI, Flavio Ricardo; CORTELLI, Sheila Cavalca; COTA, Luís Otávio de Miranda; COSTA, Fernando Oliveira

2017-01-01

Abstract Background and objectives Few studies have evaluated the effect of the topical application of sodium alendronate (ALN) on the treatment of intrabuccal bone defects, especially those caused by periodontitis. This 6-month randomized placebo controlled clinical trial aimed at evaluating the effect of non-surgical periodontal treatment associated with the use of 1% ALN, through clinical evaluations and cone-beam computed tomography (CBCT). Material and Methods Twenty individuals with chronic periodontitis underwent periodontal examination at the baseline as well as 3 and 6 months after periodontal treatment, registering clinical attachment level (CAL), periodontal probing depth (PPD), and bleeding on probing (BOP) as the clinical outcomes. After manual scaling and root planing, 40 bilateral sites with interproximal vertical bone defects were randomly treated with either 1% ALN gel or a placebo. Bone defects were evaluated through CBCT at the baseline and 6 months post-treatment. The clinical and CBCT parameters were compared using the Wilcoxon and Friedman tests (p<0.05). Results Although ALN produced a greater CAL gain when compared to the placebo at 6 months post-treatment (p=0.021), both treatments produced similar effects on the PPD, BOP, and bone height. Significant differences in bone fill were observed only in patients of the ALN group (4.5 to 3.8 mm; p=0.003) at 6 months post-treatment. Conclusions Topical application of 1% ALN might be a beneficial adjuvant to non-surgical periodontal therapy. PMID:28678950

Study on clinical application of nano-hydroxyapatite bone in bone defect repair.

PubMed

Zhu, Weimin; Wang, Daping; Xiong, Jianyi; Liu, Jianquan; You, Wei; Huang, Jianghong; Duan, Li; Chen, Jielin; Zeng, Yanjun

2015-01-01

To study the clinical effect of bone defect treated with nano-hydroxyapatite(Nano-HA) artificial bone. From September 2009 to June 2012, 27 cases of bone defect were analyzed retrospectively. The position of bone defect included humerus, radius, ulna, femur, tibia and calcaneus. The range of bone defect was from 0.3 × 1.0 cm to 3 × 6.5 cm. Among them, there were 22 cases with fractures and 5 cases with tumors. All patients were treated with Nano-HA artificial bone. The ability of bone defect repair was evaluated by X-ray exams performed preoperatively and postoperatively. HSS scores were adopted for final evaluation at the latest follow-up. The patients were followed up from 11 to 26 months (average of 18.5 months). No general side effects occurred. X-ray photo showed an integrity interface between Nano-HA and bone. Primary healing was obtained in all cases without any complication. The Nano-HA artificial bone had a good biocompatibility and could be an ideal artificial bone in the reconstruction of bone defect.

Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimus dorsi muscle flap in an 11-year-old patient.

PubMed

Morice, Anne; Kolb, Frédéric; Picard, Arnaud; Kadlub, Natacha; Puget, Stéphanie

2017-01-01

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm 2 and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.

Gene Therapy of Bone Morphogenetic Protein for Periodontal Tissue Engineering

PubMed Central

Jin, Q-M.; Anusaksathien, O.; Webb, S.A.; Rutherford, R.B.; Giannobile, W.V.

2009-01-01

Background The reconstruction of lost periodontal support including bone, ligament, and cementum is a major goal of therapy. Bone morphogenetic proteins (BMPs) have shown much potential in the regeneration of the periodontium. Limitations of BMP administration to periodontal lesions include need for high-dose bolus delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene transfer offers promise as an alternative treatment strategy to deliver BMPs to periodontal tissues. Methods This study utilized ex vivo BMP-7 gene transfer to stimulate tissue engineering of alveolar bone wounds. Syngeneic dermal fibroblasts (SDFs) were transduced ex vivo with adenoviruses encoding either green fluorescent protein (Ad-GFP or control virus), BMP-7 (Ad-BMP-7), or an antagonist of BMP bioactivity, noggin (Ad-noggin). Transduced cells were seeded onto gelatin carriers and then transplanted to large mandibular alveolar bone defects in a rat wound repair model. Results Ad-noggin treatment tended to inhibit osteogenesis as compared to the control-treated and Ad-BMP-7-treated specimens. The osseous lesions treated by Ad-BMP-7 gene delivery demonstrated rapid chrondrogenesis, with subsequent osteogenesis, cementogenesis and predictable bridging of the periodontal bone defects. Conclusion These results demonstrate the first successful evidence of periodontal tissue engineering using ex vivo gene transfer of BMPs and offers a new approach for repairing periodontal defects. PMID:12666709

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

PubMed

Lee, Kang-Gon; Lee, Kang-Sik; Kang, Yu-Jeoung; Hwang, Jong-Hyun; Lee, Se-Hwan; Park, Sang-Hyug; Park, Yongdoo; Cho, Young-Sam; Lee, Bu-Kyu

2018-05-01

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

PubMed

Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

2012-01-01

Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

Effects of bovine lactoferrin in surgically created bone defects on bone regeneration around implants.

PubMed

Görmez, Ulaş; Kürkcü, Mehmet; E Benlidayi, Mehmet; Ulubayram, Kezban; Sertdemir, Yaşar; Dağlioğlu, Kenan

2015-03-01

The aim of this experimental study was to evaluate the effect of bovine lactoferrin (bLF)-loaded gelatin microspheres (GM) used in combination with anorganic bovine bone on bone regeneration in surgically created bone defects around tooth implants. Twenty-four uniform bone defects were created in the frontal bone via an extraoral approach in 12 domestic pigs. Twenty-four implants were placed at the center of the defects. In eight animals one of these defects was filled with 0.3 mL anorganic bovine bone while the other was left empty. In four animals, all defects were filled with 3 mg/defect bLF-loaded GM and anorganic bovine bone. All the defects were covered with collagen membranes. All animals were sacrificed after 10 weeks of healing, and the implants with the surrounding bone defects were removed en bloc. Undecalcified sections were prepared for histomorphometric analysis. The mean total area of hard tissue was 26.9 ± 6.0% in the empty defect group, 31.8 ± 8.4% in the graft group, and 47.6 ± 5.0% in the lactoferrin group (P < 0.001). The mean area of newly formed bone was 26.9 ± 6.0% in the empty defect group, 22.4 ± 8.2% in the graft group, and 46.1 ± 5.1% in the lactoferrin group (P < 0.001). The mean residual graft area was 9.4 ± 3.2% in the graft group and 1.5 ± 0.6% in the lactoferrin group (P < 0.001). The mean proportion of bone-implant contact in the defect region was 21.9 ± 8.4% in the empty defect group, 26.9 ± 10.1% in the graft group and 29.9 ± 10.3% in the lactoferrin group (P = 0.143). These data indicate that a combination of 3 mg bLF-loaded GM and bovine-derived HA promotes bone regeneration in defects around implants.

Systemic Treatment with Strontium Ranelate Accelerates the Filling of a Bone Defect and Improves the Material Level Properties of the Healing Bone

PubMed Central

Zacchetti, Giovanna; Rizzoli, René

2014-01-01

Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively. PMID:25243150

Improvement of an anterior infrabone defect using combined periodontal and orthodontic therapy: A 6-year follow-up case report.

PubMed

de Molon, Rafael Scaf; Kim, Yeon Jung; Dos Santos-Pinto, Ary; Cirelli, Joni Augusto

2014-07-01

Extensive intraosseous lesions represent a clinical challenge for the periodontist. Sites with bone defects have been shown to be at higher risk of periodontitis progression in patients who had not received periodontal therapy. Thus, the aim of this case report was to describe a novel approach for the treatment of 1-walled intraosseous defect by combining nonsurgical periodontal therapy and orthodontic movement toward the bone defect, avoiding regenerative and surgical procedures. A 47-year-old woman underwent the proposed procedures for the treatment of her left central incisor with 9 mm probing depth and 1-walled intraosseous defect in its mesial aspect. Initially, basic periodontal therapy with scaling and root planning was accomplished. Two months later, an orthodontic treatment was planned to eliminate the intraosseous lesion and to improve the interproximal papillary area. Orthodontic root movement toward the osseous defect was performed for 13 months with light forces. After 6 years postoperative it was concluded that combined basic periodontal therapy and orthodontic movement was capable of eliminating the intraosseous defect and improve the esthetics in the interproximal papillary area between the central incisors.

In Situ Splitting of a Rib Bone Graft for Reconstruction of Orbital Floor and Medial Wall.

PubMed

Uemura, Tetsuji; Yanai, Tetsu; Yasuta, Masato; Harada, Yoshimi; Morikawa, Aya; Watanabe, Hidetaka; Kurokawa, Masato

2017-06-01

In situ splitting of rib bone graft was conducted in 22 patients for the repair of orbital fracture with no other complicating fractures. A bone graft was harvested from the sixth or seventh rib in the right side. The repair of the orbital floor and medial wall was successful in all the cases. Ten patients had bone grafting to the orbital floor, eight had it done onto medial wall, and 4 onto both floor and wall after reduction. The mean length of in situ rib bone graft was 40.9 mm (range, 20-70 mm), the mean width of these was 14.9 mm (range, 8-20 mm). The bone grafting was done by one leaf for 15 cases and two leafs for 7 cases in size of defects. The technique of in situ splitting of a rib bone graft for the repair of the orbital floor and medial wall is a simple and safe procedure, easily taking out the in situ splitting of a rib, and less pain in donor site. It has proved to be an optimal choice in craniofacial reconstruction, especially the defects of orbital floor and medial wall.

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

PubMed

Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

2015-07-01

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cementoblast Delivery for Periodontal Tissue Engineering

PubMed Central

Zhao, Ming; Jin, Qiming; Berry, Janice E.; Nociti, Francisco H.; Giannobile, William V.; Somerman, Martha J.

2008-01-01

Background Predictable periodontal regeneration following periodontal disease is a major goal of therapy. The objective of this proof of concept investigation was to evaluate the ability of cementoblasts and dental follicle cells to promote periodontal regeneration in a rodent periodontal fenestration model. Methods The buccal aspect of the distal root of the first mandibular molar was denuded of its periodontal ligament (PDL), cementum, and superficial dentin through a bony window created bilaterally in 12 athymic rats. Treated defects were divided into three groups: 1) carrier alone (PLGA polymer sponges), 2) carrier + follicle cells, and 3) carrier + cementoblasts. Cultured murine primary follicle cells and immortalized cementoblasts were delivered to the defects via biodegradable PLGA polymer sponges, and mandibulae were retrieved 3 weeks and 6 weeks post-surgery for histological evaluation. In situ hybridization, for gene expression of bone sialoprotein (BSP) and osteocalcin (OCN), and histomorphometric analysis were further done on 3-week specimens. Results Three weeks after surgery, histology of defects treated with carrier alone indicated PLGA particles, fibrous tissue, and newly formed bone scattered within the defect area. Defects treated with carrier + follicle cells had a similar appearance, but with less formation of bone. In contrast, in defects treated with carrier + cementoblasts, mineralized tissues were noted at the healing site with extension toward the root surface, PDL region, and laterally beyond the buccal plate envelope of bone. No PDL-bone fibrous attachment was observed in any of the groups at this point. In situ hybridization showed that the mineralized tissue formed by cementoblasts gave strong signals for both BSP and OCN genes, confirming its nature as cementum or bone. The changes noted at 3 weeks were also observed at 6 weeks. Cementoblast-treated and carrier alone-treated defects exhibited complete bone bridging and PDL formation, whereas follicle cell-treated defects showed minimal evidence of osteogenesis. No new cementum was formed along the root surface in the above two groups. Cementoblast-treated defects were filled with trabeculated mineralized tissue similar to, but more mature, than that seen at 3 weeks. Furthermore, the PDL region was maintained with well-organized collagen fibers connecting the adjacent bone to a thin layer of cementum-like tissue observed on the root surface. Neoplastic changes were observed at the superficial portions of the implants in two of the 6-week cementoblast-treated specimens, possibly due in part to the SV40-transformed nature of the implanted cell line. Conclusions This pilot study demonstrates that cementoblasts have a marked ability to induce mineralization in periodontal wounds when delivered via polymer sponges, while implanted dental follicle cells seem to inhibit periodontal healing. These results confirm the selective behaviors of different cell types in vivo and support the role of cementoblasts as a tool to better understand periodontal regeneration and cementogenesis. PMID:15025227

* Hypoxia Biomimicry to Enhance Monetite Bone Defect Repair.

PubMed

Drager, Justin; Ramirez-GarciaLuna, Jose Luis; Kumar, Abhishek; Gbureck, Uwe; Harvey, Edward J; Barralet, Jake E

2017-12-01

Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 μL (200 μM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm 2 vs. 33.2 mm 2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of this medication, the results of this study support further investigation into the use of iron chelators in creating a biomimetic environment for bone healing in segmental bone loss.

Restoration of small bone defects at craniotomy using autologous bone dust and fibrin glue.

PubMed

Matsumoto, K; Kohmura, E; Kato, A; Hayakawa, T

1998-10-01

Bone gaps or burr holes often result in small but undesirable scalp or skin depressions after craniotomy. Whereas a number of reports have discussed cranioplasties to avoid large bone defects, little has been written about the problem of small bone defects which, despite their minor size, could result in bothersome cosmetic problems. This study was designed to assess a simple method to repair burr hole defects and bridge bone gaps with autologous bone dust and fibrin glue. Bone dust was collected when burr holes were created or craniectomy was performed. After replacement of the bone flap, the burr holes or bone gap were filled with a mixture of bone dust and fibrin glue. The mixture of bone dust and fibrin glue was easily shaped to fit bone defects, resulting in favorable cosmetic outcomes 1 to 5 years after operation.

Development of a Moldable, Biodegradable Polymeric Bone Repair Material

DTIC Science & Technology

1994-03-30

minimally encapsulated by fibrous tissue. Histomorphometric analysis of day 14 specimens showed a very mild foreign body response in terms of area. This...significant visual evidence of foreign body response seen for any Atrix test article. A mass of dense fibrotic tissue was found near the defect site...article in the defect and medullary cavity. The test article was minimally encapsulated by fibrotic tissue. Histomorphometric analysis showed this

[The method of accelerating osteanagenesis and revascularization of tissue engineered bone in big animal in vivo].

PubMed

Chen, Bin; Pei, Guo-xian; Wang, Ke; Jin, Dan; Wei, Kuan-hai; Ren, Gao-hong

2003-02-01

To study whether tissue engineered bone can repair the large segment bone defect of large animal or not. To observe what character the fascia flap played during the osteanagenesis and revascularization process of tissue engineered bone. 9 Chinese goats were made 2 cm left tibia diaphyseal defect. The repairing effect of the defects was evaluated by ECT, X-ray and histology. 27 goats were divided into three groups: group of CHAP, the defect was filled with coral hydroxyapatite (CHAP); group of tissue engineered bone, the defect was filled with CHAP + bone marrow stroma cells (BMSc); group of fascia flap, the defect was filled with CHAP + BMSc + fascia flap. After finished culturing and inducing the BMSc, CHAP of group of tissue engineered bone and of fascia flap was combined with it. Making fascia flap, different materials as described above were then implanted separately into the defects. Radionuclide bone imaging was used to monitor the revascularization of the implants at 2, 4, 8 weeks after operation. X-ray examination, optical density index of X-ray film, V-G staining of tissue slice of the implants were used at 4, 8, 12 weeks after operation, and the biomechanical character of the specimens were tested at 12 weeks post operation. In the first study, the defect showed no bone regeneration phenomenon. 2 cm tibia defect was an ideal animal model. In the second study, group of CHAP manifested a little trace of bone regeneration, as to group of tissue engineered bone, the defect was almost repaired totally. In group of fascia flap, with the assistance of fascia flap which gave more chance to making implants to get more nutrient, the repair was quite complete. The model of 2 cm caprine tibia diaphyseal defect cannot be repaired by goat itself and can satisfy the tissue engineering's demands. Tissue engineered bone had good ability to repair large segment tibia defect of goat. Fascia flap can accelerate the revascularization process of tissue engineered bone. And by this way, it augment the ability of tissue engineered bone to repair the large bone defect of goat.

[Prefabrication of bone transplants].

PubMed

Jagodzinski, M; Kokemüller, H; Jehn, P; Vogt, P; Gellrich, N-C; Krettek, C

2015-03-01

Prefabrication of bone transplants is a promising option for large defects of the long bones, especially if there is compromised vascularization of the defect. This is especially true for postinfection bone defects and other types of atrophic nonunion. The generation of a foreign body membrane (Masquelet's technique) has been investigated in order to ameliorate the response of the host tissue surrounding the defect. In an experimental animal study, a blood vessel within a bone construct could be used to generate customized, vascularized osteogenic constructs that can be used to treat large bone defects in the future.

Three-dimensional model simulation and reconstruction of composite total maxillectomy defects with fibula osteomyocutaneous flap flow-through from radial forearm flap.

PubMed

He, Yue; Zhu, Han Guang; Zhang, Zhi Yuan; He, Jie; Sader, Robert

2009-12-01

A total maxillectomy always causes composite defects of maxilla, zygomatic bone, orbital floor or rim, and palatal and nasal mucosa lining. This leads to significant functional and cosmetic consequences after ablative surgery. The purpose of this clinical study was to preliminarily 3-dimensionally reconstruct the defect of total maxillectomy with sufficient bone support and soft tissue lining. Three-dimensional model simulation technique and free fibula osteomyocutaneous flap flow-through from radial forearm flap were used to reconstruct a total maxillectomy defect for a 21-year-old female patient. Preoperatively, the 3-dimensional (3D) simulated resin models of skeleton and fibula were used to design the osteotomies and bone segment replacement. At surgery, a 22-cm-length free fibula was divided into 4 segments to make 1 maxilla skeletal framework in the schedule of the preoperative model surgical planning with a radial forearm flap flow-through for the free fibula flap with skin paddle to repair the palatal and nasal region. Free fibula and radial forearm flap were alive, and the patient was satisfied with the results both esthetically and functionally after dental rehabilitation which was carried out 6 months after surgery. This preliminarily clinical study and case demonstrated that: the fibula osteomyocutaneous flap is an ideal donor site in 3D total maxillectomy defect reconstruction, because of its thickness, length, and bone uniformity which makes ideal support for dental rehabilitation; the flow-through forearm radial flap not only serves as the vascular bridge to midface reconstruction, but also provides sufficient soft tissue cover for the intraoral defect; and the 3D model simulation and preoperative surgical planning are effective methods to refine reconstruction surgery, shorten the surgical time, and predict the outcome after operation.

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

PubMed Central

Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

2015-01-01

Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

Repair of sheep long bone cortical defects filled with COLLOSS, COLLOSS E, OSSAPLAST, and fresh iliac crest autograft.

PubMed

Huffer, William E; Benedict, James J; Turner, A S; Briest, Arne; Rettenmaier, Robert; Springer, Marco; Walboomers, X F

2007-08-01

COLLOSS and COLLOSS E are osteoinductive bone void fillers consisting of bone collagen and noncollagenous proteins from bovine and equine bone, respectively. The aim of this study was to compare COLLOSS, COLLOSS E, iliac bone autograft, sintered beta tricalcium phosphate (beta-TCP; OSSAPLAST), and COLLOSS E plus OSSAPLAST. Materials were placed for 4, 8, or 24 weeks in 5-mm cortical bone defects in sheep long bones. Histological sections in a plane perpendicular to the long axis of the bone were used to measure the total repair area (original defect plus callus) and the area of bone within the total repair area. The incidence of defect union was also evaluated. At 4 and 8 weeks, defects treated with COLLOSS and COLLOSS E with or without OSSAPLAST had total repair and bone areas equivalent to autograft, and larger than OSSAPLAST-treated defects. At 8 weeks, the incidence of defect union was higher in defects treated with autograft or COLLOSS E plus OSSAPLAST than in untreated defects. At 24 weeks, the incidence of union was 100% in all treatment groups and 0% in untreated defects. The incidence of union was related to the degree of remodeling between 8 and 24 weeks. This was greater in all treated than nontreated defects. In conclusion, COLLOSS and COLLOSS E were equivalent to each other and to autograft, and superior to beta-TCP, in this study model.

Guided bone regeneration using individualized ceramic sheets.

PubMed

Malmström, J; Anderud, J; Abrahamsson, P; Wälivaara, D-Å; Isaksson, S G; Adolfsson, E

2016-10-01

Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Micro-CT evaluation of bone defects: applications to osteolytic bone metastases, bone cysts, and fracture.

PubMed

Buie, Helen R; Bosma, Nick A; Downey, Charlene M; Jirik, Frank R; Boyd, Steven K

2013-11-01

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Spmax) by 72.8%. Regression modeling revealed SpSD (β=0.974, p<0.0001) to be a significant predictor of the defect volume (R(2)=0.949) and Spmax (β=0.712, p<0.0001) and SpSD (β=0.271, p=0.022) to be significant predictors of the defect diameter (R(2)=0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Ilizarov bone transport versus fibular graft for reconstruction of tibial bone defects in children.

PubMed

Abdelkhalek, Mostafa; El-Alfy, Barakat; Ali, Ayman M

2016-11-01

The aim of this study was to compare the results of treatment of segmental tibial defects in the pediatric age group using an Ilizarov external fixator versus a nonvascularized fibular bone graft. This study included 24 patients (age range from 5.5 to 15 years) with tibial bone defects: 13 patients were treated with bone transport (BT) and 11 patients were treated with a nonvascularized fibular graft (FG). The outcome parameters were bone results (union, deformity, infection, leg-length discrepancy) and functional results: external fixation index and external fixation time. In group A (BT), one patient developed refracture at the regenerate site, whereas, in group B (FG), after removal of the external fixator, one of the FGs developed a stress fracture. The external fixator time in group A was 10.7 months (range 8-14.5) versus 7.8 months (range 4-11.5 months) in group B (FG). In group A (BT), one patient had a limb-length discrepancy (LLD), whereas, in group B (FG), three patients had LLD. The functional and bone results of the Ilizarov BT technique were excellent in 23.1 and 30.8%, good in 38.5 and 46.2, fair in 30.8 and 15.4, and poor in 7.6 and 7.6%, respectively. The poor functional result was related to the poor bone result because of prolonged external fixator time resulting in significant pain, limited ankle motion, whereas the functional and bone results of fibular grafting were excellent in 9.1 and 18.2%, good in 63.6 and 45.5%, fair in 18.2 and 27.2%, and poor in 9.1 and 9.1%, respectively. Segmental tibial defects can be effectively treated with both methods. The FG method provides satisfactory results, with early removal of the external fixator. However, it had a limitation in patients with severe infection and those with LLD. Also, it requires a long duration of limb bracing until adequate hypertrophy of the graft. The Ilizarov method has the advantages of early weight bearing, treatment of postinfection bone defect in a one-stage surgery, and the possibility to treat the associated LLD. However, it has a long external fixation time.

Periodontal and peri-implant bone regeneration: clinical and histologic observations.

PubMed

Artzi, Z; Zohar, R; Tal, H

1997-02-01

The principle of guided tissue regeneration by barrier membranes to restore lost periodontal tissue around natural teeth has also been used around osseointegrated implants in an attempt to restore alveolar ridge defects. While most periodontal procedures in the literature describe root coverage by mucogingival surgery, which achieves healing through soft tissue attachment, regeneration of denuded root surfaces is performed by guided tissue regeneration using expanded polytetrafluoroethylene barrier membranes and demineralized freeze-dried bone allografts as inductive/conductive materials. In this study the technique is applied in two partially exposed cylindrical hydroxyapatite-coated implants in extraction sites in one patient. Surgical reentry in both sites is presented, with histologic examination revealing new bone formation on the exposed root surface and the hydroxyapatite-coated implants.

Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

PubMed

Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

2011-08-01

The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

Surface micromorphology of cross-linked tetrafunctional polylactide scaffolds inducing vessel growth and bone formation.

PubMed

Kuznetsova, D; Ageykin, A; Koroleva, A; Deiwick, A; Shpichka, A; Solovieva, A; Kostjuk, S; Meleshina, A; Rodimova, S; Akovanceva, A; Butnaru, D; Frolova, A; Zagaynova, E; Chichkov, B; Bagratashvili, V; Timashev, P

2017-04-28

In the presented study, we have developed a synthetic strategy allowing a gradual variation of a polylactide arms' length, which later influences the micromorphology of the scaffold surface, formed by a two-photon polymerization technique. It has been demonstrated that the highest number of cells is present on the scaffolds with the roughest surface made of the polylactide with longer arms (PLA760), and osteogenic differentiation of mesenchymal stem cells is most pronounced on such scaffolds. According to the results of biological testing, the PLA760 scaffolds were implanted into a created cranial defect in a mouse for an in vivo assessment of the bone tissue formation. The in vivo experiments have shown that, by week 10, deposition of calcium phosphate particles occurs in the scaffold at the defect site, as well as, the formation of a new bone and ingrowth of blood vessels from the surrounding tissues. These results demonstrate that the cross-linked microstructured tetrafunctional polylactide scaffolds are promising microstructures for bone regeneration in tissue engineering.

Is It Safe to Re-Harvest the Anterior Iliac Crest to Manage Le Fort I Interpositional Defects in Young Adults With a Repaired Cleft?

PubMed

Posnick, Jeffrey C; Gray, James A

2015-12-01

Re-harvesting the anterior iliac crest to obtain autogenous bone grafts is a controversial practice. The purpose of this study was to assess the feasibility and associated disability of re-harvesting the anterior iliac crest. To address the research purpose, the authors executed a retrospective case series study. The sample consisted of young adult patients with cleft (<26 yr old) with prior harvesting of the anterior iliac crest during mixed dentition for management of an alveolar cleft(s) and then re-harvesting of the same donor site for management of interpositional defects after Le Fort I advancement. Wound-healing parameters were reviewed at the donor and recipient sites. A survey questionnaire was provided after completion of treatment to document patient perception of early and any long-term donor-site disability. Descriptive statistics were computed for the variables. The sample was composed of 27 patients with a mean age at re-harvesting of 17 years (range, 14 to 25 yr). Patients underwent on average 7.4-mm horizontal advancement, 2.4-mm lengthening, and 2.6-mm transverse expansion of the maxilla. Adequate bone graft was re-harvested to accomplish objectives in all cases. There were no perioperative complications at the donor or recipient sites. Twenty-six of the 27 patients (97%) had fewer donor-site recovery difficulties at the time of re-harvesting compared with the first time graft was taken. There were no cases of lateral femoral cutaneous nerve injury and no long-term discomfort with walking, running, or other activities. The study confirms the safety and efficacy of re-harvesting corticocancellous bone from the anterior iliac crest for management of interpositional defects associated with Le Fort I advancement in young adults with a repaired cleft. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Transforming Growth Factor-β1 Accelerates Resorption of a Calcium Carbonate Biomaterial in Periodontal Defects.

PubMed

Koo, Ki-Tae; Susin, Cristiano; Wikesjö, Ulf M E; Choi, Seong-Ho; Kim, Chong-Kwan

2007-04-01

In a previous study, recombinant human transforming growth factor-beta1 (rhTGF-β 1 ) in a calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for guided tissue regeneration (GTR) to study whether rhTGF-β 1 would enhance or accelerate periodontal regeneration. The results showed minimal benefits of rhTGF-β 1 , and a clear account for this could not be offered. One potential cause may be that the rhTGF-β 1 formulation was biologically inactive. Several growth or differentiation factors have been suggested to accelerate degradation of biomaterials used as carriers. The objective of this study was to evaluate possible activity of rhTGF-β 1 on biodegradation of the calcium carbonate carrier. rhTGF-β 1 in a putty-formulated particulate calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for GTR in five beagle dogs. Contralateral defects received the calcium carbonate carrier combined with GTR without rhTGF-β 1 (control). The animals were euthanized at week 4 post-surgery and block biopsies of the defect sites were collected for histologic and histometric analysis. Radiographs were obtained at defect creation and weeks 2 and 4 after defect creation. No statistically significant differences were observed in new bone formation (bone height and area) among the treatments. However, total residual carrier was significantly reduced in sites receiving rhTGF-β 1 compared to control (P = 0.04). Similarly, carrier density was considerably reduced in sites receiving rhTGF-β 1 compared to control; the difference was borderline statistically significant (P = 0.06). Within the limitations of the study, it may be concluded that rhTGF-β 1 accelerates biodegradation of a particulate calcium carbonate biomaterial, indicating a biologic activity of the rhTGF-β 1 formulation apparently not encompassing enhanced or accelerated periodontal regeneration. © 2007 American Academy of Periodontology.

Transforming growth factor-beta1 accelerates resorption of a calcium carbonate biomaterial in periodontal defects.

PubMed

Koo, Ki-Tae; Susin, Cristiano; Wikesjö, Ulf M E; Choi, Seong-Ho; Kim, Chong-Kwan

2007-04-01

In a previous study, recombinant human transforming growth factor-beta1 (rhTGF-beta(1)) in a calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for guided tissue regeneration (GTR) to study whether rhTGF-beta(1) would enhance or accelerate periodontal regeneration. The results showed minimal benefits of rhTGF-beta(1), and a clear account for this could not be offered. One potential cause may be that the rhTGF-beta(1) formulation was biologically inactive. Several growth or differentiation factors have been suggested to accelerate degradation of biomaterials used as carriers. The objective of this study was to evaluate possible activity of rhTGF-beta(1) on biodegradation of the calcium carbonate carrier. rhTGF-beta(1) in a putty-formulated particulate calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for GTR in five beagle dogs. Contralateral defects received the calcium carbonate carrier combined with GTR without rhTGF-beta(1) (control). The animals were euthanized at week 4 post-surgery and block biopsies of the defect sites were collected for histologic and histometric analysis. Radiographs were obtained at defect creation and weeks 2 and 4 after defect creation. No statistically significant differences were observed in new bone formation (bone height and area) among the treatments. However, total residual carrier was significantly reduced in sites receiving rhTGF-beta(1) compared to control (P = 0.04). Similarly, carrier density was considerably reduced in sites receiving rhTGF-beta(1) compared to control; the difference was borderline statistically significant (P = 0.06). Within the limitations of the study, it may be concluded that rhTGF-beta(1) accelerates biodegradation of a particulate calcium carbonate biomaterial, indicating a biologic activity of the rhTGF-beta(1) formulation apparently not encompassing enhanced or accelerated periodontal regeneration.

Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots

PubMed Central

Berninger, Markus T.; Wexel, Gabriele; Rummeny, Ernst J.; Imhoff, Andreas B.; Anton, Martina

2013-01-01

The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects is much more complex and a far greater surgical and therapeutic challenge. The damaged tissue does not only include the superficial cartilage layer but also the subchondral bone. For deep, osteochondral damage, as it occurs for example with osteochondrosis dissecans, the full thickness of the defect needs to be replaced to restore the joint surface 1. Eligible therapeutic procedures have to consider these two different tissues with their different intrinsic healing potential 2. In the last decades, several surgical treatment options have emerged and have already been clinically established 3-6. Autologous or allogeneic osteochondral transplants consist of articular cartilage and subchondral bone and allow the replacement of the entire osteochondral unit. The defects are filled with cylindrical osteochondral grafts that aim to provide a congruent hyaline cartilage covered surface 3,7,8. Disadvantages are the limited amount of available grafts, donor site morbidity (for autologous transplants) and the incongruence of the surface; thereby the application of this method is especially limited for large defects. New approaches in the field of tissue engineering opened up promising possibilities for regenerative osteochondral therapy. The implantation of autologous chondrocytes marked the first cell based biological approach for the treatment of full-thickness cartilage lesions and is now worldwide established with good clinical results even 10 to 20 years after implantation 9,10. However, to date, this technique is not suitable for the treatment of all types of lesions such as deep defects involving the subchondral bone 11. The sandwich-technique combines bone grafting with current approaches in Tissue Engineering 5,6. This combination seems to be able to overcome the limitations seen in osteochondral grafts alone. After autologous bone grafting to the subchondral defect area, a membrane seeded with autologous chondrocytes is sutured above and facilitates to match the topology of the graft with the injured site. Of course, the previous bone reconstruction needs additional surgical time and often even an additional surgery. Moreover, to date, long-term data is missing 12. Tissue Engineering without additional bone grafting aims to restore the complex structure and properties of native articular cartilage by chondrogenic and osteogenic potential of the transplanted cells. However, again, it is usually only the cartilage tissue that is more or less regenerated. Additional osteochondral damage needs a specific further treatment. In order to achieve a regeneration of the multilayered structure of osteochondral defects, three-dimensional tissue engineered products seeded with autologous/allogeneic cells might provide a good regeneration capacity 11. Beside autologous chondrocytes, mesenchymal stem cells (MSC) seem to be an attractive alternative for the development of a full-thickness cartilage tissue. In numerous preclinical in vitro and in vivo studies, mesenchymal stem cells have displayed excellent tissue regeneration potential 13,14. The important advantage of mesenchymal stem cells especially for the treatment of osteochondral defects is that they have the capacity to differentiate in osteocytes as well as chondrocytes. Therefore, they potentially allow a multilayered regeneration of the defect. In recent years, several scaffolds with osteochondral regenerative potential have therefore been developed and evaluated with promising preliminary results 1,15-18. Furthermore, fibrin glue as a cell carrier became one of the preferred techniques in experimental cartilage repair and has already successfully been used in several animal studies 19-21 and even first human trials 22. The following protocol will demonstrate an experimental technique for isolating mesenchymal stem cells from a rabbit's bone marrow, for subsequent proliferation in cell culture and for preparing a standardized in vitro-model for fibrin-cell-clots. Finally, a technique for the implantation of pre-established fibrin-cell-clots into artificial osteochondral defects of the rabbit's knee joint will be described. PMID:23728213

Repair of rabbit cartilage defect based on the fusion of rabbit bone marrow stromal cells and Nano-HA/PLLA composite material.

PubMed

Zhu, Weimin; Guo, Daiqi; Peng, Liangquan; Chen, Yun Fang; Cui, Jiaming; Xiong, Jianyi; Lu, Wei; Duan, Li; Chen, Kang; Zeng, Yanjun; Wang, Daping

2017-02-01

Objective To assess the effect of the fusion of rabbit bone marrow stromal cells (rBMSCs) and Nano-hydroxyapatite/poly (l-lactic acid) (Nano-HA/PLLA) in repairing the rabbit knee joint with full-thickness cartilage defect. Method The rBMSCs were isolated and cultured in vitro, and the third generation of rBMSCs was co-cultured with the Nano-HA/PLLA to construct the tissue-engineered cartilage (TEC). Eighteen New Zealand white rabbits were selected and randomly divided into three groups, namely, TEC group, Nano-HA/PLLA group, and control group. A cartilage defect model with the diameter of 4.5 mm and depth of 5 mm was constructed on the articular surface of medial malleolus of rabbit femur. General observation, histological observation, and Wakitani's histological scoring were conducted in the 12th and 24th week postoperatively. Results The results of TEC group indicated that new cartilage tissue was formed on the defect site and subchondral bone achieved physiological integration basically. Histological and immunohistochemical analyses indicated the generation of massive extracellular matrix. In contrast, limited regeneration and reconstruction of cartilage was achieved in the Nano-HA/PLLA group and control group, with a significant difference from the TEC group (p < 0.05). Moreover, the effect of cartilage repair was positively correlated with time. Conclusion The porous Nano-HA/PLLA combined with BMSCs promoted the repair of weight-bearing bone of adult rabbit's knee joint with cartilage defect.

Influence of titanium implant surface characteristics on bone regeneration in dehiscence-type defects: an experimental study in dogs.

PubMed

Schwarz, Frank; Sager, Martin; Kadelka, Ines; Ferrari, Daniel; Becker, Jürgen

2010-05-01

The aim of the present study was to compare bone regeneration in dehiscence-type defects at titanium implants with chemically modified sandblasted/acid-etched (modSLA) or dual acid-etched surfaces with a calcium phosphate nanometre particle modification (DCD/CaP). Buccal dehiscence-type defects were surgically created following implant site preparation in both the upper and the lower jaws of 12 fox hounds. Both types of implants were randomly allocated in a split-mouth design and left to heal in a submerged position for 2 and 8 weeks. Dissected blocks were processed for histomorphometrical analysis [e.g. new bone height (NBH), percentage of bone-to-implant contact (BIC), area of new bone fill (BF), and area of mineralized tissue (MT) within BF]. At 2 and 8 weeks, both groups revealed comparable mean BF (2.3+/-0.6 to 2.5+/-0.6 mm(2)versus 2.0+/-0.6 to 1.4+/-0.5 mm(2)) and MT (31.1+/-14.3-83.2+/-8.2%versus 38.9+/-15.9-84.4+/-6.3%) values. However, modSLA implants revealed significantly higher mean NBH (2.4+/-0.8 to 3.6+/-0.3 mm versus 0.9+/-0.8 to 1.8+/-1.4 mm) and BIC (53.3+/-11.3-79.5+/-6.6%versus 19.3+/-16.4-47.2+/-30.7%) values than DCD/CaP implants. ModSLA implants may have a higher potential to support osseointegration in dehiscence-type defects than DCD/CaP implants.

Clinical and Radiological Regeneration of Large and Deep Osteochondral Defects of the Knee by Bone Augmentation Combined With Matrix-Guided Autologous Chondrocyte Transplantation.

PubMed

Zellner, Johannes; Grechenig, Stephan; Pfeifer, Christian G; Krutsch, Werner; Koch, Matthias; Welsch, Goetz; Scherl, Madeleine; Seitz, Johannes; Zeman, Florian; Nerlich, Michael; Angele, Peter

2017-11-01

Large osteochondral defects of the knee are a challenge for regenerative treatment. While matrix-guided autologous chondrocyte transplantation (MACT) represents a successful treatment for chondral defects, the treatment potential in combination with bone grafting by cancellous bone or bone block augmentation for large and deep osteochondral defects has not been evaluated. To evaluate 1- to 3-year clinical outcomes and radiological results on magnetic resonance imaging (MRI) after the treatment of large osteochondral defects of the knee with bone augmentation and MACT. Special emphasis is placed on different methods of bone grafting (cancellous bone grafting or bone block augmentation). Case series; Level of evidence, 4. Fifty-one patients were included. Five patients were lost to follow-up. This left 46 patients (mean age, 28.2 years) with a median follow-up time of 2 years. The 46 patients had 47 deep, large osteochondral defects of the knee joint (1 patient with bilateral defects; mean defect size, 6.7 cm 2 ). The origin of the osteochondral defects was osteochondritis dissecans (n = 34), osteonecrosis (n = 8), or subchondral cysts (n = 5). Depending on the depth, all defects were treated by cancellous bone grafting (defect depth ≤10 mm; n = 16) or bone block augmentation (defect depth >10 mm; n = 31) combined with MACT. Clinical outcomes were followed at 3 months, 6 months, 1 year, 2 years, and 3 years and evaluated using the International Knee Documentation Committee (IKDC) score and Cincinnati score. A magnetic resonance imaging (MRI) evaluation was performed at 1 and 2 years, and the magnetic resonance observation of cartilage repair tissue (MOCART) score with additional specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes, sclerotic areas, and edema) was analyzed. The clinical outcome scores revealed a significant increase at follow-up (6 months to 3 years) compared with the preclinical results. The median IKDC score increased from 42.6 preoperatively to 75.3 at 1 year, 79.7 at 2 years, and 84.3 at 3 years. The median Cincinnati score significantly increased from 39.8 preoperatively to 72.0 at 1 year, 78.0 at 2 years, and 80.3 at 3 years. The MRI evaluation revealed a MOCART score of 82.6 at 1 year without a deterioration at the later follow-up time point. Especially, the subchondral bone analysis showed successful regeneration. All bone blocks and cancellous bone grafts were integrated in the bony defects, and no chondrocyte transplant failure could be detected throughout the follow-up. Large and deep osteochondral defects of the knee joint can be treated successfully with bone augmentation and MACT. The treatment of shallow bony defects with cancellous bone grafting and deep bony defects with bone block augmentation shows promising results.

Buccal bone deficiency in fresh extraction sockets: a prospective single cohort study.

PubMed

Barone, Antonio; Ricci, Massimiliano; Romanos, Georgios E; Tonelli, Paolo; Alfonsi, Fortunato; Covani, Ugo

2015-07-01

The purpose of this prospective single cohort study was to evaluate the use of xenograft and collagen membranes in treating full or partial buccal bone defects of fresh extraction sockets in the esthetic zone. Thirty-three patients requiring tooth extraction in the anterior maxillary area and showing a complete or partial buccal bone plate deficiency (more than 2 mm) were consecutively enrolled and treated. Corticocancellous porcine bone and platelet-rich fibrin (PRF) with a collagen membrane were used to graft the extraction sockets, and the membranes were left exposed to the oral cavity with a secondary soft tissue healing. The outcome variables were as follows: width of keratinized mucosa, facial soft tissue levels, clinical bone changes (measured with a clinical splint), implant and prosthesis failures, and peri-implant marginal bone changes. All treated sites allowed the placement of implants; the width of keratinized mucosa at the mid-facial aspect showed an increase of 2.3 mm 5 months after the grafting procedure, and its value was 3.2 ± 0.6 mm at 1-year follow-up. The mean values of the facial soft tissue level indicated an increase over time. The bone level showed an improvement of 0.8 ± 0.1 mm and 0.7 ± 0.1 mm at mesial and distal sites, respectively, when compared to the baseline measurements. Finally, in the palatal area, no bone changes were observed. No implant failed during the entire observation period. Findings from this study showed that xenograft and PRF, used for ridge preservation of the extraction sockets with buccal bone plate dehiscence in the esthetic zone, can be considered effective in repairing bone defects before implant placement. The secondary soft tissue healing over the grafted sockets did not compromise bone formation; moreover, the soft tissue level and the width of keratinized gingiva showed a significant improvement over time. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of platelet-rich plasma in the treatment of periodontal intrabony defects in humans.

PubMed

Ouyang, Xiang-ying; Qiao, Jing

2006-09-20

Platelet-rich plasma (PRP) is a kind of natural source of autologous growth factors, and has been used successfully in medical community. However, the effect of PRP in periodontal regeneration is not clear yet. This study was designed to evaluate the effectiveness of PRP as an adjunct to bovine porous bone mineral (BPBM) graft in the treatment of human intrabony defects. Seventeen intrabony defects in 10 periodontitis patients were randomly treated either with PRP and BPBM (test group, n = 9) or with BPBM alone (control group, n = 8). Clinical parameters were evaluated including changes in probing depth, relative attachment level (measured by Florida Probe and a stent), and bone probing level between baseline and 1 year postoperatively. Standardized periapical radiographs of each defect were taken at baseline, 2 weeks, and 1 year postoperatively, and analyzed by digital subtraction radiography (DSR). Both treatment modalities resulted in significant attachment gain, reduction of probing depth, and bone probing level at 1-year post-surgery compared to baseline. The test group exhibited statistically significant improvement compared to the control sites in probing depth reduction: (4.78 +/- 0.95) mm versus (3.48 +/- 0.41) mm (P < 0.01); clinical attachment gain: (4.52 +/- 1.14) mm versus (2.85 +/- 0.80) mm (P < 0.01); bone probing reduction: (4.56 +/- 1.04) mm versus (2.88 +/- 0.79) mm (P < 0.01); and defect bone fill: (73.41 +/- 14.78)% versus (47.32 +/- 11.47)% (P < 0.01). DSR analysis of baseline and 1 year postoperatively also showed greater radiographic gains in alveolar bone mass in the test group than in the control group: gray increase (580 +/- 50) grays versus (220 +/- 32) grays (P = 0.0001); area with increased gray were (5.21 +/- 1.25) mm(2) versus (3.02 +/- 1.22) mm(2) (P = 0.0001). The treatment with a combination of PRP and BPBM led to a significantly favorable clinical improvement in periodontal intrabony defects compared to using BPBM alone. Further studies are necessary to assess the long-term effectiveness of PRP, and a larger sample size is needed.

Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation.

PubMed

Carlisle, Patricia L; Guda, Teja; Silliman, David T; Lien, Wen; Hale, Robert G; Brown Baer, Pamela R

2016-02-01

To validate a critical-size mandibular bone defect model in miniature pigs. Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

Comparison of applying particulate demineralized bone matrix (DBM), putty DBM and open flap debridement in periodontal horizontal bone defects. A 12-month longitudinal, multi-centre, triple-blind, split-mouth, randomized, controlled clinical study. Part 2 - evaluation of the interdental soft tissue.

PubMed

Kaya, Y; Yalim, M; Bahçecitapar, M; Baloş, K

2009-07-01

To date, there have been many studies clinically evaluating periodontal regenerative procedures by the help of routinely used hard and soft tissue parameters; however, these parameters are not capable of assessing interdental soft tissue located above the regenerative periodontal surgery area. The purpose of this study was to assess interproximal soft tissue changes following application of (i) particulate form demineralized bone matrix (DBM), (ii) putty form DBM and (ii) open flap debridement (OFD, control), using modified curtain technique in the treatment of interproximal suprabony (horizontal) defects located in anterior maxillary region, as previously reported. Twenty-five chronic periodontitis patients with 125 interproximal surgery sites (radiologically >or=4 mm horizontal bone defect) were also participate in this second stage of the triple-blind, split mouth, randomized, controlled clinical trial. Surgery sites were assessed by (i) plaque index (PI), (ii) gingival index (GI), (iii) the presence of interdental soft tissue clefts or craters and (iv) the loss of interdental papilla height by using papilla presence index (PPI), during the healing period. At the baseline and 3, 6, 9 and 12 months after the operations, these measurements were repeated. In all groups, there is a significant increase in the prevalence of soft tissue cleft and crater formation (P < 0.01), with increase in PI and GI scores at interdental soft tissue defect areas (P < 0.001), 3 months after the operations. There was also an increase in PPI scores after the operations in all treatment groups (P < 0.01). Three procedures affected the interproximal soft tissues similarly. There was no significant difference among groups in terms of all parameters (P > 0.05). Particulate DBM, putty DBM and OFD demostrated similar interproximal soft tissue changes especially increasing interproximal PI and GI scores in 3 months follow-up.

Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

PubMed Central

2013-01-01

Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

Bone Ceramic® at Implants Installed Immediately into Extraction Sockets in the Molar Region: An Experimental Study in Dogs.

PubMed

Pereira, Flávia Priscila; Hochuli-Vieira, Eduardo; Maté Sánchez de Val, José E; De Santis, Enzo; Salata, Luiz Antonio; Botticelli, Daniele

2016-04-01

The aim of this paper was to study the healing of 1-1.4 mm wide buccal defects at implants placed immediately into extraction sockets (IPIES) filled with a mixture of synthetic hydroxyapatite (HA) 60% and beta-tricalciumphosphate (TCP) 40% or left with the clot alone and both covered with collagen membranes. Eight Labrador dogs were used and implants were placed immediately into the extraction sockets of the first molar bilaterally. A mixture of synthetic HA 60% and beta-TCP 40% at the test or the clot alone at the control sites were used to fill the defects. All surgical sites were subsequently covered by a resorbable collagen membrane and a non-submerged healing was allowed. After 4 months, the animals were euthanized, biopsies harvested and processed for histomorphometric analysis. At the time of installation, residual buccal defects occurred that were 1.1 mm and 1.4 mm wide and 3 mm and 4 mm deep at the control and test sites, respectively. After 4 months of healing, the top of the bony crest and the coronal level of osseointegration were located respectively at 0.1 ± 1.8 mm and 1.5 ± 1.8 mm at the test, and 0.6 ± 1.6 mm and 1.2 ± 0.7 mm at the control sites apically to the implant shoulder. Bone-to-implant contact at the buccal aspect was 34.9 ± 25.9% and 36.4 ± 17.3% at the test and control sites, respectively. No statistically significant differences were found between test and control sites for any of the variables analyzed at the buccal aspects. The use of a mixture of synthetic HA 60% and beta-TCP 40% to fill residual buccal defects 1-1.4 mm wide at IPIES did not improve significantly the results of healing. © 2015 Wiley Periodicals, Inc.

Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold.

PubMed

Liu, Zeping; Yin, Xing; Ye, Qingsong; He, Wulin; Ge, Mengke; Zhou, Xiaofu; Hu, Jing; Zou, Shujuan

2016-07-01

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagen-hydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells - collagen-hydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 ± 20 µm and 203 ± 18 µm and porosity of 69 ± 0.5% and 50 ± 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells - collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells - collagen-hydroxyapatite and collagen-hydroxyapatite scaffold - induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation. © The Author(s) 2016.

Lasp1 misexpression influences chondrocyte differentiation in the vertebral column.

PubMed

Hermann-Kleiter, Natascha; Ghaffari-Tabrizi, Nassim; Blumer, Michael J F; Schwarzer, Christoph; Mazur, Magdalena A; Artner, Isabella

2009-01-01

The mouse mutant wavy tail Tg(Col1a1-lacZ)304ng was created through transgene insertion and exhibits defects of the vertebral column. Homozygous mutant animals have compressed tail vertebrae and wedge-shaped intervertebral discs, resulting in a meandering tail. Delayed closure of lumbar neural arches and lack of processus spinosi have been observed; these defects become most prominent during the transition from cartilage to bone. The spina bifida was resistant to folic acid treatment, while retinoic acid administration caused severe skeletal defects in the mutant, but none in wild type control animals. The transgene integrated at chromosome 11 band D, in an area of high gene density. The insertion site was located between the transcription start sites of the Rpl23 and Lasp1 genes. LASP1 (an actin binding protein involved in cell migration and survival) was found to be produced in resting and hypertrophic chondrocytes in the vertebrae. In mutant vertebrae, temporal and spatial misexpression of Lasp1 was observed, indicating that alterations in Lasp1 transcription are most likely responsible for the observed phenotype. These data reveal a yet unappreciated role of Lasp1 in chondrocyte differentiation during cartilage to bone transition.

Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial.

PubMed

Bajestan, Mona N; Rajan, Archana; Edwards, Sean P; Aronovich, Sharon; Cevidanes, Lucia H S; Polymeri, Angeliki; Travan, Suncica; Kaigler, Darnell

2017-10-01

Stem cell therapy with bone marrow-derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone. To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma. Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re-entered and the bone width re-assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading. The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re-treated with autogenous block bone graft. The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate. © 2017 Wiley Periodicals, Inc.

Immediate Implant Placement into Extraction Sockets with Labial Plate Dehiscence Defects: A Clinical Case Series.

PubMed

Sarnachiaro, Guido O; Chu, Stephen J; Sarnachiaro, Evangelina; Gotta, Sergio Luis; Tarnow, Dennis P

2016-08-01

To measure the buccal plate reconstruction of extraction sockets with labial plate dehiscence defects using a bone allograft in combination with an absorbable collagen membrane and a custom-healing abutment at the time of tooth removal. Ten patients underwent immediate implant placement and reconstruction of the buccal plate. Cone beam computed tomography (CBCT) was performed preextraction, immediately after bone grafting and implant placement (day 0), and between 6 and 9 months following implant surgery. Measurements were taken at three levels: coronal (L1), middle (L2), and apical (L3) level. Implants placed into sockets with labial plate dehiscence defects demonstrated radiographic reformation of the labial plate dehiscence defect at 6 to 9 months posttreatment. The net gain in labial plate on cone beam computerized tomography (CBCT) in L1 and L2 was 3.0 mm, where 0 mm existed at pretreatment. The minimum amount of labial plate thickness of 2.0 mm was achieved in all treated sites, evaluated radiographically at 6 to 9 months postoperatively, in a single procedure, without flap elevation and maintaining the gingival architecture and satisfactory esthetics. Placing an absorbable membrane, bone graft, and custom-healing abutment at the time of flapless anterior tooth extraction and immediate implant placement into a socket with a labial osseous dehiscence is a viable clinical technique to reconstitute the absence of the labial bone plate. © 2015 Wiley Periodicals, Inc.

Liquid nitrogen-treated autogenous dentin as bone substitute: an experimental study in a rabbit model.

PubMed

Atiya, Basim K; Shanmuhasuntharam, Palasuntharam; Huat, Siar; Abdulrazzak, Shurooq; Oon, Ha

2014-01-01

Different forms of dentin, including untreated, undemineralized, demineralized, boiled, or mixed with other materials, have been evaluated for efficacy as bone substitutes. However, the effects of application of liquid nitrogen-treated dentin for bone grafting remain unknown. The objective of this study was to chronologically evaluate bone healing following grafting with liquid nitrogen-treated dentin in a rabbit model. Autogenous dentin treated with liquid nitrogen at -196°C for 20 minutes was used. In 16 New Zealand White rabbits, a bone defect (5 mm in diameter) was created in each femur and randomly grafted with either autogenous dentin (experimental group) or autogenous bone grafts (positive control). In another four rabbits (negative control), a similar defect in each femur was left empty. The rabbits were sacrificed at 2, 4, 8, and 12 weeks. Explants of grafted sites were harvested for histologic and histomorphometric analysis. At 2 and 4 weeks in both the experimental and positive control groups, accelerated formation of new bone was observed, which was undergoing remodeling at 8 and 12 weeks. The mean new bone score was higher in the experimental than in the negative control groups, but this was not statistically significant. The present results demonstrated that liquid nitrogen-treated autogenous dentin has both osteoconductive and osteoinductive properties and therefore has potential as a bone substitute.

Inorganic-organic shape memory polymers and foams for bone defect repairs

NASA Astrophysics Data System (ADS)

Zhang, Dawei

The ultimate goal of this research was to develop a "self-fitting" shape memory polymer (SMP) scaffold for the repair of craniomaxillofacial (CMF) bone defects. CMF defects may be caused by trauma, tumor removal or congenital abnormalities and represent a major class of bone defects. Their repair with autografts is limited by availability, donor site morbidity and complex surgical procedures. In addition, shaping and positioning of these rigid grafts into irregular defects is difficult. Herein, we have developed SMP scaffolds which soften at T > ˜56 °C, allowing them to conformally fit into a bone defect. Upon cooling to body temperature, the scaffold becomes rigid and mechanically locks in place. This research was comprised of four major studies. In the first study, photocrosslinkable acrylated (AcO) SMP macromers containing a poly(epsilon-caprolactone) (PCL) segment and polydimethylsiloxane (PDMS) segments were synthesized with the general formula: AcO-PCL40-block-PDMS m-block-PCL40-OAc. By varying the PDMS segment length (m), solid SMPs with highly tunable mechanical properties and excellent shape memory abilities were prepared. In the second study, porous SMP scaffolds were fabricated based on AcO-PCL 40-block-PDMS37-block-PCL 40-OAc via a revised solvent casting particulate leaching (SCPL) method. By tailoring scaffold parameters including salt fusion, macromer concentration and salt size, scaffold properties (e.g. pore features, compressive modulus and shape memory behavior) were tuned. In the third study, porous SMP scaffolds were produced from macromers with variable PDMS segment lengths (m = 0 -- 130) via an optimized SCPL method. The impact on pore features, thermal, mechanical, and shape memory properties as well as degradation rates were investigated. In the final study, a bioactive polydopamine coating was applied onto pore surfaces of the SMP scaffold prepared from PCL diacrylate. The thin coating did not affect intrinsic bulk properties of the scaffold. However, the coating significantly increased its bioactivity, giving rise to the formation of "bone-bonding" hydroxyapatite (HAp) when exposed to simulated body fluid (SBF). It was also shown that the coating largely enhanced the scaffold's capacities to support osteoblasts adhesion, proliferation and osteogenesis. Thus, the polydopamine coating should enhance the performance of the "self-fitting" SMP scaffolds for the repair of bone defects.

Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.

PubMed

Kawai, Tadashi; Suzuki, Osamu; Matsui, Keiko; Tanuma, Yuji; Takahashi, Tetsu; Kamakura, Shinji

2017-05-01

Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2

PubMed Central

2015-01-01

The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2) has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies. PMID:26043112

Long-term follow-up for ossification of autologous bone plug and skin sinking after periosteum-preserved burr hole surgery.

PubMed

Kubota, Hisashi; Sanada, Yasuhiro; Murakami, Saori; Miyauchi, Masaharu; Iwakura, Michihiro; Nagatsuka, Kazuhiro; Furukawa, Kentaro; Kato, Amami; Fujita, Mitsugu

2017-01-01

The demand of a burr hole surgery for chronic subdural hematoma (CSDH) is increasing in the global aging society. Burr hole-derived autologous bone dusts are not associated with extra costs compared with other commonly used synthetic materials. In addition, postoperative calvarium ossification requires periosteum-mediated blood supply, which is lacking after using avascular synthetic materials. Based on these findings, we hypothesized that the combination of the bone plugs and the preserved periosteum during burr hole surgeries for CSDH would induce efficient calvarium ossification. We evaluated the long-term effects of bone plugs on the degree of ossification and cosmetic appearance of the skin covering the burr hole sites. We included 8 patients (9 burr holes) who received the autologous bone dust derived from burr holes. As the control group, 9 burr holes that did not receive any burr hole plugs were retrospectively selected. These burr holes were evaluated by computed tomography (CT) scan for the calvarium defect ratios, CT value-based ossification, and the degree of skin sinking. Ossification was observed in all the bone plugs by the bone density CT scans; they maintained their volume at 12 months after the surgeries. The calvarium defect ratios (volume ratios of the unossified parts in the burr holes) gradually increased during the first 6 months and reached 0.44 at 12 months. The mean CT values also increased from 527 HU to 750 HU for the first 6 months and reached 905 HU at 12 months. The degrees of skin sinking at the burr hole sites with the bone plugs were 1.24 mm whereas those without the bone plugs were 2.69 mm ( P = 0.004). Application of burr hole-derived autologous bone dust is associated with better ossification and objective cosmetic result following burr hole surgery after CSDH.

Comparison of naturally occurring and ligature-induced peri-implantitis bone defects in humans and dogs.

PubMed

Schwarz, Frank; Herten, Monika; Sager, Martin; Bieling, Katrin; Sculean, Anton; Becker, Jürgen

2007-04-01

The aim of the present study was to evaluate and compare naturally occuring and ligature-induced peri-implantitis bone defects in humans and dogs. Twenty-four partially and fully edentulous patients undergoing peri-implant bone augmentation procedures due to advanced peri-implant infections were included in this study (n=40 implants). Furthermore, peri-implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri-implant bone loss were recorded in both humans and dogs. Open flap surgery generally revealed two different classes of peri-implant bone defects. While Class I defects featured well-defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia-e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively). Within the limits of the present study, it might be concluded that configurations and sizes of ligature-induced peri-implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans.

Porous titanium scaffolds with injectable hyaluronic acid-DBM gel for bone substitution in a rat critical-sized calvarial defect model.

PubMed

van Houdt, C I A; Cardoso, D A; van Oirschot, B A J A; Ulrich, D J O; Jansen, J A; Leeuwenburgh, S C G; van den Beucken, J J J P

2017-09-01

Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12 weeks. For the calvarial defects, mean percentages of newly formed bone at 2 weeks were significantly higher for Ti-Empty compared to Ti-HA + DBM HCl , but not compared to Ti-HA + DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA + DBM HCl, but not for Ti-HA + DBM EDTA. At 8 weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8 weeks, which were lower than using the empty porous titanium scaffold. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Experimental study on repair of the defect of the pars interarticularis in rat with bone morphogenetic protein and fibrin glue].

PubMed

Nakamura, T

1992-07-01

The possibility of repairing the defect of the pars interarticularis (pars defect) with Bone Morphogenetic Protein (BMP) and fibrin glue was studied. The pars defect established in the 5th lumbar vertebra of Wistar rat was treated with surgical implantation of a composite consisting of BMP, fibrin glue and autologous cancellous bone. At 3, 6, 9 and 12 weeks after implantation, the osteoinductive activity in the pars defect was observed histologically and compared with that of other composite implants such as BMP with fibrin glue, autologous cancellous bone alone and autologous cancellous bone with fibrin glue. Although perfect bone fusion was not obtained with any of the composites employed, a significant increase in bone formation was seen in a composite of BMP, fibrin glue and autologous cancellous bone (p less than 0.01) as compared with that seen in the others. Consequently, implantation of BMP and fibrin glue combined with some biomaterials which support osteo-induction of BMP and stabilize the pars defect might be successfully applied to repair the pars defect.

Autologous platelet-rich plasma gel to reduce donor-site morbidity after patellar tendon graft harvesting for anterior cruciate ligament reconstruction: a randomized, controlled clinical study.

PubMed

Cervellin, M; de Girolamo, L; Bait, C; Denti, M; Volpi, P

2012-01-01

Bone-patellar tendon-bone technique (BPTB) for anterior cruciate ligament injuries is associated with a higher risk of donor-site morbidity. To evaluate whether platelet-rich plasma (PRP), due to its anti-inflammatory properties and capacity to stimulate tissue regeneration, was able to reduce the anterior knee pain, the kneeling pain, and donor-site morbidity, as evidenced by evaluation of VISA and VAS scoring scales and MRI analysis of the tendon and bone defect, we performed a clinical randomized controlled study where PRP gel was applied to donor site after ACL reconstruction with BPTB. Forty young athletes with the indication of ACL reconstruction with patellar tendon grafts were randomly assigned to group A (n = 20 patients, control group) or group B (n = 20 patients, PRP group). The autologous PRP gel was applied to both the patellar and tendon bone plug harvest site and stabilized by the peritenon suture. At 12-month follow-up, all patients underwent clinical examination and VAS and VISA questionnaires, respectively, evaluating the average daily pain of the knee and the pain during particular activities involving the knee, were filled. MRI at the same time point was also performed. VISA scores were significantly higher in the patients treated with PRP (84.5 ± 11.8 and 97.8 ± 2.5 for group A and for group B; P = 0.041), whereas no significant difference in postoperative VAS scores between the two groups was observed (1 ± 1.4 and 0.6 ± 0.9 for group A and group B, n.s.). In 85% of PRP group patients, the tibial and patellar bone defect was satisfactorily filled by new bony tissue (>70% of bone gap filled), whereas this percentage was just of 60% in control group patients, but this difference was not statistically significant. The study shows the usefulness of PRP in reducing subjective pain at the donor-site level after ACL reconstruction with BPTB. However, this approach deserves further investigations to confirm PRP efficacy and to elucidate its mechanism of action. Prospective randomized controlled study, Level I.

Rapid orthodontic treatment after the ridge-splitting technique--a combined surgical-orthodontic approach for implant site development: case report.

PubMed

Amato, Francesco; Mirabella, A Davide; Borlizzi, Diego

2012-08-01

This article presents a clinical case of bilateral partial edentulism in the posterior mandible with severe horizontal and moderate vertical bone atrophy. A new technique using rapid orthodontics after ridge splitting is presented. The split-crest technique was carried out using piezosurgical instruments in the first molar and second premolar areas to widen the bone crest and open a channel for tooth movement. Immediately after, orthodontic appliances were used to move the first premolars distally and the second molars mesially into the surgical site. The rationale was to facilitate and accelerate orthodontic movement of the teeth, which is otherwise difficult in a cortical knife-edged ridge. The bone defect was filled with the alveolar bone of the adjacent teeth that were moved into the surgically opened path. Adequate bone volume for implant placement was generated in the first premolar area. Implants were then inserted, and the patient was rehabilitated.

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

PubMed Central

Padilla, Ricardo; Urkasemsin, Ganokon; Yoon, Kun; Goeckner, Kelly; Hu, Wei-Shou

2013-01-01

Adequate bony support is the key to re-establish both function and esthetics in the craniofacial region. Autologous bone grafting has been the gold standard for regeneration of problematic large bone defects. However, poor graft availability and donor-site complications have led to alternative bone tissue-engineering approaches combining osteoinductive biomaterials and three-dimensional cell aggregates in scaffolds or constructs. The goal of the present study was to generate novel cell aggregate-loaded macroporous scaffolds combining the osteoinductive properties of titanium dioxide (TiO2) with hydroxyapatite–gelatin nanocomposites (HAP-GEL) for regeneration of craniofacial defects. Here we investigated the in vivo applicability of macroporous (TiO2)-enriched HAP-GEL scaffolds with undifferentiated and osteogenically differentiated multipotent adult progenitor cell (MAPC and OD-MAPC, respectively) aggregates for calvaria bone regeneration. The silane-coated HAP-GEL with and without TiO2 additives were polymerized and molded to produce macroporous scaffolds. Aggregates of the rat MAPC were precultured, loaded into each scaffold, and implanted to rat calvaria critical-size defects to study bone regeneration. Bone autografts were used as positive controls and a poly(lactic-co-glycolic acid) (PLGA) scaffold for comparison purposes. Preimplanted scaffolds and calvaria bone from pig were tested for ultimate compressive strength with an Instron 4411® and for porosity with microcomputerized tomography (μCT). Osteointegration and newly formed bone (NFB) were assessed by μCT and nondecalcified histology, and quantified by calcium fluorescence labeling. Results showed that the macroporous TiO2-HAP-GEL scaffold had a comparable strength relative to the natural calvaria bone (13.8±4.5 MPa and 24.5±8.3 MPa, respectively). Porosity was 1.52±0.8 mm and 0.64±0.4 mm for TiO2-HAP-GEL and calvaria bone, respectively. At 8 and 12 weeks postimplantation into rat calvaria defects, greater osteointegration and NFB were significantly present in the TiO2-enriched HAP-GEL constructs with OD-MAPCs, compared to the undifferentiated MAPC-loaded constructs, cell-free HAP-GEL with and without titanium, and PLGA scaffolds. The tissue-engineered TiO2-enriched HAP-GEL constructs with OD-MAPC aggregates present a potential useful therapeutic approach for calvaria bone regeneration. PMID:23495972

A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

PubMed Central

Winkler, T.; Sass, F. A.; Schmidt-Bleek, K.

2018-01-01

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit femoral defect study.

PubMed

Xie, Ruiqi; Hu, Jinlian; Hoffmann, Oskar; Zhang, Yuanchi; Ng, Frankie; Qin, Tingwu; Guo, Xia

2018-04-01

Although tissue engineering has been attracted greatly for healing of critical-sized bone defects, great efforts for improvement are still being made in scaffold design. In particular, bone regeneration would be enhanced if a scaffold precisely matches the contour of bone defects, especially if it could be implanted into the human body conveniently and safely. In this study, polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated as a scaffold substrate to facilitate bone regeneration. The minimally invasive delivery and the self-fitting behavior of the SMP foam were systematically evaluated to demonstrate its feasibility in the treatment of bone defects in vivo. Results showed that the SMP foam could be conveniently implanted into bone defects with a compact shape. Subsequently, it self-matched the boundary of bone defects upon shape-recovery activation in vivo. Micro-computed tomography determined that bone ingrowth initiated at the periphery of the SMP foam with a constant decrease towards the inside. Successful vascularization and bone remodeling were also demonstrated by histological analysis. Thus, our results indicate that the SMP foam demonstrated great potential for bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

NASA Astrophysics Data System (ADS)

Gheith, Mostafa E.; Khairy, Maggie A.

2014-02-01

Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

Assessment of periodontal bone level revisited: a controlled study on the diagnostic accuracy of clinical evaluation methods and intra-oral radiography.

PubMed

Christiaens, Véronique; De Bruyn, Hugo; Thevissen, Eric; Koole, Sebastiaan; Dierens, Melissa; Cosyn, Jan

2018-01-01

The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2). The study sample included 49 interdental sites in 17 periodontitis patients. Evaluation methods included vertical relative probing attachment level (RAL-V), analogue and digital intra-oral radiography and bone sounding without and with flap elevation. The latter was considered the true bone level. Five examiners evaluated all radiographs. Significant underestimation of the true bone level was observed for all evaluation methods pointing to 2.7 mm on average for analogue radiography, 2.5 mm for digital radiography, 1.8 mm for RAL-V and 0.6 mm for bone sounding without flap elevation (p < 0.001). Radiographic underestimation of the true bone level was higher in the (pre)molar region (p ≤ 0.047) and increased with defect depth (p < 0.001). Variation between clinicians was huge (range analogue radiography 2.2-3.2 mm; range digital radiography 2.1-3.0 mm). All evaluation methods significantly underestimated the true bone level. Bone sounding was most accurate, whereas intra-oral radiographs were least accurate. Deep periodontal defects in the (pre)molar region were most underrated by intra-oral radiography. Bone sounding had the highest accuracy in assessing interdental bone level.

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

PubMed

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

NASA Astrophysics Data System (ADS)

Lan, Sheeny K.

Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (< 10 microm) as well as the most extensive bone growth into micropores to date with bone penetration throughout rods 394 microm in diameter. The result is the first truly osteointegrated bone scaffolds with integration occurring at both the macro and micro length scales, leaving no "dead space" or discontinuities of bone in the defect site. The scaffold forms a living composite upon integration with regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold undergoes in vivo modifications involving formation of a biological apatite layer within scaffold micropores and possibly co-precipitation of endogenous osteoinductive proteins. To further investigate the effects of scaffold osteoinductivity, BCP scaffolds were implanted in porcine mandibular defects with rhBMP-2, which was partially sequestered in the micropores. Cell migration into osteoinductive scaffold micropores can be enhanced through the delivery of exogenous rhBMP-2 further promoting multi-scale osteointegration. Finally, endothelial colony forming cells (ECFCs) isolated from human umbilical cord blood (UCB) were evaluated in terms of their in vivo vasculogenic potential in the context of bone formation. This work was completed to determine if ECFCs could be utilized in a bone tissue engineering construct to promote neovascularization. ECFCs were combined with a BCP scaffold and rhBMP-2 and implanted subcutaneously on the abdominal wall of NOD/SCID mice. The result was formation of perfused human vessels within BCP scaffold macropores that were present at 4 weeks. The high density and persistence of human vessels at four weeks indicates that human UCB ECFCs exceed their reported in vivo vasculogenic potential when combined with rhBMP-2 and a BCP scaffold. This shows a dual role for BMP-2 in the context of bone regeneration. Collectively, the thesis demonstrates that (1) the design of synthetic bone scaffolds should include controlled multi-scale porosity to promote multi-scale osteointegration, which may significantly improve scaffold mechanical properties and (2) human umbilical cord blood-derived endothelial colony forming cells have potential for promoting neovascularization in a bone defect when combined with rhBMP-2.

Comparative evaluation of guided tissue regeneration with use of collagen-based barrier freeze-dried dura mater allograft for mandibular class 2 furcation defects (a comparative controlled clinical study).

PubMed

Patel, Sandeep; Kubavat, Ajay; Ruparelia, Brijesh; Agarwal, Arvind; Panda, Anup

2012-01-01

The aim of periodontal surgery is complete regeneration. The present study was designed to evaluate and compare clinically soft tissue changes in form of probing pocket depth, gingival shrinkage, attachment level and hard tissue changes in form of horizontal and vertical bone level using resorbable membranes. Twelve subjects with bilateral class 2 furcation defects were selected. After initial phase one treatment, open debridement was performed in control site while freezedried dura mater allograft was used in experimental site. Soft and hard tissue parameters were registered intrasurgically. Nine months reentry ensured better understanding and evaluation of the final outcome of the study. Guided tissue regeneration is a predictable treatment modality for class 2 furcation defect. There was statistically significant reduction in pocket depth as compared to control (p < 0.01). There is statistically significant increase in periodontal attachment level within control and experimental sites showed better results (p < 0.01). For hard tissue parameter, significant defect fill resulted in experimental group, while in control group, less significant defect fill was found in horizontal direction and nonsignificant defect fill was found in vertical direction. The results showed statistically significant improvement in soft and hard tissue parameters and less gingival shrinkage in experimental sites compared to control site. The use of FDDMA in furcation defects helps us to achieve predictable results. This cross-linked collagen membrane has better handling properties and ease of procurement as well as economic viability making it a logical material to be used in regenerative surgeries.

Long bone reconstruction using multilevel lengthening of bone defect fragments.

PubMed

Borzunov, Dmitry Y

2012-08-01

This paper presents experimental findings to substantiate the use of multilevel bone fragment lengthening for managing extensive long bone defects caused by diverse aetiologies and shows its clinical introduction which could provide a solution for the problem of reducing the total treatment time. Both experimental and clinical multilevel lengthening to bridge bone defect gaps was performed with the use of the Ilizarov method only. The experimental findings and clinical outcomes showed that multilevel defect fragment lengthening could provide sufficient bone formation and reduction of the total osteosynthesis time in one stage as compared to traditional Ilizarov bone transport. The method of multilevel regeneration enabled management of critical-size defects that measured on average 13.5 ± 0.7 cm in 78 patients. The experimental and clinical results proved the efficiency of the Ilizarov non-free multilevel bone plasty that can be recommended for practical use.

Reconstruction of the maxilla following hemimaxillectomy defects with scapular tip grafts and dental implants.

PubMed

Mertens, Christian; Freudlsperger, Christian; Bodem, Jens; Engel, Michael; Hoffmann, Jürgen; Freier, Kolja

2016-11-01

Treatment of post-resective defects of the maxilla can be challenging and usually requires dental obturation or microvascular reconstruction. As compared to soft-tissue microvascular grafts, bone reconstruction can additionally allow for facial support and retention of dental implants. The aim of this study was to evaluate scapular tip grafts with respect to their applicability for maxillary reconstruction and their potential to retain dental implants for later dental rehabilitation. In this retrospective study, 14 patients with hemimaxillectomy defects were reconstructed with free scapular tip grafts, oriented horizontally, to rebuild the palate and alveolar ridge. After bone healing, three-dimensional virtual implant planning was performed, and a radiographic guide was fabricated to enable implant placement in the optimal anatomic and prosthetic position. All patients' mastication and speech were evaluated, along with the extent of defect closure, suitability of the graft sites for implant placement, and soft-tissue stability. Pre- and postsurgical radiographs were also evaluated. A good postoperative outcome was achieved in all patients, with complete closure of maxillary defects that were class II, according to the system of Brown and Shaw. Additional bone augmentation was necessary in two patients in order to increase vertical bone height. Patients were subsequently treated with 50 dental implants to retain dental prostheses. In all cases, additional soft-tissue surgery was necessary to achieve a long-term stable periimplant situation. No implants were lost during the mean observation period of 34 months. Due to its specific form, the scapular tip graft is well suited to reconstruct the palate and maxillary alveolar ridge and to enable subsequent implant-retained rehabilitation. Due to the limited bone volume, an accurate three-dimensional graft orientation is essential. Furthermore, most cases require additional soft-tissue surgery to achieve a long-term stable periimplant situation. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Wound healing of osteotomy defects prepared with piezo or conventional surgical instruments: a pilot study in rabbits.

PubMed

Ma, Li; Mattheos, Nikos; Sun, Yan; Liu, Xi Ling; Yip Chui, Ying; Lang, Niklaus Peter

2015-08-01

The aim of the present study was to evaluate and compare the wound-healing process following osteotomies performed with either conventional rotary burs or piezoelectric surgery in a rabbit model. Two types of osteotomy window defects of the nasal cavities were prepared on the nasal bone of 16 adult New Zealand white rabbits with either a conventional rotary bur or piezo surgery. The defects were covered with a resorbable membrane. Four animals were killed at 1, 2, 3, and 5 weeks after the surgical procedure, respectively. Histological and morphometric evaluations were performed to assess the volumetric density of various tissue components: the blood clot, vascularized structures, provisional matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone. Significantly more bone debris was found at 1 week in the conventionally-prepared defects compared to the piezo surgically-prepared defects. At 2 and 3 weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was seen; however, no statistically-significant differences were observed. At 5 weeks, the defects were completely filled with newly-formed bone. The defects prepared by piezo surgery showed a significantly decreased proportion of bone debris at 1 week, compared to conventional rotary bur defect. © 2014 Wiley Publishing Asia Pty Ltd.

Clinical and radiographic evaluation of nanocrystalline hydroxyapatite with or without platelet-rich fibrin membrane in the treatment of periodontal intrabony defects

PubMed Central

Elgendy, Enas Ahmed; Abo Shady, Tamer Elamer

2015-01-01

Background: Nano-sized ceramics may represent a promising class of bone graft substitutes due to their improved osseointegrative properties. Nanocrystalline hydroxyapatite (NcHA) binds to bone and stimulate bone healing by stimulation of osteoblast activity. Platelet-rich fibrin (PRF), an intimate assembly of cytokines, glycan chains, and structural glycoproteins enmeshed within a slowly polymerized fibrin network, has the potential to accelerate soft and hard tissue healing. The present study aims to explore the clinical and radiographical outcome of NcHA bone graft with or without PRF, in the treatment of intrabony periodontal defects. Materials and Methods: In a split-mouth study design, 20 patients having two almost identical intrabony defects with clinical probing depth of at least 6 mm were selected for the study. Selected sites were randomly divided into two groups. In Group I, mucoperiosteal flap elevation followed by the placement of NcHA was done. In Group II, mucoperiosteal flap elevation, followed by the placement of NcHA with PRF was done. Clinical and radiographic parameters were recorded at baseline and at 6-month postoperatively. Results: Both treatment groups showed a significant probing pocket depth (PPD) reduction, clinical attachment gain, increase bone density 6-month after surgery compared with baseline. However, there was a significantly greater PPD reduction and clinical attachment gain when PRF was added to NcHA. Conclusion: The NcHA bone graft in combination with PRF demonstrated clinical advantages beyond that achieved by the NcHA alone. PMID:25810595

Effects of low-level laser therapy on the expression of osteogenic genes related in the initial stages of bone defects in rats

NASA Astrophysics Data System (ADS)

Fernandes, Kelly Rossetti; Ribeiro, Daniel Araki; Rodrigues, Natália Camargo; Tim, Carla; Santos, Anderson Amaro; Parizotto, Nivaldo Antônio; de Araujo, Heloisa Selistre; Driusso, Patrícia; Rennó, Ana Claudia Muniz

2013-03-01

We evaluate the effects of low-level laser therapy (LLLT) on the histological modifications and temporal osteogenic genes expression during the initial phase of bone healing in a model of bone defect in rats. Sixty-four Wistar rats were divided into control and treated groups. Noncritical size bone defects were surgically created at the upper third of the tibia. Laser irradiation (Ga-Al-As laser 830 nm, 30 mW, 0.028 cm2, 1.071 W/cm2, 1 min and 34 s, 2.8 Joules, 100 J/cm2) was performed for 1, 2, 3, and 5 sessions. Histopathology revealed that treated animals presented higher inflammatory cells recruitment, especially 12 and 36 h postsurgery. Also, a better tissue organization at the site of the injury, with the presence of granulation tissue and new bone formation was observed on days three and five postsurgery in the treated animals. The quantitative real time polymerase chain reaction showed that LLLT produced a significantly increase in mRNA expression of Runx-2, 12 h and three days post-surgery, a significant upregulation of alkaline phosphatase mRNA expression after 36 h and three days post-surgery and a significant increase of osteocalcin mRNA expression after three and five days. We concluded that LLLT modulated the inflammatory process and accelerated bone repair, and this advanced repair pattern in the laser-treated groups may be related to the higher mRNA expression of genes presented by these animals.

Subtraction micro-computed tomography of angiogenesis and osteogenesis during bone repair using synchrotron radiation with a novel contrast agent.

PubMed

Matsumoto, Takeshi; Goto, Daichi; Sato, Syota

2013-09-01

Quantitative three-dimensional (3D) imaging of angiogenesis during bone repair remains an experimental challenge. We developed a novel contrast agent containing 0.07- to 0.1-μm particles of zirconium dioxide (ZrCA) and established subtraction μCT using synchrotron radiation (sSRCT) for quantitative imaging of angiogenesis and bone repair. This method was applied to a rat model of tibial bone repair 3 days (DAY3; n = 2), 5 days (DAY5; n = 8), or 10 days (DAY10; n = 8) after drill-hole injury. Using the same drill-hole defect model, its potential use was illustrated by comparison of bone repair between hindlimbs subjected to mechanical unloading (n = 6) and normal weight bearing (n = 6) for 10 days. Following vascular casting with ZrCA, the defect site was scanned with 17.9- and 18.1-keV X-rays. In the latter, image contrast between ZrCA-filled vasculature and bone was enhanced owing to the sharp absorption jump of zirconium dioxide at 18.0 keV (k-edge). The two scan data sets were reconstructed with 2.74-μm voxel resolution, registered by mutual information, and digitally subtracted to extract the contrast-enhanced vascular image. K2HPO4 phantom solutions were scanned at 17.9 keV for quantitative evaluation of bone mineral. Angiogenesis had already started, but new bone formation was not found on DAY3. New bone emerged near the defect boundary on DAY5 and took the form of trabecular-like structure invaded by microvessels on DAY10. Vascular and bone volume fractions, blood vessel and bone thicknesses, and mineralization were higher on DAY10 than on DAY5. All these parameters were found to be decreased after 10 days of hindlimb unloading, indicating the possible involvement of angiogenesis in bone repair impairment caused by reduced mechanical stimuli. In conclusion, the combined technique of sSRCT and ZrCA vascular casting is suitable for quantitative 3D imaging of angiogenesis and its surrounding bone regeneration. This method will be useful for better understanding the linkage between angiogenesis and bone repair.

Achieving interconnected pore architecture in injectable PolyHIPEs for bone tissue engineering.

PubMed

Robinson, Jennifer L; Moglia, Robert S; Stuebben, Melissa C; McEnery, Madison A P; Cosgriff-Hernandez, Elizabeth

2014-03-01

Template polymerization of a high internal phase emulsion (polyHIPE) is a relatively new method to produce tunable high-porosity scaffolds for tissue regeneration. This study focuses on the development of biodegradable injectable polyHIPEs with interconnected porosity that have the potential to fill bone defects and enhance healing. Our laboratory previously fabricated biodegradable polyHIPEs that cure in situ upon injection; however, these scaffolds possessed a closed-pore morphology, which could limit bone ingrowth. To address this issue, HIPEs were fabricated with a radical initiator dissolved in the organic phase rather than the aqueous phase of the emulsion. Organic-phase initiation resulted in macromer densification forces that facilitated pore opening during cure. Compressive modulus and strength of the polyHIPEs were found to increase over 2 weeks to 43±12 MPa and 3±0.2 MPa, respectively, properties comparable to cancellous bone. The viscosity of the HIPE before cure (11.0±2.3 Pa·s) allowed for injection and filling of the bone defect, retention at the defect site during cure under water, and microscale integration of the graft with the bone. Precuring the materials before injection allowed for tuning of the work and set times. Furthermore, storage of the HIPEs before cure for 1 week at 4°C had a negligible effect on pore architecture after injection and cure. These findings indicate the potential of these emulsions to be stored at reduced temperatures and thawed in the surgical suite before injection. Overall, this work highlights the potential of interconnected propylene fumarate dimethacrylate polyHIPEs as injectable scaffolds for bone tissue engineering.

An experimental study on the application of radionuclide imaging in repair of the bone defect

PubMed Central

Zhu, Weimin; Wang, Daping; Zhang, Xiaojun; Lu, Wei; Liu, Jianquan; Peng, Liangquan; Li, Hao; Han, Yun; Zeng, Yanjun

2011-01-01

The aim of our study was to validate the effect of radionuclide imaging in early monitoring of the bone’s reconstruction, the animal model of bone defect was made on the rabbits repaired with HA artificial bone. The ability of bone defect repair was evaluated by using radionuclide bone imaging at 2, 4, 8 and 12 weeks postoperatively. The results indicate that the experimental group stimulated more bone formation than that of the control group. The differences of the bone reconstruction ability were statistically significant (p<0.05). The nano-HA artificial has good bone conduction, and it can be used for the treatment of bone defects. Radionuclide imaging may be an effective and first choice method for the early monitoring of the bone’s reconstruction. PMID:21875418

3D printing of high-strength bioscaffolds for the synergistic treatment of bone cancer

NASA Astrophysics Data System (ADS)

Ma, Hongshi; Li, Tao; Huan, Zhiguang; Zhang, Meng; Yang, Zezheng; Wang, Jinwu; Chang, Jiang; Wu, Chengtie

2018-04-01

The challenges in bone tumor therapy are how to repair the large bone defects induced by surgery and kill all possible residual tumor cells. Compared to cancellous bone defect regeneration, cortical bone defect regeneration has a higher demand for bone substitute materials. To the best of our knowledge, there are currently few bifunctional biomaterials with an ultra-high strength for both tumor therapy and cortical bone regeneration. Here, we designed Fe-CaSiO3 composite scaffolds (30CS) via 3D printing technique. First, the 30CS composite scaffolds possessed a high compressive strength that provided sufficient mechanical support in bone cortical defects; second, synergistic photothermal and ROS therapies achieved an enhanced tumor therapeutic effect in vitro and in vivo. Finally, the presence of CaSiO3 in the composite scaffolds improved the degradation performance, stimulated the proliferation and differentiation of rBMSCs, and further promoted bone formation in vivo. Such 30CS scaffolds with a high compressive strength can function as versatile and efficient biomaterials for the future regeneration of cortical bone defects and the treatment of bone cancer.

Structural and mechanical implications of PMMA implant shape and interface geometry in cranioplasty--A finite element study.

PubMed

Ridwan-Pramana, Angela; Marcián, Petr; Borák, Libor; Narra, Nathaniel; Forouzanfar, Tim; Wolff, Jan

2016-01-01

This computational study investigates the effect of shape (defect contour curvature) and bone-implant interface (osteotomy angle) on the stress distribution within PMMA skull implants. Using finite element methodology, 15 configurations--combinations of simplified synthetic geometric shapes (circular, square, triangular, irregular) and interface angulations--were simulated under 50N static loads. Furthermore, the implant fixation devices were modelled and analysed in detail. Negative osteotomy configurations demonstrated the largest stresses in the implant (275 MPa), fixation devices (1258 MPa) and bone strains (0.04). The circular implant with zero and positive osteotomy performed well with maximum observed magnitudes of--implant stress (1.2 MPa and 1.2 MPa), fixation device stress (11.2 MPa and 2.2 MPa), bone strain (0.218e-3 and 0.750e-4). The results suggest that the preparation of defect sites is a critical procedure. Of the greatest importance is the angle at which the edges of the defect are sawed. If under an external load, the implant has no support from the interface and the stresses are transferred to the fixation devices. This can endanger their material integrity and lead to unphysiological strains in the adjacent bone, potentially compromising the bone morphology required for anchoring. These factors can ultimately weaken the stability of the entire implant assembly. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

[Advances in research and application of beta-tricalcium phosphate, collagen and beta-tricalcium phosphate/collagen composite in bone tissue engineering].

PubMed

Han, Xiang-Yong; Fu, Yuan-Fei; Zhang, Fu-Qiang

2007-02-01

Bone defects in oral and maxillofacial region was a common problem. To repair the defect, bone grafts including autograft, allograft and artificial bone graft were used in clinic despite of their disadvantages. Nowadays, bone tissue engineering has become a commonly used method to repair bone defect. This paper reviewed the application of beta-TCP, collagen and beta-TCP/collagen composite in bone tissue engineering. It was concluded that beta-TCP/collagen composite was a promising materials in bone tissue engineering.

Low-level laser therapy, at 60 J/cm2 associated with a Biosilicate® increase in bone deposition and indentation biomechanical properties of callus in osteopenic rats

NASA Astrophysics Data System (ADS)

Fangel, Renan; Sérgio Bossini, Paulo; Cláudia Renno, Ana; Araki Ribeiro, Daniel; Chenwei Wang, Charles; Luri Toma, Renata; Okino Nonaka, Keico; Driusso, Patrícia; Antonio Parizotto, Nivaldo; Oishi, Jorge

2011-07-01

We investigate the effects of a novel bioactive material (Biosilicate®) and low-level laser therapy (LLLT), at 60 J/cm2, on bone-fracture consolidation in osteoporotic rats. Forty female Wistar rats are submitted to the ovariectomy, to induce osteopenia. Eight weeks after the ovariectomy, the animals are randomly divided into four groups, with 10 animals each: bone defect control group; bone defect filled with Biosilicate group; bone defect irradiated with laser at 60 J/cm2 group; bone defect filled with Biosilicate and irradiated with LLLT, at 60 J/cm2 group. Laser irradiation is initiated immediately after surgery and performed every 48 h for 14 days. Histopathological analysis points out that bone defects are predominantly filled with the biomaterial in specimens treated with Biosilicate. In the 60-J/cm2 laser plus Biosilicate group, the biomaterial fills all bone defects, which also contained woven bone and granulation tissue. Also, the biomechanical properties are increased in the animals treated with Biosilicate associated to lasertherapy. Our results indicate that laser therapy improves bone repair process in contact with Biosilicate as a result of increasing bone formation as well as indentation biomechanical properties.

Establishment of a bilateral femoral large segmental bone defect mouse model potentially applicable to basic research in bone tissue engineering.

PubMed

Xing, Junchao; Jin, Huiyong; Hou, Tianyong; Chang, Zhengqi; Luo, Fei; Wang, Pinpin; Li, Zhiqiang; Xie, Zhao; Xu, Jianzhong

2014-12-01

To understand the cellular mechanism underlying bone defect healing in the context of tissue engineering, a reliable, reproducible, and standardized load-bearing large segmental bone defect model in small animals is indispensable. The aim of this study was to establish and evaluate a bilateral femoral defect model in mice. Donor mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from six mice (FVB/N) and incorporated into partially demineralized bone matrix scaffolds to construct tissue-engineered bones. In total, 36 GFP(+) mice were used for modeling. Titanium fixation plates with locking steel wires were attached to the femurs for stabilization, and 2-mm-long segmental bone defects were created in the bilateral femoral midshafts. The defects in the left and right femurs were transplanted with tissue-engineered bones and control scaffolds, respectively. The healing process was monitored by x-ray radiography, microcomputed tomography, and histology. The capacity of the transplanted mBMSCs to recruit host CD31(+) cells was investigated by immunofluorescence and real-time polymerase chain reaction. Postoperatively, no complication was observed, except that two mice died of unknown causes. Stable fixation of femurs and implants with full load bearing was achieved in all animals. The process of bone defect repair was significantly accelerated due to the introduction of mBMSCs. Moreover, the transplanted mBMSCs attracted more host CD31(+) endothelial progenitors into the grafts. The present study established a feasible, reproducible, and clinically relevant bilateral femoral large segmental bone defect mouse model. This model is potentially suitable for basic research in the field of bone tissue engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative.

PubMed

Nevins, Marc L; Camelo, Marcelo; Schupbach, Peter; Nevins, Myron; Kim, Soo-Woo; Kim, David M

2011-01-01

The objective of this study was to assess the osseous healing of buccal plate extraction socket defects. There were four cohorts: group A (mineral collagen bone substitute [MCBS] scaffold alone), group B (MCBS with recombinant human platelet-derived growth factor BB [rhPDGF-BB; 0.3 mg/mL]), group C (MCBS with enamel matrix derivative [EMD]), and group D (combination of EMD with bone ceramic). The primary outcome of bone quality was evaluated using light microscopy, backscatter scanning electron microscopy, and histomorphometrics. Reentry surgery provided an opportunity for clinical observation of the healed ridge morphology. Sixteen patients with buccal wall extraction socket defects were randomized into four treatment groups of equal size. Grafting was provided at the time of extraction with advancement of the buccal flap for primary closure. A trephine core biopsy of the implant site preparation was performed after 5 months for implant placement. Histologic examination identified new bone healing around the biomaterial scaffolds. Statistically significant differences in new bone formation were not observed among the treatment groups. There was a histomorphometric trend toward more new bone for the rhPDGF-BB-treated group (group B). This group had the most favorable ridge morphology for optimal implant placement.

Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

PubMed

Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

2016-03-01

The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model.

PubMed

Handschel, Jörg; Wiesmann, Hans Peter; Stratmann, Udo; Kleinheinz, Johannes; Meyer, Ulrich; Joos, Ulrich

2002-04-01

Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.

Influence of defect dimensions on periodontal wound healing/regeneration in intrabony defects following implantation of a bovine bone biomaterial and provisions for guided tissue regeneration: an experimental study in the dog.

PubMed

Stavropoulos, Andreas; Wikesjö, Ulf M E

2010-06-01

To evaluate the influence of defect dimensions on periodontal wound healing/regeneration in intrabony defects following implantation of a deproteinized bovine bone/collagen matrix under provisions for guided tissue regeneration. Contra-lateral one-wall intrabony [6 x 6 mm (wide/deep) versus 4 x 4 mm (narrow/shallow)] periodontal defects were surgically created at the edentulated mesial aspect of the mandibular first molars in three Labradors, i.e., three defects in each category. The defects were implanted with the bovine bone/collagen matrix and covered with a collagen membrane. Histologic/histometric analysis followed an 18-month healing interval. New cementum encompassed the entire intrabony component in both wide/deep (5.6 +/- 0.5 mm) and narrow/shallow (4.2 +/- 0.1 mm) defects; bone formation amounted to 5.6 +/- 0.6 and 4.0 +/- 0.8 mm, respectively. Mineralized bone encompassed 57.5%versus 65% and the bone biomaterial 11.6%versus 13.1% of the defect space. A periodontal ligament with a width and composition similar to that of the resident periodontal ligament encompassing the entire aspect of the defects was observed. Root resorption/ankylosis was rare. Both wide/deep and narrow/shallow intrabony defects showed a substantial potential for periodontal regeneration in this pre-clinical model. The contribution of the bovine bone/collagen matrix and guided tissue regeneration to this regenerative potential is not clear.

New nano-hydroxyapatite in bone defect regeneration: A histological study in rats.

PubMed

Kubasiewicz-Ross, Paweł; Hadzik, Jakub; Seeliger, Julia; Kozak, Karol; Jurczyszyn, Kamil; Gerber, Hanna; Dominiak, Marzena; Kunert-Keil, Christiane

2017-09-01

Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss ® ; 2) nano-hydroxyapatite+β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

Degradable Bone Graft Substitute for Effective Delivery of Multiple Growth Factors in the Treatment of Nonunion Fractures

DTIC Science & Technology

2012-08-01

growth factors directly to the bone defect site can enhance repair of non-union fractures. In this study, a new chitosan /xylan composite hydrogel was...delivery aspect of this study did not succeed, treatment with the new xylan/ chitosan hydrogel alone was enough to heal serious fractures that did not...characteristics of the hydrogel in question could be tested as well as performing in vitro cell work. The previous supplier of chitosan , the main polymer

A Resorbable Antibiotic-Eluting Polymer Composite Bone Void Filler for Perioperative Infection Prevention in a Rabbit Radial Defect Model

PubMed Central

Brooks, Benjamin D.; Sinclair, Kristofer D.; Grainger, David W.; Brooks, Amanda E.

2015-01-01

Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 107 CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results. PMID:25815727

Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect.

PubMed

Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo

2015-12-01

Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects.

Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

PubMed

Choo, Tina; Marino, Victor; Bartold, P Mark

2013-02-01

The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering.

PubMed

Sefcik, Lauren S; Petrie Aronin, Caren E; Wieghaus, Kristen A; Botchwey, Edward A

2008-07-01

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-co-glycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects, and healing of bony defects was assessed by radiograph X-ray, microcomputed tomography (muCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

PubMed Central

Sefcik, Lauren S.; Petrie Aronin, Caren E.; Wieghaus, Kristen A.

2009-01-01

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cells types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-co-glycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects and healing of bony defects was assessed by radiograph x-ray, microcomputed tomography (μCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies. PMID:18405965

[The treatment of infected diaphyseal femoral defects by lengthening one of the bone fragments by Ilizarov].

PubMed

Tomić, S; Krajcinović, O; Blagojević, Z; Apostolović, M; Lalosević, V

2006-01-01

We analyzed 30 patients with infected diaphyseal defect of femur, which have been treated by lengthening one of the bone fragments with Ilizarov apparatus. The mean length of the bone defect was 6 cm. Substitution of the defect, bone healing and elimination of the infection was achieved in 27 patients. The mean time of apparatus fixation was 10 months. According to Palley scoring system, 10 patients had excellent functional results.

Application of Computer-Assisted Design and Manufacturing-Fabricated Artificial Bone in the Reconstruction of Craniofacial Bone Defects.

PubMed

Liang, Weiqiang; Yao, Yuanyuan; Huang, Zixian; Chen, Yuhong; Ji, Chenyang; Zhang, Jinming

2016-07-01

The purpose of this study was to evaluate the clinical application of individual craniofacial bone fabrications using computer-assisted design (CAD)-computer-assisted manufacturing technology for the reconstruction of craniofacial bone defects. A total of 8 patients diagnosed with craniofacial bone defects were enrolled in this study between May 2007 and August 2010. After computed tomography scans were obtained, the patients were fitted with artificial bone that was created using CAD software, rapid prototyping technology, and epoxy-methyl acrylate resin and hydroxyapatite materials. The fabrication was fixed to the defect area with titanium screws, and soft tissue defects were repaired if necessary. The fabrications were precisely fixed to the defect areas, and all wounds healed well without any serious complications except for 1 case with intraoral incision dehiscence, which required further treatment. Postoperative curative effects were retrospectively observed after 6 to 48 months, acceptable anatomic and cosmetic outcomes were obtained, and no rejections or other complications occurred. The use of CAD-computer-assisted manufacturing technology-assisted epoxy-methyl acrylate resin and hydroxyapatite composite artificial bone to treat patients with craniofacial bone defects could enable the precise reconstruction of these defects and obtain good anatomic and cosmetic outcomes. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Tri-Layered Nanocomposite Hydrogel Scaffold for the Concurrent Regeneration of Cementum, Periodontal Ligament, and Alveolar Bone.

PubMed

Sowmya, S; Mony, Ullas; Jayachandran, P; Reshma, S; Kumar, R Arun; Arzate, H; Nair, Shantikumar V; Jayakumar, R

2017-04-01

A tri-layered scaffolding approach is adopted for the complete and concurrent regeneration of hard tissues-cementum and alveolar bone-and soft tissue-the periodontal ligament (PDL)-at a periodontal defect site. The porous tri-layered nanocomposite hydrogel scaffold is composed of chitin-poly(lactic-co-glycolic acid) (PLGA)/nanobioactive glass ceramic (nBGC)/cementum protein 1 as the cementum layer, chitin-PLGA/fibroblast growth factor 2 as the PDL layer, and chitin-PLGA/nBGC/platelet-rich plasma derived growth factors as the alveolar bone layer. The tri-layered nanocomposite hydrogel scaffold is cytocompatible and favored cementogenic, fibrogenic, and osteogenic differentiation of human dental follicle stem cells. In vivo, tri-layered nanocomposite hydrogel scaffold with/without growth factors is implanted into rabbit maxillary periodontal defects and compared with the controls at 1 and 3 months postoperatively. The tri-layered nanocomposite hydrogel scaffold with growth factors demonstrates complete defect closure and healing with new cancellous-like tissue formation on microcomputed tomography analysis. Histological and immunohistochemical analyses further confirm the formation of new cementum, fibrous PDL, and alveolar bone with well-defined bony trabeculae in comparison to the other three groups. In conclusion, the tri-layered nanocomposite hydrogel scaffold with growth factors can serve as an alternative regenerative approach to achieve simultaneous and complete periodontal regeneration. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High doses of ionizing radiation on bone repair: is there effect outside the irradiated site?

PubMed

Rocha, Flaviana Soares; Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Lara, Vitor Carvalho; Batista, Jonas Dantas; Dechichi, Paula

2017-03-01

Local ionizing radiation causes damage to bone metabolism, it reduces blood supply and cellularity over time. Recent studies indicate that radiation promotes biological response outside the treatment field. The aim of this study was to investigate the effects of ionizing radiation on bone repair outside the irradiated field. Ten healthy male Wistar rats were used; and five animals were submitted to radiotherapy on the left femur. After 4 weeks, in all animals were created bone defects in the right and left femurs. Seven days after surgery, animals were euthanized. The femurs were removed and randomly divided into 3 groups (n=5): Control (C) (right femur of the non-irradiated animals); Local ionizing radiation (IR) (left femur of the irradiated animals); Contralateral ionizing radiation (CIR) (right femur of the irradiated animals). The femurs were processed and embedded in paraffin; and bone histologic sections were evaluated to quantify the bone neoformation. Histomorphometric analysis showed that there was no significant difference between groups C (24.6±7.04) and CIR (25.3±4.31); and IR group not showed bone neoformation. The results suggest that ionizing radiation affects bone repair, but does not interfere in bone repair distant from the primary irradiated site. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects

DTIC Science & Technology

2016-08-01

successful production of chimeric mice after irradiation and GFP+ bone marrow transplantation; reproducible implementation of uniform cranial lesions of ~1.5...cranial defect model in chimeric mice transplanted with GFP+ bone marrow. We follow defect closure by three dimensional microcomputed tomography (µCT...histolomorphometry and immunohistochemistry, respectively. 2. Keywords GFP+ chimeric mice, cranial defect closure, relaxin, angiogenesis

Development and Assessment of a 3D-Printed Scaffold with rhBMP-2 for an Implant Surgical Guide Stent and Bone Graft Material: A Pilot Animal Study.

PubMed

Bae, Ji Cheol; Lee, Jin-Ju; Shim, Jin-Hyung; Park, Keun-Ho; Lee, Jeong-Seok; Bae, Eun-Bin; Choi, Jae-Won; Huh, Jung-Bo

2017-12-16

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/ β -tricalcium phosphate ( β -TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.

Evaluating the effectiveness of gel formulation of irradiated seed lectin Cratylia mollis during bone repair in rats

PubMed Central

Santos-Oliveira, Ralph; Lima-Ribeiro, Maria Helena Madruga; Carneiro-Leão, Ana Maria dos Anjos; Cruz, Adriana Ferreira; de Santana, Mauricélia Firmino; Cavalcanti, Carmelita de Lima Bezerra; de Pontes Filho, Nicodemos Teles; Coelho, Luana Cassandra Breitenbach Barroso; dos Santos Correia, Maria Tereza

2013-01-01

Context: Regeneration corresponds to the replacement of damaged cells with ones that have the same morphology and function. For experimental evaluation of materials that may favor the process of bone healing, defects are created with dimensions that prevent spontaneous regeneration. For the development and use of new drugs, it is necessary to study its effects in vitro, which depends on the formulation, concentration, and rate of irradiation in vivo and the route and frequency of administration; thus, it is possible to characterize the physiological and molecular mechanisms involved in the response and cellular effects. Objective: The objective of this study was to assess the effect of Cramoll-1,4 on the process of bone repair. Materials and Methods: A formulation of biopharmaceutical lectin Cramoll-1,4 at a concentration of 300 mg/100 mL was applied in a single application via gamma radiation and its effect on the process of bone repair in rats was assessed. Results: Histologically, it was observed that the bone defect is coated by loose connective tissue rich in fibroblasts, providing a range similar to the thick bone original and competing with site of new bone formation. This prevented direct contact between the formulation and experimental bone tissue, as, despite its proven effectiveness in experiments on the repair of skin lesions, the formulation used did not promote bone stimulation that would have promoted the tissue repair process. Conclusion: Because of the direct interference of loose tissue repair that prevented direct contact of the implant with the bone interface, the formulation did not promote bone stimulation. PMID:24083142

[Reconstruction of tangential and circular infected bone defects].

PubMed

Schmidt, H G; Neikes, M; Zimmer, W

1987-12-01

In the treatment of bone infections the reconstruction and rehabilitation of bone defects is a problem that often requires treatment secondary to curative treatment of the infection. For the reconstruction of smaller and more extensive defects we used predominantly (92.7%) autogenous (autologous) untreated spongiosa and in only 7% of the cases allogenic (homologous) spongiosa from an organ bank, this being added if necessary. Recently the additionally introduced vascularized bone chip has become a useful extension of the therapy concept. The problems and complications of defect reconstruction are demonstrated for 705 cases of bone infection with 472 defects of different sizes, based on a comprehensive classification with defect calculation. Surgical technical approach and special aspects of after-treatment are described, as well as the results for every group of cases. We achieved stability and freedom from infection in a total of 93.7% of the patients. As was to be expected, the problems grow with the size of the defect. Particularly problematic are joint infections with adjacent extensive circular defect.

Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

2016-10-01

Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin-chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects.

ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

PubMed Central

Rentsch, C.; Rentsch, B.; Heinemann, S.; Bernhardt, R.; Bischoff, B.; Förster, Y.; Scharnweber, D.; Rammelt, S.

2014-01-01

Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

Horizontal alveolar bone loss: A periodontal orphan

PubMed Central

Jayakumar, A.; Rohini, S.; Naveen, A.; Haritha, A.; Reddy, Krishnanjeneya

2010-01-01

Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for this type of bone loss. This study should be an impetus for greater attention to an otherwise ubiquitous periodontal challenge. PMID:21760673

[Surgical Techniques for Patella Replacement in Cases of Deficient Bone Stock in Revision TKA].

PubMed

Ritschl, P; Machacek, F; Strehn, L; Kloiber, J

2015-06-01

The patella replacement in revision surgery is a challenge especially in cases of unsufficient bone stock. Depending on the extent of the bone defect, the following videos demonstrate different approaches: Video 1: bone sparing removal of the patella implant: onlay-type patella implants. Video 2: complete cortical bone rim of the patella, residual thickness between 6 to 10 mm: biconvex patella implant. Video 3 and 4: small defects of the cortical bone rim of the patella, residual thickness 1 to 5 mm (patella shell): gull-wing osteotomy, patella bone grafting techniques. Video 5: partial necrosis/defect of the patella shell with incomplete cortical bone rim: porous tantalum patella prosthesis. On account of the various surgical options for different bone defects of the patella, patellectomy and pure patelloplasty should be avoided to prevent functional shortcomings. Georg Thieme Verlag KG Stuttgart · New York.

Biomechanical analysis of iliac crest loading following cortico-cancellous bone harvesting.

PubMed

Schmitz, Paul; Cornelius Neumann, Christoph; Neumann, Carsten; Nerlich, Michael; Dendorfer, Sebastian

2018-05-09

Iliac crest bone harvesting is a frequently performed surgical procedure widely used to treat bone defects. The objective of this study is to assess the biomechanical quantities related to risk for pelvic fracture after harvesting an autologous bone graft at the anterior iliac crest. Finite element models with a simulated harvest site (sized 15 × 20 mm, 15 × 35 mm, 30 × 20 mm and 30 × 35 mm) in the iliac wing are created. The relevant loading case is when the ipsilateral leg is lifted off the ground. Musculoskeletal analysis is utilized to compute the muscle and joint forces involved in this motion. These forces are used as boundary conditions for the finite element analyses. Bone tissue stress is analyzed. Critical stress peaks are located between the anterior superior iliac spine (ASIS) and the anterior edge of the harvest site. Irrespective of the graft size, the iliac wing does not show any significant stress peaks with the harvest site being 20 to 25 mm posterior to the ASIS. The harvest area itself inhibits the distribution of the forces applied on the ASIS to extend to the posterior iliac wing. This leads to a lack of stress posterior to the harvest site. A balanced stress distribution with no stress peaks appears when the bone graft is taken below the iliac crest. A harvest site located at least 20 to 25 mm posterior to the ASIS should be preferred to minimize the risk of iliac fatigue fracture.

Effect of autogenous and fresh-frozen bone grafts on osteoblast differentiation.

PubMed

Ferraz, E P; Xavier, S P; Azevedo, F G; de Oliveira, F S; Beloti, M M; Rosa, A L

2015-01-01

Fresh-frozen bone allograft (FFBA) is an alternative to autogenous bone (AB) for reconstructing maxillary bone. Despite the promising clinical results, cell responses to FFBA and AB were not evaluated. Thus, our aim was to compare cells harvested from maxillary reconstructed sites with either AB or FFBA in terms of osteoblast differentiation and to evaluate the effect of culturing cells in contact with FFBA. Cells harvested from three patients submitted to bilateral maxillary reconstruction with AB and FFBA were cultured to evaluate: proliferation, alkaline phosphatase activity, extracellular matrix mineralization and gene expression of osteoblastic markers. The effect of FFBA on osteoblast differentiation was studied by culturing cells harvested from AB in contact with FFBA and evaluating the same parameters. Data were compared using either two-way ANOVA followed by Tukey-b test or Student's t test (p≤0.05). Cell proliferation was higher in cultures from AB grafted sites and extracellular matrix mineralization was higher in cultures derived from FFBA grafted sites. The gene expression of alkaline phosphatase, RUNX2, bone sialoprotein and osteocalcin was higher in cells derived from FFBA compared with cells from AB grafted sites. However, the exposure of cells derived from AB to FFBA particles did not have any remarkable effect on osteoblast differentiation. These results indicate the higher osteogenic activity of cells derived from FFBA compared with AB reconstructed sites, offering an explanation at cellular level of why FFBA could be a suitable alternative to AB for reconstructing maxillary bone defects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of bone repair after application of a norbixin membrane scaffold with and without laser photobiomodulation (λ 780 nm).

PubMed

Alves, Adrielle Martins Monteiro; de Miranda Fortaleza, Lílian Melo; Filho, Antonio Luiz Martins Maia; Ferreira, Danniel Cabral Leão; da Costa, Charllyton Luis Sena; Viana, Vicente Galber Freitas; Santos, José Zilton Lima Verde; de Oliveira, Rauirys Alencar; de Meira Gusmão, Gustavo Oliveira; Soares, Luís Eduardo Silva

2018-05-04

Biocompatible membranes are widely used in medicine to stimulate bone repair. Several studies have demonstrated that laser photobiomodulation (PBM) also stimulates osteoblast proliferation and osteogenesis at the fracture site, leading to a greater deposition of bone mass and accelerating the process of bone consolidation. This work assessed the therapeutic effect of 780-nm laser PBM and a polystyrene membrane coated with norbixin and collagen (PSNC) on bone healing in rats with calvarial bone defect. Histological staining, Raman spectroscopy, and scanning electron microscopy (SEM) were used to evaluate the bone repair process. Four experimental treatment groups were compared: C, control; M, membrane only; L, laser PBM only; and ML, membrane + laser PBM. A bone defect was created in the calvaria of each animal, with each group subdivided into two subgroups that underwent euthanasia after 15 and 30 days treatment. The L and ML groups were irradiated (λ = 780 nm, ED = 6 J/cm 2 , P = 60 mW, t = 4 s) postoperatively on alternate days until they were euthanized. The bone concentration of hydroxyapatite (CHA) showed a clear gradation with increasing phosphate area in the order B (normal cortical bone) > L > M > ML > C for both periods. The PSNC membrane was effective in reducing the inflammatory process and served as a scaffold for bone repair. The laser PBM also showed positive effects on the bone repair process with increased deposition and organization of the newly formed bone. However, laser PBM failed to improve the bioactive properties of the membrane scaffold.

Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model.

PubMed

Liu, Weiqing; Kang, Ning; Dong, Yuliang; Guo, Yuchen; Zhao, Dan; Zhang, Shiwen; Zhou, Liyan; Seriwatanachai, Dutmanee; Liang, Xing; Yuan, Quan

2016-04-01

The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (μCT) and histological analysis. The μCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair.

PubMed

Zhang, Ya-Dong; Wang, Gang; Sun, Yan; Zhang, Chang-Qing

2011-02-01

Porous scaffold biomaterials may offer a clinical alternative to bone grafts; however, scaffolds alone are typically insufficient to heal large bone defects. Numerous studies have demonstrated that osteoinductive growth factor significantly improves bone repair. In this study, a strategy combining degradable bioactive borate glass (BG) scaffolds with platelet-rich plasma (PRP) was tested. The bone defect was filled with BG alone, BG combined with autologous PRP or left empty. Bone formation was analyzed at 4, 8 and 12 weeks using both histology and radiology. The PRP treated group yielded better bone formation than the pure BG scaffold as determined by both histology and microcomputer tomography after 12 weeks. In conclusion, PRP improved bone healing in a diaphyseal rabbit model on BG. The combination of PRP and BG may be an effective approach to repair critical defects.

Evaluation of the presence of VEGF, BMP2 and CBFA1 proteins in autogenous bone graft: histometric and immunohistochemical analysis.

PubMed

Guskuma, Marcos Heidy; Hochuli-Vieira, Eduardo; Pereira, Flávia Priscila; Rangel-Garcia, Idelmo; Okamoto, Roberta; Okamoto, Tetuo; Filho, Osvaldo Magro

2014-06-01

The purpose of this study was to evaluate the expression of proteins that participate in the osteoinduction stage (VEGF, BMP2 and CBFA1) of the process of bone regeneration of defects created in rat calvariae and filled with autogenous bone block grafts. 10 adult male rats (Rattus norvegicus albinus, Wistar) were used, who received two bone defects measuring 5 mm each in the calvariae. The bone defects constituted two experimental groups (n = 10): Control Group (CONT) (defects filled with a coagulum); Graft Group (GR) (defects filled with autogenous bone removed from the contralateral defect). The animals were submitted to euthanasia at 7 and 30 days post-operatively. Quantitative analysis demonstrated significantly greater bone formation in Group GR, but the presence of the studied proteins was significantly greater in the CONT Group in both time intervals of observation. It was not possible in this study in cortical bone block groups to detect the osteoinductive proteins in a significant amount during the repair process. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

PubMed

Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

2009-12-15

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

Treatment of periodontal intrabony defects using β-TCP alone or in combination with rhPDGF-BB: a randomized controlled clinical and radiographic study.

PubMed

Maroo, Sneha; Murthy, K Raja V

2014-01-01

The need to increase the predictability of periodontal regeneration has encouraged clinicians and researchers to employ cell-stimulating proteins in combination with osteoconductive scaffolds, based on the principles of tissue engineering. The purpose of this clinical and radiographic study was to compare the regenerative potential of the combination of β-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB (rhPDGF-BB) in the grafting of intraosseous defects with the established technique of bone grafting with (β-TCP alone. A total of 30 sites from 15 patients with infrabony defects in two different quadrants were selected, and the sites were randomly divided into test sites (rhPDGF + β-TCP) and control sites (β-TCP alone) using a split-mouth design. Clinical parameters, including probing pocket depth, clinical attachment level, and gingival recession, were recorded at baseline, 6 months, and 9 months. Radiographic evaluation was carried out to evaluate defect fill, change in alveolar crest height, and percentage of defect fill at baseline, 6 months, and 9 months. Both the experimental groups showed statistically significant reduction in probing pocket depth and gain in clinical attachment level. On intergroup comparison, sites treated with rhPDGF + β-TCP demonstrated a significantly greater pocket depth reduction (P < .05) and greater gain in clinical attachment level (P < .01). Mean percentage defect fill was significantly greater in test sites as compared with control sites at 6 and 9 months (P < .01). rhPDGF + β-TCP-treated sites demonstrated a significant gain in mean alveolar crest height at 6 and 9 months (P < .05), while β-TCP-treated sites demonstrated crestal resorption. Both groups demonstrated potential in enhancing periodontal regeneration; however, on comparison between the two groups, the results obtained by rhPDGF + β-TCP were significantly better with respect to both clinical and radiographic parameters.

Design variables for mechanical properties of bone tissue scaffolds.

PubMed

Howk, Daniel; Chu, Tien-Min G

2006-01-01

The reconstruction of segmental defect in long bone is a clinical challenge. Multiple surgeries are typically required to restore the structure and function of the affected defect site. In order to overcome this defect a biodegradable bone tissue engineering scaffold is used. This scaffold acts as a carrier of proteins and growth factors, while also supporting the load that the bone would normally sustain, until the natural bone can regenerate in its place. Work was done to optimize an existing solid free-form scaffold design. The goal of the optimization was to increase the porosity of the scaffold while maintaining the strength of a previously-tested prototype design. With this in mind, eight new designs were created. These designs were drawn using CAD software and then through the use of finite element analysis the theoretical ultimate compressive strength of each design was obtained. Each scaffold design was constructed by casting a thermal-curable poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) suspension into wax molds fabricated on inkjet printing rapid prototyping machine. The constructs were then experimentally tested by applying a uniaxial compressive load. The theoretical and experimental values of ultimate compressive strength and specific strength of each design were compared. Theoretically, the best scaffold design produced from this work improved upon the current design by increasing the porosity by 46% and also increasing the ultimate compressive strength by 27%. The experimental data was found to match the theoretical strength in four designs, but deviate from the theoretical strength in five designs. The reasons for the deviations and their relation to the rapid prototyping manufacturing technique were discussed. The results of this work show that it is possible to increase the porosity and strength of a bone tissue engineering scaffold through simple iterations in architectural design.

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

PubMed

Hu, Bin; Li, Yan; Wang, Mohan; Zhu, Youming; Zhou, Yong; Sui, Baiyan; Tan, Yu; Ning, Yujie; Wang, Jie; He, Jiacai; Yang, Chi; Zou, Duohong

2018-06-10

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-L-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/β-tricalcium phosphate (β-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/β-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/β-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Acellular dermal matrix in soft tissue reconstruction prior to bone grafting. A case report.

PubMed

Ruiz-Magaz, Vanessa; Hernández-Alfaro, Federico; Díaz-Carandell, Artur; Biosca-Gómez-de-Tejada, María-José

2010-01-01

When hard tissue augmentation is scheduled as a part of an oral rehabilitation, prior to the treatment, it is important to assess if the quality of the underlying gingiva at the recipient site can support the bone grafting procedure. The most frequent complication during autologous onlay grafts are wound dehiscences in the recipient site, so the integrity of soft tissues is a basic aspect of successful reconstructive and plastic surgical procedure. Connective tissue grafts can improve the quality and quantity of soft tissue in oral sites where a hard tissue reconstruction is going to take place. However, particularly when large grafts are harvested, the autogenous donor site can present significant postoperative morbidity, such as necrosis of the palate fibromucosa and bone exposition, pain and bleeding. Another important limitation with the use of autogenous grafts is the limited supply of donor connective tissue. If a large site needs to be grafted, more than one surgical procedure may be required. An Acellular Dermal Matrix (ADM) graft has become increasingly popular as a substitute for donor connective tissue, eliminating the disadvantages described for the autogenous donor graft. The amount of tissue harvested is unlimited, so it gives an option for treating patients that have inadequate harvestable tissue or that present a large defect to be treated. The outcome of using ADM as a matrix for soft tissue reconstruction 12 weeks before bone grafting can reduce the risk of exposure and failure of the bone graft.

Bone repair using a new injectable self-crosslinkable bone substitute.

PubMed

Fellah, Borhane H; Weiss, Pierre; Gauthier, Olivier; Rouillon, Thierry; Pilet, Paul; Daculsi, Guy; Layrolle, Pierre

2006-04-01

A new injectable and self-crosslinkable bone substitute (IBS2) was developed for filling bone defects. The IBS2 consisted of a chemically modified polymer solution mixed with biphasic calcium phosphate (BCP) ceramic particles. The polymer hydroxypropylmethyl cellulose was functionalized with silanol groups (Si-HPMC) and formed a viscous solution (3 wt %) in alkaline medium. With a decrease in pH, self-hardening occurred due to the formation of intermolecular -Si-O- bonds. During setting, BCP particles, 40 to 80 microm in diameter, were added to the polymer solution at a weight ratio of 50/50. The resulting injectable material was bilaterally implanted into critically sized bone defects at the distal femoral epiphyses of nine New Zealand White rabbits. The IBS2 filled the bone defects entirely and remained in place. After 8 weeks, bone had grown centripetally and progressed towards the center of the defects. Newly formed bone, ceramic, and nonmineralized tissue ratios were 24.6% +/- 5.6%, 21.6% +/- 5.8%, and 53.7% +/- 0.1%, respectively. Mineralized and mature bone was observed between and in contact with the BCP particles. The bone/ceramic apposition was 73.4% +/- 10.6%. The yield strength for the IBS2-filled defects was 16.4 +/- 7.2 MPa, significantly higher than for the host trabecular bone tissue (2.7 +/- 0.4 MPa). This study showed that BCP particles supported the bone healing process by osteoconduction while the Si-HPMC hydrogel created intergranular space for bone ingrowth. This new injectable and self-crosslinkable bone substitute could be used conveniently in orthopedic surgery for filling critical-size bone defects. Copyright 2006 Orthopaedic Research Society

Attempts to obtain re-osseointegration following experimental peri-implantitis in dogs.

PubMed

Wetzel, A C; Vlassis, J; Caffesse, R G; Hämmerle, C H; Lang, N P

1999-04-01

The purpose of this study was to examine the healing potential and re-osseointegration in peri-implant infection defects adjacent to various implant surfaces. In 7 female Beagle dogs, a total of 41 titanium oral implants (ITI, Straumann, Waldenburg; Switzerland) with a sink depth of 6 mm (diameter 2.8 mm) were placed transmucosally. Four different surface configurations (TPS: titanium plasma sprayed (10); SLA: sand blasted and acid-etched (13); M: machined and smooth (11); TPS furc.: titanium plasma sprayed with coronally placed perforation to mimic a furcation (7) were distributed among the animals and locations. Following a healing period of 3 months, silk ligatures were placed and oral cleaning procedures abolished for 4 months to induce a vertical bone loss of about 40%. Following mechanical and chemical cleansing (chlorhexidine and metronidazole) and disinfection, the lesions were either sham operated (11) or subjected to a GTR procedure using ePTFE (30). After 6 months of healing the animals were killed and the jaws histologically evaluated. Six membranes were lost TPS: (1); SLA: (2); M: (2); TPS furc: (1) and 3 membranes exposed TPS: (1); M: (2) and excluded from further evaluation. Owing to the loss of 1 implant and infection of the membranes in the TPS furc group, this implant configuration was discarded from further analysis. For TPS surfaces, bone fill was 2.6 mm (73% of the distance from the bottom of the defect to the shoulder of the implant) sites with (4 GTR) and 0.33 mm (14%) for sites without membrane (2 controls). Re-osseointegration was 0.5 mm (14%) in the test group and 0.3 mm (14%) in the control. For SLA surfaces bone fill was 2.3 mm (83%) for sites with (7 GTR) and 0.41 mm (15%) for sites without membranes (4 controls). Re-osseointegration was 0.6 mm (20%) and 0.3 mm (11%) respectively. Corresponding values for M surfaces were 2.2 mm (62%) with 4 GTR) and 0.82 mm (31%) without membranes. Re-osseointegration was 0.07 mm (2%) and 0.19 mm (7%) respectively. This study has documented that peri-implant infections defects may heal with bone fill provided that the infection is controlled through effective antibacterial therapy. However, true reosseointegration appears to be difficult to achieve.

Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

DTIC Science & Technology

2011-04-01

tissue and polymer: mineralized tissue stained dark green, osteoid and collagen bright red, soft tissue pink to light green, and erythrocytes bright...of bone, soft tissue , and polymer, high-resolution digital images were acquired at 1.25 · or 20 · . The area of interest comprising the bone defect...bone, soft tissue , and polymer (when present) within the defect were quantified using Metamorph software (Molecular Devices, Inc.) and were calculated

Knee arthrodesis with lengthening: experience of using Ilizarov techniques to salvage large asymmetric defects following infected peri-articular fractures.

PubMed

Barwick, Thomas W; Montgomery, Richard J

2013-08-01

We present four patients with large bone defects due to infected internal fixation of knee condylar fractures. All were treated by debridement of bone and soft tissue and stabilisation with flap closure if required, followed by bone transport arthrodesis of the knee with simultaneous lengthening. Four patients (three male and one female), mean age 46.5 years (37-57 years), with posttraumatic osteomyelitis at the knee (three proximal tibia and one distal femur) were treated by debridement of infected tissue and removal of internal fixation. Substantial condylar bone defects resulted on the affected side of the knee joint (6-10 cm) with loss of the extensor mechanism in all tibial cases. Two patients required muscle flaps after debridement. All patients received intravenous antibiotics for at least 6 weeks. Bone transport with a circular frame was used to achieve an arthrodesis whilst simultaneously restoring a functional limb length. In three cases a 'peg in socket' docking technique was fashioned to assist stability and subsequent consolidation of the arthrodesis. Arthrodesis of the knee, free of recurrent infection, was successfully achieved in all cases. None has since required further surgery. Debridement to union took an average of 25 months (19-31 months). The median number of interventions undertaken was 9 (8-12). Two patients developed deep vein thrombosis (DVT), one complicated by PE, which delayed treatment. Two required surgical correction of pre-existent equinus contracture using frames. The median limb length discrepancy (LLD) at the end of treatment was 3 cm (3-4 cm). None has required subsequent amputation. Bone loss and infection both reduce the success rate of any arthrodesis. However, by optimising the host environment with eradication of infection by radical debridement, soft-tissue flaps when necessary and bone transport techniques to close the defect, one can achieve arthrodesis and salvage a useful limb. The residual LLD can result from not accounting for later impaction at peg and socket sites, which had the effect of increasing LLD beyond the desirable amount. We therefore recommend continuing the lengthening for an additional 1-2 cm to allow for this. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone compositional study during healing of subcritical calvarial defects in rats by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ahmed, Rafay; Wing Lun Law, Alan; Cheung, Tsz Wing; Lau, Condon

2017-07-01

Subcritical calvarial defects are important to study bone regeneration during healing. In this study 1mm calvarial defects were created using trephine in the parietal bones of Sprague-Dawley rats (n=7) that served as in vivo defects. Subjects were sacrificed after 7 days and the additional defects were created on the harvested skull with the same method to serve as control defects. Raman spectroscopy is established to investigate mineral/matrix ratio, carbonate/phosphate ratio and crystallinity of three different surfaces; in vivo defects, control defects and normal surface. Results show 21% and 23% decrease in mineral/matrix after 7 days of healing from surface to in vivo and control to in vivo defects, respectively. Carbonate to phosphate ratio was found to be increased by 39% while crystallinity decreased by 26% in both surface to in vivo and control to in vivo defects. This model allows to study the regenerated bone without mechanically perturbing healing surface.

Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments

PubMed Central

Pneumaticos, Spyros G; Triantafyllopoulos, Georgios K; Basdra, Efthimia K; Papavassiliou, Athanasios G

2010-01-01

Abstract Several conditions in clinical orthopaedic practice can lead to the development of a diaphyseal segmental bone defect, which cannot heal without intervention. Segmental bone defects have been traditionally treated with bone grafting and/or distraction osteogenesis, methods that have many advantages, but also major drawbacks, such as limited availability, risk of disease transmission and prolonged treatment. In order to overcome such limitations, biological treatments have been developed based on specific pathways of bone physiology and healing. Bone tissue engineering is a dynamic field of research, combining osteogenic cells, osteoinductive factors, such as bone morphogenetic proteins, and scaffolds with osteoconductive and osteoinductive attributes, to produce constructs that could be used as bone graft substitutes for the treatment of segmental bone defects. Scaffolds are usually made of ceramic or polymeric biomaterials, or combinations of both in composite materials. The purpose of the present review is to discuss in detail the molecular and cellular basis for the development of bone tissue engineering constructs. PMID:20345845

Treatment of open tibial fracture with bone defect caused by high velocity missiles: a case report.

PubMed

Golubović, Zoran; Vukajinović, Zoran; Stojiljković, Predrag; Golubović, Ivan; Visnjić, Aleksandar; Radovanović, Zoran; Najman, Stevo

2013-01-01

Tibia fracture caused by high velocity missiles is mostly comminuted and followed by bone defect which makes their healing process extremely difficult and prone to numerous complications. A 34-year-old male was wounded at close range by a semi-automatic gun missile. He was wounded in the distal area of the left tibia and suffered a massive defect of the bone and soft tissue. After the primary treatment of the wound, the fracture was stabilized with an external fixator type Mitkovic, with convergent orientation of the pins. The wound in the medial region of the tibia was closed with the secondary stitch, whereas the wound in the lateral area was closed with the skin transplant after Thiersch. Due to massive bone defect in the area of the rifle-missile wound six months after injury, a medical team placed a reconstructive external skeletal fixator type Mitkovic and performed corticotomy in the proximal metaphyseal area of the tibia. By the method of bone transport (distractive osteogenesis), the bone defect of the tibia was replaced. After the fracture healing seven months from the secondary surgery, the fixator was removed and the patient was referred to physical therapy. Surgical treatment of wounds, external fixation, performing necessary debridement, adequate antibiotic treatment and soft and bone tissue reconstruction are essential in achieving good results in patients with the open tibial fracture with bone defect caused by high velocity missiles. Reconstruction of bone defect can be successfully treated by reconstructive external fixator Mitkovic.

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Repair of segmental bone defects in the maxilla by transport disc distraction osteogenesis: Clinical experience with a new device

PubMed Central

Boonzaier, James; Vicatos, George; Hendricks, Rushdi

2015-01-01

The bones of the maxillary complex are vital for normal oro-nasal function and facial cosmetics. Maxillary tumor excision results in large defects that commonly include segments of the alveolar and palatine processes, compromising eating, speech and facial appearance. Unlike the conventional approach to maxillary defect repair by vascularized bone grafting, transport disc distraction osteogenesis (TDDO) stimulates new bone by separating the healing callus, and stimulates growth of surrounding soft tissues as well. Bone formed in this way closely mimics the parent bone in form and internal structure, producing a superior anatomical, functional and cosmetic result. Historically, TDDO has been successfully used to close small horizontal cleft defects in the maxilla, not exceeding 25 mm. Fujioka et al. reported in 2012 that “no bone transporter corresponding to the (large) size of the oro-antral fistula is marketed. The authors report the successful treatment of 4 cases involving alveolar defects of between 25 mm and 80 mm in length. PMID:26389041

Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry.

PubMed

Siverino, Claudia; Tabisz, Barbara; Lühmann, Tessa; Meinel, Lorenz; Müller, Thomas; Walles, Heike; Nickel, Joachim

2018-03-29

Different therapeutic strategies for the treatment of non-healing long bone defects have been intensively investigated. Currently used treatments present several limitations that have led to the use of biomaterials in combination with osteogenic growth factors, such as bone morphogenetic proteins (BMPs). Commonly used absorption or encapsulation methods require supra-physiological amounts of BMP2, typically resulting in a so-called initial burst release effect that provokes several severe adverse side effects. A possible strategy to overcome these problems would be to covalently couple the protein to the scaffold. Moreover, coupling should be performed in a site-specific manner in order to guarantee a reproducible product outcome. Therefore, we created a BMP2 variant, in which an artificial amino acid (propargyl-L-lysine) was introduced into the mature part of the BMP2 protein by codon usage expansion (BMP2-K3Plk). BMP2-K3Plk was coupled to functionalized beads through copper catalyzed azide-alkyne cycloaddition (CuAAC). The biological activity of the coupled BMP2-K3Plk was proven in vitro and the osteogenic activity of the BMP2-K3Plk-functionalized beads was proven in cell based assays. The functionalized beads in contact with C2C12 cells were able to induce alkaline phosphatase (ALP) expression in locally restricted proximity of the bead. Thus, by this technique, functionalized scaffolds can be produced that can trigger cell differentiation towards an osteogenic lineage. Additionally, lower BMP2 doses are sufficient due to the controlled orientation of site-directed coupled BMP2. With this method, BMPs are always exposed to their receptors on the cell surface in the appropriate orientation, which is not the case if the factors are coupled via non-site-directed coupling techniques. The product outcome is highly controllable and, thus, results in materials with homogeneous properties, improving their applicability for the repair of critical size bone defects.

[Ex Vivo Testing of Mechanical Properties of Canine Metacarpal/Metatarsal Bones after Simulated Implant Removal].

PubMed

Srnec, R; Fedorová, P; Pěnčík, J; Vojtová, L; Sedlinská, M; Nečas, A

2016-01-01

PURPOSE OF THE STUDY In a long-term perspective, it is better to remove implants after fracture healing. However, subsequent full or excessive loading of an extremity may result in refracture, and the bone with holes after screw removal may present a site with predilection for this. The aim of the study was to find ways of how to decrease risk factors for refracture in such a case. This involved support to the mechanical properties of a bone during its remodelling until defects following implant removal are repaired, using a material tolerated by bone tissue and easy to apply. It also included an assessment of the mechanical properties of a bone after filling the holes in it with a newly developed biodegradable polymer-composite gel ("bone paste"). The composite also has a prospect of being used to repair bony defects produced by pathological processes. MATERIAL AND METHODS Experiments were carried out on intact weight-bearing small bones in dogs. A total of 27 specimens of metacarpal/metatarsal bones were used for ex vivo testing. They were divided into three groups: K1 (n = 9) control undamaged bones; K2 (n = 9) control bones with iatrogenic damage simulating holes left after cortical screw removal; EXP (n = 9) experimental specimens in which simulated holes in bone were filled with the biodegradable self-hardening composite. The bone specimens were subjected to three-point bending in the caudocranial direction by a force acting parallel to the direction of drilling in their middiaphyses. The value of maximum load achieved (N) and the corresponding value of a vertical displacement (mm) were recorded in each specimen, then compared and statistically evaluated. RESULTS On application of a maximum load (N), all bone specimens broke in the mid-part of their diaphyses. In group K1 the average maximum force of 595.6 ± 79.5 N was needed to break the bone; in group K2 it was 347.6 ± 58.6 N; and in group EXP it was 458.3 ± 102.7 N. The groups with damaged bones, K2 and EXP, were compared and the difference was found to be statistically significant (p ≤ 0.05). CONCLUSIONS The recently developed biodegradable polymer-composite gel is easy and quick to apply to any defect, regardless of its shape, in bone tissue. The ex vivo mechanical tests on canine short bones showed that the composite applied to defects, which simulated holes left after screw removal, provided sufficient mechanical support to the bone architecture. The results of measuring maximum loading forces were statistically significant. However, before the composite could be recommended for use in veterinary or human medical practice, thorough pre-clinical studies will be required. fracture fixation, mechanical testing, bone plate, cortical screw, refracture.

[Imaging analysis of jaw defects reparation with antigen-extracted porcine cancellous bone].

PubMed

Chen, Xufeng; Lu, Lihong; Feng, Zhiqiang; Yin, Zhongda; Lai, Renfa

2017-12-01

At present, most of the bone xenograft for clinical application comes from bovine. In recent years, many studies have been done on the clinical application of porcine xenograft bone. The goal of this study was to evaluate the effect of canine mandibular defects reparation with antigen-extracted porcine cancellous bone by imaging examination. Four dogs' bilateral mandibular defects were created, with one side repaired with autologous bone (set as control group) while the other side repaired with antigen-extracted porcine cancellous bone (set as experimental group). Titanium plates and titanium screws were used for fixation. Cone beam computed tomography (CBCT), computed tomography (CT), single-photon emission computed tomography (SPECT) were undertaken at week 12 and 24 postoperatively, and SPECT and CT images were fused. The results demonstrated that the remodeling of antigen-extracted porcine cancellous bone was slower than that of autologous bone, but it can still be used as scaffold for jaw defects. The results in this study provide a new choice for materials required for clinical reparation of jaw defects.

[Bone defect replacement under conditions of transosseous osteosynthesis and titanium nickelide implant application].

PubMed

Ir'ianov, Iu M; Ir'ianova, T Iu

2012-01-01

In the experiment conducted on 30 Wistar rats, the peculiarities of tibial bone defect replacement under conditions of transosseous osteosynthesis and implantation of titanium nickelide mesh structures were studied using the methods of scanning electron microscopy and x-ray electron probe microanalysis. It was demonstrated that implant osseointegration occured 7 days after surgery, and after 30 days the defect was replaced with bone tissue by the type of primary bone wound healing, thus the organotypical remodeling of regenerated bone took place.

Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Soares, Luiz G P; Cangussú, Maria Cristina T; Santos, Nicole R S; Barbosa, Artur Felipe S; Silveira Júnior, Landulfo

2012-09-01

We studied peaks of calcium hydroxyapatite (CHA) and protein and lipid CH groups in defects grafted with mineral trioxide aggregate (MTA) treated or not with LED irradiation, bone morphogenetic proteins and guided bone regeneration. A total of 90 rats were divided into ten groups each of which was subdivided into three subgroups (evaluated at 15, 21 and 30 days after surgery). Defects were irradiated with LED light (wavelength 850 ± 10 nm) at 48-h intervals for 15 days. Raman readings were taken at the surface of the defects. There were no statistically significant differences in the CHA peaks among the nonirradiated defects at any of the experimental time-points. On the other hand, there were significant differences between the defects filled with blood clot and the irradiated defects at all time-points (p < 0.001, p = 0.02, p < 0.001). There were significant differences between the mean peak CHA in nonirradiated defects at all the experimental time-points (p < 0.01). The mean peak of the defects filled with blood clot was significantly different from that of the defects filled with MTA (p < 0.001). There were significant differences between the defects filled with blood clot and the irradiated defects (p < 0.001). The results of this study using Raman spectral analysis indicate that infrared LED light irradiation improves the deposition of CHA in healing bone grafted or not with MTA.

Numerical optimization of open-porous bone scaffold structures to match the elastic properties of human cortical bone.

PubMed

Wieding, Jan; Wolf, Andreas; Bader, Rainer

2014-09-01

Treatment of large segmental bone defects, especially in load bearing areas, is a complex procedure in orthopedic surgery. The usage of additive manufacturing processes enables the creation of customized bone implants with arbitrary open-porous structure satisfying both the mechanical and the biological requirements for a sufficient bone ingrowth. Aim of the present numerical study was to optimize the geometrical parameters of open-porous titanium scaffolds to match the elastic properties of human cortical bone with respect to an adequate pore size. Three different scaffold designs (cubic, diagonal and pyramidal) were numerically investigated by using an optimization approach. Beam elements were used to create the lattice structures of the scaffolds. The design parameters strut diameter and pore size ranged from 0.2 to 1.5mm and from 0 to 3.0mm, respectively. In a first optimization step, the geometrical parameters were varied under uniaxial compression to obtain a structural modulus of 15GPa (Young׳s modulus of cortical bone) and a pore size of 800µm was aimed to enable cell ingrowth. Furthermore, the mechanical behavior of the optimized structures under bending and torsion was investigated. Results for bending modulus were between 9.0 and 14.5GPa. In contrast, shear modulus was lowest for cubic and pyramidal design of approximately 1GPa. Here, the diagonal design revealed a modulus of nearly 20GPa. In a second step, large-sized bone scaffolds were created and placed in a biomechanical loading situation within a 30mm segmental femoral defect, stabilized with an osteosynthesis plate and loaded with physiological muscle forces. Strut diameter for the 17 sections of each scaffold was optimized independently in order to match the biomechanical stability of intact bone. For each design, highest strut diameter was found at the dorsal/medial site of the defect and smallest strut diameter in the center. In conclusion, we demonstrated the possibility of providing optimized open-porous scaffolds for bone regeneration by considering both mechanical and biological aspects. Furthermore, the results revealed the need of the investigation and comparison of different load scenarios (compression, bending and torsion) as well as complex biomechanical loading for a profound characterization of different scaffold designs. The usage of a numerical optimization process was proven to be a feasible tool to reduce the amount of the required titanium material without influencing the biomechanical performance of the scaffold negatively. By using fully parameterized models, the optimization approach is adaptable to other scaffold designs and bone defect situations. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Dental implantation and soft tissue augmentation after ridge preservation in a molar site: a case report].

PubMed

Zhao, L P; Zhan, Y L; Hu, W J; Wang, H J; Wei, Y P; Zhen, M; Xu, T; Liu, Y S

2016-12-18

For ideal implant rehabilitation, an adequate bone volume, optical implant position, and stable and healthy soft tissue are required. The reduction of alveolar bone and changes in its morphology subsequent to tooth extraction will result in insufficient amount of bone and adversely affect the ability to optimally place dental implants in edentulous sites. Preservation of alveolar bone volume through ridge preservation has been demonstrated to reduce the vertical and horizontal contraction of the alveolar bone crest after tooth extraction and reduce the need for additional bone augmentation procedures during implant placement. In this case, a patient presented with a mandible molar of severe periodontal disease, the tooth was removed as atraumatically as possible and the graft material of Bio-Oss was loosely placed in the alveolar socket without condensation and covered with Bio-Gide to reconstruct the defects of the alveolar ridge. Six months later, there were sufficient height and width of the alveolar ridge for the dental implant, avoiding the need of additional bone augmentation and reducing the complexity and unpredictability of the implant surgery. Soft tissue defects, such as gingival and connective tissue, played crucial roles in long-term implant success. Peri-implant plastic surgery facilitated development of healthy peri-implant structure able to withstand occlusal forces and mucogingival stress. Six months after the implant surgery, the keratinized gingiva was absent in the buccal of the implant and the vestibular groove was a little shallow. The free gingival graft technique was used to solve the vestibulum oris groove supersulcus and the absence of keratinized gingiva around the implant. The deepening of vestibular groove and broadening of keratinized gingiva were conducive to the long-term health and stability of the tissue surrounding the implant. Implant installation and prosthetic restoration showed favorable outcome after six months.

Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metaizeau, J.P.; Olive, D.; Bey, P.

1984-04-01

In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used amore » free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors.« less

In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

NASA Astrophysics Data System (ADS)

Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wang, Zhonglei; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei

2016-03-01

Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

PubMed Central

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy

2012-01-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 µg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls. PMID:21863314

Periodontal regeneration around natural teeth.

PubMed

Garrett, S

1996-11-01

1. Evidence is conclusive (Table 2) that periodontal regeneration in humans is possible following the use of bone grafts, guided tissue regeneration procedures, both without and in combination with bone grafts, and root demineralization procedures. 2. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change beyond that achieved with debridement alone in treating mandibular and maxillary (buccal only) Class II furcations. Similar data exist for intraosseous defects. Evidence suggests that the use of bone grafts or GTR procedures produce equal clinical benefit in treating intraosseous defects. Further research is necessary to evaluate GTR procedures compared to, or combined with, bone grafts in treating intraosseous defects. 3. Although there are some data suggesting hopeful results in Class II furcations, the clinical advantage of procedures combining present regenerative techniques remains to be demonstrated. Additional randomized controlled trials with sufficient power are needed to demonstrate the potential usefulness of these techniques. 4. Outcomes following regenerative attempts remain somewhat variable with differences in results between studies and individual subjects. Some of this variability is likely patient related in terms of compliance with plaque control and maintenance procedures, as well as personal habits; e.g., smoking. Variations in the defects selected for study may also affect predictability of outcomes along with other factors. 5. There is evidence to suggest that present regenerative techniques lead to significant amounts of regeneration at localized sites on specific teeth. However, if complete regeneration is to become a reality, additional stimuli to enhance the regenerative process are likely needed. Perhaps this will be accomplished in the future, with combined procedures that include appropriate polypeptide growth factors or tissue factors to provide additional stimulus.

Effect of collagen sponge and fibrin glue on bone repair

PubMed Central

SANTOS, Thiago de Santana; ABUNA, Rodrigo Paolo Flores; de ALMEIDA, Adriana Luisa Gonçalves; BELOTI, Marcio Mateus; ROSA, Adalberto Luiz

2015-01-01

ABSTRACT The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. Material and Methods Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p≤0.05). Results Three-dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. Conclusion Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous. PMID:26814464

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

PubMed

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

A computer-guided bone block harvesting procedure: a proof-of-principle case report and technical notes.

PubMed

De Stavola, Luca; Fincato, Andrea; Albiero, Alberto Maria

2015-01-01

During autogenous mandibular bone harvesting, there is a risk of damage to anatomical structures, as the surgeon has no three-dimensional control of the osteotomy planes. The aim of this proof-of-principle case report is to describe a procedure for harvesting a mandibular bone block that applies a computer-guided surgery concept. A partially dentate patient who presented with two vertical defects (one in the maxilla and one in the mandible) was selected for an autogenous mandibular bone block graft. The bone block was planned using a computer-aided design process, with ideal bone osteotomy planes defined beforehand to prevent damage to anatomical structures (nerves, dental roots, etc) and to generate a surgical guide, which defined the working directions in three dimensions for the bone-cutting instrument. Bone block dimensions were planned so that both defects could be repaired. The projected bone block was 37.5 mm in length, 10 mm in height, and 5.7 mm in thickness, and it was grafted in two vertical bone augmentations: an 8 × 21-mm mandibular defect and a 6.5 × 18-mm defect in the maxilla. Supraimposition of the preoperative and postoperative computed tomographic images revealed a procedure accuracy of 0.25 mm. This computer-guided bone harvesting technique enables clinicians to obtain sufficient autogenous bone to manage multiple defects safely.

Comparative evaluation of hydroxyapatite and nano-bioglass in two forms of conventional micro- and nano-particles in repairing bone defects (an animal study).

PubMed

Nosouhian, Saied; Razavi, Mohammad; Jafari-Pozve, Nasim; Rismanchian, Mansour

2015-01-01

Many synthetic bone materials have been introduced for repairing bone defects. The aim of this study is to comparatively evaluate the efficacy of nano-hydroxyapatite (HA) and nano-bioglass bone materials with their traditional micro counterparts in repairing bone defects. In this prospective animal study, four healthy dogs were included. First to fourth premolars were extracted in each quadrant and five cavities in each quadrant were created using trephine. Sixteen cavities in each dog were filled by HA, nano-HA, bioglass, and nano-bioglass and four defects were left as the control group. All defects were covered by a nonrestorable membrane. Dogs were sacrificed after 15, 30, 45, and 60 days sequentially. All 20 samples were extracted by trephine #8 with a sufficient amount of surrounding bone. All specimens were investigated under an optical microscope and the percentage of total regenerated bone, lamellar, and woven bone were evaluated. Data analysis was carried out by SPSS Software ver. 15 and Mann-Whitney U-test (α =0.05). After 15 days, the bone formation percentage showed a significant difference between HA and nano-HA and between HA and bioglass (P < 0.001). The nano-HA group showed the highest rate of bone formation after 15 days. Nano-bioglass and bioglass and nano-HA and nano-bioglass groups represented a significant difference and nano-bioglass showed the highest rate of bone formation after 30 days (P = 0.01). After 45 days, the bone formation percentage showed a significant difference between nano-bioglass and bioglass and between nano-HA and nano-bioglass groups (P = 0.01). Nano-HA and nano-bioglass biomaterials showed promising results when compared to conventional micro-particles in the repair of bone defects.

Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature.

PubMed

Morad, Golnaz; Kheiri, Lida; Khojasteh, Arash

2013-12-01

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration. An electronic search of English-language papers was conducted on PubMed database. Studies that assessed the use of DPSCs in bone regeneration in vivo were included and experiments evaluating regeneration of hard tissues other than bone were excluded. The retrieved articles were thoroughly reviewed according to the source of stem cell, cell carrier, the in vivo experimental model, defect type, method of evaluating bone regeneration, and the obtained results. Further assessment of the results was conducted by classifying the studies based on the defect type. Seventeen papers formed the basis of this systematic review. Sixteen out of 17 experiments were performed on animal models with mouse and rat being the most frequently used animal models. Seven out of 17 animal studies, contained subcutaneous pockets on back of the animal for stem cell implantation. In only one study hard tissue formation was not observed. Other types of defects used in the retrieved studies, included cranial defects and mandibular bone defects, in all of which bone formation was reported. When applied in actual bone defects, DPSCs were capable of regenerating bone. Nevertheless, a precise conclusion regarding the efficiency of DPSCs for bone regeneration is yet to be made, considering the limited number of the in vivo experiments and the heterogeneity within their methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

Torque test measurement in segmental bone defects using porous calcium phosphate cement implants.

PubMed

Kroese-Deutman, Henriette C; Wolke, Joop G C; Spauwen, Paul H M; Jansen, John A

2010-10-01

This study was performed to assess the bone healing supporting characteristics of porous calcium phosphate (Ca-P) cement when implanted in a rabbit segmental defect model as well as to determine the reliability of torque testing as a method to verify bone healing. The middiaphyseal radius was chosen as the area to create bilaterally increasing defect sizes (5, 10, and 15 mm), which were either filled with porous Ca-P cement or left open as a control. After 12 weeks of implantation, torque test measurements as well as histological and radiographic evaluation were performed. In two of the open 15 mm control defects, bone bridging was visible at the radiographic and histological evaluation. Bone was observed to be present in all porous Ca-P cement implants (5, 10, and 15 mm defects) after 12 weeks. No significant differences in torque measurements were observed between the 5 and 10 mm filled and open control defects using a t-test. In addition, the mechanical strength of all operated specimens was similar compared with nonoperated bone samples. The torsion data for the 15 mm open defect appeared to be lower compared with the filled 15 mm defect, but no significant difference could be proven. Within the limitation of the study design, porous Ca-P cement implants demonstrated osteoconductive properties and confirmed to be a suitable scaffold material in a weight-bearing situation. Further, the used torque testing method was found to be unreliable for testing the mechanical properties of the healed bone defect.

A combined approach of enamel matrix derivative gel and autogenous bone grafts in treatment of intrabony periodontal defects. A case report.

PubMed

Leung, George; Jin, Lijian

2003-04-01

Enamel matrix derivative (EMD) has recently been introduced as a new modality in regenerative periodontal therapy. This case report demonstrates a combined approach in topical application of EMD gel (Emdogain) and autogenous bone grafts for treatment of intrabony defects and furcation involvement defects in a patient with chronic periodontitis. The seven-month post-surgery clinical and radiographic results were presented. The combined application of EMD gel with autogenous bone grafts in intrabony osseous defects resulted in clinically significant gain of attachment on diseased root surfaces and bone fill on radiographs. Further controlled clinical studies are required to confirm the long-term effectiveness of the combination of EMD gel and autogenous bone grafts in treatment of various osseous defects in subjects with chronic periodontitis.

Effect of scaling and root planing on alveolar bone as measured by subtraction radiography.

PubMed

Hwang, You-Jeong; Fien, Matthew Jonas; Lee, Sam-Sun; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul; Chung, Chong-Pyoung; Han, Soo-Boo

2008-09-01

Scaling and root planing of diseased periodontal pockets is fundamental to the treatment of periodontal disease. Although various clinical parameters have been used to assess the efficacy of this therapy, radiographic analysis of changes in bone density following scaling and root planing has not been extensively researched. In this study, digital subtraction radiography was used to analyze changes that occurred in the periodontal hard tissues following scaling and root planing. Thirteen subjects with a total of 39 sites that presented with >3 mm of vertical bone loss were included in this study. Clinical examinations were performed and radiographs were taken prior to treatment and were repeated 6 months following scaling and root planing. Radiographic analysis was performed with computer-assisted radiographic evaluation software. Three regions of interest (ROI) were defined as the most coronal, middle, and apical portions of each defect. A fourth ROI was used for each site as a control region and was placed at a distant, untreated area. Statistical analysis was carried out to evaluate changes in the mean gray level at the coronal, middle, and apical region of each treated defect. Digital subtraction radiography revealed an increase in radiographic density in 101 of the 117 test regions (83.3%). A 256 gray level was used, and a value >128 was assumed to represent a density gain in the ROI. The average gray level increase was 18.65. Although the coronal, middle, and apical regions displayed increases in bone density throughout this study, the bone density of the apical ROI (gray level = 151.27 +/- 20.62) increased significantly more than the bone density of the coronal ROI (gray level = 139.19 +/- 21.78). A significant increase in bone density was seen in probing depths >5 mm compared to those <5 mm in depth. No significant difference was found with regard to bone-density changes surrounding single- versus multiple-rooted teeth. Scaling and root planing of diseased periodontal pockets can significantly increase radiographic alveolar bone density as demonstrated through the use of digital subtraction radiography.

Resorption of Autogenous Bone Graft in Cranioplasty: Resorption and Reintegration Failure

PubMed Central

Lee, Si Hoon; Lee, Uhn; Park, Cheol Wan; Lee, Sang Gu; Kim, Woo Kyung

2014-01-01

Objective Re-implantation of autologous skull bone has been known to be difficult because of its propensity for resorption. Moreover, the structural characteristics of the area of the defect cannot tolerate physiologic loading, which is an important factor for graft healing. This paper describes our experiences and results with cranioplasty following decompressive craniectomy using autologous bone flaps. Methods In an institutional review, the authors identified 18 patients (11 male and 7 female) in whom autologous cranioplasty was performed after decompressive craniectomy from January 2008 to December 2011. We examined the age, reasons for craniectomy, size of the skull defect, presence of bony resorption, and postoperative complications. Results Postoperative bone resorption occurred in eight cases (44.4%). Among them, two experienced symptomatic breakdown of the autologous bone graft that required a second operation to reconstruct the skull contour using porous polyethylene implant (Medpor®). The incidence of bone resorption was more common in the pediatric group and in those with large cranial defects (>120 cm2). No significant correlation was found with sex, reasons for craniectomy, and cryopreservation period. Conclusion The use of autologous bone flap for reconstruction of a skull defect after decompressive craniectomy is a quick and cost-effective method. But, the resorption rate was greater in children and in patients with large skull defects. As a result, we suggest compressive force of the tightened scalp, young age, large skull defect, the gap between bone flap and bone edge and heat sterilization of autologous bone as risk factors for bone resorption. PMID:27169026

Bone marrow stimulation of the medial femoral condyle produces inferior cartilage and bone repair compared to the trochlea in a rabbit surgical model.

PubMed

Chen, Hongmei; Chevrier, Anik; Hoemann, Caroline D; Sun, Jun; Picard, Genevieve; Buschmann, Michael D

2013-11-01

The influence of the location of cartilage lesions on cartilage repair outcome is incompletely understood. This study compared cartilage and bone repair in medial femoral condylar (MFC) versus femoral trochlear (TR) defects 3 months after bone marrow stimulation in mature rabbits. Intact femurs from adult rabbits served as controls. Results from quantitative histomorphometry and histological scoring showed that bone marrow stimulation produced inferior soft tissue repair in MFC versus TR defects, as indicated by significantly lower % Fill (p = 0.03), a significant increase in collagen type I immunostaining (p < 0.00001) and lower O'Driscoll scores (p < 0.05). 3D micro-CT analysis showed that repaired TR defects regained normal un-operated values of bone volume fraction, trabecular thickness, and trabecular number, whereas in MFC defects the repaired bone architecture appeared immature and less dense compared to intact un-operated MFC controls (p < 0.0001). Severe medial meniscal damage was found in 28% of operated animals and was strongly correlated with (i) low cartilage defect fill, (ii) incomplete bone repair in MFC, and (iii) with a more posterior defect placement in the weight-bearing region. We conclude that the location of cartilage lesions influences cartilage repair, with better outcome in TR versus MFC defects in rabbits. Meniscal degeneration is associated with cartilage damage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A clinical evaluation of resorbable hydroxylapatite for the repair of human intra-osseous defects.

PubMed

Corsair, A

1990-01-01

One of the goals of periodontal therapy is actual hard- and soft-tissue regeneration or at least the functional repair of periodontal defects. Alloplastic materials used in the past included dense hydroxylapatite grafts which were non-resorbable and often exfoliated. A new resorbable hydroxylapatite biomaterial [OsteoGen (HA RESORB)] was used during flap surgery. After the usual initial therapy, full-thickness flaps were elevated. A through debridement of the roots and osseous defects was accomplished. The defects were measured and then filled with OsteoGen. The mean initial bone defect depth was 4.47 mm. These defects were re-evaluated by the probing of bone levels after a 4-6-month healing period. A mean of 2.26 mm of new bone fill was obtained. This represents an average fill of 51%. Seventeen of the 22 defects had 42% or more actual new bone fill. No foreign body reaction or exfoliation occurred.

Bone Augmentation in Rabbit Tibia Using Microfixed Cobalt-Chromium Membranes with Whole Blood and Platelet-Rich Plasma.

PubMed

Decco, Oscar A; Beltrán, Víctor; Zuchuat, Jésica I; Cura, Andrea C; Lezcano, María F; Engelke, Wilfried

2015-07-30

Bone augmentation is a subject of intensive investigation in regenerative bone medicine and constitutes a clinical situation in which autogenous bone grafts or synthetic materials are used to aid new bone formation. Based on a non-critical defect, Co-Cr barrier membranes were placed on six adult Fauve de Bourgogne rabbits, divided into two groups: whole blood and PRP. Three densitometric controls were performed during the experiment. The animals were euthanized at 30, 45, 60, and 110 days. The presence of newly formed bone was observed. Samples for histological studies were taken from the augmentation center. External and internal bone tissue augmentation was observed in almost all cases. Significant differences between PRP- and whole blood-stimulated bone augmentation were not observed. At 60 days, bones with PRP presented higher angiogenesis, which may indicate more proliferation and cellular activity. PRP activates the bone regeneration process under optimized conditions by stimulation of osteoblast proliferation after six weeks, when a significant difference in cellular activity was observed. Membranes could stimulate bone augmentation at the site of placement and in the surrounding areas.

The effects of a CO2 laser on the healing of a bone defect.

PubMed

Corsair, A

1997-03-01

This case report illustrates a potentially valuable application of the CO2 laser in periodontal surgery. An intrabony defect was treated with a bone allograft. During the 28-day postsurgical period, epithelialization of the wound was delayed by lasing the soft tissue over the bony defect at weekly intervals for 4 weeks. This procedure resulted in complete regeneration of the bone defect in this case. Controlled studies need to be carried out to determine if the use of the laser to retard epithelial downgrowth has a clinically significant effect on bone regeneration.

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

PubMed

Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

2017-11-01

To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cranioplasty Enhanced by Three-Dimensional Printing: Custom-Made Three-Dimensional-Printed Titanium Implants for Skull Defects.

PubMed

Park, Eun-Kyung; Lim, Jun-Young; Yun, In-Sik; Kim, Ju-Seong; Woo, Su-Heon; Kim, Dong-Seok; Shim, Kyu-Won

2016-06-01

The authors studied to demonstrate the efficacy of custom-made three-dimensional (3D)-printed titanium implants for reconstructing skull defects. From 2013 to 2015, 21 patients (8-62 years old, mean = 28.6-year old; 11 females and 10 males) with skull defects were treated. Total disease duration ranged from 6 to 168 months (mean = 33.6 months). The size of skull defects ranged from 84 × 104 to 154 × 193 mm. Custom-made implants were manufactured by Medyssey Co, Ltd (Jecheon, South Korea) using 3D computed tomography data, Mimics software, and an electron beam melting machine. The team reviewed several different designs and simulated surgery using a 3D skull model. During the operation, the implant was fit to the defect without dead space. Operation times ranged from 85 to 180 minutes (mean = 115.7 minutes). Operative sites healed without any complications except for 1 patient who had red swelling with exudation at the skin defect, which was a skin infection and defect at the center of the scalp flap reoccurring since the initial head injury. This patient underwent reoperation for skin defect revision and replacement of the implant. Twenty-one patients were followed for 6 to 24 months (mean = 14.1 months). The patients were satisfied and had no recurrent wound problems. Head computed tomography after operation showed good fixation of titanium implants and satisfactory skull-shape symmetry. For the reconstruction of skull defects, the use of autologous bone grafts has been the treatment of choice. However, bone use depends on availability, defect size, and donor morbidity. As 3D printing techniques are further advanced, it is becoming possible to manufacture custom-made 3D titanium implants for skull reconstruction.

Restoration of a Critical Mandibular Bone Defect Using Human Alveolar Bone-Derived Stem Cells and Porous Nano-HA/Collagen/PLA Scaffold

PubMed Central

Wang, Xing; Xing, Helin; Zhang, Guilan; Wu, Xia; Zou, Xuan; Feng, Lin; Wang, Dongsheng; Li, Meng; Zhao, Jing; Du, Jianwei; Lv, Yan; E, Lingling; Liu, Hongchen

2016-01-01

Periodontal bone defects occur in a wide variety of clinical situations. Adult stem cell- and biomaterial-based bone tissue regeneration are a promising alternative to natural bone grafts. Recent evidence has demonstrated that two populations of adult bone marrow mesenchymal stromal cells (BMSCs) can be distinguished based on their embryonic origins. These BMSCs are not interchangeable, as bones preferentially heal using cells that share the same embryonic origin. However, the feasibility of tissue engineering using human craniofacial BMSCs was unclear. The goal of this study was to explore human craniofacial BMSC-based therapy for the treatment of localized mandibular defects using a standardized, minimally invasive procedure. The BMSCs' identity was confirmed. Scanning electron microscopy, a cell proliferation assay, and supernatant detection indicated that the nHAC/PLA provided a suitable environment for aBMSCs. Real-time PCR and electrochemiluminescence immunoassays demonstrated that osteogenic markers were upregulated by osteogenic preinduction. Moreover, in a rabbit critical-size mandibular bone defect model, total bone formation in the nHAC/PLA + aBMSCs group was significantly higher than in the nHAC/PLA group but significantly lower than in the nHAC/PLA + preinduced aBMSCs. These findings demonstrate that this engineered bone is a valid alternative for the correction of mandibular bone defects. PMID:27118977

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.

PubMed

Solchaga, Luis A; Temenoff, Johnna S; Gao, Jizong; Mikos, Antonios G; Caplan, Arnold I; Goldberg, Victor M

2005-04-01

The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Influence of hydroxyapatite granule size, porosity, and crystallinity on tissue reaction in vivo. Part A: synthesis, characterization of the materials, and SEM analysis.

PubMed

Maté Sánchez de Val, José E; Calvo-Guirado, José L; Gómez-Moreno, Gerardo; Pérez-Albacete Martínez, Carlos; Mazón, Patricia; De Aza, Piedad N

2016-11-01

The aim of this study was the synthesis and analysis of the tissue reaction to three different Hydroxyapatite (HA)-based bone substitute materials differing only in granule size, porosity, and crystallinity through an animal experimental model at 60 days. Three different HA-based biomaterials were synthesized and characterized by X-ray diffraction, SEM, and EDS analysis, the resultant product was ground in three particle sizes: Group I (2000-4000 μm), Group II (1000-2000 μm), and Group III (600-1000 μm). Critical size defects were created in both tibias of 15 rabbits. Four defects per rabbit for a total of 60 defects were grafted with the synthesized materials as follows: Group I (15 defects), Group II (15 defects), Group III (15 defects), and empty (15 defects control). After animals sacrifice at 60 days samples were obtained and processed for SEM and EDS evaluation of Ca/P ratios, elemental mapping was performed to determine the chemical degradation process and changes to medullary composition in all the four study groups. The tendency for the density was to increase with the increasing annealing temperature; in this way it was possible to observe that the sample that shows highest crystallinity and crystal size corresponding to that of group I. The SEM morphological examination showed that group III implant showed numerous resorption regions, group II implant presented an average resorption rate of all the implants. The group I displayed smoother surface features, in comparison with the other two implants. The data from this study show that changing the size, porosity, and crystallinity of one HA-based bone substitute material can influence the integration of the biomaterials within the implantation site and the new bone formation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modified classification and single-stage microsurgical repair of posttraumatic infected massive bone defects in lower extremities.

PubMed

Yang, Yun-fa; Xu, Zhong-he; Zhang, Guang-ming; Wang, Jian-wei; Hu, Si-wang; Hou, Zhi-qi; Xu, Da-chuan

2013-11-01

Posttraumatic infected massive bone defects in lower extremities are difficult to repair because they frequently exhibit massive bone and/or soft tissue defects, serious bone infection, and excessive scar proliferation. This study aimed to determine whether these defects could be classified and repaired at a single stage. A total of 51 cases of posttraumatic infected massive bone defect in lower extremity were included in this study. They were classified into four types on the basis of the conditions of the bone defects, soft tissue defects, and injured limb length, including Type A (without soft tissue defects), Type B (with soft tissue defects of 10 × 20 cm or less), Type C (with soft tissue defects of 10 × 20 cm or more), and Type D (with the limb shortening of 3 cm or more). Four types of single-stage microsurgical repair protocols were planned accordingly and implemented respectively. These protocols included the following: Protocol A, where vascularized fibular graft was implemented for Type A; Protocol B, where vascularized fibular osteoseptocutaneous graft was implemented for Type B; Protocol C, where vascularized fibular graft and anterior lateral thigh flap were used for Type C; and Protocol D, where limb lengthening and Protocols A, B, or C were used for Type D. There were 12, 33, 4, and 2 cases of Types A, B, C, and D, respectively, according to this classification. During the surgery, three cases of planned Protocol B had to be shifted into Protocol C; however, all microsurgical repairs were completed. With reference to Johner-Wruhs evaluation method, the total percentage of excellent and good results was 82.35% after 6 to 41 months of follow-up. It was concluded that posttraumatic massive bone defects could be accurately classified into four types on the basis of the conditions of bone defects, soft tissue coverage, and injured limb length, and successfully repaired with the single-stage repair protocols after thorough debridement. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Radiological Assessment of Bioengineered Bone in a Muscle Flap for the Reconstruction of Critical-Size Mandibular Defect

PubMed Central

Al-Fotawei, Randa; Ayoub, Ashraf F.; Heath, Neil; Naudi, Kurt B.; Tanner, K. Elizabeth; Dalby, Matthew J.; McMahon, Jeremy

2014-01-01

This study presents a comprehensive radiographic evaluation of bone regeneration within a pedicled muscle flap for the reconstruction of critical size mandibular defect. The surgical defect (20 mm×15 mm) was created in the mandible of ten experimental rabbits. The masseter muscle was adapted to fill the surgical defect, a combination of calcium sulphate/hydroxyapatite cement (CERAMENT™ |SPINE SUPPORT), BMP-7 and rabbit mesenchymal stromal cells (rMSCs) was injected inside the muscle tissue. Radiographic assessment was carried out on the day of surgery and at 4, 8, and 12 weeks postoperatively. At 12 weeks, the animals were sacrificed and cone beam computerized tomography (CBCT) scanning and micro-computed tomography (µ-CT) were carried out. Clinically, a clear layer of bone tissue was identified closely adherent to the border of the surgical defect. Sporadic radio-opaque areas within the surgical defect were detected radiographically. In comparison with the opposite non operated control side, the estimated quantitative scoring of the radio-opacity was 46.6% ±15, the mean volume of the radio-opaque areas was 63.4% ±20. Areas of a bone density higher than that of the mandibular bone (+35% ±25%) were detected at the borders of the surgical defect. The micro-CT analysis revealed thinner trabeculae of the regenerated bone with a more condensed trabecular pattern than the surrounding native bone. These findings suggest a rapid deposition rate of the mineralised tissue and an active remodelling process of the newly regenerated bone within the muscle flap. The novel surgical model of this study has potential clinical application; the assessment of bone regeneration using the presented radiolographic protocol is descriptive and comprehensive. The findings of this research confirm the remarkable potential of local muscle flaps as local bioreactors to induce bone formation for reconstruction of maxillofacial bony defects. PMID:25226170

Evaluating the oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol in periodontal regeneration using periodontal ligament stem cells and alveolar bone healing models.

PubMed

Lee, Jin-Sun; Kim, EunJi; Han, Seonggu; Kang, Kyung Lhi; Heo, Jung Sun

2017-12-06

Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect. To evaluate the effects of the combined oxysterols on PDLSC biology, we studied the SS-induced osteogenic differentiation of PDLSCs by assessing alkaline phosphatase activity, intracellular calcium levels [Ca 2+ ] i , matrix mineralization, and osteogenic marker mRNA expression and protein levels. To verify the effect of oxysterols on alveolar bone regeneration, we employed tooth extraction bone defect models. Oxysterols increased the osteogenic activity of PDLSCs compared with the control group. The expression of liver X receptor (LXR) α and β, the nuclear receptors for oxysterols, and their target gene, ATP-binding cassette transporter A1 (ABCA1), increased significantly during osteogenesis. Oxysterols also increased protein levels of the hedgehog (Hh) receptor Smo and the transcription factor Gli1. We further confirmed the reciprocal reaction between the LXRs and Hh signaling. Transfection of both LXRα and LXRβ siRNAs decreased Smo and Gli1 protein levels. In contrast, the inhibition of Hh signaling attenuated the LXRα and LXRβ protein levels. Subsequently, SS-induced osteogenic activity of PDLSCs was suppressed by the inhibition of LXRs or Hh signaling. The application of SS also enhanced bone formation in the defect sites of in-vivo models, showing equivalent efficacy to recombinant human bone morphogenetic protein-2. These findings suggest that a specific combination of oxysterols promoted periodontal regeneration by regulating PDLSC activity and alveolar bone regeneration.

Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects

PubMed Central

Lu, Haiping; Liu, Yi; Guo, Jing; Wu, Huiling; Wang, Jingxiao; Wu, Gang

2016-01-01

The repair of infected bone defects is still challenging in the fields of orthopedics, oral implantology and maxillofacial surgery. In these cases, the self-healing capacity of bone tissue can be significantly compromised by the large size of bone defects and the potential/active bacterial activity. Infected bone defects are conventionally treated by a systemic/local administration of antibiotics to control infection and a subsequent implantation of bone grafts, such as autografts and allografts. However, these treatment options are time-consuming and usually yield less optimal efficacy. To approach these problems, novel biomaterials with both antibacterial and osteoinductive properties have been developed. The antibacterial property can be conferred by antibiotics and other novel antibacterial biomaterials, such as silver nanoparticles. Bone morphogenetic proteins are used to functionalize the biomaterials with a potent osteoinductive property. By manipulating the carrying modes and release kinetics, these biomaterials are optimized to maximize their antibacterial and osteoinductive functions with minimized cytotoxicity. The findings, in the past decade, have shown a very promising application potential of the novel biomaterials with the dual functions in treating infected bone defects. In this review, we will summarize the current knowledge of novel biomaterials with both antibacterial and osteoinductive properties. PMID:26950123

Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects.

PubMed

Lu, Haiping; Liu, Yi; Guo, Jing; Wu, Huiling; Wang, Jingxiao; Wu, Gang

2016-03-03

The repair of infected bone defects is still challenging in the fields of orthopedics, oral implantology and maxillofacial surgery. In these cases, the self-healing capacity of bone tissue can be significantly compromised by the large size of bone defects and the potential/active bacterial activity. Infected bone defects are conventionally treated by a systemic/local administration of antibiotics to control infection and a subsequent implantation of bone grafts, such as autografts and allografts. However, these treatment options are time-consuming and usually yield less optimal efficacy. To approach these problems, novel biomaterials with both antibacterial and osteoinductive properties have been developed. The antibacterial property can be conferred by antibiotics and other novel antibacterial biomaterials, such as silver nanoparticles. Bone morphogenetic proteins are used to functionalize the biomaterials with a potent osteoinductive property. By manipulating the carrying modes and release kinetics, these biomaterials are optimized to maximize their antibacterial and osteoinductive functions with minimized cytotoxicity. The findings, in the past decade, have shown a very promising application potential of the novel biomaterials with the dual functions in treating infected bone defects. In this review, we will summarize the current knowledge of novel biomaterials with both antibacterial and osteoinductive properties.

Application of modern computer-aided technologies in the production of individual bone graft: A case report.

PubMed

Mirković, Sinisa; Budak, Igor; Puskar, Tatjana; Tadić, Ana; Sokac, Mario; Santosi, Zeljko; Djurdjević-Mirković, Tatjana

2015-12-01

An autologous bone (bone derived from the patient himself) is considered to be a "golden standard" in the treatment of bone defects and partial atrophic alveolar ridge. However, large defects and bone losses are difficult to restore in this manner, because extraction of large amounts of autologous tissue can cause donor-site problems. Alternatively, data from computed tomographic (CT) scan can be used to shape a precise 3D homologous bone block using a computer-aided design-computer-aided manufacturing (CAD-CAM) system. A 63-year old male patient referred to the Clinic of Dentistry of Vojvodina in Novi Sad, because of teeth loss in the right lateral region of the lower jaw. Clinical examination revealed a pronounced resorption of the residual ridge of the lower jaw in the aforementioned region, both horizontal and vertical. After clinical examination, the patient was referred for 3D cone beam (CB)CT scan that enables visualization of bony structures and accurate measurement of dimensions of the residual alveolar ridge. Considering the large extent of bone resorption, the required ridge augmentation was more than 3 mm in height and 2 mm in width along the length of some 2 cm, thus the use of granular material was excluded. After consulting prosthodontists and engineers from the Faculty of Technical Sciences in Novi Sad we decided to fabricate an individual (custom) bovine-derived bone graft designed according to the obtained-3D CBCT scan. Application of 3D CBCT images, computer-aided systems and software in manufacturing custom bone grafts represents the most recent method of guided bone regeneration. This method substantially reduces time of recovery and carries minimum risk of postoperative complications, yet the results fully satisfy the requirements of both the patient and the therapist.

BMP-7 Preserves Surface Integrity of Degradable-ceramic Cranioplasty in a Göttingen Minipig Model

PubMed Central

Schulz, Peter; Klünter, Tim; Deisinger, Ulrike; Diez, Claudius; Waiss, Waltraud; Kirschneck, Christian; Reichert, Torsten E.; Detsch, Rainer

2017-01-01

Background: The aim of the study was to evaluate the integrity of a craniotomy grafted site in a minipig model using different highly porous calcium phosphate ceramic scaffolds either loaded or nonloaded with bone morphogenetic protein-7 (BMP-7). Methods: Four craniotomies with a diameter of 15 mm (critical-size defect) were grafted with different highly porous (92–94 vol%) calcium phosphate ceramics [hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP; a mixture of HA and TCP)] in 10 Göttingen minipigs: (a) group I (n = 5): HA versus BCP; (b) group II (n = 5): TCP versus BCP. One scaffold of each composition was supplied with 250 μg of BMP-7. In vivo computed tomography scan and fluorochrome bone labeling were performed. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, and Giemsa staining histology. Results: BMP-7 significantly enhanced bone formation in TCP (P = 0.047). Slightly enhanced bone formation was observed in BCP (P = 0.059) but not in HA implants. BMP-7 enhanced ceramic degradation in TCP (P = 0.05) and BCP (P = 0.05) implants but not in HA implants. Surface integrity of grafted site was observed in all BMP-7-loaded implants after successful creeping substitution by the newly formed bone. In 9 of 10 HA implants without BMP-7, partial collapse of the implant site was observed. All TCP implants without BMP-7 collapsed. Fluorescent labeling showed bone formation at week 1 in BMP-7-stimulated implants. Conclusions: BMP-7 supports bone formation, ceramic degradation, implant integration, and surface integrity of the grafted site. PMID:28458969

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Huiwu; Health and Science Center, SIBS CAS and SSMU, 225 South Chongqing Road, Shanghai 200025; Dai Kerong

2007-05-18

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a {beta}-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified bymore » BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals.« less

Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect.

PubMed

Fujishiro, Takaaki; Bauer, Thomas W; Kobayashi, Naomi; Kobayashi, Hideo; Sunwoo, Moon Hae; Seim, Howard B; Turner, A Simon

2007-09-01

Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

PubMed

Janner, Simone F M; Bosshardt, Dieter D; Cochran, David L; Chappuis, Vivianne; Huynh-Ba, Guy; Jones, Archie A; Buser, Daniel

2017-11-01

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5 weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM + membrane (group D + M), autogenous bone chips + DBBM + membrane (group A + D + M), DBBM alone (group D) or autogenous bone chips + DBBM (group A + D). Four animals were sacrificed after 3 weeks of healing and four animals after 12 weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P < 0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12 weeks of healing (P < 0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P < 0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transformation of a vascularised iliac crest or scapula bone to a pedicled osteomuscular transplant for reconstruction of distant defects in the head and neck region: a new method of transforming two island flaps to one longer island flap.

PubMed

Kärcher, Hans; Feichtinger, Matthias

2014-12-01

Bone defects in the maxillofacial region after ablative surgery require reconstructive surgery, usually using microvascular free flaps. This paper presents a new method of reconstructing extensive defects in patients not suitable for microvascular surgery using prefabrication of a vascularised osteomuscular flap from the scapula or iliac crest bone. Three patients who were treated with this new technique are presented. Two patients (one mandibular defect and one defect in the maxillary region) received prefabricated osteomuscular flaps from the iliac crest bone using the latissimus dorsi muscle as a pedicle. One patient also presenting a mandibular defect after tumour surgery received a scapula transplant for reconstruction of the defect using the pectoralis major muscle as pedicle. In all three cases vital bone could be transplanted. The pedicle was strainless in all three cases. Minor bone loss could be seen initially only in one case. The results are stable now and one patient received dental implants for later prosthetic treatment. The presented two-step surgery provides an excellent method for reconstruction of bony defects in the maxillofacial region in patients where microvascular surgery is not possible due to reduced state of health or lack of recipient vessels. Copyright © 2010. Published by Elsevier Ltd.

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis.

PubMed

Harms, Christoph; Helms, Kai; Taschner, Tibor; Stratos, Ioannis; Ignatius, Anita; Gerber, Thomas; Lenz, Solvig; Rammelt, Stefan; Vollmar, Brigitte; Mittlmeier, Thomas

2012-01-01

The synthetic material Nanobone(®) (hydroxyapatite nanocrystallines embedded in a porous silica gel matrix) was examined in vivo using a standardized bone defect model in the ovine tibial metaphysis. A standardized 6 × 12 × 24-mm bone defect was created below the articular surface of the medial tibia condyles on both hind legs of 18 adult sheep. The defect on the right side was filled with Nanobone(®), while the defect on the contralateral side was left empty. The tibial heads of six sheep were analyzed after 6, 12, and 26 weeks each. The histological and radiological analysis of the defect on the control side did not reveal any bone formation after the total of 26 weeks. In contrast, the microcomputed tomography analysis of the defect filled with Nanobone(®) showed a 55%, 72%, and 74% volume fraction of structures with bone density after 6, 12, and 26 weeks, respectively. Quantitative histomorphological analysis after 6, and 12 weeks revealed an osteoneogenesis of 22%, and 36%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity. Nanobone(®) appears to be a highly potent bone substitute material with osteoconductive properties in a loaded large animal defect model, supporting the potential use of Nanobone(®) also in humans.

Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

PubMed Central

Harms, Christoph; Helms, Kai; Taschner, Tibor; Stratos, Ioannis; Ignatius, Anita; Gerber, Thomas; Lenz, Solvig; Rammelt, Stefan; Vollmar, Brigitte; Mittlmeier, Thomas

2012-01-01

The synthetic material Nanobone® (hydroxyapatite nanocrystallines embedded in a porous silica gel matrix) was examined in vivo using a standardized bone defect model in the ovine tibial metaphysis. A standardized 6 × 12 × 24-mm bone defect was created below the articular surface of the medial tibia condyles on both hind legs of 18 adult sheep. The defect on the right side was filled with Nanobone®, while the defect on the contralateral side was left empty. The tibial heads of six sheep were analyzed after 6, 12, and 26 weeks each. The histological and radiological analysis of the defect on the control side did not reveal any bone formation after the total of 26 weeks. In contrast, the microcomputed tomography analysis of the defect filled with Nanobone® showed a 55%, 72%, and 74% volume fraction of structures with bone density after 6, 12, and 26 weeks, respectively. Quantitative histomorphological analysis after 6, and 12 weeks revealed an osteoneogenesis of 22%, and 36%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity. Nanobone® appears to be a highly potent bone substitute material with osteoconductive properties in a loaded large animal defect model, supporting the potential use of Nanobone® also in humans. PMID:22745551

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies.

PubMed

Reichert, Johannes C; Epari, Devakara R; Wullschleger, Martin E; Saifzadeh, Siamak; Steck, Roland; Lienau, Jasmin; Sommerville, Scott; Dickinson, Ian C; Schütz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

2010-02-01

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties; however, they are limited in access and availability and associated with donor-site morbidity, hemorrhage, risk of infection, insufficient transplant integration, graft devitalization, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench-to-bedside translations are still infrequent as the process toward approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence, commercialization, is referred to as the "Valley of Death" and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes and scalable designs and to apply these in preclinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopedic bone engineering from bench to bedside by establishing a preclinical ovine critical-sized tibial segmental bone defect model, and we discuss our preliminary data relating to this decisive step.

In vivo bone regeneration with injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Huang, Zhi; Chen, Yan; Feng, Qing-Ling; Zhao, Wei; Yu, Bo; Tian, Jing; Li, Song-Jian; Lin, Bo-Miao

2011-09-01

For reconstruction of irregular bone defects, injectable biomaterials are more appropriate than the preformed biomaterials. We herein develop a biomimetic in situ-forming composite consisting of chitosan (CS) and mineralized collagen fibrils (nHAC), which has a complex hierarchical structure similar to natural bone. The CS/nHAC composites with or without mesenchymal stem cells (MSCs) are injected into cancellous bone defects at the distal end of rabbit femurs. Defects are assessed by radiographic, histological diagnosis and Raman microscopy until 12 weeks. The results show that MSCs improve the biocompatibility of CS/nHAC composites and enhance new bone formation in vivo at 12 weeks. It can be concluded that the injectable CS/nHAC composites combined with MSCs may be a novel method for reconstruction of irregular bone defects.

Repair of massively defected hemi-joints using demineralized osteoarticular allografts with protected cartilage.

PubMed

Li, Siming; Yang, Xiaohong; Tang, Shenghui; Zhang, Xunmeng; Feng, Zhencheng; Cui, Shuliang

2015-08-01

Surgical replacement of massively defected joints necessarily relies on osteochondral grafts effective to both of bone and cartilage. Demineralized bone matrix (DBM) retains the osteoconductivity but destroys viable chondrocytes in the cartilage portion essential for successful restoration of defected joints. This study prepared osteochondral grafts of DBM with protected cartilage. Protected cartilage portions was characterized by cellular and molecular biology and the grafts were allogenically used for grafting. Protected cartilage showed similar histomorphological structure and protected proteins estimated by total proteins and cartilage specific proteins as in those of fresh controls when DBMs were generated in bone portions. Such grafts were successfully used for simultaneously repair of bone and cartilage in massively defected osteoarticular joints within 16 weeks post-surgery. These results present an allograft with clinical potential for simultaneous restoration of bone and cartilage in defected joints.

Bone regenerative medicine: classic options, novel strategies, and future directions

PubMed Central

2014-01-01

This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future. PMID:24628910

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

PubMed Central

Fernandes, Gabriela; Yang, Shuying

2016-01-01

Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors (GFs), it makes stem cells the ideal agents for bone regeneration. Furthermore, platelet-rich plasma (PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future. PMID:28018706

Reconstruction Of Glenoid Bone Deficiency With Porous Titanium Nickelide In Recurrent Anterior Shoulder Instability.

PubMed

Prokhorenko, Valery M; Fomenko, Sergey M; Filipenko, Pavel V; Turkov, Petr S

2015-01-01

One of the main causes of recurrent shoulder instability is a bone defect of the front edge of the glenoid. The available techniques for reconstruction of this bone defect, however, have some disadvantages. The aim of this study was to develop a new method that can reduce the number of postoperative complications and improve the efficiency of surgical treatment of recurrent anterior shoulder instability with glenoid bone defect. We present here a new method for surgical treatment of post-traumatic recurrent anterior shoulder instability with bony defects using porous NiTi. We operated 5 patients using this method. Computed tomography was used in the preoperative preparation of the NiTi graft. The graft was sawed from a cylindrical billet about 1 cm in thickness. Two screw holes were then made with a drill. The prepared graft was subsequently installed in the area of the glenoid bone defect. There were no recurrences of the dislocation after the surgical treatment. All patients returned to their previous levels of physical activity. The proposed method is an alternative to Latarjet procedure and iliac crest bone grafting. The advantages of this method are accurate reconstruction of the bone defect, minimal risk of recurrences, no resorption, and reduction of procedure time.

The Role of Three-Dimensional Scaffolds in Treating Long Bone Defects: Evidence from Preclinical and Clinical Literature-A Systematic Review.

PubMed

Roffi, Alice; Krishnakumar, Gopal Shankar; Gostynska, Natalia; Kon, Elizaveta; Candrian, Christian; Filardo, Giuseppe

2017-01-01

Long bone defects represent a clinical challenge. Bone tissue engineering (BTE) has been developed to overcome problems associated with conventional methods. The aim of this study was to assess the BTE strategies available in preclinical and clinical settings and the current evidence supporting this approach. A systematic literature screening was performed on PubMed database, searching for both preclinical (only on large animals) and clinical studies. The following string was used: "(Scaffold OR Implant) AND (Long bone defect OR segmental bone defect OR large bone defect OR bone loss defect)." The search retrieved a total of 1573 articles: 51 preclinical and 4 clinical studies were included. The great amount of preclinical papers published over the past few years showed promising findings in terms of radiological and histological evidence. Unfortunately, this in vivo situation is not reflected by a corresponding clinical impact, with few published papers, highly heterogeneous and with small patient populations. Several aspects should be further investigated to translate positive preclinical findings into clinical protocols: the identification of the best biomaterial, with both biological and biomechanical suitable properties, and the selection of the best choice between cells, GFs, or their combination through standardized models to be validated by randomized trials.

Influence of External Beam Radiotherapy on the Properties of Polymethyl Methacrylate-Versus Silicone-Induced Membranes in a Bilateral Segmental Bone Defect in Rats.

PubMed

Sagardoy, Thomas; Ehret, Camille; Bareille, Reine; Benoit, Jérôme; Amedee, Joëlle; De Mones, Erwan

2018-05-01

Standard care for malignant tumors arising next to a bone structure is surgical removal with safety margins, followed by external beam radiotherapy (EBRT). Complete tumor removal can result in large bone defects. A two-step bone reconstruction technique using the induced membrane (IM) technique has proven its efficacy to bridge gap nonunion. During the first step, a spacer is placed in the bone gap. The spacer then is removed and the IM around it is filled with autologous cancellous bone graft. However, the feasibility of this technique with the addition of adjuvant EBRT between the two reconstruction steps has not yet been studied. Polymethyl methacrylate (PMMA) used to be the standard spacer material for the first step. Silicone spacers could replace them owing to their good behavior when submitted to EBRT and their easier removal from the surgical site during the second step. The aim of this study was to evaluate the influence of EBRT on the histological and biochemical properties of IM induced using PMMA or silicone as spacer. The analyses were performed on PMMA- or silicone-IM with and without EBRT in a 6-mm bilateral femoral defect in 32 rats. Thickness and vessel content were measured in both groups. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) content in lysates of the crushed membranes were measured by enzyme immunoassay. Finally, alkaline phosphatase activity was analyzed in human bone marrow stromal cell cultures in contact with the same lysates. EBRT did not change the histological structure of the cellular internal layer or the fibrous outer layer. The nature of the spacer only influenced IM thickness, PMMA-IM with external radiotherapy being significantly thicker. EBRT decreased the vascular density of IM but was less effective on VEGF/BMP2 production. In vitro, IM could have an osteoinductive potential on human bone marrow stem cells. EBRT did not modify the histological properties of IMs but decreased their vascular density. VEGF and BMP2 production within IMs was not affected by EBRT. Silicone spacers are able to induce membranes with similar histological characteristics to PMMA-IM.

Alterations of collagen matrix in weight-bearing bones during skeletal unloading

NASA Technical Reports Server (NTRS)

Shiiba, M.; Arnaud, S. B.; Tanzawa, H.; Uzawa, K.; Yamauchi, M.

2001-01-01

Skeletal unloading induces loss of bone mineral density in weight-bearing bones. The objectives of this study were to characterize the post-translational modifications of collagen of weight-bearing bones subjected to hindlimb unloading for 8 weeks. In unloaded bones, tibiae and femurs, while the overall amino acid composition was essentially identical in the unloaded and control tibiae and femurs, the collagen cross-link profile showed significant differences. Two major reducible cross-links (analyzed as dihydroxylysinonorleucine and hydroxylysinonorleucine) were increased in the unloaded bones. In addition, the ratios of the former to the latter as well as pyridinoline to deoxypyridinoline were significantly decreased in the unloaded bones indicating a difference in the extent of lysine hydroxylation at the cross-linking sites between these two groups. These results indicate that upon skeletal unloading the relative pool of newly synthesized collagen is increased and it is post-translationally altered. The alteration could be associated with impaired osteoblastic differentiation induced by skeletal unloading that results in a mineralization defect.

3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

PubMed

Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

2016-12-01

Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model

PubMed Central

Xie, Yilin; Su, Yingying; Tang, Jianxia; Goh, Bee Tin; Saigo, Leonardo; Zhang, Chunmei; Wang, Jinsong; Khojasteh, Arash; Wang, Songlin

2017-01-01

Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair. PMID:28401163

Immediate implant placement into posterior sockets with or without buccal bone dehiscence defects: A retrospective cohort study.

PubMed

Hu, Chen; Gong, Ting; Lin, Weimin; Yuan, Quan; Man, Yi

2017-10-01

To evaluate bone reconstruction and soft tissue reactions at immediate implants placed into intact sockets and those with buccal bone dehiscence defects. Fifty-nine internal connection implants from four different manufacturers were immediately placed in intact sockets(non-dehiscence group, n=40), and in alveoli with buccal bone dehiscence defects: 1) Group 1(n= N10), the defect depth measured 3-5 mm from the gingival margin. 2) Group 2(n=9), the depth ranged from 5mm to 7mm. The surrounding bony voids were grafted with deproteinized bovine bone mineral (DBBM) particles. Cone beam computed tomography(CBCT) was performed immediately after surgery (T1), and at 6 months later(T2). Radiographs were taken at prosthesis placement and one year postloading(T3). Soft tissue parameters were measured at baseline (T0), prosthesis placement and T3. No implants were lost during the observation period. For the dehiscence groups, the buccal bone plates were radiographically reconstructed to comparable horizontal and vertical bone volumes compared with the non-dehiscence group. Marginal bone loss occurred between the time of final restoration and 1-year postloading was not statistically different(P=0.732) between groups. Soft tissue parameters did not reveal inferior results for the dehiscence groups. Within the limitations of this study, flapless implant placement into compromised sockets in combination with DBBM grafting may be a viable technique to reconstitute the defected buccal bone plates due to space maintenance and primary socket closure provided by healing abutments and bone grafts. Immediate implants and DBBM grafting without using membranes may be indicated for sockets with buccal bone defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo experimental study on bone regeneration in critical bone defects using PIB nanogels/boron-containing mesoporous bioactive glass composite scaffold

PubMed Central

Chen, Xiaohui; Zhao, Yanbing; Geng, Shinan; Miron, Richard J; Zhang, Qiao; Wu, Chengtie; Zhang, Yufeng

2015-01-01

Purpose In the present study, the fabrication of novel p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogels was combined with boron-containing mesoporous bioactive glass (B-MBG) scaffolds in order to improve the mechanical properties of PIB nanogels alone. Scaffolds were tested for mechanical strength and the ability to promote new bone formation in vivo. Patients and methods To evaluate the potential of each scaffold in bone regeneration, ovariectomized rats were chosen as a study model to determine the ability of PIB nanogels to stimulate bone formation in a complicated anatomical bone defect. PIB nanogels and PIB nanogels/B-MBG composites were respectively implanted into ovariectomized rats with critical-sized femur defects following treatment periods of 2, 4, and 8 weeks post-implantation. Results Results from the present study demonstrate that PIB nanogels/B-MBG composites showed greater improvement in mechanical strength when compared to PIB nanogels alone. In vivo, hematoxylin and eosin staining revealed significantly more newly formed bone in defects containing PIB nanogels/B-MBG composite scaffolds when compared to PIB nanogels alone. Tartrate-resistant acid phosphatase-positive staining demonstrated that both scaffolds were degraded over time and bone remodeling occurred in the surrounding bone defect as early as 4 weeks post-implantation. Conclusion The results from the present study indicate that PIB nanogels are a potential bone tissue engineering biomaterial able to treat defects of irregular shapes and deformities as an injectable, thermoresponsive, biocompatible hydrogel which undergoes rapid thermal gelation once body temperature is reached. Furthermore, its combination with B-MBG scaffolds improves the mechanical properties and ability to promote new bone formation when compared to PIB nanogels alone. PMID:25653525

In vivo experimental study on bone regeneration in critical bone defects using PIB nanogels/boron-containing mesoporous bioactive glass composite scaffold.

PubMed

Chen, Xiaohui; Zhao, Yanbing; Geng, Shinan; Miron, Richard J; Zhang, Qiao; Wu, Chengtie; Zhang, Yufeng

2015-01-01

In the present study, the fabrication of novel p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogels was combined with boron-containing mesoporous bioactive glass (B-MBG) scaffolds in order to improve the mechanical properties of PIB nanogels alone. Scaffolds were tested for mechanical strength and the ability to promote new bone formation in vivo. To evaluate the potential of each scaffold in bone regeneration, ovariectomized rats were chosen as a study model to determine the ability of PIB nanogels to stimulate bone formation in a complicated anatomical bone defect. PIB nanogels and PIB nanogels/B-MBG composites were respectively implanted into ovariectomized rats with critical-sized femur defects following treatment periods of 2, 4, and 8 weeks post-implantation. Results from the present study demonstrate that PIB nanogels/B-MBG composites showed greater improvement in mechanical strength when compared to PIB nanogels alone. In vivo, hematoxylin and eosin staining revealed significantly more newly formed bone in defects containing PIB nanogels/B-MBG composite scaffolds when compared to PIB nanogels alone. Tartrate-resistant acid phosphatase-positive staining demonstrated that both scaffolds were degraded over time and bone remodeling occurred in the surrounding bone defect as early as 4 weeks post-implantation. The results from the present study indicate that PIB nanogels are a potential bone tissue engineering biomaterial able to treat defects of irregular shapes and deformities as an injectable, thermoresponsive, biocompatible hydrogel which undergoes rapid thermal gelation once body temperature is reached. Furthermore, its combination with B-MBG scaffolds improves the mechanical properties and ability to promote new bone formation when compared to PIB nanogels alone.

Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model

PubMed Central

Cheng, Ning; Dai, Jing; Cheng, Xiangrong; Li, Shu’e; Miron, Richard J.; Wu, Tao; Chen, Wenli; Zhang, Yufeng

2018-01-01

The most common complication for patients with postmenopausal osteoporosis is bone-related defects and fractures. While routine medication has a high probability of undesirable side effects, new approaches have aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss. Recently, we have synthesized a new hybrid CaP/silk scaffold with a CaP-phase distribution and pore architecture better suited to facilitate cell differentiation and bone formation. The aim of the present study was to compare the involved remodeling process and therapeutic effect of porous CaP/silk composite scaffolds upon local implantation into osteoporotic defects. Wistar rats were used to induce postmenopausal osteoporotic model by bilateral ovariectomy. The pure silk and hybrid CaP/silk scaffolds were implanted into critical sized defects created in distal femoral epiphysis. After 14 and 28 days, the in vivo osteogenetic efficiency was evaluated by μCT analysis, hematoxylin and eosin staining, Safranin O staining, tartrate-resistant acid phosphatase staining, and immunohistochemical assessment. Animals with or without critical-sized defects were used as drill or blank controls, respectively. The osteoporotic defect model was well established with significantly decreased μCT parameters of BV/TV, Tb.N and increased Tb.Sp, porosity, combined with changes in histological observations. During the healing process, the critical-sized drill control defects failed to regenerate appreciable bone tissue, while more significantly increased bone formation and mineralization with dynamic scaffold degradation and decreased osteoclastic bone resorption could be detected within defects with hybrid CaP/silk scaffolds compared to pure silk scaffolds. PMID:23674058

Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model.

PubMed

Cheng, Ning; Dai, Jing; Cheng, Xiangrong; Li, Shu'e; Miron, Richard J; Wu, Tao; Chen, Wenli; Zhang, Yufeng; Shi, Bin

2013-08-01

The most common complication for patients with postmenopausal osteoporosis is bone-related defects and fractures. While routine medication has a high probability of undesirable side effects, new approaches have aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss. Recently, we have synthesized a new hybrid CaP/silk scaffold with a CaP-phase distribution and pore architecture better suited to facilitate cell differentiation and bone formation. The aim of the present study was to compare the involved remodeling process and therapeutic effect of porous CaP/silk composite scaffolds upon local implantation into osteoporotic defects. Wistar rats were used to induce postmenopausal osteoporotic model by bilateral ovariectomy. The pure silk and hybrid CaP/silk scaffolds were implanted into critical sized defects created in distal femoral epiphysis. After 14 and 28 days, the in vivo osteogenetic efficiency was evaluated by μCT analysis, hematoxylin and eosin staining, Safranin O staining, tartrate-resistant acid phosphatase staining, and immunohistochemical assessment. Animals with or without critical-sized defects were used as drill or blank controls, respectively. The osteoporotic defect model was well established with significantly decreased μCT parameters of BV/TV, Tb.N and increased Tb.Sp, porosity, combined with changes in histological observations. During the healing process, the critical-sized drill control defects failed to regenerate appreciable bone tissue, while more significantly increased bone formation and mineralization with dynamic scaffold degradation and decreased osteoclastic bone resorption could be detected within defects with hybrid CaP/silk scaffolds compared to pure silk scaffolds.

USE OF BIOCERAMICS IN FILLING BONE DEFECTS

PubMed Central

Garrido, Carlos Antõnio; Sampaio, Tania Clarete Fonseca Vieira Sales

2015-01-01

Objective: To present the results from using biological ceramics for filling bone defects resulting from post-traumatic or orthopedic injuries. Methods: Thirty-six patients with bone defects caused by trauma or orthopedic injury were evaluated. Nineteen patients were male (52.8%) and 17 were female (47.2%). Their ages ranged from 19 to 84 years, with a mean of 45.7 years and median of 37 years. Only patients with defects that required at least five grams of biological ceramic were included. Eighteen cases were classified as orthopedic: bone defects were observed in 11 cases of total hip arthroplasty; one case of primary total hip arthroplasty, due to coxarthrosis; five cases of femoral or tibial open wedge osteotomy; and one case of tarsal arthrodesis. There were 18 cases of trauma-related defects; uninfected pseudarthrosis, eight cases; recent fractures of the tibial plateau with compression of the spongy bone, three cases; and exposed fractures treated with external fixators, seven cases. The surgical technique consisted of curetting and debriding the injury until bone suitable for grafting was found. Biological ceramic was then used to fill the defect and some kind of fixation was applied. Results: Among the 36 patients evaluated, it was seen that 35 (97.2%) presented integration of the biological ceramic, while one case of open fracture treated with external fixation had poor integration of the biological ceramic. Conclusion: Treatment of bone defects of orthopedic or post-traumatic etiology using a phosphocalcium ceramic composed of hydroxyapatite was shown to be a practical, effective and safe method. PMID:27022576

Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and Biomechanical Assessment.

PubMed

Ramalingam, Sundar; Basudan, Amani; Babay, Nadir; Al-Rasheed, Abdulaziz; Nooh, Nasser; Nagshbandi, Jafar; Aldahmash, Abdullah; Atteya, Muhammad; Al-Hezaimi, Khalid

2016-01-01

Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft [MG], Geistlich) has not yet been reported. The aim of this histologic and biomechanical study was to compare the efficacy of MG versus resorbable collagen membranes (RCMs) in facilitating GBR around standardized rat calvarial defects. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm-diameter standardized calvarial defect was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) MG group: the defect was covered with MG; (2) RCM group: the defect was covered with an RCM; (3) MG + bone group: the defect was filled with bone graft particles and covered by MG; and (4) RCM + bone group: the defect was filled with bone graft particles and covered by an RCM. Primary closure was achieved using interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the surgical procedures. Qualitative histologic analysis and biomechanical assessment to identify hardness and elastic modulus of newly formed bone (NFB) were performed. Collected data were statistically analyzed using one-way analysis of variance. Histologic findings revealed NFB with fibrous connective tissue in all groups. The quantity of NFB was highest in the RCM + bone group. Statistically significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P < .001) and elastic modulus (F = 294.19, dfN = 3, dfD = 36, P < .001) of NFB were found between the groups. Although the RCM + bone group had the highest mean ± standard deviation (SD) hardness of NFB (531.4 ± 24.9 MPa), the RCM group had the highest mean ± SD elastic modulus of NFB (18.63 ± 1.89 GPa). The present study demonstrated that RCMs are better than MG at enhancing new bone formation in standardized rat calvarial defects when used along with mineralized particulate graft material.

* Composite Biomaterial as a Carrier for Bone-Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats.

PubMed

Horstmann, Peter Frederik; Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Lidgren, Lars; Petersen, Michael Mørk; Tägil, Magnus

2017-12-01

Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.

Hydrogel Delivery of Mesenchymal Stem Cell–Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair

PubMed Central

Hsiao, Hui-Yi; Yang, Shu-Rui; Brey, Eric M.; Chu, I-Ming

2016-01-01

Background: The application of bone tissue engineering for repairing bone defects has gradually shown some satisfactory progress. One of the concerns raising scientific attention is the poor supply of growth factors. A number of growth factor delivery approaches have been developed for promoting bone formation. However, there is no systematic comparison of those approaches on efficiency of neobone formation. In this study, the approaches using periosteum, direct supply of growth factors, or gene transfection of growth factors were evaluated to determine the osteogenic capacity on the repair of bone defect. Methods: In total, 42 male 21-week-old Sprague-Dawley rats weighing 250 to 400 g were used as the bone defect model to evaluate the bone repair efficiency. Various tissue engineered constructs of poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogel with periosteum, with external supply of bone morphogenetic protein-2 (BMP2), or with BMP2-transfected bone marrow–derived mesenchymal stem cells (BMMSCs) were filled in a 7-mm bone defect region. Animals were euthanized at 3 months, and the hydrogel constructs were harvested. The evaluation with histological staining and radiography analysis were performed for the volume of new bone formation. Results: The PEG-PLLA scaffold with BMMSCs promotes bone regeneration with the addition of periosteum. The group with BMP2-transfected BMMSCs demonstrated the largest volume of new bone among all the testing groups. Conclusions: Altogether, the results of this study provide the evidence that the combination of PEG-PLLA hydrogels with BMMSCs and sustained delivery of BMP2 resulted in the maximal bone regeneration. PMID:27622106

Evaluation of autogenous PRGF+β-TCP with or without a collagen membrane on bone formation and implant osseointegration in large size bone defects. A preclinical in vivo study.

PubMed

Batas, Leonidas; Stavropoulos, Andreas; Papadimitriou, Serafim; Nyengaard, Jens R; Konstantinidis, Antonios

2016-08-01

The aim of this study was to evaluate whether the adjunctive use of a collagen membrane enhances bone formation and implant osseointegration in non-contained defects grafted with chair-side prepared autologous platelet-rich growth factor (PRGF) adsorbed on a β-TCP particulate carrier. Large box-type defects (10 × 6 mm; W × D) were prepared in the edentulated and completely healed mandibles of six Beagles dogs. An implant with moderately rough surface was placed in the center of each defect leaving the coronal 6 mm of the implant not covered with bone. The remaining defect space was then filled out with chair-side prepared autologous PRGF adsorbed on β-TCP particles and either covered with a collagen membrane (PRGF/β-TCP+CM) (6 defects) or left without a membrane (PRGF/β-TCP) (5 defects). Histology 4 months post-op showed new lamellar and woven bone formation encompassing almost entirely the defect and limited residual β-TCP particles. Extent of osseointegration of the previously exposed portion of the implants varied, but in general was limited. Within the defect, new mineralized bone (%) averaged 43.2 ± 9.86 vs. 39.9 ± 13.7 in the PRGF/β-TCP+CM and PRGF/β-TCP group (P = 0.22) and relative mineralized bone-to-implant contact (%) averaged 26.2 ± 16.45 vs. 35.91 ± 24.45, respectively (P = 0.5). First, bone-to-implant contact from the implant top was 4.1 ± 1.5 and 3.2 ± 2.3 (P = 0.9), in the PRGF/β-TCP+CM and PRGF/β-TCP group, respectively. Implantation of chair-side prepared autologous PRGF adsorbed on a β-TCP carrier in non-contained peri-implant defects resulted in large amounts of bone regeneration, but osseointegration was limited. Provisions for GBR with a collagen membrane did not significantly enhance bone regeneration or implant osseointegration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human intrabony defect regeneration with micro-grafts containing dental pulp stem cells: A randomized controlled clinical trial.

PubMed

Ferrarotti, Francesco; Romano, Federica; Gamba, Mara Noemi; Quirico, Andrea; Giraudi, Marta; Audagna, Martina; Aimetti, Mario

2018-05-19

The goal of this study was to evaluate if dental pulp stem cells (DPSCs) delivered into intrabony defects in a collagen scaffold would enhance the clinical and radiographic parameters of periodontal regeneration. In this randomized controlled trial, 29 chronic periodontitis patients presenting one deep intrabony defect and requiring extraction of one vital tooth were consecutively enrolled. Defects were randomly assigned to test or control treatments which both consisted of the use of minimally invasive surgical technique. The dental pulp of the extracted tooth was mechanically dissociated to obtain micro-grafts rich in autologous DPSCs. Test sites (n=15) were filled with micro-grafts seeded onto collagen sponge, whereas control sites (n=14) with collagen sponge alone. Clinical and radiographic parameters were recorded at baseline, 6 and 12 months postoperatively. Test sites exhibited significantly more PD reduction (4.9 mm versus 3.4 mm), CAL gain (4.5 versus 2.9 mm) and bone defect fill (3.9 versus 1.6 mm) than controls. Moreover, residual PD < 5 mm (93% versus 50%) and CAL gain ≥ 4 mm (73% versus 29%) was significantly more frequent in the test group. Application of DPSCs significantly improved clinical parameters of periodontal regeneration one year after treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy of combination therapy using anorganic bovine bone graft with resorbable GTR membrane vs. open flap debridement alone in the management of grade II furcation defects in mandibular molars – A comparative study

PubMed Central

Kannan, Anitha Logaranjani; Bose, Buvaneshwari Birla; Muthu, Jananni; Perumalsamy, Rajapriya; Pushparajan, Saravanan; Namasivayam, Ambalavanan

2014-01-01

Context: Invasion of the bifurcation and trifurcation of the multi-rooted teeth resulting in furcation involvement is one of the serious complications of periodontitis. Aim: The purpose of the study was to evaluate the efficacy of combination therapy using anorganic bovine bone graft and resorbable guided tissue regeneration (GTR) membrane versus open flap debridement alone in the management of Grade II furcation defects in mandibular molars. Materials and Methods: The study included a total number of 20 sites in 10 patients with bilateral mandibular furcation defects, out of which 10 sites were treated as test group and 10 as control group. The test group was treated with combination therapy and the control group with open flap debridement alone. The parameters were recorded on 0 day (baseline), 90th day, and 180th day, which included vertical probing depth and horizontal probing depth of the furcation defect, clinical attachment level, and defect fill. Statistical Analysis Used: Mean and standard deviation were calculated for different variables in each study group at different time points. Mean values were compared by using Wilcoxon signed ranks test, after adjusting the P values for multiple comparison by using Bonferroni correction method. Results: Both the test and control groups showed a definitive improvement in clinical parameters, which was statistically significant. On comparison, the vertical probing depth showed significant reduction in the test group with a mean reduction of 3.1 ± 0.7 mm, when compared to the control group which showed a mean reduction of 1.5 ± 0.5 mm. The horizontal probing depth of furcation defects was also significantly reduced in the test group with a mean reduction of 2.2 ± 0.6 mm, when compared to the control group in which the mean reduction was 0.9 ± 0.3 mm. There was also significant gain in attachment level in the test group which showed a mean gain of 3.2 ± 0.6 mm, when compared to the control group which showed a gain of 1.2 ± 0.6 mm. Radiographic defect fill was found to be more in the test group with a mean gain of 2.0 ± 0.1 mm, when compared to the control group which showed a defect fill of 0.2 ± 0.1 mm. Conclusions: The results of this study demonstrated that the combined use of anorganic bovine bone graft and resorbable GTR membrane is effective than open flap debridement alone in the treatment of mandibular grade II furcation defects. PMID:25452926

The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect

PubMed Central

Lee, So-Hyoun; Moon, Jong-Hoon; Jeong, Chang-Mo; Bae, Eun-Bin; Park, Chung-Eun; Jeon, Gye-Rok; Lee, Jin-Ju; Jeon, Young-Chan

2017-01-01

The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM) to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS-) PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM) randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR). The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %), the bone-to-implant contact (BIC, %), distance from the new bone to the old bone (NB-OB, %), and distance from the osseointegration to the old bone (OI-OB, %) were significantly higher in the 3D-PFTM group than the CM group (p < .001). It was verified that the 3D-PFTM increased mechanical properties which were effective in supporting the space maintenance ability and stabilizing the particulate bone grafts, which led to highly efficient bone regeneration. PMID:29018818

Open tibial fractures grade IIIC treated successfully with external fixation, negative-pressure wound therapy and recombinant human bone morphogenetic protein 7.

PubMed

Babiak, Ireneusz

2014-10-01

The aim of the therapy in open tibial fractures grade III was to cover the bone with soft tissue and achieve healed fracture without persistent infection. Open tibial fractures grade IIIC with massive soft tissue damage require combined orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC of the tibia diaphysis, healed extensive soft tissue defect with exposure of the bone. NPWT eventually allowed for wound closure by split skin graft within 21-25 days. Ilizarov external fixator combined with application of recombinant human bone morphogenetic protein-7 at the site of delayed union enhanced definitive bone healing within 16-18 months. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic.

PubMed

Fahmy, Rania A; Mahmoud, Naguiba; Soliman, Samia; Nouh, Samir R; Cunningham, Larry; El-Ghannam, Ahmed

2015-12-01

The aim of the present study was to evaluate the effect of a porous silica-calcium phosphate composite (SCPC50) loaded with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) on alveolar ridge augmentation in saddle-type defects. Micro-granules of SCPC50 resorbable bioactive ceramic were coated with rhBMP-2 10 mg and then implanted into a saddle-type defect (12 × 7 mm) in a dog mandible and covered with a collagen membrane. Control groups included defects grafted with SCPC50 granules without rhBMP-2 and un-grafted defects. Bone healing was evaluated at 8 and 16 weeks using histologic and histomorphometric techniques. The increase in bone height and total defect fill were assessed for each specimen using the ImageJ 1.46 program. The release kinetics of rhBMP-2 was determined in vitro. The height of the bone in the grafted defects and the total defect fill were statistically analyzed. SCPC50 enhanced alveolar ridge augmentation as indicated by the increased vertical bone height, bone surface area, and bone volume after 16 weeks. SCPC50-rhBMP-2 provided a sustained release profile of a low effective dose (BMP-2 4.6 ± 1.34 pg/mL per hour) during the 1- to 21-day period. The slow rate of release of rhBMP-2 from SCPC50 accelerated synchronized complete bone regeneration and graft material resorption in 8 weeks. Successful rapid reconstruction of the alveolar ridge by SCPC50 and SCPC50-rhBMP-2 occurred without any adverse excessive bone formation, inflammation, or fluid-filled voids. Results of this study suggest that SCPC50 is an effective graft material to preserve the alveolar ridge after tooth extraction. Coating SCPC50-rhBMP-2 further accelerated bone regeneration and a considerable increase in vertical bone height. These findings make SCPC50 the primary choice as a carrier for rhBMP-2. SCPC50-rhBMP-2 can serve as an alternative to autologous bone grafting. Published by Elsevier Inc.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

PubMed

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

2012-03-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Participation of GATA-3 in regulation of bone healing through transcriptional upregulation of bcl-xL expression

PubMed Central

Liao, Mei-Hsiu; Lin, Pei-I; Ho, Wei-Pin; Chan, Wing P; Chen, Ta-Liang; Chen, Ruei-Ming

2017-01-01

We have previously demonstrated the expression of GATA-DNA-binding protein (GATA)-3, a transcription factor, in osteoblasts and have verified its function in transducing cell survival signaling. This translational study was further designed to evaluate the roles of GATA-3 in regulating bone healing and to explore its possible mechanisms. A metaphyseal bone defect was created in the left femurs of male ICR mice. Analysis by micro-computed topography showed that the bone volume, trabecular bone number and trabecular thickness were augmented and that the trabecular pattern factor decreased. Interestingly, immunohistological analyses showed specific expression of GATA-3 in the defect area. In addition, colocalized expression of GATA-3 and alkaline phosphatase was observed at the wound site. As the fracture healed, the amounts of phosphorylated and non-phosphorylated GATA-3 concurrently increased. Separately, GATA-3 mRNA was induced during bone healing, and, levels of Runx2 mRNA and protein were also increased. The results of confocal microscopy and co-immunoprecipitation showed an association between nuclear GATA-3 and Runx2 in the area of insult. In parallel with fracture healing, Bcl-XL mRNA was significantly triggered. A bioinformatic search revealed the existence of a GATA-3-specific DNA-binding element in the promoter region of the bcl-xL gene. Analysis by chromatin immunoprecipitation assays further demonstrated transactivation activity by which GATA-3 regulated bcl-xL gene expression. Therefore, this study shows that GATA-3 participates in the healing of bone fractures via regulating bcl-xL gene expression, owing to its association with Runx2. In the clinic, GATA-3 may be used as a biomarker for diagnoses/prognoses or as a therapeutic target for bone diseases, such as bone fractures. PMID:29170477

Effects of Calcium Sulfate Combined with Platelet-rich Plasma on Restoration of Long Bone Defect in Rabbits

PubMed Central

Chen, Hua; Ji, Xin-Ran; Zhang, Qun; Tian, Xue-Zhong; Zhang, Bo-Xun; Tang, Pei-Fu

2016-01-01

Background: The treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration. Methods: A radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study. Results: The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87%) and positive control (52.21 ± 4.53%) groups were significantly greater than those in the CS group (12.34 ± 2.17%) and PRP group (16.52 ± 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 ± 4.10%) was significantly greater than that of the CS group (20.10 ± 3.70%) or PRP group (25.10 ± 2.10%) (P < 0.001). Conclusion: CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength. PMID:26904990

Tibial bone fractures occurring after medioproximal tibial bone grafts for oral and maxillofacial reconstruction.

PubMed

Kim, Il-Kyu; Cho, Hyun-Young; Pae, Sang-Pill; Jung, Bum-Sang; Cho, Hyun-Woo; Seo, Ji-Hoon

2013-12-01

Oral and maxillofacial defects often require bone grafts to restore missing tissues. Well-recognized donor sites include the anterior and posterior iliac crest, rib, and intercalvarial diploic bone. The proximal tibia has also been explored as an alternative donor site. The use of the tibia for bone graft has many benefits, such as procedural ease, adequate volume of cancellous and cortical bone, and minimal complications. Although patients rarely complain of pain, swelling, discomfort, or dysfunction, such as gait disturbance, both patients and surgeons should pay close attention to such after effects due to the possibility of tibial fracture. The purpose of this study is to analyze tibial fractures that occurring after osteotomy for a medioproximal tibial graft. An analysis was intended for patients who underwent medioproximal tibial graft between March 2004 and December 2011 in Inha University Hospital. A total of 105 subjects, 30 females and 75 males, ranged in age from 17 to 78 years. We investigated the age, weight, circumstance, and graft timing in relation to tibial fracture. Tibial fractures occurred in four of 105 patients. There were no significant differences in graft region, shape, or scale between the fractured and non-fractured patients. Patients who undergo tibial grafts must be careful of excessive external force after the operation.

Polymeric membranes for guided bone regeneration.

PubMed

Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

2011-10-01

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment laser phototherapy on bone defects grafted or not with biphasic synthetic micro-granular HA + β-tricalcium phosphate: histological study in an animal model

NASA Astrophysics Data System (ADS)

Soares, Luiz Guilherme P.; Marques, Aparecida M. C.; Aciole, Jouber Mateus S.; Trindade, Renan; Santos, Jean N.; Pinheiro, Antônio Luiz B.

2014-02-01

Beside of biomaterials, Laser phototherapy has shown positive results as auxiliary therapy on bone repair. The aim of this study was to evaluate, through histological analysis, the influence of Laser phototherapy in the process of repair of bone defects grafted or not with Hydroxyapatite. Forty rats were divided into 4 groups each subdivided into 2 subgroups according to the time of sacrifice. Surgical bone defects were made on femur of each animal with a trephine drill. On animals of group Clot the defect was filled only by blood, on group Laser the defect filled with the clot and further irradiated. In group Biomaterial the defect was filled with HA + β-TCP graft. In group Laser + Biomaterial, the defect was filled with biomaterial and further irradiated. The irradiation protocols were performed every 48 hours during for 15 days. Animal death occurred after 15 and 30 days. The specimens were routinely processed and evaluated by light microscopy. Qualitative analysis showed that group Laser + Biomaterial was in a more advanced stage of repair at the end of the experimental time. It was concluded that the Laser irradiation improved the repair of bone defects grafted or not.

Analysis of the results of replacement of large bone defects in the patients who underwent segmental bone resection for tumor

NASA Astrophysics Data System (ADS)

Anastasieva, E. A.; Voropaeva, A. A.; Sadovoy, M. A.; Kirilova, I. A.

2017-09-01

The problem of large bone defects replacement, formed after segmental bone resections, remains an actual issue of modern orthopedics. It is known that the autograft is the most acceptable material for the replacement of bone tissue; however, due to its small volume and physical properties, it has limited usage. Our goal is to analyze the results of the experiments and studies on replacement of large bone defects after resection of the bone tumor. The problem is justified by the complicated osteoconduction and osteointegration; because it is proved that the reconstruction of the microcirculatory bloodstream is difficult in the presence of damage more than 4 cm2. It was revealed that using of allograft in combination with additional components is comparable in effectiveness, including long-term period, with autograft usage. It is promising to combine plastic allogenous material, capable of reconstructing defects of various configuration intraoperatively, with the necessary chemotherapy with controlled desorption to maintain effective concentration of drug.

Bioactive borate glass promotes the repair of radius segmental bone defects by enhancing the osteogenic differentiation of BMSCs.

PubMed

Zhang, Jieyuan; Guan, Junjie; Zhang, Changqing; Wang, Hui; Huang, Wenhai; Guo, Shangchun; Niu, Xin; Xie, Zongping; Wang, Yang

2015-11-20

Bioactive borate glass (BG) has emerged as a promising alternative for bone regeneration due to its high osteoinductivity, osteoconductivity, compressive strength, and biocompatibility. However, the role of BG in large segmental bone repair is unclear and little is known about the underlying mechanism of BG's osteoinductivity. In this study, we demonstrated that BG possessed pro-osteogenic effects in an experimental model of critical-sized radius defects. Transplanting BG to radius defects resulted in better repair of bone defects as compared to widely used β-TCP. Histological and morphological analysis indicated that BG significantly enhanced new bone formation. Furthermore, the degradation rate of the BG was faster than that of β-TCP, which matched the higher bone regeneration rate. In addition, ions from BG enhanced cell viability, ALP activity, and osteogenic-related genes expression. Mechanistically, the critical genes Smad1/5 and Dlx5 in the BMP pathway and p-Smad1/5 proteins were significantly elevated after BG transplantation, and these effects could be blocked by the BMP/Smad specific inhibitor. Taken together, our findings suggest that BG could repair large segmental bone defects through activating the BMP/Smad pathway and osteogenic differentiation in BMSCs.

A prospective, randomized controlled preclinical trial to evaluate different formulations of biphasic calcium phosphate in combination with a hydroxyapatite collagen membrane to reconstruct deficient alveolar ridges.

PubMed

Nevins, Myron; Nevins, Marc L; Schupbach, Peter; Kim, Soo-Woo; Lin, Zhao; Kim, David M

2013-04-01

Many patients and clinicians would prefer a synthetic particulate bone replacement graft, but most available alloplastic biomaterials have limited osteogenic potential. An alloplast with increased regenerative capacity would be advantageous for the treatment of localized alveolar ridge defects. This prospective, randomized controlled preclinical trial utilized 6 female foxhounds to analyze the osteogenic impact of different formulations of biphasic calcium phosphate (BCP) in combination with an hydroxyapatite-collagen membrane and their ability to reconstruct deficient alveolar ridges for future implant placement. The grafted sites were allowed to heal 3 months, and then trephine biopsies were obtained to perform light microscopic and histomorphometric analyses. All treated sites healed well with no early membrane exposure or adverse soft tissue responses during the healing period. The grafted sites exhibited greater radiopacity than the surrounding native bone with BCP particles seen as radiopaque granules. The graft particles appeared to be well-integrated and no areas of loose particles were observed. Histologic evaluation demonstrated BCP particles embedded in woven bone with dense connective tissue/marrow space. New bone growth was observed around the graft particles as well as within the structure of the graft particulate. There was intimate contact between the graft particles and newly formed bone, and graft particles were bridged by the newly formed bone in all biopsies from the tested groups. The present study results support the potential of these BCP graft particulates to stimulate new bone formation. Clinical studies are recommended to confirm these preclinical findings.

Computed Tomography and Optical Imaging of Osteogenesis-angiogenesis Coupling to Assess Integration of Cranial Bone Autografts and Allografts.

PubMed

Cohn Yakubovich, Doron; Tawackoli, Wafa; Sheyn, Dmitriy; Kallai, Ilan; Da, Xiaoyu; Pelled, Gadi; Gazit, Dan; Gazit, Zulma

2015-12-22

A major parameter determining the success of a bone-grafting procedure is vascularization of the area surrounding the graft. We hypothesized that implantation of a bone autograft would induce greater bone regeneration by abundant blood vessel formation. To investigate the effect of the graft on neovascularization at the defect site, we developed a micro-computed tomography (µCT) approach to characterize newly forming blood vessels, which involves systemic perfusion of the animal with a polymerizing contrast agent. This method enables detailed vascular analysis of an organ in its entirety. Additionally, blood perfusion was assessed using fluorescence imaging (FLI) of a blood-borne fluorescent agent. Bone formation was quantified by FLI using a hydroxyapatite-targeted probe and µCT analysis. Stem cell recruitment was monitored by bioluminescence imaging (BLI) of transgenic mice that express luciferase under the control of the osteocalcin promoter. Here we describe and demonstrate preparation of the allograft, calvarial defect surgery, µCT scanning protocols for the neovascularization study and bone formation analysis (including the in vivo perfusion of contrast agent), and the protocol for data analysis. The 3D high-resolution analysis of vasculature demonstrated significantly greater angiogenesis in animals with implanted autografts, especially with respect to arteriole formation. Accordingly, blood perfusion was significantly higher in the autograft group by the 7(th) day after surgery. We observed superior bone mineralization and measured greater bone formation in animals that received autografts. Autograft implantation induced resident stem cell recruitment to the graft-host bone suture, where the cells differentiated into bone-forming cells between the 7(th) and 10(th) postoperative day. This finding means that enhanced bone formation may be attributed to the augmented vascular feeding that characterizes autograft implantation. The methods depicted may serve as an optimal tool to study bone regeneration in terms of tightly bounded bone formation and neovascularization.

[Biomaterials in bone repair].

PubMed

Puska, Mervi; Aho, Allan J; Vallittu, Pekka K

2013-01-01

In orthopedics, traumatology, and craniofacial surgery, biomaterials should meet the clinical demands of bone that include shape, size and anatomical location of the defect, as well as the physiological load-bearing stresses. Biomaterials are metals, ceramics, plastics or materials of biological origin. In the treatment of large defects, metallic endoprostheses or bone grafts are employed, whereas ceramics in the case of small defects. Plastics are employed on the artificial joint surfaces, in the treatment of vertebral compression fractures, and as biodegradable screws and plates. Porosity, bioactivity, and identical biomechanics to bone are fundamental for achieving a durable, well-bonded, interface between biomaterial and bone. In the case of severe bone treatments, biomaterials should also imply an option to add biologically active substances.

In vitro cytotoxicity and in vivo osseointergration properties of compression-molded HDPE-HA-Al2O3 hybrid biocomposites.

PubMed

Tripathi, Garima; Gough, Julie E; Dinda, Amit; Basu, Bikramjit

2013-06-01

The aim of this study was to investigate the in vivo biocompatibility in terms of healing of long segmental bone defect in rabbit model as well as in vitro cytotoxicity of eluates of compression-molded High density polyethylene (HDPE)-hydroxyapatite (HA)-aluminum oxide (Al2O3) composite-based implant material. Based on the physical property in terms of modulus and strength properties, as reported in our recent publication, HDPE-40 wt % HA and HDPE-20 wt % HA-20 wt % Al2O3 hybrid composites were used for biocompatibility assessment. Osteoblasts cells were cultured in conditioned media, which contains varying amount of composite eluate (0.01, 0.1, and 1.0 wt %). In vitro, the eluates did not exhibit any significant negative impact on proliferation, mineralization or on morphology of human osteoblast cells. In vivo, the histological assessment revealed neobone formation at the bone/implant interface, characterized by the presence of osteoid and osteoblasts. The observation of osteoclastic activity indicates the process of bone remodeling. No inflammation to any noticeable extent was observed at the implantation site. Overall, the combination of in vitro and in vivo results are suggestive of potential biomedical application of compression-molded HDPE- 20 wt % HA- 20 wt % Al2O3 composites to heal long segmental bone defects without causing any toxicity of bone cells. Copyright © 2012 Wiley Periodicals, Inc.

Fabrication and Characterization of Carbon Fiber-Reinforced Nano-Hydroxyapatite/Polyamide46 Biocomposite for Bone Substitute.

PubMed

Deng, Zhennan; Han, Hongjuan; Yang, Jingyuan; Li, Yuanyuan; Du, Shengnan; Ma, Jianfeng

2017-05-24

BACKGROUND Ideal bone repair material should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to those of natural bone. The objective of this study was to fabricate a novel biocomposite suitable for load-bearing bone defect repair. MATERIAL AND METHODS A novel biocomposite composed of carbon fiber, hydroxyapatite and polyamide46 (CF/HA/PA46) was fabricated, and its mechanical performances and preliminary cell responses were evaluated to explore its feasibility for load-bearing bone defect repair. RESULTS The resultant CF/HA/PA46 biocomposite showed a bending strength of 159-223 MPa, a tensile strength of 127-199 MPa and a tensile modulus of 7.7-10.8 GPa, when the CF content was 5-20% (mass fraction) in biocomposite. The MG63 cells, showing an osteogenic phenotype, were well adhered and spread on the surface of the CF/HA/PA46 biocomposite. Moreover, the cells vitality and differentiation on the CF/HA/PA46 biocomposite surface were obviously increased during the culture time and there was no significant difference between the CF/HA/PA46 biocomposite and HA/PA (as control) at all the experimental time (P>0.05). CONCLUSIONS The addition of CF into HA/PA46 composite manifest improved the mechanical performances and showed favorable effects on biocompatibility of MG63 cells. The obtained biocomposite has high potential for bone repair in load-bearing sites.

Fabrication and Characterization of Carbon Fiber-Reinforced Nano-Hydroxyapatite/Polyamide46 Biocomposite for Bone Substitute

PubMed Central

Deng, Zhennan; Han, Hongjuan; Yang, Jingyuan; Li, Yuanyuan; Du, Shengnan; Ma, Jianfeng

2017-01-01

Background Ideal bone repair material should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to those of natural bone. The objective of this study was to fabricate a novel biocomposite suitable for load-bearing bone defect repair. Material/Methods A novel biocomposite composed of carbon fiber, hydroxyapatite and polyamide46 (CF/HA/PA46) was fabricated, and its mechanical performances and preliminary cell responses were evaluated to explore its feasibility for load-bearing bone defect repair. Results The resultant CF/HA/PA46 biocomposite showed a bending strength of 159–223 MPa, a tensile strength of 127–199 MPa and a tensile modulus of 7.7–10.8 GPa, when the CF content was 5–20% (mass fraction) in biocomposite. The MG63 cells, showing an osteogenic phenotype, were well adhered and spread on the surface of the CF/HA/PA46 biocomposite. Moreover, the cells vitality and differentiation on the CF/HA/PA46 biocomposite surface were obviously increased during the culture time and there was no significant difference between the CF/HA/PA46 biocomposite and HA/PA (as control) at all the experimental time (P>0.05). Conclusions The addition of CF into HA/PA46 composite manifest improved the mechanical performances and showed favorable effects on biocompatibility of MG63 cells. The obtained biocomposite has high potential for bone repair in load-bearing sites. PMID:28536416

A novel ciliopathic skull defect arising from excess neural crest.

PubMed

Tabler, Jacqueline M; Rice, Christopher P; Liu, Karen J; Wallingford, John B

2016-09-01

The skull is essential for protecting the brain from damage, and birth defects involving disorganization of skull bones are common. However, the developmental trajectories and molecular etiologies by which many craniofacial phenotypes arise remain poorly understood. Here, we report a novel skull defect in ciliopathic Fuz mutant mice in which only a single bone pair encases the forebrain, instead of the usual paired frontal and parietal bones. Through genetic lineage analysis, we show that this defect stems from a massive expansion of the neural crest-derived frontal bone. This expansion occurs at the expense of the mesodermally-derived parietal bones, which are either severely reduced or absent. A similar, though less severe, phenotype was observed in Gli3 mutant mice, consistent with a role for Gli3 in cilia-mediated signaling. Excess crest has also been shown to drive defective palate morphogenesis in ciliopathic mice, and that defect is ameliorated by reduction of Fgf8 gene dosage. Strikingly, skull defects in Fuz mutant mice are also rescued by loss of one allele of fgf8, suggesting a potential route to therapy. In sum, this work is significant for revealing a novel skull defect with a previously un-described developmental etiology and for suggesting a common developmental origin for skull and palate defects in ciliopathies. Copyright © 2016 Elsevier Inc. All rights reserved.

The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds.

PubMed

Ren, Tianbin; Ren, Jie; Jia, Xiaozhen; Pan, Kefeng

2005-09-15

Highly porous scaffolds of poly(lactide-co-glycolide) (PLGA) were prepared by solution-casting/salt-leaching method. The in vitro degradation behavior of PLGA scaffold was investigated by measuring the change of normalized weight, water absorption, pH, and molecular weight during degradation period. Mesenchymal stem cells (MSCs) were seeded and cultured in three-dimensional PLGA scaffolds to fabricate in vitro tissue engineering bone, which was investigated by cell morphology, cell number and deposition of mineralized matrix. The proliferation of seeded MSCs and their differentiated function were demonstrated by experimental results. To compare the reconstructive functions of different groups, mandibular defect repair of rabbit was made with PLGA/MSCs tissue engineering bone, control PLGA scaffold, and blank group without scaffold. Histopathologic methods were used to estimate the reconstructive functions. The result suggests that it is feasible to regenerate bone tissue in vitro using PLGA foams with pore size ranging from 100-250 microm as scaffolding for the transplantation of MSCs, and the PLGA/MSCs tissue engineering bone can greatly promote cell growth and have better healing functions for mandibular defect repair. The defect can be completely recuperated after 3 months with PLGA/MSCs tissue engineering bone, and the contrastive experiments show that the defects could not be repaired with blank PLGA scaffold. PLGA/MSCs tissue engineering bone has great potential as appropriate replacement for successful repair of bone defect. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

PubMed

Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

2016-01-01

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc.

Reconstruction of radial bone defect in rat by calcium silicate biomaterials.

PubMed

Oryan, Ahmad; Alidadi, Soodeh

2018-05-15

Despite many attempts, an appropriate therapeutic method has not yet been found to enhance bone formation, mechanical strength and structural and functional performances of large bone defects. In the present study, the bone regenerative potential of calcium silicate (CS) biomaterials combined with chitosan (CH) as calcium silicate/chitosan (CSC) scaffold was investigated in a critical radial bone defect in a rat model. The bioimplants were bilaterally implanted in the defects of 20 adult Sprague-Dawley rats. The rats were euthanized and the bone specimens were harvested at the 56th postoperative day. The healed radial bones were evaluated by three-dimensional CT, radiology, histomorphometric analysis, biomechanics, and scanning electron microscopy. The XRD analysis of the CS biomaterial showed its similarity to wollastonite (β-SiCO 3 ). The degradation rate of the CSC scaffold was much higher and it induced milder inflammatory reaction when compared to the CH alone. More bone formation and higher biomechanical performance were observed in the CSC treated group in comparison with the CH treated ones in histological, CT scan and biomechanical examinations. Scanning electron microscopic observation demonstrated the formation of more hydroxyapatite crystals in the defects treated with CSC. This study showed that the CSC biomaterials could be used as proper biodegradable materials in the field of bone reconstruction and tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

An Endochondral Ossification-Based Approach to Bone Repair: Chondrogenically Primed Mesenchymal Stem Cell-Laden Scaffolds Support Greater Repair of Critical-Sized Cranial Defects Than Osteogenically Stimulated Constructs In Vivo.

PubMed

Thompson, Emmet M; Matsiko, Amos; Kelly, Daniel J; Gleeson, John P; O'Brien, Fergal J

2016-03-01

The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair. However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification (IMO), leads to poor vascularization. In this study, we speculate that mimicking an endochondral ossification (ECO) approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair. We hypothesized that stimulation of mesenchymal stem cell (MSC) chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularization and bone formation when implanted within a critical-sized bone defect in vivo. To produce ECO-based constructs, two distinct scaffolds, collagen-hyaluronic acid (CHyA) and collagen-hydroxyapatite (CHA), with proven potential for cartilage and bone repair, respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors. To produce IMO-based constructs, CHA scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo. The results demonstrated that IMO- and ECO-based constructs were capable of supporting enhanced bone repair compared to empty defects. However, it was clear that the scaffolds, which were previously shown to support the greatest cartilage formation in vitro (CHyA), led to the highest new bone formation (p < 0.05) within critical-sized bone defects 8 weeks postimplantation. We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs before implantation leading to the greater blood vessel ingrowth. This study thus demonstrates the ability of recapitulating a developmental process of bone formation to develop tissue-engineered constructs that manifest appreciable promise for bone defect repair.

Biomimetic coatings for bone tissue engineering of critical-sized defects.

PubMed

Liu, Yuelian; Wu, Gang; de Groot, Klaas

2010-10-06

The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a low concentration to be effective. This then mimics the natural method of cytokine release. For this purpose, a suitable vehicle was developed, the so-called biomimetic coating, which can be deposited on metal implants as well as on biomaterials. Materials that are currently used to fill bony defects cannot by themselves trigger bone formation. Therefore, biological functionalization of such materials by the biomimetic method resulted in a novel biomimetic coating onto different biomaterials. Bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic coating can be a solution for a large bone defect repair in the fields of dental implantology, maxillofacial surgery and orthopaedics. Here, we review the performance of the biomimetic coating both in vitro and in vivo.

Stem cells applications in bone and tooth repair and regeneration: New insights, tools, and hopes.

PubMed

Abdel Meguid, Eiman; Ke, Yuehai; Ji, Junfeng; El-Hashash, Ahmed H K

2018-03-01

The exploration of stem and progenitor cells holds promise for advancing our understanding of the biology of tissue repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different tissue-species defects or disorders such as bone, cartilages, and tooth defects or disorders. Bone is a specialized connective tissue, with mineralized extracellular components that provide bones with both strength and rigidity, and thus enable bones to function in body mechanical supports and necessary locomotion process. New insights have been added to the use of different types of stem cells in bone and tooth defects over the last few years. In this concise review, we briefly describe bone structure as well as summarize recent research progress and accumulated information regarding the osteogenic differentiation of stem cells, as well as stem cell contributions to bone repair/regeneration, bone defects or disorders, and both restoration and regeneration of bones and cartilages. We also discuss advances in the osteogenic differentiation and bone regeneration of dental and periodontal stem cells as well as in stem cell contributions to dentine regeneration and tooth engineering. © 2017 Wiley Periodicals, Inc.

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

PubMed Central

Gao, Liang; Orth, Patrick; Müller-Brandt, Kathrin; Goebel, Lars K. H.; Cucchiarini, Magali; Madry, Henning

2017-01-01

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques. PMID:28345610

Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

PubMed

Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

2015-10-01

To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

Defect nonunion of a metatarsal bone fracture in a cow: successful management with bone plating and autogenous cancellous bone graft.

PubMed

Raghunath, M; Singh, N; Singh, T; Gopinathan, A; Mohindroo, J; Atri, K

2013-01-01

A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.

Chin Symphysis Bone, Allograft, and Platelet-Rich Fibrin: Is the Combination Effective in Repair of Alveolar Cleft?

PubMed

Movahedian Attar, Bijan; Naghdi, Navid; Etemadi Sh, Milad; Mehdizadeh, Mojdeh

2017-05-01

Secondary grafting of alveolar defects with iliac crest bone is a common treatment method in cleft patients. The aim of this study was to evaluate the effectiveness of the combination of symphysis bone, allograft, and platelet-rich fibrin in regeneration of alveolar defects compared with iliac bone graft. In this randomized clinical trial, patients with unilateral alveolar defects were divided randomly into two categories. Group A comprised patients in whom the combination of chin symphysis bone plus allogeneic bone material plus leukocyte- and platelet-rich fibrin was considered for treatment. Group B comprised patients in whom iliac bone graft was considered. Cone beam computed tomography before treatment and 1 year postoperatively was used for measurement of bone formation (bone volume in cubic centimeters). The data were analyzed by paired t and χ 2 tests via SPSS software (version 23; IBM, Armonk, NY). P < .05 was considered significant. Each group included 10 patients (with 6 male patients in group A and 5 male patients in group B). The mean age of patients in groups A and B was 9.5 ± 1.5 years and 9.9 ± 1.9 years, respectively. The mean volume of alveolar defects was 0.89 ± 0.29 cm 3 in group A and 0.95 ± 0.27 cm 3 in group B. The percentage of bone regeneration in groups A and B was 69.5% and 73.8%, respectively. It seems that chin symphysis bone plus allogeneic bone material plus platelet-rich fibrin is a proper combination for bone regeneration in alveolar defects with a small to moderate volume range. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

PubMed Central

Tang, Cheng; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Min, Byoung-Hyun; Xu, Yan

2014-01-01

Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair. PMID:24666429

Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

PubMed

Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

2015-04-01

The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair.

PubMed

Das, Anusuya; Fishero, Brian A; Christophel, J Jared; Li, Ching-Ju; Kohli, Nikita; Lin, Yong; Dighe, Abhijit S; Cui, Quanjun

2016-04-01

We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres. The scaffolds were chemically cross-linked with 200 ng recombinant human VEGF (P(VEGF)) or BMP-6 (P(BMP-6)) or both (P(VEGF+BMP-6)) by the EDC-NHS-MES method. Release of the proteins from the scaffolds was detected for 21 days in vitro which confirmed their comparable potential to supply the proteins in vivo. The scaffolds were delivered to a critical-sized mandibular defect created in 32 Sprague Dawley rats. Significant bone regeneration was observed only in rats with P(VEGF+BMP-6) scaffolds at weeks 2, 8 and 12 as revealed by micro-computer tomography. Vascular ingrowth was higher in the P(VEGF+BMP-6) group as seen by microfil imaging than in other groups. Trichrome staining revealed that a soft callus formed in P(VEGF), P(BMP-6) and P(VEGF+BMP-6) but not in P. MSCs isolated from rat femurs displayed expression of the bone-specific marker osteocalcin when cultured with P(VEGF), P(BMP-6), or P(VEGF+BMP-6) but not with P. Robust mineralization and increased alkaline phosphatase gene expression were seen in rat MSCs when cultured on P(VEGF+BMP-6) but not on P, P(VEGF), or P(BMP-6). Thus, unlike the delivery of VEGF or BMP-6 alone, the combined delivery of VEGF and BMP-6 to the bone defect significantly enhanced bone repair through the enhancement of angiogenesis and the differentiation of endogenously recruited MSCs into the bone repair site.

Effect of Alendronate with β - TCP Bone Substitute in Surgical Therapy of Periodontal Intra-Osseous Defects: A Randomized Controlled Clinical Trial.

PubMed

Naineni, Rohini; Ravi, Vishali; Subbaraya, Dwijendra Kocherlakota; Prasanna, Jammula Surya; Panthula, Veerendranath Reddy; Koduganti, Rekha Rani

2016-08-01

Alendronate (ALN), an aminobisphosphonate, inhibits osteoclastic bone resorption and also stimulates osteogenesis. Beta-Tricalcium Phosphate (β-TCP) is an osteoconductive graft material which provides a scaffold for bone formation and also a widely used drug delivery vehicle for growth factors and antibiotics. Drug delivery vehicles, like β-TCP, improve the potency of the drugs by specific local site delivery of the drug, optimal release characteristics and easy handling. The aim of the this study was to evaluate the bone formation potential of 400μg ALN delivered in β-TCP in the treatment of periodontal intra-osseous defects. Thirty patients with periodontal defects were randomly assigned to 400μg ALN + β-TCP + Saline (test) group and β-TCP + Saline (active-control) group. Clinical parameters like Clinical Attachment Level (CAL) gain, Probing Depth (PD) reduction, post-operative Gingival Recession (GR) were assessed from the baseline, 3 months and 6 months recordings. Radiographic parameters like Linear Bone Growth (LBG), Percentage Bone Fill (%BF), and change in alveolar crest height (ACH) were assessed from baseline and 6 months radiographs. Mean measurements in the ALN test group for CAL gain (3.4 ± 0.74 mm), PD reduction (4.33 ± 0.82 mm), LBG (2.88 ± 0.88 mm), and %BF (51.98 ± 15.84%) were significantly greater with a p-value <0.05 compared to the mean measurements of CAL gain (2.20 ± 0.86 mm), PD reduction (3.20 ± 1.15 mm), LBG (1.70 ± 0.39 mm), and %BF (30.35 ± 6.88%) of the control group. There was mild alveolar crestal apposition (0.32 ± 0.68 mm) in the ALN test group and mild alveolar crestal resorption (-0.24 ± 0.40 mm) in the control group. 400μg ALN combined with β-TCP bone graft material was effective in improving soft tissue parameters, inhibiting alveolar crestal resorption and enhancing bone formation, compared to β-TCP alone.

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

PubMed

Nakajima, Kengo; Kunimatsu, Ryo; Ando, Kazuyo; Ando, Toshinori; Hayashi, Yoko; Kihara, Takuya; Hiraki, Tomoka; Tsuka, Yuji; Abe, Takaharu; Kaku, Masato; Nikawa, Hiroki; Takata, Takashi; Tanne, Kazuo; Tanimoto, Kotaro

2018-03-11

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Bone repair in mandibular body osteotomy after using 2.0 miniplate system – histological and histometric analysis in dogs

PubMed Central

Sverzut, Cássio Edvard; Lucas, Marina Amaral; Sverzut, Alexander Tadeu; Trivellato, Alexandre Elias; Beloti, Marcio Mateus; Rosa, Adalberto Luiz; de Oliveira, Paulo Tambasco

2008-01-01

The objective of this study was to evaluate the bone repair along a mandibular body osteotomy after using a 2.0 miniplate system. Nine adult mongrel dogs were subjected to unilateral continuous defect through an osteotomy between the mandibular 3rd and 4th premolars. Two four-hole miniplates were placed in accordance with the Arbeitgeimeinschaft für Osteosynthesefragen Manual. Miniplates adapted to the alveolar processes were fixed monocortically with 6.0-mm-length titanium alloy self-tapping screws, whereas miniplates placed near the mandible bases were fixed bicortically. At 2, 6 and 12 weeks, three dogs were sacrificed per period, and the osteotomy sites were removed, divided into three thirds (Tension Third, TT; Intermediary Third, IT; Compression Third, CT) and prepared for conventional and polarized light microscopy. At 6 weeks, while the CT repaired faster and showed bone union by woven bone formation, the TT and IT exhibited a ligament-like fibrous connective tissue inserted in, and connecting, newly formed woven bone overlying the parent lamellar bone edges. At 12 weeks, bone repair took place at all thirds. Histometrically, proportions of newly formed bone did not alter at TT, IT and CT, whereas significantly enhanced bone formation was observed for the 12-week group, irrespective of the third. The results demonstrated that although the method used to stabilize the mandibular osteotomy allowed bone repair to occur, differences in the dynamics of bone healing may take place along the osteotomy site, depending on the action of tension and compression forces generated by masticatory muscles. PMID:18336526

Osteoinductive ceramics as a synthetic alternative to autologous bone grafting

PubMed Central

Yuan, Huipin; Fernandes, Hugo; Habibovic, Pamela; de Boer, Jan; Barradas, Ana M. C.; de Ruiter, Ad; Walsh, William R.; van Blitterswijk, Clemens A.; de Bruijn, Joost D.

2010-01-01

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of “smart” biomaterials. PMID:20643969

Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits.

PubMed

Chen, Jianghao; Liu, Wei; Zhao, Jinxiu; Sun, Cong; Chen, Jie; Hu, Kaijin; Zhang, Linlin; Ding, Yuxiang

2017-03-01

To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model. Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit osteoporotic bone defective model. From micro-computed tomography imaging results, 10 nM CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree; similar effects were observed with the microspheres containing 1 µM substance P. Histological analysis showed that the gelatin microspheres containing CGRP or substance P, regardless of the concentration, effectively promoted osteogenesis, and the highest effect was achieved in the groups containing 1 µM CGRP or 1 µM substance P. Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit osteoporotic bone defect model dose-dependently, though their effects in repairing human alveolar ridge defects still need further investigation.

Pathophysiology of osteoporosis: new mechanistic insights.

PubMed

Armas, Laura A G; Recker, Robert R

2012-09-01

Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Allogeneic adipose-derived stem cells regenerate bone in a critical-sized ulna segmental defect

PubMed Central

Wen, Congji; Yan, Hai; Fu, Shibo; Qian, Yunliang

2016-01-01

Adipose-derived stem cells (ASCs) with multilineage potential can be induced into osteoblasts, adipocytes and chondrocytes. ASCs as seed cell are widely used in the field of tissue engineering, but most studies either use autologous cells as the source or an immunodeficient animal as the host. In our present study, we explored the feasibility of applying allogeneic ASCs and demineralized bone matrix (DBM) scaffolds for repairing tubular bone defects without using immunosuppressive therapy. Allogeneic ASCs were expanded and seeded on DBM scaffolds and induced to differentiate along the osteogenic lineage. Eight Sprague–Dawley (SD) rats were used in this study and bilateral critical-sized defects (8 mm) of the ulna were created and divided into two groups: with ASC-DBM constructs or DBM alone. The systemic immune response and the extent of bone healing were evaluated post-operatively. Twenty-four weeks after implantation, digital radiography (DR) testing showed that new bones had formed in the experimental group. By contrast, no bone tissue formation was observed in the control group. This study demonstrated that allogeneic ASCs could promote bone regeneration and repair tubular bone defects combined with DBM by histologically typical bone without systemic immune response PMID:25819682

The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

PubMed Central

2012-01-01

Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

Evaluation of Soft Tissue Coverage over Porous Polymethylmethacrylate Space Maintainers Within Nonhealing Alveolar Bone Defects

PubMed Central

Kretlow, James D.; Shi, Meng; Young, Simon; Spicer, Patrick P.; Demian, Nagi; Jansen, John A.; Wong, Mark E.; Kasper, F. Kurtis

2010-01-01

Current treatment of traumatic craniofacial injuries often involves early free tissue transfer, even if the recipient site is contaminated or lacks soft tissue coverage. There are no current tissue engineering strategies to definitively regenerate tissues in such an environment at an early time point. For a tissue engineering approach to be employed in the treatment of such injuries, a two-stage approach could potentially be used. The present study describes methods for fabrication, characterization, and processing of porous polymethylmethacrylate (PMMA) space maintainers for temporary retention of space in bony craniofacial defects. Carboxymethylcellulose hydrogels were used as a porogen. Implants with controlled porosity and pore interconnectivity were fabricated by varying the ratio of hydrogel:polymer and the amount of carboxymethylcellulose within the hydrogel. The in vivo tissue response to the implants was observed by implanting solid, low-porosity, and high-porosity implants (n = 6) within a nonhealing rabbit mandibular defect that included an oral mucosal defect to allow open communication between the oral cavity and the mandibular defect. Oral mucosal wound healing was observed after 12 weeks and was complete in 3/6 defects filled with solid PMMA implants and 5/6 defects filled with either a low- or high-porosity PMMA implant. The tissue response around and within the pores of the two formulations of porous implants tested in vivo was characterized, with the low-porosity implants surrounded by a minimal but well-formed fibrous capsule in contrast to the high-porosity implants, which were surrounded and invaded by almost exclusively inflammatory tissue. On the basis of these results, PMMA implants with limited porosity hold promise for temporary implantation and space maintenance within clean/contaminated bone defects. PMID:20524844

Bone Augmentation in Rabbit Tibia Using Microfixed Cobalt-Chromium Membranes with Whole Blood and Platelet-Rich Plasma

PubMed Central

Decco, Oscar A.; Beltrán, Víctor; Zuchuat, Jésica I.; Cura, Andrea C.; Lezcano, María F.; Engelke, Wilfried

2015-01-01

Background: Bone augmentation is a subject of intensive investigation in regenerative bone medicine and constitutes a clinical situation in which autogenous bone grafts or synthetic materials are used to aid new bone formation. Method: Based on a non-critical defect, Co-Cr barrier membranes were placed on six adult Fauve de Bourgogne rabbits, divided into two groups: whole blood and PRP. Three densitometric controls were performed during the experiment. The animals were euthanized at 30, 45, 60, and 110 days. The presence of newly formed bone was observed. Samples for histological studies were taken from the augmentation center. Results: External and internal bone tissue augmentation was observed in almost all cases. Significant differences between PRP- and whole blood–stimulated bone augmentation were not observed. At 60 days, bones with PRP presented higher angiogenesis, which may indicate more proliferation and cellular activity. Conclusion: PRP activates the bone regeneration process under optimized conditions by stimulation of osteoblast proliferation after six weeks, when a significant difference in cellular activity was observed. Membranes could stimulate bone augmentation at the site of placement and in the surrounding areas. PMID:28793476

Infected nonunion of tibia

PubMed Central

Chaudhary, Milind Madhav

2017-01-01

Infected nonunions of tibia pose many challenges to the treating surgeon and the patient. Challenges include recalcitrant infection, complex deformities, sclerotic bone ends, large bone gaps, shortening, and joint stiffness. They are easy to diagnose and difficult to treat. The ASAMI classification helps decide treatment. The nonunion severity score proposed by Calori measures many parameters to give a prognosis. The infection severity score uses simple clinical signs to grade severity of infection. This determines number of surgeries and allows choice of hardware, either external or internal for definitive treatment. Co-morbid factors such as smoking, diabetes, nonsteroidal anti-inflammatory drug use, and hypovitaminosis D influence the choice and duration of treatment. Thorough debridement is the mainstay of treatment. Removal of all necrotic bone and soft tissue is needed. Care is exercised in shaping bone ends. Internal fixation can help achieve union if infection was mild. Severe infections need external fixation use in a second stage. Compression at nonunion site achieves union. It can be combined with a corticotomy lengthening at a distant site for equalization. Soft tissue deficit has to be covered by flaps, either local or microvascular. Bone gaps are best filled with the reliable technique of bone transport. Regenerate bone may be formed proximally, distally, or at both sites. Acute compression can fill bone gaps and may need a fibular resection. Gradual reduction of bone gap happens with bone transport, without need for fibulectomy. When bone ends dock, union may be achieved by vertical or horizontal compression. Biological stimulus from iliac crest bone grafts, bone marrow aspirate injections, and platelet concentrates hasten union. Bone graft substitutes add volume to graft and help fill defects. Addition of rh-BMP-7 may help in healing albeit at a much higher cost. Regeneration may need stimulation and augmentation. Induced membrane technique is an alternative to bone transport to fill gaps. It needs large amounts of bone graft from iliac crest or femoral canal. This is an expensive method physiologically and economically. Infection can resorb the graft and cause failure of treatment. It can be done in select cases after thorough eradication of infection. Patience and perseverance are needed for successful resolution of infection and achieving union. PMID:28566776

The three-dimensional reconstruction of the jaw with "bone slat technique" in conjunction with third molar removal.

PubMed

Santagata, Mario; Cecere, Atirge; Prisco, Rosario V E; Tartaro, Gianpaolo; D'Amato, Salvatore

2017-01-01

The purpose of this study was to report the outcome of the management of both horizontal and vertical defects of alveolar crest using the bone slat technique approach in conjunction with third molar removal prior to implant placement in the aesthetic area. We present a 20-year-old female patient who lost a maxillary lateral incisor. The objective of treatment was to replace the lateral incisor with an implant-supported crown restoration without interfering with the integrity and topography of the adjacent gingival tissues. Because the future implant site showed horizontal and vertical bone defect the Authors decided to perform bone regeneration. The need for such bone augmentation in the younger patient often coincides with the timing for third molar removal. By combining third molar extraction with bone harvest and alveolar grafting, the patient undergoes only one surgical approach. The bone height (9.5 mm) and width (5.7 mm) were measured at the point of interest (tooth 12) both before and after implant placement in the reconstructed panoramic and parasagittal views by Cone Beam Computed Tomography (CBCT) scan. The final results demonstrated an increase in length of 5 mm after bone slat technique (from 9.5 mm to 13.5 mm) and an increase in width of 1 mm (from 5.7 mm to 6.7 mm). ISQ measurements were recorded at the time of implant placement (the mean was: 68.5) and immediately after individualized screw-retained provisional crown (the mean was: 77). This technique is reliable and aesthetic and functional results appear to be stable and respect this requisite: simple and fast graft harvesting and low risk of morbidity especially in conjunction with third molar removal.

The three-dimensional reconstruction of the jaw with “bone slat technique” in conjunction with third molar removal

PubMed Central

Santagata, Mario; Cecere, Atirge; Prisco, Rosario V.E.; Tartaro, Gianpaolo

2017-01-01

Summary Background The purpose of this study was to report the outcome of the management of both horizontal and vertical defects of alveolar crest using the bone slat technique approach in conjunction with third molar removal prior to implant placement in the aesthetic area. Methods We present a 20-year-old female patient who lost a maxillary lateral incisor. The objective of treatment was to replace the lateral incisor with an implant-supported crown restoration without interfering with the integrity and topography of the adjacent gingival tissues. Because the future implant site showed horizontal and vertical bone defect the Authors decided to perform bone regeneration. The need for such bone augmentation in the younger patient often coincides with the timing for third molar removal. By combining third molar extraction with bone harvest and alveolar grafting, the patient undergoes only one surgical approach. The bone height (9.5 mm) and width (5.7 mm) were measured at the point of interest (tooth 12) both before and after implant placement in the reconstructed panoramic and parasagittal views by Cone Beam Computed Tomography (CBCT) scan. Results The final results demonstrated an increase in length of 5 mm after bone slat technique (from 9.5 mm to 13.5 mm) and an increase in width of 1 mm (from 5.7 mm to 6.7 mm). ISQ measurements were recorded at the time of implant placement (the mean was: 68.5) and immediately after individualized screw-retained provisional crown (the mean was: 77). Conclusions This technique is reliable and aesthetic and functional results appear to be stable and respect this requisite: simple and fast graft harvesting and low risk of morbidity especially in conjunction with third molar removal. PMID:29682225

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

[Early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect].

PubMed

Xiao, Jian; Mao, Zhao-Guang; Zhu, Hui-Hua; Guo, Liang

2017-03-25

To discuss the curative effect of the early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect. From December 2013 to January 2015, 36 cases of lower limb open comminuted fractures complicated with bone defects were treated by the vancomycin ALBC combined with the external fixation support, including 26 males and 10 females with an average age of 38.0 years old ranging from 19 to 65 years old. The included cases were all open fractures of lower limbs complicated with bone defects with different degree of soft tissue injuries. Among them, 25 cases were tibial fractures, 11 cases were femoral fractures. The radiographs indicated a presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0 cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12 cases were typr IIIB. The percentage of wound infection, bone grafting time, fracture healing time and postoperative joint function of lower limb were observed. The function of injured limbs was evaluated at 1 month after the clinical healing of fracture based on Paley evaluation criterion. All cases were followed up for 3 to 24 months with an average of (6.0±3.0) months. The wound surface was healed well, neither bone infections nor unhealed bone defects were presented. The reoperation of bone grafting was done at 6 weeks after the patients received an early treatment with ALBC, some of them were postponed to 8 weeks till the approximate healing of fractures, the treatment course lasted for 4 to 8 months with an average of(5.5±1.5) months. According to Paley and other grading evaluations of bone and function, there were 27 cases as excellent, 5 cases as good, 3 cases as ordinary. The ALBC combined with external fixation support was an effective method for early treatment to treat the traumatic lower limb open fractures complicated with bone defects. This method was typified with the advantages such as easy operation, short operation time, overwhelming superiority in controlling infection and provision of good bone grafting bed, a good bone healing can be realized by the use of membrane induction technology for bone grafting.

[Current treatment situation and progress on bone defect of collapsed tibial plateau fractures].

PubMed

Luo, Chang-qi; Fang, Yue; Tu, Chong-qi; Yang, Tian-fu

2016-02-01

Characteristics of collapsed tibial plateau fracture determines that the joint surface must remain anatomical reduction,line of force in tibial must exist and internal fixation must be strong. However, while renewing articular surface smoothness, surgeons have a lot of problems in dealing with bone defect under the joint surface. Current materials used for bone defect treatment include three categories: autologous bone, allograft bone and bone substitutes. Some scholars think that autologous bone grafts have a number of drawbacks, such as increasing trauma, prolonged operation time, the limited source, bone area bleeding,continuous pain, local infection and anesthesia,but most scholars believe that the autologous cancellous bone graft is still the golden standard. Allograft bone has the ability of bone conduction, but the existence of immune responses, the possibility of a virus infection, and the limited source of the allograft cannot meet the clinical demands. Likewise, bone substitutes have the problem that osteogenesis does not match with degradation in rates. Clinical doctors can meet the demand of the patient's bone graft according to patient's own situation and economic conditions.

[Experimental study on vascular bundle implantation combined with cellular transplantation in treating rabbit femoral head necrosis].

PubMed

Chen, Shuang-Tao; Zhang, Wei-Ping; Liu, Chang-An; Wang, Jun-Jiang; Song, Heng-Yi; Chai, Zhi-wen

2013-03-01

To discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis. Thirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically. In group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B. Allogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood supply, and promote the formation of bone trabecula.

Strontium-Doped Calcium Phosphate and Hydroxyapatite Granules Promote Different Inflammatory and Bone Remodelling Responses in Normal and Ovariectomised Rats

PubMed Central

Xia, Wei; Emanuelsson, Lena; Norlindh, Birgitta; Omar, Omar; Thomsen, Peter

2013-01-01

The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone. PMID:24376855

Bone regeneration by means of a three-dimensional printed scaffold in a rat cranial defect.

PubMed

Kwon, Doo Yeon; Park, Ji Hoon; Jang, So Hee; Park, Joon Yeong; Jang, Ju Woong; Min, Byoung Hyun; Kim, Wan-Doo; Lee, Hai Bang; Lee, Junhee; Kim, Moon Suk

2018-02-01

Recently, computer-designed three-dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer-designed 3D scaffold to drive new bone formation in a bone defect. Poly-L-lactide (PLLA) and bioactive β-tricalcium phosphate (TCP) were simply mixed to prepare ink. PLLA + TCP showed good printability from the micronozzle and solidification within few seconds, indicating that it was indeed printable ink for layer-by-layer printing. In the images, TCP on the surface of (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG-63 cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP scaffold was implanted into a full-thickness cranial bone defect in rats. The new bone formation was monitored by microcomputed tomography and histological analysis of the in vivo PLLA + TCP scaffold with or without MG-63 cells. The bone defect was gradually spontaneously replaced with new bone tissues when we used both bioactive TCP and MG-63 cells in the PLLA scaffold. Bone formation driven by the PLLA + TCP30 scaffold with MG-63 cells was significantly greater than that in other experimental groups. Furthermore, the PLLA + TCP scaffold gradually degraded and matched well the extent of the gradual new bone formation on microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold effectively supports new bone formation in a cranial bone defect. Copyright © 2017 John Wiley & Sons, Ltd.

Scanning electron microscopy study of new bone formation following small and large defects preserved with xenografts supplemented with pamidronate-A pilot study in Fox-Hound dogs at 4 and 8 weeks.

PubMed

Lozano-Carrascal, Naroa; Satorres-Nieto, Marta; Delgado-Ruiz, Rafael; Maté-Sánchez de Val, José Eduardo; Gehrke, Sergio Alexandre; Gargallo-Albiol, Jorge; Calvo-Guirado, José Luis

2017-01-01

The aim of the present study was to evaluate the feasibility of SEM and EDX microanalysis on evaluating the effect of porcine xenografts (MP3 ® ) supplemented with pamidronate during socket healing. Mandibular second premolars (P2) and first molars (M1) were extracted from six Beagle dogs. P2 were categorized as small defects (SD) and M1 as large defects (LD). Four random groups were created: SC (small control defects with MP3 ® ), ST (small test defects MP3 ® +pamidronate), LC (large control defects with MP3 ® ), and LT (large test defects MP3 ® +pamidronate). At four and eight weeks of healing the samples were evaluated fisically through scanning electron microscopy (SEM), and chemical element mapping was carried out by Energy dispersive X-ray spectroscopy (EDX). After four weeks of healing, SEM and EDX analysis revealed more mineralized bone in ST and LT groups compared with control groups (p<0.05). After eight weeks, Ca/P ratios were slightly higher for small defects (groups SC and ST); in SEM description, in both control and test groups, trabecular bone density was similar to the adjacent mineralized cortical bone. Within the limitations of this experimental study, SEM description and EDX elemental microanalysis have demonstrated to be useful techniques to assess bone remodelling of small and large defects. Both techniques show increased bone formation in test groups (MP3 ® modified with pamidronate) after four and eight weeks of healing. Copyright © 2016 Elsevier GmbH. All rights reserved.

BMP-2-regenerated calvarial bone: a biomechanical appraisal in a large animal model.

PubMed

Cray, James; Henderson, Sarah E; Smith, Darren M; Kinsella, Christopher R; Bykowski, Michael; Cooper, Gregory M; Almarza, Alejandro J; Losee, Joseph E

2014-11-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is gaining popularity in craniofacial applications. Calvarial defects are, under normal circumstances, subjected to only minimal levels of the biomechanical stresses known to play an important role in osteogenesis, yet regenerated calvarial bone must be capable of withstanding traumatic forces such that the underlying neurocapsule is protected. The aim of this study is to, for the first time, assess the biomechanical properties of calvarial bone regenerated with derivations of a commercially available rhBMP-2-based system. Standardized calvarial defects were created in 23 adult male canines. These defects were treated with rhBMP-2 on one of several carriers. After 24 weeks, the biomechanical properties of the rhBMP-2-generated bone were compared to those of controls with a modified punch-out test (Bluehill 2; Instron, Norwood, Mass) and compared using a paired nonparametric analyses (SPSS, 17.0, Chicago, Ill). In a previously published report, defects across all the rhBMP-2 therapy groups were observed to have a mean rate of 99.5% radio-opacity at 24 weeks indicating nearly full bony coverage of the calvarial defect (compared to 32.7% in surgical controls). For ultimate load, ultimate energy, and first peak energy, there were significant differences (P<0.05) with the control native bone having more robust biomechanical properties than the rhBMP-2-generated bone. We conclude from these findings that rhBMP-2-generated calvarial bone is significantly less protective against trauma than native bone at 6 months. Further investigation is required to assess the efficacy of rhBMP-2 in healing calvarial defects in the longer term.

Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect.

PubMed

Shao, Huifeng; Ke, Xiurong; Liu, An; Sun, Miao; He, Yong; Yang, Xianyan; Fu, Jianzhong; Liu, Yanming; Zhang, Lei; Yang, Guojing; Xu, Sanzhong; Gou, Zhongru

2017-04-12

Three-dimensional (3D) printing bioactive ceramics have demonstrated alternative approaches to bone tissue repair, but an optimized materials system for improving the recruitment of host osteogenic cells into the bone defect and enhancing targeted repair of the thin-wall craniomaxillofacial defects remains elusive. Herein we systematically evaluated the role of side-wall pore architecture in the direct-ink-writing bioceramic scaffolds on mechanical properties and osteogenic capacity in rabbit calvarial defects. The pure calcium silicate (CSi) and dilute Mg-doped CSi (CSi-Mg6) scaffolds with different layer thickness and macropore sizes were prepared by varying the layer deposition mode from single-layer printing (SLP) to double-layer printing (DLP) and then by undergoing one-, or two-step sintering. It was found that the dilute Mg doping and/or two-step sintering schedule was especially beneficial for improving the compressive strength (∼25-104 MPa) and flexural strength (∼6-18 MPa) of the Ca-silicate scaffolds. The histological analysis for the calvarial bone specimens in vivo revealed that the SLP scaffolds had a high osteoconduction at the early stage (4 weeks) but the DLP scaffolds displayed a higher osteogenic capacity for a long time stage (8-12 weeks). Although the DLP CSi scaffolds displayed somewhat higher osteogenic capacity at 8 and 12 weeks, the DLP CSi-Mg6 scaffolds with excellent fracture resistance also showed appreciable new bone tissue ingrowth. These findings demonstrate that the side-wall pore architecture in 3D printed bioceramic scaffolds is required to optimize for bone repair in calvarial bone defects, and especially the Mg doping wollastontie is promising for 3D printing thin-wall porous scaffolds for craniomaxillofacial bone defect treatment.

Assessment of bone repair in critical-size defect in the calvarium of rats after the implantation of tricalcium phosphate beta (β-TCP).

PubMed

de Freitas Silva, Leonardo; de Carvalho Reis, Erik Neiva Ribeiro; Barbara, Tânia Aparecida; Bonardi, João Paulo; Garcia, Idelmo Rangel; de Carvalho, Paulo Sérgio Perri; Ponzoni, Daniela

2017-07-01

Evaluating the osteoconductive property of tricalcium phosphate beta (β-TCP) in comparison to that of inorganic bovine bone for repair in a critical-size defect in the rat calvarium. Critical-size defects of 7mm were made with a trephine in the calvaria of 48 Wistar rats. The animals were divided into four groups, and the defects in each group were filled with tricalcium phosphate beta (β-TCP), inorganic bovine bone (Bio-Oss), autogenous bone, or left empty. The animals were euthanized at two different time points (30 and 60days post-operation). All defects were recovered with a absorbable membrane of bovine cortical bone. Histological, histometric, and immunohistochemical (osteocalcin) assessments were carried out at 30 and 60days post-operation. At 30days post-operation, all groups showed areas of bone formation, predominantly when autogenous grafts were used. However, there were no statistically significant differences between the treatment groups (p>0.05). After 60days, there were similarities in the bone formation patterns between the β-TCP (26.32±) and Bio-Oss (17.35±) groups (p=0.549). In terms of the immunohistochemical assessment of osteocalcin, the clot group showed light to moderate staining at 30 and 60days. The autogenous group showed moderate staining at 30days and moderate to intense staining after 60days. The Bio-Oss group showed light to moderate staining after 30days and intense staining at 60days. The β-TCP group showed moderate staining at 30 and 60days post-operation. β-TCP is a good osteoconductive material with similar effects to those of inorganic bovine bone graft and is suitable for utilization in the repair of bone defects. Copyright © 2017 Elsevier GmbH. All rights reserved.

Repair of bony lateral skull base defects equal to or larger than 10 mm by extracorporeally sewed unit-sandwich graft.

PubMed

Indorewala, Shabbir; Nemade, Gaurav; Indorewala, Abuzar; Mahajan, Gauri

2018-06-23

To see effectiveness of the senior author's repair technique for repair of large (equal to or larger than 10 mm) bony lateral skull base defects. Retrospective. Secondary/tertiary care center. We performed retrospective review of 9 surgeries done in our institution between January 2010 and December 2013 for repair of large lateral bony skull base defects. We defined skull base defects extra-cranially and repaired them intra-cranially. We made an extracorporeal sandwich of autologous fascia-bone-fascia (fascia lata and nasal septal bone) and sewed it together to make it into a unit-sandwich graft. This extracorporeally sewed unit-sandwich graft was then inserted to close the large skull base defects either via (1) a cranial slit-window, or (2) the skull base defect itself. Since skull base is bony, bony repair is preferred. Bone plates that are easily available for skull base repair are calvarial and nasal septal bone. Occasionally, harvest of split calvarial bone carries risk of major complications. We preferred nasal septal bone. Harvesting of septal bone even in children using a posterior incision should not disturb the cartilage growth centers. All nine patients were operated by this technique. We had four patients with cerebrospinal fluid leak, and five patients with brain herniation. All these patients had complete reversal of herniation of cranial contents and cessation of cerebrospinal fluid leak. On imaging, in 6 cases the bone graft remained in original intended position after 12 months of surgery. The bone graft was not identifiable in 3 cases. The senior author's technique using autologous multi-layered graft is simple to master, repeatable and very effective.

The study of mechanical behavior on the interface between calcar-defect femur and restorations by means of finite element analysis

NASA Astrophysics Data System (ADS)

Shi, X. H.; Jiang, W.; Chen, H. Z.; Zou, W.; Wang, W. D.; Guo, Z.; Luo, J. M.; Gu, Z. W.; Zhang, X. D.

2008-11-01

The mechanical behaviors of calcar-defected femur and restorations under physiological load are the key factors that will greatly influence the success of femur calcar defect repairing, especially the stress distribution on the bone-restoration interface. 3D finite elements analysis (FEA) was used to analyze the mechanical characters on the interfaces between femoral calcar defects and bone cement or HA restorations. Under the load of two times of a human weight (1436.03 N) and with the increase of the defect dimension from 6 mm to 12 mm, the maximal stresses on the surface of restorations are from 7.06 MPa to 11.89 MPa for bone cement and 2.97-9 MPa for HA separately. In this condition, HA restoration will probably be broken on the bone-restoration interface when the defect diameter is beyond 8 mm. Furthermore, under the load of 1.5 times of a human weight, HA restoration would not be safe unless the defect dimension is smaller than 10 mm, because the maximal stress (4.62 MPa) on the restoration is only a little lower than compressive strength of HA, otherwise the bone fixation device should be applied to ensure the safety. It is relatively safe for all restorations under all the tested defect sizes when the load is just the weight of a human body.

Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/β-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration.

PubMed

Hwang, Kyoung-Sub; Choi, Jae-Won; Kim, Jae-Hun; Chung, Ho Yun; Jin, Songwan; Shim, Jin-Hyung; Yun, Won-Soo; Jeong, Chang-Mo; Huh, Jung-Bo

2017-04-17

The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.

Phosphoserine-modified calcium phosphate cements: bioresorption and substitution.

PubMed

Offer, Liliana; Veigel, Bastian; Pavlidis, Theodoros; Heiss, Christian; Gelinsky, Michael; Reinstorf, Antje; Wenisch, Sabine; Lips, Katrin Susanne; Schnettler, Reinhard

2011-01-01

This work reports the effects of phosphoserine addition on the biodegradability of calcium phosphate cements. The characteristics of a phosphoserine-modified calcium phosphate cement without collagen in a large animal model are presented here for the first time. Critical size bone defects in the proximal tibia of 10 sheep were filled with the bone cement, and five sheep with empty defects were included as controls. The sheep were sacrificed after either 10 days or 12 weeks, and bones were processed for histological, histomorphometric and enzyme histochemical analyses as well as transmission electron microscopic examination. After 12 weeks, there was no significant reduction in either the implant or the bone defect cross-sectional area. Different amounts of fibrous tissue were observed around the implant and in the bone defect after 12 weeks. The direct bone-implant contact decreased after 12 weeks (p = 0.034). Although the implanted material properly filled the defect and promoted an initial activation of macrophages and osteoblasts, the resorption and simultaneous substitution did not reach expected levels during the experimental time course. Although other studies have shown that the addition of phosphoserine to calcium phosphate cements that have already been modified with collagen I resulted in an acceleration of cement resorption and bone regeneration, this study demonstrates that phosphoserine-modified calcium phosphate cements without collagen perform poorly in the treatment of bone defects. Efforts to use phosphoserine in the development of new composites should take into consideration the need to improve osteoconduction simultaneously via other means. Copyright © 2010 John Wiley & Sons, Ltd.

Peri-implant assessment via cone beam computed tomography and digital periapical radiography: an ex vivo study.

PubMed

Silveira-Neto, Nicolau; Flores, Mateus Ericson; De Carli, João Paulo; Costa, Max Dória; Matos, Felipe de Souza; Paranhos, Luiz Renato; Linden, Maria Salete Sandini

2017-11-01

This research evaluated detail registration in peri-implant bone using two different cone beam computer tomography systems and a digital periapical radiograph. Three different image acquisition protocols were established for each cone beam computer tomography apparatus, and three clinical situations were simulated in an ex vivo fresh pig mandible: buccal bone defect, peri-implant bone defect, and bone contact. Data were subjected to two analyses: quantitative and qualitative. The quantitative analyses involved a comparison of real specimen measures using a digital caliper in three regions of the preserved buccal bone - A, B and E (control group) - to cone beam computer tomography images obtained with different protocols (kp1, kp2, kp3, ip1, ip2, and ip3). In the qualitative analyses, the ability to register peri-implant details via tomography and digital periapical radiography was verified, as indicated by twelve evaluators. Data were analyzed with ANOVA and Tukey's test (α=0.05). The quantitative assessment showed means statistically equal to those of the control group under the following conditions: buccal bone defect B and E with kp1 and ip1, peri-implant bone defect E with kp2 and kp3, and bone contact A with kp1, kp2, kp3, and ip2. Qualitatively, only bone contacts were significantly different among the assessments, and the p3 results differed from the p1 and p2 results. The other results were statistically equivalent. The registration of peri-implant details was influenced by the image acquisition protocol, although metal artifacts were produced in all situations. The evaluators preferred the Kodak 9000 3D cone beam computer tomography in most cases. The evaluators identified buccal bone defects better with cone beam computer tomography and identified peri-implant bone defects better with digital periapical radiography.

Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma.

PubMed

Nair, Manitha B; Varma, H K; Menon, K V; Shenoy, Sachin J; John, Annie

2009-06-01

Segmental bone defects resulting from trauma or pathology represent a common and significant clinical problem. In this study, a triphasic ceramic (calcium silicate, hydroxyapatite and tricalcium phosphate)-coated hydroxyapatite (HASi) having the benefits of both HA (osteointegration, osteoconduction) and silica (degradation) was used as a bone substitute for the repair of segmental defect (2 cm) created in a goat femur model. Three experimental goat femur implant groups--(a) bare HASi, (b) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi (HASi+C) and (c) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi+platelet-rich plasma (HASi+CP)--were designed and efficacy performance in the healing of the defect was evaluated. In all the groups, the material united with host bone without any inflammation and an osseous callus formed around the implant. This reflects the osteoconductivity of HASi where the cells have migrated from the cut ends of host bone. The most observable difference between the groups appeared in the mid region of the defect. In bare HASi groups, numerous osteoblast-like cells could be seen together with a portion of material. However, in HASi+C and HASi+CP, about 60-70% of that area was occupied by woven bone, in line with material degradation. The interconnected porous nature (50-500 microm), together with the chemical composition of the HASi, facilitated the degradation of HASi, thereby opening up void spaces for cellular ingrowth and bone regeneration. The combination of HASi with cells and PRP was an added advantage that could promote the expression of many osteoinductive proteins, leading to faster bone regeneration and material degradation. Based on these results, we conclude that bare HASi can aid in bone regeneration but, with the combination of cells and PRP, the sequence of healing events are much faster in large segmental bone defects in weight-bearing areas in goats.

Prototyped grafting plate for reconstruction of mandibular defects.

PubMed

Zhou, Libin; Wang, Peilin; Han, Haolun; Li, Baowei; Wang, Hongnan; Wang, Gang; Zhao, Jinlong; Liu, Yanpu; Wu, Wei

2014-12-01

To esthetically and functionally restore a 40-mm canine mandibular discontinuity defect using a custom-made titanium bone-grafting plate in combination with autologous iliac bone grafts. Individualized titanium bone-grafting plates were manufactured using a series of techniques, including reverse engineering, computer aided design, rapid prototyping and titanium casting. A 40-mm discontinuous defect in the right mandibular body was created in 9 hybrid dogs. The defect was restored immediately using the customized plate in combination with autologous cancellous iliac blocks. Sequential radionuclide bone imaging was performed to evaluate the bone metabolism and reconstitution of the grafts. The specimens were evaluated by biomechanical testing, 3-dimensional microcomputed tomographic scanning, and histological examination. The results revealed that the symmetry of the mandibles was reconstructed using the customized grafting plate, and the bony continuity of the mandibles was restored. By 12 weeks after the operation, the cancellous iliac grafts became a hard bone block, which was of comparable strength to native mandibles. A fibrous tissue intermediate was found between the remodelled bone graft and the titanium plate. The results indicate that the prototyped grafting plate can be used to restore mandibular discontinuous defects, and satisfactory aesthetical and functional reconstruction can be achieved. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Chitosan-Graphene Oxide 3D scaffolds as Promising Tools for Bone Regeneration in Critical-Size Mouse Calvarial Defects.

PubMed

Hermenean, Anca; Codreanu, Ada; Herman, Hildegard; Balta, Cornel; Rosu, Marcel; Mihali, Ciprian Valentin; Ivan, Alexandra; Dinescu, Sorina; Ionita, Mariana; Costache, Marieta

2017-11-30

Limited self-regenerating capacity of human skeleton makes the reconstruction of critical size bone defect a significant challenge for clinical practice. Aimed for regenerating bone tissues, this study was designed to investigate osteogenic differentiation, along with bone repair capacity of 3D chitosan (CHT) scaffolds enriched with graphene oxide (GO) in critical-sized mouse calvarial defect. Histopathological/histomorphometry and scanning electron microscopy(SEM) analysis of the implants revealed larger amount of new bone in the CHT/GO-filled defects compared with CHT alone (p < 0.001). When combined with GO, CHT scaffolds synergistically promoted the increase of alkaline phosphatase activity both in vitro and in vivo experiments. This enhanced osteogenesis was corroborated with increased expression of bone morphogenetic protein (BMP) and Runx-2 up to week 4 post-implantation, which showed that GO facilitates the differentiation of osteoprogenitor cells. Meanwhile, osteogenesis was promoted by GO at the late stage as well, as indicated by the up-regulation of osteopontin and osteocalcin at week 8 and overexpressed at week 18, for both markers. Our data suggest that CHT/GO biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.

Osteogenic effect of tricalcium phosphate substituted by magnesium associated with Genderm® membrane in rat calvarial defect model.

PubMed

Costa, Neusa M F; Yassuda, Debora H; Sader, Marcia S; Fernandes, Gustavo V O; Soares, Glória D A; Granjeiro, José M

2016-04-01

Beta-tricalcium phosphate (β-TCP) is one of the most widely employed bioresorbable materials for bone repair since it shows excellent biological compatibility, osteoconductivity and resorbability. The incorporation of divalent cations such as magnesium onto the β-TCP structure (β-TCMP) may improve the biological response to the material through the release of bioactive ions. The objective of this study was to evaluate, on a rat calvarial critical size grafting model, the bone regeneration process using β-TCP and β-TMCP granules by histomorphometric analysis. Results demonstrated that six months after bone grafting, the association of GBR (guided bone regeneration) using a membrane (GenDerm®) and granules of β-TCP and β-TCMP significantly improves bone repair in the treatment of critical-size defect in rat skulls, in comparison to untreated defects or GBR alone, leading to a bone level approximately four to five-fold greater than in the blood clot group. The β-TCMP+GenDerm® membrane group presented 40.5% of the defect area filled by newly-formed bone, even at the central part of the defect, rather than only at the border, as seen in the other experimental groups. Copyright © 2015 Elsevier B.V. All rights reserved.

Biomechanical study of prophylactic internal fixation of the radial osteocutaneous donor site using the sheep tibia model.

PubMed

Avery, C M E; Best, A; Patterson, P; Rolton, J; Ponter, A R S

2007-09-01

This study investigated the strengthening effect of different types of plate and position after osteotomy of the sheep tibia, which is a model for the radial osteocutaneous donor site. Fifty matched pairs of adult sheep tibias were tested in torsion and four-point bending. Firstly, the weakening effect of an osteotomy was compared with the intact bone. Then pairs of bones with an osteotomy were compared with and without reinforcement with different types of 3.5mm plate. The plate was placed in either the anterior (over the defect) or posterior (on the intact cortex) position. In torsion the mean strength of the intact bone was 45% greater than after osteotomy (P=0.02). The reinforced bone was on average 61% stronger than the unreinforced bone (P<0.001). In bending the mean strength of the intact bone was 188% greater than after osteotomy (P=0.02). The reinforced bone was on average 184% stronger then the unreinforced bone (P<0.001). The tibia was able to withstand much greater loads in bending. The dynamic compression plate was the strongest reinforcement in both torsion and bending. The position of the plate did not alter the strengthening effect in torsion but the posterior position resisted greater bending loads (P=0.01). This may not be relevant in clinical practice as the radius is likely to fracture first as a result of lower torsional forces.

[Use of free vascularized fibular graft flap in the treatment of large bone defects after limb injury].

PubMed

Bumbasirević, Marko Z; Lesić, Aleksandar R; Atkinson, Henry Dushan Edward; Tulić, Goran C

2013-01-01

Free vascularized fibular graft is of the greatest importance in the orthopaedics and trauma. Bone, skeletal defects due to the trauma, infections and congenital anomalies could be successfully solved by the free vascularized fibular grafts. In this article the main anatomical data of fibular graft, surgical techniques, indications for the FVFG in the treatment of trauma caused bone defects or its complications -sequels are described.

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Internal Prosthetic Replacement of Skeletal Segments Lost in Combat Injuries.

DTIC Science & Technology

1973-08-31

osteo- articular bone grafts. Clin. Ortho., 87: 156, 1972. 8. Tuli, S. M.: Bridging of bone defects by massive bone grafts in tumorous conditions. Clin...fashion in its proximal one-third to "prevent distractic ,n of the fragments. The fiber metal segment was then placed in the appropriate defect and the...defect slightly oversized and also osteotomizing the fibula to delete any possible distracting forces or angulating forces. The only complication in

New options for vascularized bone reconstruction in the upper extremity.

PubMed

Houdek, Matthew T; Wagner, Eric R; Wyles, Cody C; Nanos, George P; Moran, Steven L

2015-02-01

Originally described in the 1970s, vascularized bone grafting has become a critical component in the treatment of bony defects and non-unions. Although well established in the lower extremity, recent years have seen many novel techniques described to treat a variety of challenging upper extremity pathologies. Here the authors review the use of different techniques of vascularized bone grafts for the upper extremity bone pathologies. The vascularized fibula remains the gold standard for the treatment of large bone defects of the humerus and forearm, while also playing a role in carpal reconstruction; however, two other important options for larger defects include the vascularized scapula graft and the Capanna technique. Smaller upper extremity bone defects and non-unions can be treated with the medial femoral condyle (MFC) free flap or a vascularized rib transfer. In carpal non-unions, both pedicled distal radius flaps and free MFC flaps are viable options. Finally, in skeletally immature patients, vascularized fibular head epiphyseal transfer can provide growth potential in addition to skeletal reconstruction.

Platelet-rich fibrin in the treatment of periodontal bone defects.

PubMed

Ranganathan, Aravindhan T; Chandran, Chitraa R

2014-05-01

Periodontitis is characterized by the formation of true pockets, bone loss and attachment loss. Various techniques have been attempted in the past to truly regenerate the lost periodontal structures, albeit with variable outcome. In this evolution, the technique being tried out widely is the use of platelet rich concentrates, namely platelet-rich fibrin (PRF). In this report, we present a case of surgical treatment of osseous bone defects namely two walled crater and dehiscence treated in posterior teeth with autologously prepared platelet rich fibrin mixed with hydroxy apatite bone graft and PRF in the form of a membrane. Our results showed clinical improvements in all the clinical parameters postoperatively namely the pocket depth reduction and gain in attachment level and hence, PRF can be used alone or in combination with the bone graft to yield successful clinical results in treating periodontal osseous defects. Platelet-rich fibrin is an effective alternative to platelet-rich plasma (PRP) in reconstructing bone defects.

A review of fibrin and fibrin composites for bone tissue engineering

PubMed Central

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications. PMID:28761338

A review of fibrin and fibrin composites for bone tissue engineering.

PubMed

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for Bone Tissue Engineering Applications.

PubMed

Rindone, Alexandra N; Nyberg, Ethan; Grayson, Warren L

2017-05-11

Millions of patients worldwide require bone grafts for treatment of large, critically sized bone defects from conditions such as trauma, cancer, and congenital defects. Tissue engineered (TE) bone grafts have the potential to provide a more effective treatment than current bone grafts since they would restore fully functional bone tissue in large defects. Most bone TE approaches involve a combination of stem cells with porous, biodegradable scaffolds that provide mechanical support and degrade gradually as bone tissue is regenerated by stem cells. 3D-printing is a key technique in bone TE that can be used to fabricate functionalized scaffolds with patient-specific geometry. Using 3D-printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB) scaffolds can be produced to have the desired mechanical properties, geometry, and osteoinductivity needed for a TE bone graft. This book chapter will describe the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds. Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these scaffolds in vitro will be described to demonstrate the osteoinductivity of the scaffolds.

Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

PubMed

Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

2017-10-02

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

Harnessing extracellular vesicles to direct endochondral repair of large bone defects

PubMed Central

Ferreira, E.

2018-01-01

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006. PMID:29922444

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis.

PubMed

Wang, Yicun; Jiang, Hui; Deng, Zhantao; Jin, Jiewen; Meng, Jia; Wang, Jun; Zhao, Jianning; Sun, Guojing; Qian, Hongbo

2017-01-01

To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156 ± 23 minutes versus 162 ± 21 minutes), and time to union (11.1 ± 3.0 months versus 10.9 ± 3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled.

The local administration of parathyroid hormone encourages the healing of bone defects in the rat calvaria: Micro-computed tomography, histological and histomorphometric evaluation.

PubMed

Auersvald, Caroline Moreira; Santos, Felipe Rychuv; Nakano, Mayara Mytie; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Scariot, Rafaela; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

2017-07-01

To evaluate the effect of a single-dose local administration of PTH on bone healing in rat calvarial bone defects by means of micro-computed tomography, histological and histomorphometric analysis. Critical-size cranial osteotomy defects were created in 42 male rats. The animals were randomly divided into 3 groups. In the C Group, the bone defect was only filled with a blood clot. In the S Group, it was filled with a collagen sponge and covered with bovine cortical membrane. In the PTH Group, the defect was filled with a collagen sponge soaked with PTH and covered with bovine cortical membrane. The groups were further split in two for euthanasia 15 and 60days post-surgery. Data was statistically analyzed with t-tests for independent samples or the nonparametric Mann-Whitney test when applicable. Intragroup comparisons were analyzed with paired t-tests (p<0.05). Micro-CT analysis results did not demonstrate statistically significant intergroup differences. At 15days post-surgery, the histomorphometric analysis showed that the PTH Group exhibited a significantly higher percentage of bone formation compared with the S Group. At 60days post-surgery, a higher percentage of new bone was observed in the PTH group. The results suggest that the local administration of PTH encouraged the bone healing in critical-size calvarial defects in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

NASA Astrophysics Data System (ADS)

Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

2011-03-01

Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis

PubMed Central

Wang, Yicun; Jiang, Hui; Deng, Zhantao; Meng, Jia; Wang, Jun

2017-01-01

Background To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. Methods 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Results Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156 ± 23 minutes versus 162 ± 21 minutes), and time to union (11.1 ± 3.0 months versus 10.9 ± 3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. Conclusions It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled. PMID:29333448

The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities

PubMed Central

Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.

2015-01-01

We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process. PMID:26098852

Treatment of open tibial shaft fracture with soft tissue and bone defect caused by aircraft bomb--case report.

PubMed

Golubović, Zoran; Vidić, Goran; Trenkić, Srbobran; Vukasinović, Zoran; Lesić, Aleksandar; Stojiljković, Predrag; Stevanović, Goran; Golubović, Ivan; Visnjić, Aleksandar; Najman, Stevo

2010-01-01

Aircraft bombs can cause severe orthopaedic injuries. Tibia shaft fractures caused by aircraft bombs are mostly comminuted and followed by bone defects, which makes the healing process extremely difficult and prone to numerous complications. The goal of this paper is to present the method of treatment and the end results of treatment of a serious open tibial fracture with soft and bone tissue defects resulting from aircraft bomb shrapnel wounds. A 26-year-old patient presented with a tibial fracture as the result of a cluster bomb shrapnel wound. He was treated applying the method of external bone fixation done two days after wounding, as well as of early coverage of the lower leg soft tissue defects done on the tenth day after the external fixation of the fracture. The external fixator was removed after five months, whereas the treatment was continued by means of functional plaster cast for another two months. The final functional result was good. Radical wound debridement, external bone fixation of the fracture, and early reconstruction of any soft tissue and bone defects are the main elements of the treatment of serious fractures.

Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

PubMed Central

Qi, Xin; Liu, Yang; Ding, Zhen-yu; Cao, Jia-qing; Huang, Jing-huan; Zhang, Jie-yuan; Jia, Wei-tao; Wang, Jing; Liu, Chang-sheng; Li, Xiao-lin

2017-01-01

In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration. PMID:28230059

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

PubMed

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-04-20

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

PubMed Central

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-01-01

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. PMID:27104525

Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

NASA Astrophysics Data System (ADS)

Qi, Xin; Liu, Yang; Ding, Zhen-Yu; Cao, Jia-Qing; Huang, Jing-Huan; Zhang, Jie-Yuan; Jia, Wei-Tao; Wang, Jing; Liu, Chang-Sheng; Li, Xiao-Lin

2017-02-01

In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration.

Management of segmental bony defects: the role of osteoconductive orthobiologics.

PubMed

McKee, Michael D

2006-01-01

Our knowledge about, and the availability of, orthobiologic materials has increased exponentially in the last decade. Although previously confined to the experimental or animal-model realm, several orthobiologics have been shown to be useful in a variety of clinical situations. As surgical techniques in vascular anastomosis, soft-tissue coverage, limb salvage, and fracture stabilization have improved, the size and frequency of bony defects (commensurate with the severity of the initial injury) have increased, as well. Because all methods of managing segmental bony defects have drawbacks, a need remains for a readily available, void-filling, inexpensive bone substitute. Such a bone substitute fulfills a permissive role in allowing new bone to grow into a given defect. Such potential osteoconductive materials include ceramics, calcium sulfate or calcium phosphate compounds, hydroxyapatite, deproteinized bone, corals, and recently developed polymers. Some materials that have osteoinductive properties, such as demineralized bone matrix, also display prominent osteoconductive properties.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone.

PubMed

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-09-24

The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using devitalized tumor-bearing bones for the repairing of segmental defects after tumor resection. Twenty-seven eligible patients treated from February 2004 to May 2012 were included. The segmental tumor bone (mean length, 14 cm) was resected, and then devitalized in 20% sterile saline at 65 °C for 30 min after the tumor tissue was removed. The devitalized bone was implanted back into the defect by using nails or plates. Complete healing of 50 osteotomy ends was achieved at a median time of 11 months (interquartile range (IQR) 9-13 months). Major complications included bone nonunion in four bone junctions (7.4%), devitalized bone fracture in one patient (3.7%), deep infection in three patients (11.1%), and fixation failure in two patients (7.4%). The bone union rates at 1 and 2 years were 74.1 and 92.6%, respectively. The average functional score according to the Musculoskeletal Tumor Society (MSTS) 93 scoring system was 93 % (IQR 80-96.7%). Incubation in 20% sterile saline at 65 °C for 30 min is an effective method of devitalization of tumor-bearing bone. The retrieved bone graft may provide as a less expensive alternative for limb salvage. The structural bone and the preserved osteoinductivity of protein may improve bone union.

Combined flaps based on the superficial temporal vascular system for reconstruction of facial defects.

PubMed

Zhou, Renpeng; Wang, Chen; Qian, Yunliang; Wang, Danru

2015-09-01

Facial defects are multicomponent deficiencies rather than simple soft-tissue defects. Based on different branches of the superficial temporal vascular system, various tissue components can be obtained to reconstruct facial defects individually. From January 2004 to December 2013, 31 patients underwent reconstruction of facial defects with composite flaps based on the superficial temporal vascular system. Twenty cases of nasal defects were repaired with skin and cartilage components, six cases of facial defects were treated with double island flaps of the skin and fascia, three patients underwent eyebrow and lower eyelid reconstruction with hairy and hairless flaps simultaneously, and two patients underwent soft-tissue repair with auricular combined flaps and cranial bone grafts. All flaps survived completely. Donor-site morbidity is minimal, closed primarily. Donor areas healed with acceptable cosmetic results. The final outcome was satisfactory. Combined flaps based on the superficial temporal vascular system are a useful and versatile option in facial soft-tissue reconstruction. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo

NASA Astrophysics Data System (ADS)

Qi, Xin; Pei, Peng; Zhu, Min; Du, Xiaoyu; Xin, Chen; Zhao, Shichang; Li, Xiaolin; Zhu, Yufang

2017-02-01

In the clinic, bone defects resulting from infections, trauma, surgical resection and genetic malformations remain a significant challenge. In the field of bone tissue engineering, three-dimensional (3D) scaffolds are promising for the treatment of bone defects. In this study, calcium sulfate hydrate (CSH)/mesoporous bioactive glass (MBG) scaffolds were successfully fabricated using a 3D printing technique, which had a regular and uniform square macroporous structure, high porosity and excellent apatite mineralization ability. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on scaffolds to evaluate hBMSC attachment, proliferation and osteogenesis-related gene expression. Critical-sized rat calvarial defects were applied to investigate the effect of CSH/MBG scaffolds on bone regeneration in vivo. The in vitro results showed that CSH/MBG scaffolds stimulated the adhesion, proliferation, alkaline phosphatase (ALP) activity and osteogenesis-related gene expression of hBMSCs. In vivo results showed that CSH/MBG scaffolds could significantly enhance new bone formation in calvarial defects compared to CSH scaffolds. Thus 3D printed CSH/MBG scaffolds would be promising candidates for promoting bone regeneration.

Osteogenic potential of a chalcone in a critical-size defect in rat calvaria bone.

PubMed

Ortolan, Xana Raquel; Fenner, Bruna Proiss; Mezadri, Telmo José; Tames, David Rivero; Corrêa, Rogério; de Campos Buzzi, Fátima

2014-07-01

This study describes the bone formation stimulated by the application of a type of chalcone to critical-size defects in rat calvarial bone. Sixty female Wistar rats were divided into 6 groups of 10 animals per group: control (no treatment), vehicle (vaseline) and the chalcone (1-phenyl-3-(4-chlorophenyl)-2-propen-1-one) suspended in vaseline at 10%. A critical-size defect of 5 mm was prepared using a trephine in the calvarial bone, after which the treatment was applied, in a single dose, according to the experimental group. The samples were evaluated macroscopically using ImageJ software, and histologically 30 and 45 days after surgery. At 30 days after surgery, there was significant bone formation (p < 0.05) in the groups treated with chalcone, compared with the other groups. Many active osteoblasts were observed adjacent to the borders of the newly formed bone tissue. 45 days after surgery in the chalcone group, the surgical defects showed complete bone closure. The results of this study suggest that chalcone has significant potential to induce the formation of new bone. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Characterization of controlled bone defects using 2D and 3D ultrasound imaging techniques.

PubMed

Parmar, Biren J; Longsine, Whitney; Sabonghy, Eric P; Han, Arum; Tasciotti, Ennio; Weiner, Bradley K; Ferrari, Mauro; Righetti, Raffaella

2010-08-21

Ultrasound is emerging as an attractive alternative modality to standard x-ray and CT methods for bone assessment applications. As of today, however, there is a lack of systematic studies that investigate the performance of diagnostic ultrasound techniques in bone imaging applications. This study aims at understanding the performance limitations of new ultrasound techniques for imaging bones in controlled experiments in vitro. Experiments are performed on samples of mammalian and non-mammalian bones with controlled defects with size ranging from 400 microm to 5 mm. Ultrasound findings are statistically compared with those obtained from the same samples using standard x-ray imaging modalities and optical microscopy. The results of this study demonstrate that it is feasible to use diagnostic ultrasound imaging techniques to assess sub-millimeter bone defects in real time and with high accuracy and precision. These results also demonstrate that ultrasound imaging techniques perform comparably better than x-ray imaging and optical imaging methods, in the assessment of a wide range of controlled defects both in mammalian and non-mammalian bones. In the future, ultrasound imaging techniques might provide a cost-effective, real-time, safe and portable diagnostic tool for bone imaging applications.

Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence.

PubMed

Gianakos, Arianna; Ni, Amelia; Zambrana, Lester; Kennedy, John G; Lane, Joseph M

2016-01-01

Long bone fractures that fail to heal or show a delay in healing can lead to increased morbidity. Bone marrow aspirate concentrate (BMAC) containing bone mesenchymal stem cells (BMSCs) has been suggested as an autologous biologic adjunct to aid long bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of BMAC with BMSCs in the treatment of segmental defects in animal long bones. The PubMed/MEDLINE and EMBASE databases were screened in July 14-25, 2014. The following search criteria were used: [("bmac" OR "bone marrow aspirate concentrate" OR "bmc" OR "bone marrow concentrate" OR "mesenchymal stem cells") AND ("bone" OR "osteogenesis" OR "fracture healing" OR "nonunion" OR "delayed union")]. Three authors extracted data and analyzed for trends. Quality of evidence score was given to each study. Results are presented as Hedge G standardized effect sizes with 95% confidence intervals. The search yielded 35 articles for inclusion. Of studies reporting statistics, 100% showed significant increase in bone formation in the BMAC group on radiograph. Ninety percent reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. Eighty-one percent reported a significant increase in bone area on micro-computed tomography. Seventy-eight percent showed a higher torsional stiffness for the BMAC-treated defects. In the in vivo studies evaluated, BMAC confer beneficial effects on the healing of segmental defects in animal long bone models when compared with a control. Proof-of-concept has been established for BMAC in the treatment of animal segmental bone defects.

Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute - in vivo animal study.

PubMed

Dau, Michael; Kämmerer, Peer W; Henkel, Kai-Olaf; Gerber, Thomas; Frerich, Bernhard; Gundlach, Karsten K H

2016-05-01

Healing characteristics as well as level of tissue integration and degradation of two different nanostructured hydroxyapatite bone substitute materials (BSM) in comparison with a deproteinized hydroxyapatite bovine BSM were evaluated in an in vivo animal experiment. In the posterior mandible of 18 minipigs, bilateral mono cortical critical size bone defects were created. Randomized augmentation procedures with NanoBone(®) (NHA1), Ostim(®) (NHA2) or Bio-Oss(®) (DBBM) were conducted (each material n = 12). Samples were analyzed after five (each material n = 6) and 8 months (each material n = 6). Defect healing, formation of soft tissue and bone as well as the amount of remaining respective BSM were quantified both macro- and microscopically. For NHA2, the residual bone defect after 5 weeks was significantly less compared to NHA1 or DBBM. There was no difference in residual BSM between NHA1 and DBBM, but the amount in NHA2 was significantly lower. NHA2 also showed the least amount of soft tissue and the highest amount of new bone after 5 weeks. Eight months after implantation, no significant differences in the amount of residual bone defects, in soft tissue or in bone formation were detected between the groups. Again, NHA2 showed significant less residual material than NHA1 and DBBM. We observed non-significant differences in the biological hard tissue response of NHA1 and DBBM. The water-soluble NHA2 initially induced an increased amount of new bone but was highly compressed which may have a negative effect in less stable augmentations of the jaw. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone Regeneration in Critical Bone Defects Using Three-Dimensionally Printed β-Tricalcium Phosphate/Hydroxyapatite Scaffolds Is Enhanced by Coating Scaffolds with Either Dipyridamole or BMP-2

PubMed Central

Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere; Ricci, John L.; Cronstein, Bruce N.

2017-01-01

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3-D) printing technology we have created custom 3-D scaffolds of hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3-D Robocasting system, and sintered at 1100°C for 4h. Scaffolds were coated with BMP-2 (200ng/ml), Dypiridamole 100µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP- dipyridamole and HA/β-TCP -BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4 and 8 weeks (n=5 per group; p≤ 0.05, p≤ 0.05 and p≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. PMID:26513656

Raman study of the repair of surgical bone defects grafted with biphasic synthetic microgranular HA + β-calcium triphosphate and irradiated or not with λ780 nm laser.

PubMed

Soares, Luiz Guilherme P; Marques, Aparecida Maria C; Barbosa, Artur Felipe S; Santos, Nicole R; Aciole, Jouber Mateus S; Souza, Caroline Mathias C; Pinheiro, Antonio Luiz B; Silveira, Landulfo

2014-09-01

The treatment of bone loss due to different etiologic factors is difficult, and many techniques aim to improve repair, including a wide range of biomaterials and, recently, photobioengineering. This work aimed to assess, through Raman spectroscopy, the level of bone mineralization using the intensities of the Raman peaks of both inorganic (∼ 960, ∼ 1,070, and ∼ 1,077 cm(-1)) and organic (∼ 1,454 and ∼ 1,666 cm(-1)) contents of bone tissue. Forty rats were divided into four groups each subdivided into two subgroups according to the time of killing (15 and 30 days). Surgical bone defects were made on femur of each animal with a trephine drill. On animals of group Clot, the defect was filled only by blood clot; on group Laser, the defect filled with the clot was further irradiated. On animals of groups Biomaterial and Laser + Biomaterial, the defect was filled by biomaterial and the last one was further irradiated (λ780 nm, 70 mW, Φ ∼ 0.4 cm(2), 20 J/cm(2) session, 140 J/cm(2) treatment) in four points around the defect at 48-h intervals and repeated for 2 weeks. At both 15th and 30th day following killing, samples were taken and analyzed by Raman spectroscopy. At the end of the experimental time, the intensities of both inorganic and organic contents were higher on group Laser + Biomaterial. It is concluded that the use of laser phototherapy associated to biomaterial was effective in improving bone healing on bone defects as a result of the increasing deposition of calcium hydroxyapatite measured by Raman spectroscopy.

Composite three-layer closure of oral antral communication with 10 months follow-up-a case study.

PubMed

Weinstock, Robert J; Nikoyan, Levon; Dym, Harry

2014-02-01

We propose a 3-layer composite closure technique for an oral antral communication (OAC) while avoiding secondary donor site morbidity. A patient had developed a 1-cm OAC after extraction of right maxillary first molar. The patient subsequently developed acute maxillary sinusitis. The patient was taken to the operating room, and a Caldwell-Luc procedure was performed. The bony window from the Caldwell-Luc was "press fit" over the bony OAC defect. Soft tissue closure was then achieved with a buccal fat pad flap and a buccal mucosal advancement flap. The patient was examined on postoperative day 5 and 1, 2, 3, 6, and 10 months postoperatively. The acute sinusitis had resolved. The soft tissue closure was successful. The bone graft remained intact, prevented sinus pneumatization, and restored continuity to the floor of the maxillary sinus. The presented technique for 3-layer closure of OACs allows for the stability of a double-layer closure of OAC with the added benefit of bone grafting from single operative site, achieving stable oral antral closure, bone grafting, and the avoidance of secondary donor site morbidity. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

[LOCAL ANTIBIOTIC THERAPY OF OSTEOMYELITIS USING NONABSORBABLE IMPLANT (REVIEW)].

PubMed

Tuleubaev, B; Saginova, D; Abiyev, T; Davletbaev, M; Koshanova, A

2016-06-01

Despite the variety of treatments available, including surgical procedures and antimicrobial therapy, bone infections is still a medical problem, because they are difficult to treat. Optimal treatment should stabilize the bone, promote the biological recovery of bone defects and destroy bacterial infection. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. In contrast, the antibiotic impregnated bone cements or fillers can act as a local anti-infective drug delivery system, which not only fills the dead space after debridement, but also provide high concentrations of antibiotics in a potential site of infection, no increase levels of antibiotics in serum. The review analyzed the use of antibiotic-impregnated cement as local delivery of antibiotics systems. Gentamycin impregnated polymethylmethacrylate (PMMA) beads, for the topical treatment of orthopedic infections clinically used for over 30 years. Application of antibiotic delivery systems using cement in the infected region is common method of treatment that continues to improve. On the downside of PMMA is that the material does not biodegradable requires subsequent invasive procedures necessary to remove the implant.

Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury.

PubMed

Lee, Sheen-Woo; Padmanabhan, Parasuraman; Ray, Pritha; Gambhir, Sanjiv Sam; Doyle, Timothy; Contag, Christopher; Goodman, Stuart B; Biswal, Sandip

2009-03-01

Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [(18)F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [(18)F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC's traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p < 0.05). Systemically administered ADMC's traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route. (c) 2008 Orthopaedic Research Society.

Computer-aided osteotomy design for harvesting autologous bone grafts in reconstructive surgery

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Zerfass, Peter; von Rymon-Lipinski, Bartosz; Jansen, Thomas; Hauck, Wolfgang; Zeilhofer, Hans-Florian U.; Sader, Robert; Keeve, Erwin

2001-05-01

Autologous grafts serve as the standard grafting material in the treatment of maxillofacial bone tumors, traumatic defects or congenital malformations. The pre-selection of a donor site depends primarily on the morphological fit of the available bone mass and the shape of the part that has to be transplanted. To achieve sufficient incorporation of the autograft into the host bone, precise planning and simulation of the surgical intervention based on 3D CT studies is required. This paper presents a method to identify an optimal donor site by performing an optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization task in the donor site CT data set. The following fully automatic optimization stage delivers a set of sub-optimal and optimal donor sites for a given template. All generated solutions can be explored interactively on the computer display using an efficient graphical interface. Reconstructive operations supported by our system were performed on 28 patients. We found that the operation time can be considerably shortened by this approach.

Internal bone transport using a cannulated screw as a mounting device in the treatment of a post-infective ulnar defect.

PubMed

Tsitskaris, Konstantinos; Havard, Heledd; Bijlsma, Paulien; Hill, Robert A

2016-04-01

Bone transport techniques can be used to address the segmental bone loss occurring after debridement for infection. Secure fixation of the bone transport construct to the bone transport segment can be challenging, particularly if the bone is small and osteopenic. We report a case of a segmental ulnar bone defect in a young child treated with internal bone transport using a cannulated screw as the mounting device. We found this technique particularly useful in the treatment of bone loss secondary to infection, where previous treatment and prolonged immobilisation had led to osteopenia. This technique has not been previously reported.

Cyclooxygenase-2 deficiency impairs muscle-derived stem cell-mediated bone regeneration via cellular autonomous and non-autonomous mechanisms.

PubMed

Gao, Xueqin; Usas, Arvydas; Lu, Aiping; Kozemchak, Adam; Tang, Ying; Poddar, Minakshi; Sun, Xuying; Cummins, James H; Huard, Johnny

2016-08-01

This study investigated the role of cyclooxygenase-2 (COX-2) expression by donor and host cells in muscle-derived stem cell (MDSC)-mediated bone regeneration utilizing a critical size calvarial defect model. We found that BMP4/green fluorescent protein (GFP)-transduced MDSCs formed significantly less bone in COX-2 knock-out (Cox-2KO) than in COX-2 wild-type (WT) mice. BMP4/GFP-transduced Cox-2KO MDSCs also formed significantly less bone than transduced WT MDSCs when transplanted into calvarial defects created in CD-1 nude mice. The impaired bone regeneration in the Cox-2KO MDSCBMP4/GFP group is associated with downregulation of BMP4-pSMAD1/5 signaling, decreased osteogenic differentiation and lowered proliferation capacity after transplantation, compared with WT MDSCBMP4/GFP cells. The Cox-2KO MDSCBMP4/GFP group demonstrated a reduction in cell survival and direct osteogenic differentiation in vitro These effects were mediated in part by the downregulation of Igf1 and Igf2. In addition, the Cox-2KO MDSCBMP4/GFP cells recruited fewer macrophages than the WT MDSC/BMP4/GFP cells in the early phase after injury. We concluded that the bone regeneration capacity of Cox-2KO MDSCs was impaired because of a reduction in cell proliferation and survival capacities, reduction in osteogenic differentiation and a decrease in the ability of the cells to recruit host cells to the injury site. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

PubMed

Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

2015-12-01

The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies.

[Interposition arthrodesis of the ankle].

PubMed

Vienne, Patrick

2005-10-01

Bony fusion of the ankle in a functionally favorable position for restitution of a painless weight bearing while avoiding a leg length discrepancy. Disabling, painful osteoarthritis of the ankle with extensive bone defect secondary to trauma, infection, or serious deformities such as congenital malformations or diabetic osteoarthropathies. Acute joint infection. Severe arterial occlusive disease of the involved limb. Lateral approach to the distal fibula. Fibular osteotomy 7 cm proximal to the tip of the lateral malleolus and posterior flipping of the distal fibula. Exposure of the ankle. Removal of all articular cartilage and debridement of the bone defect. Determination of the size of the defect and harvesting of a corresponding tricortical bone graft from the iliac crest. Also harvesting of autogenous cancellous bone either from the iliac crest or from the lateral part of the proximal tibia. Insertion of the tricortical bone graft and filling of the remaining defect with cancellous bone. Fixation with three 6.5-mm titanium lag screws. Depending on the extent of the defect additional stabilization of the bone graft with a titanium plate. Fixation of the lateral fibula on talus and tibia with two 3.5-mm titanium screws for additional support. Wound closure in layers. Split below-knee cast with the ankle in neutral position. Between January 2002 and January 2004 this technique was used in five patients with extensive bone defects (four women, one man, average age 57 years [42-77 years]). No intra- or early postoperative complications. The AOFAS (American Orthopedic Foot and Ankle Society) Score was improved from 23 points preoperatively to 76 points postoperatively (average follow-up time of 25 months). Two patients developed a nonunion and underwent a revision with an ankle arthrodesis nail. A valgus malposition after arthrodesis in one patient was corrected with a supramalleolar osteotomy.

Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

PubMed Central

Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

2014-01-01

Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields. PMID:24728277

The Composite of Bone Marrow Concentrate and PRP as an Alternative to Autologous Bone Grafting

PubMed Central

Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

2014-01-01

One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting. PMID:24950251

Bone regeneration in strong porous bioactive glass (13–93) scaffolds with an oriented microstructure implanted in rat calvarial defects

PubMed Central

Liu, Xin; Rahaman, Mohamed N.; Fu, Qiang

2012-01-01

There is a need for synthetic bone graft substitutes to repair large bone defects resulting from trauma, malignancy, and congenital diseases. Bioactive glass has attractive properties as a scaffold material but factors that influence its ability to regenerate bone in vivo are not well understood. In the present work, the ability of strong porous scaffolds of 13–93 bioactive glass with an oriented microstructure to regenerate bone was evaluated in vivo using a rat calvarial defect model. Scaffolds with an oriented microstructure of columnar pores (porosity = 50%; pore diameter = 50–150 µm) showed mostly osteoconductive bone regeneration, and new bone formation, normalized to the available pore area (volume) of the scaffolds, increased from 37% at 12 weeks to 55% at 24 weeks. Scaffolds of the same glass with a trabecular microstructure (porosity = 80%; pore width = 100–500 µm), used as the positive control, showed bone regeneration in the pores of 25% and 46% at 12 and 24 weeks, respectively. The brittle mechanical response of the as-fabricated scaffolds changed markedly to an elasto-plastic response in vivo at both implantation times. These results indicate that both groups of 13–93 bioactive glass scaffolds could potentially be used to repair large bone defects, but scaffolds with the oriented microstructure could also be considered for the repair of loaded bone. PMID:22922251

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

PubMed

Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

2017-06-01

Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural properties of fracture haematoma: current status and future clinical implications.

PubMed

Wang, Xin; Friis, Thor; Glatt, Vaida; Crawford, Ross; Xiao, Yin

2017-10-01

Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Osteogenesis Imperfecta due to Mutations in Non-Collagenous Genes-Lessons in the Biology of Bone Formation

PubMed Central

Marini, Joan C.; Reich, Adi; Smith, Simone M.

2014-01-01

Purpose of Review Osteogenesis imperfecta (OI), or “brittle bone disease”, has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for OI as a collagen-related disorder, where autosomal dominant type I collagen defects cause most cases, while rare, mostly recessive forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development and future of this paradigm shift in the understanding of OI. Recent Findings BRIL and PEDF defects cause types V and VI OI via defective bone mineralization, while defects in CRTAP, P3H1 and CyPB cause types VII-IX via defective collagen post-translational modification. Hsp47 and FKBP65 defects cause types X and XI OI via aberrant collagen crosslinking, folding and chaperoning, while defects in SP7, WNT1, TRIC-B and OASIS disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase BMP1 causes type XII OI due to altered collagen maturation/processing. Summary Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of OI types by shared mechanism to simplify current nosology, and should prod investigations into common pathways in OI. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients. PMID:25007323

Histology of 8 atypical femoral fractures: remodeling but no healing.

PubMed

Schilcher, Jörg; Sandberg, Olof; Isaksson, Hanna; Aspenberg, Per

2014-06-01

The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself may provide clues. Between 2008 and 2013, we collected bone biopsies including the fracture line from 4 complete and 4 incomplete atypical femoral fractures. 7 female patients reported continuous bisphosphonate use for 10 years on average. 1 patient was a man who was not using bisphosphonates. Dual-energy X-ray absorptiometry of the hip and spine showed no osteoporosis in 6 cases. The bone biopsies were evaluated by micro-computed tomography, infrared spectroscopy, and qualitative histology. Incomplete fractures involved the whole cortical thickness and showed a continuous gap with a mean width of 180 µm. The gap contained amorphous material and was devoid of living cells. In contrast, the adjacent bone contained living cells, including active osteoclasts. The fracture surfaces sometimes consisted of woven bone, which may have formed in localized defects caused by surface fragmentation or resorption. Atypical femoral fractures show signs of attempted healing at the fracture site. The narrow width of the fracture gap and its necrotic contents are compatible with the idea that micromotion prevents healing because it leads to strains within the fracture gap that preclude cell survival.

Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft : An experimental study in rabbit.

PubMed

Sadeghi, Rokhsareh; Najafi, Mohammad; Semyari, Hassan; Mashhadiabbas, Fatemeh

2017-03-01

Bone regeneration is an important concern in periodontal treatment and implant dentistry. Different biomaterials and surgical techniques have been used for this purpose. The aim of the present study was to compare the effect of nanocrystalline hydroxyapatite and human freeze-dried bone graft (FDBG) in regeneration of rabbit calvarium bony defects by histologic and histomorphometric evaluation. In this experimental study, three similar defects, measuring 8 mm in diameter, were created in the calvaria of 16 white New Zealand rabbits. Two defects were filled with FDBG and nanocrystalline hydroxyapatite silica gel, while the other one remained unfilled to be considered as control. All the defects were covered with collagen membranes. During the healing period, two animals perished; so 14 rabbits were divided into two groups: half of them were euthanized after 6 weeks of healing and the other half after 12 weeks. The specimens were subjected to histologic and histomorphometric examinations for assessment of the following variables: percentage of bone formation and residual graft material, inflammation scores, patterns of bone formation and type of newly formed bone. The percentages of new bone formation after 6 weeks were 14.22 ± 7.85, 21.57 ± 6.91, and 20.54 ± 10.07% in FDBG, NanoBone, and control defects. These values were 27.54 ± 20.19, 23.86 ± 6.27, and 26.48 ± 14.18% in 12-week specimens, respectively. No significant differences were found in the amount of bone formation between the groups. With regard to inflammation, the control and NanoBone groups showed significantly less inflammation compared to FDBG at the 6-week healing phase (P = 0.04); this difference was not significant in the 12-week specimens. Based on the results of this experimental study, both NanoBone and FDBG exhibited a similar effect on bone formation.

Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

PubMed Central

2011-01-01

A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. PMID:21902614

Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

PubMed

O'Keefe, Regis J; Mao, Jeremy

2011-12-01

A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

Bone tumor

MedlinePlus

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

In vitro evaluation of the torsional strength reduction of neonate calf metatarsal bones with Bicortical defects resulting from the removal of external fixation implants.

PubMed

Brianza, Stefano; Vogel, Susan; Rothstock, Stephan; Desrochers, Andrè; Boure, Ludovic

2013-01-01

To compare the torsional strength of calf metatarsal bones with defects produced by removal of 2 different implants. In vitro mechanical comparison of paired bones with bicortical defects resulting from the implantation of 2 different external fixation systems: the transfixation pin (TP) and the pin sleeve system (PS). Neonatal calf metatarsal bones (n = 6 pairs). From each pair, 1 bone was surgically instrumented with 2 PS implants and the contralateral bone with 2 TP implants. Implants were removed immediately leaving bicortical defects at identical locations between paired metatarsi. Each bone was tested in torque until failure. The mechanical variables statistically compared were the torsional stiffness, the torque and angle at failure, and work to failure. For TP and PS constructs, respectively, there were no significant differences between construct types for any of the variables tested. Mean ± SD torsional stiffness: 5.50 ± 2.68 and 5.35 ± 1.79 (Nm/°), P = .75; torque: 57.42 ± 14.84 and 53.43 ± 10.16 (Nm); P = .34; angle at failure: 14.76 ± 4.33 and 15.45 ± 4.84 (°), P = .69; and work to failure 7.45 ± 3.19 and 8.89 ± 3.79 (J), P = .17). Bicortical defects resulting from the removal of PS and TP implants equally affect the investigated mechanical properties of neonate calf metatarsal bones. © Copyright 2012 by The American College of Veterinary Surgeons.

Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il; National Research Tomsk Polytechnic University, Tomsk, 634050

The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were dividedmore » in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.« less

Efficacy of Bone Source™ and Cementek™ in comparison with Endobon™ in critical size metaphyseal defects, using a minipig model.

PubMed

Spies, Christian K G; Schnürer, Stefan; Gotterbarm, Tobias; Breusch, Steffen J

2010-01-01

To examine and compare biocompatibility, osteocompatibility, rate of resorption, and remodelling dynamics of 2 calcium phosphate cements in comparison with a well-established hydroxyapatite ceramic. In a randomised fashion, Bone Source™, Cementek™, and Endobon™ were implanted bilaterally into the proximal metaphyseal tibiae of 35 Göttinger minipigs in a direct right vs. left intra-individual comparison. Fluorescent labelling was used. Histological and morphometric evaluations were carried out at 6, 12, and 52 weeks. All bone substitutes showed good biocompatibility, bioactivity, and osteoconductivity. Endobon™ was not degraded over the follow-up period. Cementek™ was degraded constantly and significantly over the time intervals, whereas Bone Source™ was degraded mainly from the 6 week to 12 week interval. After 52 weeks, a significant difference of residual material within the defect zone was detected between all substitutes, with the highest resorption rate for Cementek™. Bone Source™ was least degraded. Defects filled with Endobon™ were characterised by a significantly continuous bony ingrowth over the time intervals. Bone formation within the defects filled with Cementek™ and Bone Source™ showed significant peaks 12 weeks after implantation. After 52 weeks, a significant difference in the amount of new bone within the defect area was detected, with the highest levels for Endobon™, followed by Cementek™. After 1 year a restitution ad integrum could not be observed in any treatment group. The ceramic Endobon™ showed the expected response histologically. Based on its porosity it excelled in osteoconductivity. Concerning the calcium phosphate cements, a thorough osseous incorporation seemed to inhibit further degradation of both bone substitute materials.

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

PubMed

Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

2014-03-01

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Repair of tegmen defect using cranial particulate bone graft.

PubMed

Greene, Arin K; Poe, Dennis S

2015-01-01

Bone paté is used to repair cranial bone defects. This material contains bone-dust collected during the high-speed burring of the cranium. Clinical and experimental studies of bone dust, however, have shown that it does not have biological activity and is resorbed. We describe the use of bone paté using particulate bone graft. Particulate graft is harvested with a hand-driven brace and 16mm bit; it is not subjected to thermal injury and its large size resists resorption. Bone paté containing particulate graft is much more likely than bone dust to contain viable osteoblasts capable of producing new bone. Copyright © 2015 Elsevier Inc. All rights reserved.

Diode λ830nm laser associated with hydroxyapatite and biological membranes: bone repair in rats

NASA Astrophysics Data System (ADS)

Carneiro, Vanda S. M.; Limeira, Francisco d. A.; Gerbi, Marleny E. M.; Menezes, Rebeca F. d.; Santos-Neto, Alexandrino P. d.; Araújo, Natália C.

2016-02-01

The aim of the present study was to histologically assess the effect of laser therapy (AsGaAl, 830nm, 40mW, CW, φ ~0,6mm, 16J/cm2 per session, four points of 4J/cm2) on the repair of surgical defects created in the femur of Wistar rats. Background data: Several techniques have been proposed for the correction of bone defects, including the use of grafts and membranes. Despite the increase in the use of laser therapy for the biomodulation of bone repair, very few studies have assessed the associations between laser light and biomaterials. Method: The defects were filled with synthetic micro granular hydroxyapatite (HA) Gen-phos® implants and associated with bovine bone membranes (Gen-derm®). Surgical bone defects were created in 48 rats and divided into four groups: Group IA (control, n=12); Group IB (laser, n=12); Group IIA (HA + membrane, n=12); Group IIB (HA + membrane + laser, n=12). The irradiated groups received the first irradiation immediately after surgery. This radiation was then repeated seven times every 48h. The animals were sacrificed after 15, 21, and 30 days. Results: When comparing the groups irradiated with implants and membranes, it was found that the repair of the defects submitted to laser therapy occurred more quickly, starting 15 and 21 days after surgery. By the 30th day, the level of repair of the defects was similar in the irradiated and the non-irradiated groups. New bone formation was confirmed inside the cavity by the implant's osteoconduction. In the irradiated groups, there was an increment of this new bone formation. Conclusions: In conclusion, the use of laser therapy, particularly when associated with hydroxyapatite and biological membranes, produced a positive biomodulation effect on the healing process of bone defects on the femurs of rats.

Effect of calcium citrate on bone integration in a rabbit femur defect model.

PubMed

Zhang, Wei; Wang, Wei; Chen, Qing-Yu; Lin, Zhong-Qin; Cheng, Shao-Wen; Kou, Dong-Quan; Ying, Xiao-Zhou; Shen, Yue; Cheng, Xiao-Jie; Nie, Peng-Fei; Li, Xiu-Cui; Rompis, Ferdinand An; Huang, Hang; Zhang, Hua; Mu, Zhong-Lin; Peng, Lei

2012-04-01

To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Raman and histological study of the repair of surgical bone defects grafted with biphasic synthetic micro-granular HA + β- calcium triphosphate and irradiated or not with λ780 nm laser

NASA Astrophysics Data System (ADS)

Pinheiro, Antonio Luiz B.; Soares, Luiz Guilherme P.; Marques, Aparecida Maria C.; Aciole, Jouber Mateus S.; dos Santos, Jean N.; Silveira, Landulfo

2014-02-01

The treatment of bone loss due to different etiologic factors is difficult and many techniques aim to improve repair, including a wide range of biomaterials and, recently, phototherapies. This work assessed, by Raman spectroscopy and histology, the mineralization of bone defects. Forty rats divided into 4 groups each subdivided into 2 subgroups according to the time of sacrifice were used. Bone defects were made on the femur of each animal with a trephine drill. On animals of group Clot the defect was filled only by blood clot, on group Laser the defect filled with the clot was further irradiated. On animals of groups Biomaterial and Laser + Biomaterial the defect was filled by biomaterial and the last one was further irradiated (λ780 nm, 70 mW, Φ ~ 0.4 cm2, 20 J/cm2-session, 140 J/cm2-treatment). At both 15th and 30th days following sacrifice, samples were taken and analyzed by Raman spectroscopy and light microscopy. Raman peaks of inorganic and organic contents and a more advanced stage of repair were seen on group Laser + Biomaterial. It is concluded that the use of Laser phototherapy associated to biomaterial was effective to improve the repair of bone defects.

Effect of gelatin sponge with colloid silver on bone healing in infected cranial defects.

PubMed

Dong, Yuliang; Liu, Weiqing; Lei, Yiling; Wu, Tingxi; Zhang, Shiwen; Guo, Yuchen; Liu, Yuan; Chen, Demeng; Yuan, Quan; Wang, Yongyue

2017-01-01

Oral infectious diseases may lead to bone loss, which makes it difficult to achieve satisfactory restoration. The rise of multidrug resistant bacteria has put forward severe challenges to the use of antibiotics. Silver (Ag) has long been known as a strong antibacterial agent. In clinic, gelatin sponge with colloid silver is used to reduce tooth extraction complication. To investigate how this material affect infected bone defects, methicillin-resistant Staphylococcus aureus (MRSA) infected 3-mm-diameter cranial defects were created in adult female Sprague-Dawley rats. One week after infection, the defects were debrided of all nonviable tissue and then implanted with gelatin sponge with colloid silver (gelatin/Ag group) or gelatin alone (gelatin group). At 2 and 3days after debridement, significantly lower mRNA expression levels of IL-6 and TNF-α and lower plate colony count value were detected in gelatin/Ag group than control. Micro-CT analysis showed a significant increase of newly formed bone volume fraction (BV/TV) in gelatin/Ag treated defects. The HE stained cranium sections also showed a faster rate of defect closure in gelatin/Ag group than control. These findings demonstrated that gelatin sponge with colloid silver can effectively reduce the infection caused by MRSA in cranial defects and accelerate bone healing process. Copyright © 2016. Published by Elsevier B.V.

Effect of defective collagen synthesis on epithelial implant interface: lathyritic model in dogs. An experimental preliminary study.

PubMed

Cengiz, Murat Inanç; Kirtiloğlu, Tuğrul; Acikgoz, Gökhan; Trisi, Paolo; Wang, Hom-Lay

2012-04-01

Peri-implant mucosa is composed of 2 compartments: a marginal junctional epithelium and a zone of connective tissue attachment. Both structures consist mainly of collagen. Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme that is essential for interfibrillar collagen cross-linking. The lathyritic agent beta-aminoproprionitrile (β-APN) is considered a suitable agent to disrupt the connective tissue metabolism. Therefore, the purpose of this study was to assess the effect of defective connective tissue metabolism on epithelial implant interface by using β-APN created chronic lathyrism in the canine model. Two 1-year-old male dogs were included in this study. A β-APN dosage of 5 mg/0.4 mL/volume 100 g/body weight was given to the test dog for 10 months, until lathyritic symptoms developed. After this, the mandibular premolar teeth (p2, p3, p4) of both dogs were atraumatically extracted, and the investigators waited 3 months before implants were placed. In the test dog, 3 implants were placed in the left mandible, and 2 implants were placed in the right mandible. In the control dog, 2 implants were placed in the left mandibular premolar site. The dogs were sacrificed 10 months after healing. Peri-implant tissues obtained from the dogs were examined histomorphologically and histopathologically. Bone to implant contact (BIC) values and bone volumes (BV) were lower in the lathyritic group compared to the control group; however, no statistical significance was found. Significant histologic and histomorphometric changes were observed in peri-implant bone, connective tissue, and peri-implant mucosal width between test and control implants. Defective collagen metabolism such as lathyrism may negatively influence the interface between implant and surrounding soft tissue attachment.

Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/β-Tricalcium Phosphate Nanotubes on Acetabular Bone Defects in Rabbits

PubMed Central

Nguyen, Thuy-Duong Thi; Bae, Tae-Sung; Yang, Dae-hyeok; Park, Myung-sik; Yoon, Sun-jung

2017-01-01

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2–4 weeks was stronger than at 6–8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo. PMID:28686210

Single-dose local administration of parathyroid hormone (1-34, PTH) with β-tricalcium phosphate/collagen (β-TCP/COL) enhances bone defect healing in ovariectomized rats.

PubMed

Tao, Zhou-Shan; Zhou, Wan-Shu; Wu, Xin-Jing; Wang, Lin; Yang, Min; Xie, Jia-Bing; Xu, Zhu-Jun; Ding, Guo-Zheng

2018-02-01

Parathyroid hormone (1-34, PTH) combined β-tricalcium phosphate (β-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by β-TCP/collagen (β-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, β-TCP/COL was prepared by mixing sieved granules of β-TCP and atelocollagen for medical use, then β-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of β-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and β-TCP/COL showed a stronger effect on accelerating the local bone formation than β-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and β-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

Quantifying glenoid bone loss in anterior shoulder instability: reliability and accuracy of 2-dimensional and 3-dimensional computed tomography measurement techniques.

PubMed

Bois, Aaron J; Fening, Stephen D; Polster, Josh; Jones, Morgan H; Miniaci, Anthony

2012-11-01

Glenoid support is critical for stability of the glenohumeral joint. An accepted noninvasive method of quantifying glenoid bone loss does not exist. To perform independent evaluations of the reliability and accuracy of standard 2-dimensional (2-D) and 3-dimensional (3-D) computed tomography (CT) measurements of glenoid bone deficiency. Descriptive laboratory study. Two sawbone models were used; one served as a model for 2 anterior glenoid defects and the other for 2 anteroinferior defects. For each scapular model, predefect and defect data were collected for a total of 6 data sets. Each sample underwent 3-D laser scanning followed by CT scanning. Six physicians measured linear indicators of bone loss (defect length and width-to-length ratio) on both 2-D and 3-D CT and quantified bone loss using the glenoid index method on 2-D CT and using the glenoid index, ratio, and Pico methods on 3-D CT. The intraclass correlation coefficient (ICC) was used to assess agreement, and percentage error was used to compare radiographic and true measurements. With use of 2-D CT, the glenoid index and defect length measurements had the least percentage error (-4.13% and 7.68%, respectively); agreement was very good (ICC, .81) for defect length only. With use of 3-D CT, defect length (0.29%) and the Pico(1) method (4.93%) had the least percentage error. Agreement was very good for all linear indicators of bone loss (range, .85-.90) and for the ratio linear and Pico surface area methods used to quantify bone loss (range, .84-.98). Overall, 3-D CT results demonstrated better agreement and accuracy compared to 2-D CT. None of the methods assessed in this study using 2-D CT was found to be valid, and therefore, 2-D CT is not recommended for these methods. However, the length of glenoid defects can be reliably and accurately measured on 3-D CT. The Pico and ratio techniques are most reliable; however, the Pico(1) method accurately quantifies glenoid bone loss in both the anterior and anteroinferior locations. Future work is required to implement valid imaging techniques of glenoid bone loss into clinical practice. This is one of the only studies to date that has investigated both the reliability and accuracy of multiple indicators and quantification methods that evaluate glenoid bone loss in anterior glenohumeral instability. These data are critical to ensure valid methods are used for preoperative assessment and to determine when a glenoid bone augmentation procedure is indicated.

Multiscale mechanobiology of de novo bone generation, remodeling and adaptation of autograft in a common ovine femur model.

PubMed

Knothe Tate, Melissa L; Dolejs, Scott; McBride, Sarah H; Matthew Miller, R; Knothe, Ulf R

2011-08-01

The link between mechanics and biology in the generation and the adaptation of bone has been studied for more than a century in the context of skeletal development and fracture healing. However, the interplay between mechanics and biology in de novo generation of bone in postnatal defects as well as healing of morcellized bone graft or massive cortical bone autografts is less well understood. To address this, here we integrate insights from our previously published studies describing the mechanobiology on both de novo bone generation and graft healing in a common ovine femoral defect model. Studying these effects in a common experimental model provides a unique opportunity to elucidate factors conducive to harnessing the regenerative power of the periosteum, and ultimately, to provide mechanistic insights into the multiscale mechanobiology of bone generation, remodeling and adaptation. Taken together, the studies indicate that, as long as adequate, directional transport of cells and molecules can be insured (e.g. with periosteum in situ or a delivery device), biological factors intrinsic to the periosteum suffice to bridge critical sized bone defects, even in the absence of a patent blood supply. Furthermore, mechanical stimuli are crucial for the success of periosteal bone generation and bone graft healing. Interestingly, areas of highest periosteal strain around defects correlate with greatest amounts albeit not greatest mineralization of newly generated bone. This may indicate a role for convection enhanced transport of cells and molecules in modulation of tissue generation by pluripotent cells that ingress into the defect center, away from the periosteum and toward the surface of the intramedullary nail that fills the medullary cavity. These insights bring us much closer to understanding the mechanobiological environment and stimuli that stimulate the proliferation and differentiation of periosteum-derived progenitor cells and ultimately drive the generation of new bone tissue. Furthermore, these insights provide a foundation to create virtual predictive computational models of bone mechanophysiology, to develop cell seeding protocols for scale up and manufacture of engineered tissues, to optimize surgical procedures, and to develop post-surgical therapies with the ultimate goal of achieving the best possible healing outcomes for treatment and/or reconstruction of postnatal bone defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Three-Dimensional Magnetic Resonance Imaging Quantification of Glenoid Bone Loss Is Equivalent to 3-Dimensional Computed Tomography Quantification: Cadaveric Study.

PubMed

Yanke, Adam B; Shin, Jason J; Pearson, Ian; Bach, Bernard R; Romeo, Anthony A; Cole, Brian J; Verma, Nikhil N

2017-04-01

To assess the ability of 3-dimensional (3D) magnetic resonance imaging (MRI, 1.5 and 3 tesla [T]) to quantify glenoid bone loss in a cadaveric model compared with the current gold standard, 3D computed tomography (CT). Six cadaveric shoulders were used to create a bone loss model, leaving the surrounding soft tissues intact. The anteroposterior (AP) dimension of the glenoid was measured at the glenoid equator and after soft tissue layer closure the specimen underwent scanning (CT, 1.5-T MRI, and 3-T MRI) with the following methods (0%, 10%, and 25% defect by area). Raw axial data from the scans were segmented using manual mask manipulation for bone and reconstructed using Mimics software to obtain a 3D en face glenoid view. Using calibrated Digital Imaging and Communications in Medicine images, the diameter of the glenoid at the equator and the area of the glenoid defect was measured on all imaging modalities. In specimens with 10% or 25% defects, no difference was detected between imaging modalities when comparing the measured defect size (10% defect P = .27, 25% defect P = .73). All 3 modalities demonstrated a strong correlation with the actual defect size (CT, ρ = .97; 1.5-T MRI, ρ = .93; 3-T MRI, ρ = .92, P < .0001). When looking at the absolute difference between the actual and measured defect area, no significance was noted between imaging modalities (10% defect P = .34, 25% defect P = .47). The error of 3-T 3D MRI increased with increasing defect size (P = .02). Both 1.5- and 3-T-based 3D MRI reconstructions of glenoid bone loss correlate with measurements from 3D CT scan data and actual defect size in a cadaveric model. Regardless of imaging modality, the error in bone loss measurement tends to increase with increased defect size. Use of 3D MRI in the setting of shoulder instability could obviate the need for CT scans. The goal of our work was to develop a reproducible method of determining glenoid bone loss from 3D MRI data and hence eliminate the need for CT scans in this setting. This will lead to decreased cost of care as well as decreased radiation exposure to patients. The long-term goal is a fully automated system that is as approachable for clinicians as current 3D CT technology. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Events of wound healing/regeneration in the canine supraalveolar periodontal defect model.

PubMed

Dickinson, Douglas P; Coleman, Brandon G; Batrice, Nathan; Lee, Jaebum; Koli, Komal; Pennington, Cathy; Susin, Cristiano; Wikesjö, Ulf M E

2013-05-01

The objective of this research was to elucidate early events in periodontal wound healing/regeneration using histological and immunohistochemical techniques. Routine critical-size, supraalveolar, periodontal defects including a space-providing titanium mesh device were created in 12 dogs. Six animals received additional autologous blood into the defect prior to wound closure. One animal from each group was killed for analysis at 2, 5, 9, 14 days, and at 4 and 8 weeks. Both groups behaved similarly. Periodontal wound healing/regeneration progressed through three temporal phases. Early phase (2-5 days): heterogeneous clot consolidation and cell activation in the periodontal ligament (PDL) and trabecular bone was associated with PDL regeneration and formation of a pre-osteoblast population. Intermediate phase (9-14 days): cell proliferation (shown by PCNA immunostaining)/migration led to osteoid/bone, PDL and cementum formation. Late phase (4-8 weeks): primarily characterized by tissue remodelling/maturation. Fibrous connective tissue from the gingival mucosa entered the wound early, competing with regeneration. By day 14, the wound space was largely filled with regenerative and reparative tissues. Activation of cellular regenerative events in periodontal wound healing/regeneration is rapid; the general framework for tissue formation is broadly outlined within 14 days. Most bone formation apparently originates from endosteally derived pre-osteoblasts; the PDL possibly acting as a supplementary source, with a primary function likely being regulatory/homeostatic. Blood accumulation at the surgical site warrants exploration; supplementation may be beneficial. © 2012 John Wiley & Sons A/S.

Custom-made composite scaffolds for segmental defect repair in long bones.

PubMed

Reichert, Johannes C; Wullschleger, Martin E; Cipitria, Amaia; Lienau, Jasmin; Cheng, Tan K; Schütz, Michael A; Duda, Georg N; Nöth, Ulrich; Eulert, Jochen; Hutmacher, Dietmar W

2011-08-01

Current approaches for segmental bone defect reconstruction are restricted to autografts and allografts which possess osteoconductive, osteoinductive and osteogenic properties, but face significant disadvantages. The objective of this study was to compare the regenerative potential of scaffolds with different material composition but similar mechanical properties to autologous bone graft from the iliac crest in an ovine segmental defect model. After 12 weeks, in vivo specimens were analysed by X-ray imaging, torsion testing, micro-computed tomography and histology to assess amount, strength and structure of the newly formed bone. The highest amounts of bone neoformation with highest torsional moment values were observed in the autograft group and the lowest in the medical grade polycaprolactone and tricalcium phosphate composite group. The study results suggest that scaffolds based on aliphatic polyesters and ceramics, which are considered biologically inactive materials, induce only limited new bone formation but could be an equivalent alternative to autologous bone when combined with a biologically active stimulus such as bone morphogenetic proteins.

Raman study of the effect of LED light on grafted bone defects

NASA Astrophysics Data System (ADS)

Soares, Luiz G. G. P.; Aciole, Jouber M. S.; Aciole, Gilbeth T. S.; Barbosa, Artur F. S.; Silveira-Júnior, Landulfo; Pinheiro, Antônio L. B.

2013-03-01

Benefits of the isolated or combined use light and biomaterials on bone healing have been suggested. Our group has used several models to assess the effects of laser on bone. A Raman spectral analysis on surgical bone defects grafted or not with Hydroxyapatite (HA), treated or not with LED was carried out. 40 rats were divided into 4 groups. On Group I the defect was filled with the clot. On Group II, the defect was filled with the HA. On groups III the defect was filled with Clot and further irradiated with LED and on group IV the defects was filled with the HA and further irradiated with LED. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 68s, 20 J/cm2 per session, 140 J/cm2 per treatment) was applied at 48 h intervals during 15 days. Specimens were taken after 15 and 30 days after surgery and kept on liquid nitrogen, and underwent Raman analysis. For this, the peak of hydroxyapatite (~960 cm-1) was used as marker of bone mineralization. Significant difference was observed at both times (p<0.05). When the biomaterial was used higher peaks were observed. Association with LED further improved the intensity. Conclusion: It is concluded that LED light improved the effect of the HA.

Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

PubMed Central

Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

2014-01-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

PubMed

Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

2014-04-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Maxillary reconstruction with bone transport distraction and implants after partial maxillectomy.

PubMed

Castro-Núñez, Jaime; González, Marcos Daniel

2013-02-01

Maxillary and mandibular bone defects can result from injury, congenital defect, or accident, or as a consequence of surgical procedures when treating pathology or defects affecting jaw bones. The glandular odontogenic cyst is an infrequent type of odontogenic cyst that can leave a bony defect after being treated by aggressive surgical means. First described in 1987 by Padayachee and Van Wyk, it is a potentially aggressive entity, having a predisposition to recur when treated conservatively, with only 111 cases having been reported hitherto. Most reports emphasize its clinical, radiographic, and histologic features, including a few considerations on rehabilitation for these patients. The aim of this article is to present the case of a 24-year-old male patient who, in 2001, was diagnosed with a glandular odontogenic cyst and to focus on the surgical approach and rehabilitation scheme. We performed an anterior partial maxillectomy. The osseous defect was treated using bone transport distraction. Dental and occlusal rehabilitation was achieved with titanium implants over transported bone and an implant-supported overdenture. A 9-year follow-up shows no evidence of recurrence of the pathology, adequate shape and amount of bone, functional occlusal and dental rehabilitation, and patient's satisfaction. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Hybrid Technique for Cranial Defect Reconstruction: Surgical Results over a 10-Year Period in a Single Institution.

PubMed

Guerrero-Suarez, Pablo David; Guerrero-López, Paola; Ortiz-Leon, Abarin; Sosa-Castillo, Haydee Samantha; Velazquez-Gonzalez, Lenny Marlene; Martinez-Anda, Jaime Jesus

2018-06-11

Decompressive craniectomy is an urgent procedure that is increasingly used for treatment of intracranial hypertension. After recovery, reconstruction of the cranial defect is necessary. Cranioplasty is an elective procedure with a high potential for morbidity if care is not taken on different surgical factors such as the material used as the cranial flap. In Latin America, high costs in some materials used in cranioplasty make its use prohibitive for some patients and institutions, and looking for alternatives has become a priority in neurosurgical centers. An autologous bone flap is an excellent option possessing the characteristics of an ideal material for cranioplasty. Nevertheless, its use is associated with high morbidity and flap failure. We report our mono-institutional experience in a 10-year period of a hybrid technique for cranioplasty using an autologous bone flap with titanium plates. Sixty-five patients underwent the technique, with good cosmetic results in 89.2% and success in functional result in 90.8% of patients . No significant statistical differences were found on the timing of the surgery or the location of the cranial defect. We had a 1.5% rate of surgical site infection, less than that reported on previous series. We propose that the hybrid technique of cranioplasty is a safety and effective option for cranial defect reconstruction. Georg Thieme Verlag KG Stuttgart · New York.

The role of 3D printing in treating craniomaxillofacial congenital anomalies.

PubMed

Lopez, Christopher D; Witek, Lukasz; Torroni, Andrea; Flores, Roberto L; Demissie, David B; Young, Simon; Cronstein, Bruce N; Coelho, Paulo G

2018-05-20

Craniomaxillofacial congenital anomalies comprise approximately one third of all congenital birth defects and include deformities such as alveolar clefts, craniosynostosis, and microtia. Current surgical treatments commonly require the use of autogenous graft material which are difficult to shape, limited in supply, associated with donor site morbidity and cannot grow with a maturing skeleton. Our group has demonstrated that 3D printed bio-ceramic scaffolds can generate vascularized bone within large, critical-sized defects (defects too large to heal spontaneously) of the craniomaxillofacial skeleton. Furthermore, these scaffolds are also able to function as a delivery vehicle for a new osteogenic agent with a well-established safety profile. The same 3D printers and imaging software platforms have been leveraged by our team to create sterilizable patient-specific intraoperative models for craniofacial reconstruction. For microtia repair, the current standard of care surgical guide is a two-dimensional drawing taken from the contralateral ear. Our laboratory has used 3D printers and open source software platforms to design personalized microtia surgical models. In this review, we report on the advancements in tissue engineering principles, digital imaging software platforms and 3D printing that have culminated in the application of this technology to repair large bone defects in skeletally immature transitional models and provide in-house manufactured, sterilizable patient-specific models for craniofacial reconstruction. © 2018 Wiley Periodicals, Inc.

Experimental Validation of the Efficiency of Gamalant-paste-FORTE Plus, a Russian Osteoinductive Material, in Oral Surgery.

PubMed

Olesova, V N; Amkhadova, M A; Simakova, T G; Mirgazizov, M Z; Pozharitskaya, M M

2017-03-01

For evaluation of the efficiency of bone substitute, nanostructurized Gamalant-paste-FORTEPlus was placed into a mandibular defect in rats. Bone tissue reparation was evaluated after 30 days by histological methods under a microscope. Use of bone substitute in experimental mandibular defect ensured more complete and rapid restructuring of the bone tissue in comparison with the control (natural healing).

Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

DTIC Science & Technology

2013-01-01

Praetorius, F. Guided tissue regeneration using de- gradable and nondegradable membranes in rabbit tibia. Clin Oral Implants Res 4, 172, 1993. 8. Queiroz... Regeneration of periodontal tissues : combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a...structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. Introduction The treatment of large-bone defects

Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

PubMed Central

Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

2016-01-01

The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

PubMed

Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

2012-03-01

This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled controls, chitosan implants solidified with thrombin elicited a more hyaline and structurally integrated osteochondral unit, features needed for long-term durability.

Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

PubMed

Thoma, Daniel S; Jung, Ui-Won; Park, Jin-Young; Bienz, Stefan P; Hüsler, Jürg; Jung, Ronald E

2017-07-01

The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the Effects of Photobiomodulation on Partial Osteotomy in Streptozotocin-Induced Diabetes in Rats.

PubMed

Mostafavinia, Ataroalsadat; Masteri Farahani, Reza; Abdollahifar, Mohammad-Amin; Ghatrehsamani, Mahdi; Ghoreishi, Seyed Kamran; Hajihossainlou, Behnam; Chien, Sufan; Dadras, Sara; Rezaei, Fatemehalsadat; Bayat, Mohammad

2018-05-31

We examined the effects of photobiomodulation (PBM) on stereological parameters, and gene expression of Runt-related transcription factor 2 (RUNX2), osteocalcin, and receptor activator of nuclear factor kappa-B ligand (RANKL) in repairing tissue of tibial bone defect in streptozotocin (STZ)-induced type 1 diabetes mellitus (TIDM) in rats during catabolic response of fracture healing. There were conflicting results regarding the efficacy of PBM on bone healing process in healthy and diabetic animals. Forty-eight rats have been distributed into four groups: group 1 (healthy control, no TIDM and no PBM), group 2 (healthy test, no TIDM and PBM), group 3 (diabetic control, TIDM and no PBM), and group 4 (diabetic test, no TIDM and PBM). TIDM was induced in the groups 3 and 4. A partial bone defect in tibia was made in all groups. The bone defects of groups second and fourth were irradiated by a laser (890 nm, 80 Hz, 1.5 J/cm 2 ). Thirty days after the surgery, all bone defects were extracted and were submitted to stereological examination and real-time polymerase chain reaction (RT-PCR). PBM significantly increased volumes of total callus, total bone, bone marrow, trabecular bone, and cortical bone, and the numbers of osteocytes and osteoblasts of callus in TIDM rats compared to those of callus in diabetic control. In addition, TIDM increased RUNX2, and osteocalcin in callus of tibial bone defect compared to healthy group. PBM significantly decreased osteocalcin gene expression in TIDM rats. PBM significantly increased many stereological parameters of bone repair in an STZ-induced TIDM during catabolic response of fracture healing. Further RT-PCR test demonstrated that bone repair was modulated in diabetic rats during catabolic response of fracture healing by significant increase in mRNA expression of RUNX2, and osteocalcin compared to healthy control rats. PBM also decreased osteocalcin mRNA expression in TIDM rats.