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Sample records for acellular cartilage sheets

  1. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    PubMed Central

    Cui, Wei-ling; Qiu, Long-hai; Lian, Jia-yan; Li, Jia-chun; Hu, Jun; Liu, Xiao-lin

    2016-01-01

    Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group) alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group). As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves. PMID:27127495

  2. Cellular and Acellular Approaches for Cartilage Repair

    PubMed Central

    2015-01-01

    There are several choices of cells to use for cartilage repair. Cells are used as internal or external sources and sometimes in combination. In this article, an analysis of the different cell choices and their use and potential is provided. Embryonic cartilage formation is of importance when finding more about how to be able to perfect cartilage repair. Some suggestions for near future research based on up-to-date knowledge on chondrogenic cells are given to hopefully stimulate more studies on the final goal of cartilage regeneration. PMID:27340516

  3. Corneal Stroma Regeneration with Acellular Corneal Stroma Sheets and Keratocytes in a Rabbit Model

    PubMed Central

    Ma, Xiao Yun; Zhang, Yun; Zhu, Dan; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie

    2015-01-01

    Acellular corneal stroma matrix has been used for corneal stroma engineering. However, because of its compact tissue structure, regrowth of keratocytes into the scaffold is difficult. Previously, we developed a sandwich model for cartilage engineering using acellular cartilage sheets. In the present study, we tested this model for corneal stroma regeneration using acellular porcine corneal stroma (APCS) sheets and keratocytes. Porcine corneas were decellularized by NaCl treatment, and the APCS was cut into 20-μm-thick sheets. A rabbit corneal stroma defect model was created by lamellar keratoplasty and repaired by transplantation of five pieces of APCS sheets with keratocytes. Six months after transplantation, transparent corneas were present in the experimental group, which were confirmed by anterior segment optical coherence tomography examination and transmittance examination. The biomechanical properties in the experimental group were similar to those of normal cornea. Histological analyses showed an even distribution of keratocytes and well-oriented matrix in the stroma layer in the experimental group. Together, these results demonstrated that the sandwich model using acellular corneal stroma sheets and keratocytes could be potentially useful for corneal stroma regeneration. PMID:26167895

  4. On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis.

    PubMed

    Boyde, A; Davis, G R; Mills, D; Zikmund, T; Cox, T M; Adams, V L; Niker, A; Wilson, P J; Dillon, J P; Ranganath, L R; Jeffery, N; Jarvis, J C; Gallagher, J A

    2014-10-01

    High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. PMID:25132002

  5. Development and Characterization of Acellular Extracellular Matrix Scaffolds from Porcine Menisci for Use in Cartilage Tissue Engineering

    PubMed Central

    Chen, Ying-Chen; Chen, Ray-Neng; Jhan, Hua-Jing; Liu, Der-Zen; Ho, Hsiu-O; Mao, Yong; Kohn, Joachim

    2015-01-01

    Given the growing number of arthritis patients and the limitations of current treatments, there is great urgency to explore cartilage substitutes by tissue engineering. In this study, we developed a novel decellularization method for menisci to prepare acellular extracellular matrix (ECM) scaffolds with minimal adverse effects on the ECM. Among all the acid treatments, formic acid treatment removed most of the cellular contents and preserved the highest ECM contents in the decellularized porcine menisci. Compared with fresh porcine menisci, the content of DNA decreased to 4.10%±0.03%, and there was no significant damage to glycosaminoglycan (GAG) or collagen. Histological staining also confirmed the presence of ECM and the absence of cellularity. In addition, a highly hydrophilic scaffold with three-dimensional interconnected porous structure was fabricated from decellularized menisci tissue. Human chondrocytes showed enhanced cell proliferation and synthesis of chondrocyte ECM including type II collagen and GAG when cultured in this acellular scaffold. Moreover, the scaffold effectively supported chondrogenesis of human bone marrow-derived mesenchymal stem cells. Finally, in vivo implantation was conducted in rats to assess the biocompatibility of the scaffolds. No significant inflammatory response was observed. The acellular ECM scaffold provided a native environment for cells with diverse physiological functions to promote cell proliferation and new tissue formation. This study reported a novel way to prepare decellularized meniscus tissue and demonstrated the potential as scaffolds to support cartilage repair. PMID:25919905

  6. Development and Characterization of Acellular Extracellular Matrix Scaffolds from Porcine Menisci for Use in Cartilage Tissue Engineering.

    PubMed

    Chen, Ying-Chen; Chen, Ray-Neng; Jhan, Hua-Jing; Liu, Der-Zen; Ho, Hsiu-O; Mao, Yong; Kohn, Joachim; Sheu, Ming-Thau

    2015-09-01

    Given the growing number of arthritis patients and the limitations of current treatments, there is great urgency to explore cartilage substitutes by tissue engineering. In this study, we developed a novel decellularization method for menisci to prepare acellular extracellular matrix (ECM) scaffolds with minimal adverse effects on the ECM. Among all the acid treatments, formic acid treatment removed most of the cellular contents and preserved the highest ECM contents in the decellularized porcine menisci. Compared with fresh porcine menisci, the content of DNA decreased to 4.10%±0.03%, and there was no significant damage to glycosaminoglycan (GAG) or collagen. Histological staining also confirmed the presence of ECM and the absence of cellularity. In addition, a highly hydrophilic scaffold with three-dimensional interconnected porous structure was fabricated from decellularized menisci tissue. Human chondrocytes showed enhanced cell proliferation and synthesis of chondrocyte ECM including type II collagen and GAG when cultured in this acellular scaffold. Moreover, the scaffold effectively supported chondrogenesis of human bone marrow-derived mesenchymal stem cells. Finally, in vivo implantation was conducted in rats to assess the biocompatibility of the scaffolds. No significant inflammatory response was observed. The acellular ECM scaffold provided a native environment for cells with diverse physiological functions to promote cell proliferation and new tissue formation. This study reported a novel way to prepare decellularized meniscus tissue and demonstrated the potential as scaffolds to support cartilage repair. PMID:25919905

  7. The properties of bioengineered chondrocyte sheets for cartilage regeneration

    PubMed Central

    Mitani, Genya; Sato, Masato; Lee, Jeong IK; Kaneshiro, Nagatoshi; Ishihara, Miya; Ota, Naoshi; Kokubo, Mami; Sakai, Hideaki; Kikuchi, Tetsutaro; Mochida, Joji

    2009-01-01

    Background Although the clinical results of autologous chondrocyte implantation for articular cartilage defects have recently improved as a result of advanced techniques based on tissue engineering procedures, problems with cell handling and scaffold imperfections remain to be solved. A new cell-sheet technique has been developed, and is potentially able to overcome these obstacles. Chondrocyte sheets applicable to cartilage regeneration can be prepared with this cell-sheet technique using temperature-responsive culture dishes. However, for clinical application, it is necessary to evaluate the characteristics of the cells in these sheets and to identify their similarities to naive cartilage. Results The expression of SOX 9, collagen type 2, 27, integrin α10, and fibronectin genes in triple-layered chondrocyte sheets was significantly increased in comparison to those in conventional monolayer culture and in a single chondrocyte sheet, implying a nature similar to ordinary cartilage. In addition, immunohistochemistry demonstrated that collagen type II, fibronectin, and integrin α10 were present in the triple-layered chondrocyte sheets. Conclusion The results of this study indicate that these chondrocyte sheets with a consistent cartilaginous phenotype and adhesive properties may lead to a new strategy for cartilage regeneration. PMID:19267909

  8. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia

    PubMed Central

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering. PMID:25755694

  9. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia.

    PubMed

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering. PMID:25755694

  10. Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig model.

    PubMed

    Ebihara, Goro; Sato, Masato; Yamato, Masayuki; Mitani, Genya; Kutsuna, Toshiharu; Nagai, Toshihiro; Ito, Satoshi; Ukai, Taku; Kobayashi, Miyuki; Kokubo, Mami; Okano, Teruo; Mochida, Joji

    2012-05-01

    Lacking a blood supply and having a low cellular density, articular cartilage has a minimal ability for self-repair. Therefore, wide-ranging cartilage damage rarely resolves spontaneously. Cartilage damage is typically treated by chondrocyte transplantation, mosaicplasty or microfracture. Recent advances in tissue engineering have prompted research on techniques to repair articular cartilage damage using a variety of transplanted cells. We studied the repair and regeneration of cartilage damage using layered chondrocyte sheets prepared on a temperature-responsive culture dish. We previously reported achieving robust tissue repair when covering only the surface layer with layered chondrocyte sheets when researching partial-thickness defects in the articular cartilage of domestic rabbits. The present study was an experiment on the repair and regeneration of articular cartilage in a minipig model of full-thickness defects. Good safranin-O staining and integration with surrounding tissues was achieved in animals transplanted with layered chondrocyte sheets. However, tissue having poor safranin-O staining-not noted in the domestic rabbit experiments-was identified in some of the animals, and the subchondral bone was poorly repaired in these. Thus, although layered chondrocyte sheets facilitate articular cartilage repair, further investigations into appropriate animal models and culture and transplant conditions are required. PMID:22369960

  11. Acellular Biomaterials: An Evolving Alternative to Cell-Based Therapies

    PubMed Central

    Burdick, Jason A.; Mauck, Robert L.; Gorman, Joseph H.; Gorman, Robert C.

    2014-01-01

    Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of applications with substantial intrinsic hurdles, but where human translation is now occurring. PMID:23486777

  12. Driving Cartilage Formation in High-Density Human Adipose-Derived Stem Cell Aggregate and Sheet Constructs Without Exogenous Growth Factor Delivery

    PubMed Central

    Dang, Phuong N.; Solorio, Loran D.

    2014-01-01

    An attractive cell source for cartilage tissue engineering, human adipose-derived stem cells (hASCs) can be easily expanded and signaled to differentiate into chondrocytes. This study explores the influence of growth factor distribution and release kinetics on cartilage formation within 3D hASC constructs incorporated with transforming growth factor-β1 (TGF-β1)-loaded gelatin microspheres. The amounts of microspheres, TGF-β1 concentration, and polymer degradation rate were varied within hASC aggregates. Microsphere and TGF-β1 loading concentrations were identified that resulted in glycosaminoglycan (GAG) production comparable to those of control aggregates cultured in TGF-β1-containing medium. Self-assembling hASC sheets were then engineered for the production of larger, more clinically relevant constructs. Chondrogenesis was observed in hASC-only sheets cultured with exogenous TGF-β1 at 3 weeks. Importantly, sheets with incorporated TGF-β1-loaded microspheres achieved GAG production similar to sheets treated with exogenous TGF-β1. Cartilage formation was confirmed histologically via observation of cartilage-like morphology and GAG staining. This is the first demonstration of the self-assembly of hASCs into high-density cell sheets capable of forming cartilage in the presence of exogenous TGF-β1 or with TGF-β1-releasing microspheres. Microsphere incorporation may bypass the need for extended in vitro culture, potentially enabling hASC sheets to be implanted more rapidly into defects to regenerate cartilage in vivo. PMID:24873753

  13. Infection in the Nasal Tip Caused by Acellular Dermal Matrix.

    PubMed

    Lee, Kun Hee

    2015-12-01

    A 19-year-old female patient visited our clinic for rhinoplasty. She complained about her low take-off point, which was apparent in profile view, and wanted slight tip projection. She refused additional cartilage harvesting from ears or ribs but consented to the use of homologous tissue, including acellular dermal matrix, for her dorsum and tip. Septoturbinoplasty was performed, and only a very small amount of septal cartilage could be harvested. It was used as both the columellar strut and the alar rim graft. Nasal dorsum and tip were augmented with acellular dermal matrix. Three months postoperatively, she experienced a few episodes of edema and redness on her nasal tip, followed by pus exudation from the nasal skin. Six months postoperatively, she underwent revision rhinoplasty for removal of inflamed grafts, and onlay tip graft with homologous rib cartilage was performed. Nasal dorsum or tip grafts are an integral part of Asian rhinoplasty. Autogenous tissue is the gold standard for grafting materials. However, the limited availability of autogenous tissue and the preference of patients and surgeons for artificial surgical implants make Asian rhinoplasty challenging. Unavailability of autogenous cartilage and patient refusal of artificial implants led to the use of acellular dermal matrix (ADM) in the nasal dorsum and tip for this case. This is the first report of postoperative complication because of infection rather than absorption after ADM use. PMID:26894006

  14. In vivo cartilage repair using adipose-derived stem cell-loaded decellularized cartilage ECM scaffolds.

    PubMed

    Kang, Hongjun; Peng, Jiang; Lu, Shibi; Liu, Shuyun; Zhang, Li; Huang, Jingxiang; Sui, Xiang; Zhao, Bin; Wang, Aiyuan; Xu, Wenjing; Luo, Zhijie; Guo, Quanyi

    2014-06-01

    We have previously reported a natural, human cartilage ECM (extracellular matrix)-derived three-dimensional (3D) porous acellular scaffold for in vivo cartilage tissue engineering in nude mice. However, the in vivo repair effects of this scaffold are still unknown. The aim of this study was to further explore the feasibility of application of cell-loaded scaffolds, using autologous adipose-derived stem cells (ADSCs), for cartilage defect repair in rabbits. A defect 4 mm in diameter was created on the patellar groove of the femur in both knees, and was repaired with the chondrogenically induced ADSC-scaffold constructs (group A) or the scaffold alone (group B); defects without treatment were used as controls (group C). The results showed that in group A all defects were fully filled with repair tissue and at 6 months post-surgery most of the repair site was filled with hyaline cartilage. In contrast, in group B all defects were partially filled with repair tissue, but only half of the repair tissue was hyaline cartilage. Defects were only filled with fibrotic tissue in group C. Indeed, histological grading score analysis revealed that an average score in group A was higher than in groups B and C. GAG and type II collagen content and biomechanical property detection showed that the group A levels approached those of normal cartilage. In conclusion, ADSC-loaded cartilage ECM scaffolds induced cartilage repair tissue comparable to native cartilage in terms of mechanical properties and biochemical components. PMID:22674864

  15. Cartilage Regeneration

    PubMed Central

    Tuan, Rocky S.; Chen, Antonia F.; Klatt, Brian A.

    2016-01-01

    Cartilage damaged by trauma has a limited capacity to regenerate. Current methods for treating small chondral defects include palliative treatment with arthroscopic debridement and lavage, reparative treatment with marrow stimulation techniques (e.g. microfracture), and restorative treatment, including osteochondral grafting and autologous chondrocyte implantation. Larger defects are treated by osteochondral allografting or total joint replacements. However, the future of treating cartilage defects lies in providing biologic solutions through cartilage regeneration. Laboratory and clinical studies have examined the treatment of larger lesions using tissue engineered cartilage. Regenerated cartilage can be derived from various cell types, including chondrocytes, mesenchymal stem cells, and pluripotent stem cells. Common scaffolding materials include proteins, carbohydrates, synthetic materials, and composite polymers. Scaffolds may be woven, spun into nanofibers, or configured as hydrogels. Chondrogenesis may be enhanced with the application of chondroinductive growth factors. Finally, bioreactors are being developed to enhance nutrient delivery and provide mechanical stimulation to tissue-engineered cartilage ex vivo. The multi-disciplinary approaches currently being developed to produce cartilage promise to bring the dream of cartilage regeneration in clinical use to reality. PMID:23637149

  16. Preparation and characterization of a decellularized cartilage scaffold for ear cartilage reconstruction.

    PubMed

    Utomo, Lizette; Pleumeekers, Mieke M; Nimeskern, Luc; Nürnberger, Sylvia; Stok, Kathryn S; Hildner, Florian; van Osch, Gerjo J V M

    2015-02-01

    Scaffolds are widely used to reconstruct cartilage. Yet, the fabrication of a scaffold with a highly organized microenvironment that closely resembles native cartilage remains a major challenge. Scaffolds derived from acellular extracellular matrices are able to provide such a microenvironment. Currently, no report specifically on decellularization of full thickness ear cartilage has been published. In this study, decellularized ear cartilage scaffolds were prepared and extensively characterized. Cartilage decellularization was optimized to remove cells and cell remnants from elastic cartilage. Following removal of nuclear material, the obtained scaffolds retained their native collagen and elastin contents as well as their architecture and shape. High magnification scanning electron microscopy showed no obvious difference in matrix density after decellularization. However, glycosaminoglycan content was significantly reduced, resulting in a loss of viscoelastic properties. Additionally, in contact with the scaffolds, human bone-marrow-derived mesenchymal stem cells remained viable and are able to differentiate toward the chondrogenic lineage when cultured in vitro. These results, including the ability to decellularize whole human ears, highlight the clinical potential of decellularization as an improved cartilage reconstruction strategy. PMID:25586138

  17. Engineering Cartilage

    MedlinePlus

    ... Method Builds Bone Lab-Grown Kidneys Function in Rats Cartilage: The Key to Healthy Joints Fast Facts ... Popular Stories An expanded map of the human brain How breast cancers resist chemotherapy Stem cells grown ...

  18. Shark cartilage

    MedlinePlus

    ... Shark cartilage is also used for arthritis, psoriasis, wound healing, damage to the retina of the eye due ... study drugs for rare conditions. Arthritis. Eye complications. Wound healing. Other conditions. More evidence is needed to rate ...

  19. Discontinuities in the endothelium of epiphyseal cartilage canals and relevance to joint disease in foals.

    PubMed

    Hellings, Ingunn Risnes; Ekman, Stina; Hultenby, Kjell; Dolvik, Nils Ivar; Olstad, Kristin

    2016-01-01

    Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122 days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118-day-old foal. Chondrifying cartilage canals in all TEM-examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty-three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in

  20. Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair.

    PubMed

    Fermor, Hazel L; Russell, Serena L; Williams, Sophie; Fisher, John; Ingham, Eileen

    2015-05-01

    It is proposed that an acellular natural osteochondral scaffold will provide a successful repair material for the early intervention treatment of cartilage lesions, to prevent or slow the progression of cartilage deterioration to osteoarthritis. Here, we investigated the efficacy of methods for the decellularisation of bovine osteochondral plugs. The plugs were subject to four freeze/thaw cycles followed by two cycles of washes in hypotonic solution and low concentration (0.1% w/v) sodium dodecyl sulphate with protease inhibitors. Plugs were treated with nuclease (DNase and RNase) treatment followed by sterilization in peracetic acid. Full tissue decellularisation was achieved as confirmed by histological analysis and DNA quantification, however the resultant acellular matrix had reduced glycosaminoglycan content which led to an increased percent deformation of cartilage. Furthermore, the acellular scaffold was not reproducibly biocompatible. Additional terminal washes were included in the process to improve biocompatibility, however, this led to visible structural damage to the cartilage. This damage was found to be minimised by reducing the cut edge to cartilage area ratio through decellularisation of larger cuts of osteochondral tissue. PMID:25893393

  1. Demonstration of fibronectin in human articular cartilage by an indirect immunoperoxidase technique.

    PubMed

    Clemmensen, I; Hølund, B; Johansen, N; Andersen, R B

    1982-01-01

    Fresh frozen tissue sections of human articular cartilage was treated without and with human testicular hyaluronidase (2 x 10(6) units/l) for 60 min at 37 degrees C and stained by the indirect immunoperoxidase technique with rabbit antihuman fibronectin. The rabbit antihuman fibronectin was purified by affinity chromatography on human fibronectin-Sepharose. Fibronectin was only found on the acellular surface of the articular cartilage in tissue sections not treated with hyaluronidase. In this surface layer, probably identical to "lamina splendens", the arrangement of fibronectin was as a membrane. No collagen was seen in this area by van Gieson staining. No staining for fibronectin was found in the cartilage matrix or in the chondrocytes. Treatment of the cartilage tissue with hyaluronidase resulted in visualization of high amount of fibronectin in the cartilage matrix, with the highest intensity around the chondrocytes. The staining of the acellular surface layer of the articular cartilage was identical with the results obtained without hyaluronidase treatment. These results indicate that articular cartilage is rich in fibronectin probably in complex with hyaluronic acid, and that the chondrocytes produce fibronectin in situ. It also demonstrates the steric hindrance of hyaluronic acid aggregates in diffusion of the antibody and the value of hyaluronidase treatment of tissue before demonstration of fibronectin. PMID:6757202

  2. Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

    PubMed Central

    Kamei, Naosuke; Adachi, Nobuo; Hamanishi, Michio; Kamei, Goki; Mahmoud, Elhussein Elbadry; Nakano, Tomohiro; Iwata, Takanori; Yamato, Masayuki; Okano, Teruo; Ochi, Mitsuo

    2015-01-01

    Cell sheet engineering has developed as a remarkable method for cell transplantation. In the field of cartilage regeneration, several studies previously reported that cartilage defects could be regenerated by transplantation of a chondrocyte sheet using cell sheet engineering. However, it remains unclear how such a thin cell sheet could repair a deep cartilage defect. We, therefore, focused on the mechanism of cartilage repair using cell sheet engineering in this study. Chondrocyte sheets and synovial cell sheets were fabricated using cell sheet engineering, and these allogenic cell sheets were transplanted to cover an osteochondral defect in a rat model. Macroscopic and histological evaluation was performed at 4 and 12 weeks after transplantation. Analysis of the gene expression of each cell sheet and of the regenerated tissue at 1 week after transplantation was performed. In addition, green fluorescent protein (GFP) transgenic rats were used as donors (transplanted chondrocyte sheets) or recipients (osteochondral defect models) to identify the cell origin of regenerated cartilage. Cartilage repair was significantly better in the group implanted with a chondrocyte sheet than in that with a synovial cell sheet. The results of gene expression analysis suggest that the possible factor contributing to cartilage repair might be TGFβ1. Cell tracking experiments using GFP transgenic rats showed that the regenerated cartilage was largely composed of cells derived from the transplanted chondrocyte sheets. PMID:25396711

  3. In vitro assessment of biodurability: acellular systems.

    PubMed Central

    de Meringo, A; Morscheidt, C; Thélohan, S; Tiesler, H

    1994-01-01

    The assessment of biodurability of man-made vitreous fibers is essential to the limitation of health hazards associated with human exposure to environments in which respirable fibers are present. In vitro acellular systems provide effective test methods of measuring fiber solubility provided care is taken to select the most suitable solvent and test conditions for the specific fiber type and dimension. PMID:7882955

  4. Automatic detection of diseased regions in knee cartilage

    NASA Astrophysics Data System (ADS)

    Qazi, Arish A.; Dam, Erik B.; Olsen, Ole F.; Nielsen, Mads; Christiansen, Claus

    2007-03-01

    Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. A central problem in clinical trials is quantification of progression and early detection of the disease. The accepted standard for evaluating OA progression is to measure the joint space width from radiographs however; there the cartilage is not visible. Recently cartilage volume and thickness measures from MRI are becoming popular, but these measures don't account for the biochemical changes undergoing in the cartilage before cartilage loss even occurs and therefore are not optimal for early detection of OA. As a first step, we quantify cartilage homogeneity (computed as the entropy of the MR intensities) from 114 automatically segmented medial compartments of tibial cartilage sheets from Turbo 3D T 1 sequences, from subjects with no, mild or severe OA symptoms. We show that homogeneity is a more sensitive technique than volume quantification for detecting early OA and for separating healthy individuals from diseased. During OA certain areas of the cartilage are affected more and it is believed that these are the load-bearing regions located at the center of the cartilage. Based on the homogeneity framework we present an automatic technique that partitions the region on the cartilage that contributes to maximum homogeneity discrimination. These regions however, are more towards the noncentral regions of the cartilage. Our observation will provide valuable clues to OA research and may lead to improving treatment efficacy.

  5. Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix

    PubMed Central

    Ye, Ken; Traianedes, Kathy; Choong, Peter F. M.; Myers, Damian E.

    2016-01-01

    Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFβ3 and BMP6. Human infrapatellar fat pad-derived adipose stem cells (IPFP-ASC) were cultured with ADM derived from rat dermis in chondrogenic (TGFβ3 and BMP6) medium in vitro for 2 and 4 weeks. Histology, qPCR, and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans). At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially, which stained positively for collagen Type II and proteoglycans. Significant cell–matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increased COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks. We believe that the principles that make ADM versatile and successful for tissue regeneration are applicable to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate, and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair. PMID:26858950

  6. Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix.

    PubMed

    Ye, Ken; Traianedes, Kathy; Choong, Peter F M; Myers, Damian E

    2016-01-01

    Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFβ3 and BMP6. Human infrapatellar fat pad-derived adipose stem cells (IPFP-ASC) were cultured with ADM derived from rat dermis in chondrogenic (TGFβ3 and BMP6) medium in vitro for 2 and 4 weeks. Histology, qPCR, and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans). At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially, which stained positively for collagen Type II and proteoglycans. Significant cell-matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increased COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks. We believe that the principles that make ADM versatile and successful for tissue regeneration are applicable to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate, and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair. PMID:26858950

  7. Data from acellular human heart matrix.

    PubMed

    Sánchez, Pedro L; Fernández-Santos, M Eugenia; Espinosa, M Angeles; González-Nicolas, M Angeles; Acebes, Judith R; Costanza, Salvatore; Moscoso, Isabel; Rodríguez, Hugo; García, Julio; Romero, Jesús; Kren, Stefan M; Bermejo, Javier; Yotti, Raquel; Del Villar, Candelas Pérez; Sanz-Ruiz, Ricardo; Elizaga, Jaime; Taylor, Doris A; Fernández-Avilés, Francisco

    2016-09-01

    Perfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to perfuse and support tissue-engineered heart constructs. This article contains additional data of our experience decellularizing and testing structural integrity and composition of a large series of human hearts, "Acellular human heart matrix: a critical step toward whole heat grafts" (Sanchez et al., 2015) [1]. Here we provide the information about the heart decellularization technique, the valve competence evaluation of the decellularized scaffolds, the integrity evaluation of epicardial and myocardial coronary circulation, the pressure volume measurements, the primers used to assess cardiac muscle gene expression and, the characteristics of donors, donor hearts, scaffolds and perfusion decellularization process. PMID:27331090

  8. [Imaging of articular cartilage].

    PubMed

    Arkun, Remide

    2007-01-01

    There have been many improvements in joint cartilage imaging in recent years with the development of new imaging methods. The purpose of cartilage imaging is to assess the integrity of the cartilage surface, the thickness and volume of the cartilage matrix and its relationship with the subchondral bone. Direct radiography, the conventional imaging method for the skeletal system, is not sufficient for assessing the joint cartilage, nor are arthrography, computed tomography, and arthrography together with computed tomography. Moreover, biomechanical changes in the joint cartilage cannot be assessed with these methods. Magnetic resonance imaging (MRI), with its superior contrast resolution and multiplanar imaging capability across tissues, has become the primary diagnostic method for assessment of joint pathologies. The morphological features of the joint cartilage can be assessed adequately with the use of MRI sequences specific to the cartilage. Appropriate use of MRI sequences to determine the type of cartilage damage, the presence and degree of accompanying pathologies in the subchondral bone will help minimize diagnostic errors. This article reviews cartilage imaging in the following aspects: the technique used in MRI for cartilage imaging, findings of cartilage pathology, and anticipation of future cartilage imaging. PMID:18180582

  9. The surface lamina of the articular cartilage of human zygapophyseal joints.

    PubMed

    Giles, L G

    1992-07-01

    Literature referring to the conflicting results of investigations into the possible existence and composition of the lamina splendens is reviewed. Two hundred micrometer thick histological sections from 80 human cadaveric lower lumbar zygapophyseal joint articular cartilages were examined by ordinary light and darkfield microscopy. The findings illustrate what appears to be an acellular surface lamina on the opposing cartilaginous surfaces. No speculation is made regarding the possible physiological significance of the lamina based on this anatomical study. PMID:1609968

  10. Equine cricoid cartilage densitometry.

    PubMed Central

    Behrens, E; Poteet, B; Cohen, N

    1993-01-01

    The density of the cricoid cartilage from 29 equine larynges collected from an abattoir was determined by dual photon absorptiometry (DPA). Densities of the right and left cricoid cartilages were highly correlated. No correlation was found between age of the horse and the density of the cricoid cartilage. PMID:8269372

  11. Scaffold-Free, Tissue Engineered Cartilage Implants for Laryngotracheal Reconstruction

    PubMed Central

    Gilpin, David A.; Weidenbecher, Mark S.; Dennis, James E.

    2016-01-01

    Objectives/Hypothesis Donor site morbidity, including pneumothorax, can be a considerable problem when harvesting cartilage grafts for laryngotracheal reconstruction (LTR). Tissue engineered cartilage may offer a solution to this problem. This study investigated the feasibility of using autologous chondrocytes to tissue engineer scaffold free cartilage grafts for LTR in rabbits in order to avoid degradation that often arises from an inflammatory reaction to the scaffold carrier matrix. Study Design Animal study. Methods Auricular cartilage was harvested from 7 New Zealand white rabbits, the chondrocytes expanded, and loaded onto a custom made bioreactor for 7–8 weeks to fabricate autologous scaffold free cartilage sheets. The sheets were cut to size and used for LTR, and the rabbits were sacrificed 4, 8, and 12 weeks after the LTR and prepared for histology. Results None of the 7 rabbits showed signs of respiratory distress. A smooth, noninflammatory scar was visible intraluminally; the remainder of the tracheal lumen was unremarkable. Histologically, the grafts showed no signs of degradation or inflammatory reaction, were covered with mucosal epithelium, but did show signs of mechanical failure at the implantation site. Conclusions These results show that autologous chondrocytes can be used to fabricate an implantable sheet of cartilage that retains a cartilage phenotype, becomes integrated, and does not produce a significant inflammatory reaction. These findings suggest that with the design of stronger implants, these implants can be successfully used as a graft for LTR. PMID:20058322

  12. Comparative anatomy of the vomeronasal cartilage in mammals: mink, cat, dog, pig, cow and horse.

    PubMed

    Salazar, I; Sánchez Quinteiro, P S; Cifuentes, J M

    1995-07-01

    The vomeronasal cartilages of mink, cat, dog, pig, cow and horse were studied by dissection, microdissection and by means of series of transverse sections. In all the species studied the cartilage is of hyaline type and the medial sheet is well-defined and perfectly moulded to the adjacent bone. However, interspecies differences are apparent in the manner in which the medial sheet associates and eventually fuses with the cartilage of the incisive duct; the morphology of the horse vomeronasal cartilage is particularly distinctive in this respect. The lateral sheet of the vomeronasal cartilage, although always present, has a different arrangement in each species studied. Similarly, the gaps in the lateral sheet (corresponding to the opening of the vomeronasal organ) differ among the species studied in form, location and number. PMID:7645743

  13. Lubricin reduces cartilage--cartilage integration.

    PubMed

    Schaefer, Dirk B; Wendt, David; Moretti, Matteo; Jakob, Marcel; Jay, Gregory D; Heberer, Michael; Martin, Ivan

    2004-01-01

    Cartilage integration in vivo does not occur, such that even cartilage fissures do not heal. This could be due not only to the limited access of chondrocytes to the wound, but also to exogenous factors. In this paper, we tested the hypothesis that lubricin, a lubricating protein physiologically present in the synovial fluid, reduces the integrative cartilage repair capacity. Disk/ring composites of bovine articular cartilage were prepared using concentric circular blades and cultured for 6 weeks with or without treatment with 250 microg/ml lubricin applied three times per week. Following culture, the percentage of contact area between the disks and the rings, as assessed by light microscopy, were equal in both groups. The adhesive strength of the integration interface, as assessed by push-out mechanical tests, was markedly and significantly lower in lubricin-treated specimens (2.5 kPa) than in the controls (28.7 kPa). Histological observation of Safranin-O stained cross-sections confirmed the reduced integration in the lubricin treated composites. Our findings suggest that the synovial milieu, by providing lubrication of cartilage surfaces, impairs cartilage--cartilage integration. PMID:15299281

  14. Acellular organ scaffolds for tumor tissue engineering

    NASA Astrophysics Data System (ADS)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

  15. Composite three-dimensional woven scaffolds with interpenetrating network hydrogels to create functional synthetic articular cartilage.

    PubMed

    Liao, I-Chien; Moutos, Franklin T; Estes, Bradley T; Zhao, Xuanhe; Guilak, Farshid

    2013-12-17

    The development of synthetic biomaterials that possess mechanical properties that mimic those of native tissues remains an important challenge to the field of materials. In particular, articular cartilage is a complex nonlinear, viscoelastic, and anisotropic material that exhibits a very low coefficient of friction, allowing it to withstand millions of cycles of joint loading over decades of wear. Here we show that a three-dimensionally woven fiber scaffold that is infiltrated with an interpenetrating network hydrogel can provide a functional biomaterial that provides the load-bearing and tribological properties of native cartilage. An interpenetrating dual-network "tough-gel" consisting of alginate and polyacrylamide was infused into a porous three-dimensionally woven poly(ε-caprolactone) fiber scaffold, providing a versatile fiber-reinforced composite structure as a potential acellular or cell-based replacement for cartilage repair. PMID:24578679

  16. Cartilage conduction hearing.

    PubMed

    Shimokura, Ryota; Hosoi, Hiroshi; Nishimura, Tadashi; Yamanaka, Toshiaki; Levitt, Harry

    2014-04-01

    Sound information is known to travel to the cochlea via either air or bone conduction. However, a vibration signal, delivered to the aural cartilage via a transducer, can also produce a clearly audible sound. This type of conduction has been termed "cartilage conduction." The aural cartilage forms the outer ear and is distributed around the exterior half of the external auditory canal. In cartilage conduction, the cartilage and transducer play the roles of a diaphragm and voice coil of a loudspeaker, respectively. There is a large gap between the impedances of cartilage and skull bone, such that cartilage vibrations are not easily transmitted through bone. Thus, these methods of conduction are distinct. In this study, force was used to apply a transducer to aural cartilage, and it was found that the sound in the auditory canal was amplified, especially for frequencies below 2 kHz. This effect was most pronounced at an application force of 1 N, which is low enough to ensure comfort in the design of hearing aids. The possibility of using force adjustments to vary amplification may also have applications for cell phone design. PMID:25234994

  17. Cartilage Engineering and Microgravity

    NASA Astrophysics Data System (ADS)

    Toffanin, R.; Bader, A.; Cogoli, A.; Carda, C.; Fantazzini, P.; Garrido, L.; Gomez, S.; Hall, L.; Martin, I.; Murano, E.; Poncelet, D.; Pörtner, R.; Hoffmann, F.; Roekaerts, D.; Ronney, P.; Triebel, W.; Tummers, M.

    2005-06-01

    The complex effects of mechanical forces and growth factors on articular cartilage development still need to be investigated in order to identify optimal conditions for articular cartilage repair. Strictly controlled in vitro studies under modelled or space microgravity conditions can improve our understanding of the fundamental role of gravity in articular cartilage development. The main objective of this Topical Team is to use modelled microgravity as a tool to elucidate the fundamental science of cartilage regeneration. Particular attention is, therefore, given to the effects of physical forces under altered gravitational conditions, applied using controlled bioreactor systems, on cell metabolism, cell differentiation and tissue development. Specific attention is also directed toward the potential advantages of using magnetic resonance methods for the non-destructive characterisation of scaffolds, chondrocytes-polymer constructs and tissue engineered cartilage.

  18. Immunology and cartilage regeneration.

    PubMed

    Smith, Benjamin; Sigal, Ian R; Grande, Daniel A

    2015-12-01

    The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them "antigen sequestered." It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins-to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation. PMID:26481914

  19. Guided Cartilage Regeneration Using Resorbable Template

    PubMed Central

    Pomahac, Bohdan; Zuhaili, Baraa; Kudsi, Yusuf

    2008-01-01

    Objective: The reconstruction of a defect involving complex cartilaginous structures such as the ear and nose is a difficult problem. Cartilage donor sites are limited, and the shaping of an ear or nose is dependent upon the surgeon's skills and experience. In this report, we propose to use resorbable plates that can be shaped to serve as a template for cartilage healing. Methods: A shell composed of polylactic/polyglycolic acid copolymer sheet was molded into different shapes. Autologous ribs harvested from 2 New Zealand rabbits were slightly crushed and bent without breaking, and placed within the pre-shaped shell. The constructs were implanted into subcutaneous pockets in the flanks of the rabbits. After 8 weeks, the implanted cartilage constructs were taken out of the shell and analyzed by the gross macroscopic appearance for preservation of the shape and by histological means for analysis of cartilage viability. Results: All of the explanted cartilage constructs retained the same pre-implanted shape and contour. Upon histological examination with hematoxylin/eosin staining, the constructs were composed of a continuous layer of viable chondrocytes. Conclusions: Construction of complex cartilaginous structures is an operator-dependent, technically difficult problem. We propose to use a resorbable template for guiding the shape and healing of the desired cartilaginous construct. Preoperative scanning and precise 3-dimensional shaping of the template could achieve further improvement in the desired cartilaginous support of the reconstructed part. In this report, we document that cartilage enclosed in a resorbable template retains its shape and viability. We believe that a prefabricated shell may help simplify and standardize outcomes of ear or nose reconstruction. PMID:18213400

  20. Semi-automatic knee cartilage segmentation

    NASA Astrophysics Data System (ADS)

    Dam, Erik B.; Folkesson, Jenny; Pettersen, Paola C.; Christiansen, Claus

    2006-03-01

    Osteo-Arthritis (OA) is a very common age-related cause of pain and reduced range of motion. A central effect of OA is wear-down of the articular cartilage that otherwise ensures smooth joint motion. Quantification of the cartilage breakdown is central in monitoring disease progression and therefore cartilage segmentation is required. Recent advances allow automatic cartilage segmentation with high accuracy in most cases. However, the automatic methods still fail in some problematic cases. For clinical studies, even if a few failing cases will be averaged out in the overall results, this reduces the mean accuracy and precision and thereby necessitates larger/longer studies. Since the severe OA cases are often most problematic for the automatic methods, there is even a risk that the quantification will introduce a bias in the results. Therefore, interactive inspection and correction of these problematic cases is desirable. For diagnosis on individuals, this is even more crucial since the diagnosis will otherwise simply fail. We introduce and evaluate a semi-automatic cartilage segmentation method combining an automatic pre-segmentation with an interactive step that allows inspection and correction. The automatic step consists of voxel classification based on supervised learning. The interactive step combines a watershed transformation of the original scan with the posterior probability map from the classification step at sub-voxel precision. We evaluate the method for the task of segmenting the tibial cartilage sheet from low-field magnetic resonance imaging (MRI) of knees. The evaluation shows that the combined method allows accurate and highly reproducible correction of the segmentation of even the worst cases in approximately ten minutes of interaction.

  1. Acellular Dermal Matrix in Rotator Cuff Surgery.

    PubMed

    Cooper, Joseph; Mirzayan, Raffy

    2016-01-01

    The success of rotator cuff repair (RCR) surgery can be measured clinically (validated outcome scores, range of motion) as well as structurally (re-tear rates using imaging studies). Regardless of repair type or technique, most studies have shown that patients do well clinically. However, multiple studies have also shown that structurally, the failure rate can be very high. A variety of factors, including poor tendon quality, age over 63 years, smoking, advanced fatty infiltration into the muscle, and the inability of the tendon to heal to bone, have been implicated as the cause of the high re-tear rate in RCRs. The suture-tendon interface is felt to be the weakest link in the RCR construct, and suture pullout through the tendon is believed to be the most common method of failure. This review of the published literature seeks to determine if there is support for augmentation of RCR with acellular dermal matrices to strengthen the suture-tendon interface and reduce the re-tear rate. PMID:27552454

  2. Bioactive Microsphere-Based Scaffolds Containing Decellularized Cartilage.

    PubMed

    Sutherland, Amanda J; Detamore, Michael S

    2015-07-01

    The aim of this study was to fabricate mechanically functional microsphere-based scaffolds containing decellularized cartilage (DCC), with the hypothesis that this approach would induce chondrogenesis of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro. The DCC was derived from porcine articular cartilage and decellularized using a combination of physical and chemical methods. Four types of scaffolds were fabricated: poly(d,l-lactic-co-glycolic acid) (PLGA) only (negative control), TGF-β-encapsulated (positive control), PLGA surface coated with DCC, and DCC-encapsulated. These scaffolds were seeded with rBMSCs and cultured up to 6 weeks. The compressive modulus of the DCC-coated scaffolds prior to cell seeding was significantly lower than all other scaffold types. Gene expression was comparable between DCC-encapsulated and TGF-β-encapsulated groups. Notably, DCC-encapsulated scaffolds contained 70% higher glycosaminoglyan (GAG) content and 85% more hydroxyproline compared to the TGF-β group at week 3 (with baseline levels subtracted out from acellular DCC scaffolds). Certainly, bioactivity was demonstrated in eliciting a biosynthetic response from the cells with DCC, although true demonstration of chondrogenesis remained elusive under the prescribed conditions. Encapsulation of DCC appeared to lead to improved cell performance relative to coating with DCC, although this finding may be a dose-dependent observation. Overall, DCC introduced via microsphere-based scaffolds appears to be promising as a bioactive approach to cartilage regeneration, although additional studies will be required to conclusively demonstrate chondroinductivity. PMID:25821206

  3. Mechanotransduction and cartilage integrity

    PubMed Central

    Leong, Daniel J.; Hardin, John A.; Cobelli, Neil J.; Sun, Hui B.

    2015-01-01

    Osteoarthritis (OA) is characterized by the breakdown of articular cartilage that is mediated in part by increased production of matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS), enzymes that degrade components of the cartilage extracellular matrix. Efforts to design synthetic inhibitors of MMPs/ADAMTS have only led to limited clinical success. In addition to pharmacologic therapies, physiologic joint loading is widely recommended as a nonpharmacologic approach to improve joint function in osteoarthritis. Clinical trials report that moderate levels of exercise exert beneficial effects, such as improvements in pain and physical function. Experimental studies demonstrate that mechanical loading mitigates joint destruction through the downregulation of MMPs/ADAMTS. However, the molecular mechanisms underlying these effects of physiologic loading on arthritic joints are not well understood. We review here the recent progress on mechanotransduction in articular joints, highlighting the mediators and pathways in the maintenance of cartilage integrity, especially in the prevention of cartilage degradation in OA. PMID:22172037

  4. Challenges to acellular biological scaffold mediated skeletal muscle tissue regeneration.

    PubMed

    Corona, Benjamin T; Greising, Sarah M

    2016-10-01

    Volumetric muscle loss (VML) injuries present a complex and heterogeneous clinical problem that results in a chronic loss of muscle tissue and strength. The primary limitation to muscle tissue regeneration after VML injury is the frank loss of all native muscle constituents in the defect, especially satellite cells and the basal lamina. Recent advancements in regenerative medicine have set forth encouraging and emerging translational and therapeutic options for these devastating injuries including the surgical implantation of acellular biological scaffolds. While these biomaterials can modulate the wound environment, the existing data do not support their capacity to promote appreciable muscle fiber regeneration that can contribute to skeletal muscle tissue functional improvements. An apparent restriction of endogenous satellite cell (i.e., pax7(+)) migration to acellular biological scaffolds likely underlies this deficiency. This work critically evaluates the role of an acellular biological scaffold in orchestrating skeletal muscle tissue regeneration, specifically when used as a regenerative medicine approach for VML injury. PMID:27472161

  5. Proteoglycans and cartilage repair.

    PubMed

    Ouzzine, Mohamed; Venkatesan, Narayanan; Fournel-Gigleux, Sylvie

    2012-01-01

    Repair of damaged articular cartilage in osteoarthritis (OA) is a clinical challenge. Because cartilage is an avascular and aneural tissue, normal mechanisms of tissue repair through recruitment of cells to the site of tissue destruction are not feasible. Proteoglycan (PG) depletion induced by the proinflammatory cytokine interleukin-1β, a principal mediator in OA, is a major factor in the onset and progression of joint destruction. Current symptomatic treatments of OA by anti-inflammatory drugs do not alter the progression of the disease. Various therapeutic strategies have been developed to antagonize the effect of proinflammatory cytokines. However, relatively few studies were conducted to stimulate anabolic activity, in an attempt to enhance cartilage repair. To this aim, a nonviral gene transfer strategy of glycosyltransferases responsible for PG synthesis has been developed and tested for its capacity to promote cartilage PG synthesis and deposition. Transfection of chondrocytes or cartilage explants by the expression vector for the glycosyltransferase β-1,3-glucuronosyltransferase-I (GlcAT-I) enhanced PG synthesis and deposition in the ECM by promoting the synthesis of chondroitin sulfate GAG chains of the cartilage matrix. This indicates that therapy mediated through GT gene delivery may constitute a new strategy for the treatment of OA. PMID:22252645

  6. Nanotechnology Biomimetic Cartilage Regenerative Scaffolds

    PubMed Central

    Sardinha, Jose Paulo; Myers, Simon

    2014-01-01

    Cartilage has a limited regenerative capacity. Faced with the clinical challenge of reconstruction of cartilage defects, the field of cartilage engineering has evolved. This article reviews current concepts and strategies in cartilage engineering with an emphasis on the application of nanotechnology in the production of biomimetic cartilage regenerative scaffolds. The structural architecture and composition of the cartilage extracellular matrix and the evolution of tissue engineering concepts and scaffold technology over the last two decades are outlined. Current advances in biomimetic techniques to produce nanoscaled fibrous scaffolds, together with innovative methods to improve scaffold biofunctionality with bioactive cues are highlighted. To date, the majority of research into cartilage regeneration has been focused on articular cartilage due to the high prevalence of large joint osteoarthritis in an increasingly aging population. Nevertheless, the principles and advances are applicable to cartilage engineering for plastic and reconstructive surgery. PMID:24883273

  7. Cartilage on the Move: Cartilage Lineage Tracing During Tadpole Metamorphosis

    PubMed Central

    Kerney, Ryan R.; Brittain, Alison L.; Hall, Brian K.; Buchholz, Daniel R.

    2012-01-01

    The reorganization of cranial cartilages during tadpole metamorphosis is a set of complex processes. The fates of larval cartilage-forming cells (chondrocytes) and sources of adult chondrocytes are largely unknown. Individual larval cranial cartilages may either degenerate or remodel, while many adult cartilages appear to form de novo during metamorphosis. Determining the extent to which adult chondrocytes/cartilages are derived from larval chondrocytes during metamorphosis requires new techniques in chondrocyte lineage tracing. We have developed two transgenic systems to label cartilage cells throughout the body with fluorescent proteins. One system strongly labels early tadpole cartilages only. The other system inducibly labels forming cartilages at any developmental stage. We examined cartilages of the skull (viscero- and neurocranium), and identified larval cartilages that either resorb or remodel into adult cartilages. Our data show that the adult otic capsules, tecti anterius and posterius, hyale, and portions of Meckel’s cartilage are derived from larval chondrocytes. Our data also suggest that most adult cartilages form de novo, though we cannot rule out the potential for extreme larval chondrocyte proliferation or de- and re-differentiation, which could dilute our fluorescent protein signal. The transgenic lineage tracing strategies developed here are the first examples of inducible, skeleton-specific, lineage tracing in Xenopus. PMID:23036161

  8. A Novel Biodegradable Polyurethane Matrix for Auricular Cartilage Repair: An In Vitro and In Vivo Study.

    PubMed

    Iyer, Kartik; Dearman, Bronwyn L; Wagstaff, Marcus J D; Greenwood, John E

    2016-01-01

    Auricular reconstruction poses a challenge for reconstructive and burns surgeons. Techniques involving cartilage tissue engineering have shown potential in recent years. A biodegradable polyurethane matrix developed for dermal reconstruction offers an alternative to autologous, allogeneic, or xenogeneic biologicals for cartilage reconstruction. This study assesses such a polyurethane matrix for this indication in vivo and in vitro. To evaluate intrinsic cartilage repair, three pigs underwent auricular surgery to create excisional cartilage ± perichondrial defects, measuring 2 × 3 cm in each ear, into which acellular polyurethane matrices were implanted. Biopsies were taken at day 28 for histological assessment. Porcine chondrocytes ± perichondrocytes were cultured and seeded in vitro onto 1 × 1 cm polyurethane scaffolds. The total culture period was 42 days; confocal, histological, and immunohistochemical analyses of scaffold cultures were performed on days 14, 28, and 42. In vivo, the polyurethane matrices integrated with granulation tissue filling all biopsy samples. Minimal neocartilage invasion was observed marginally on some samples. Tissue composition was identical between ears whether perichondrium was left intact, or not. In vitro, the polyurethane matrix was biocompatible with chondrocytes ± perichondrocytes and supported production of extracellular matrix and Type II collagen. No difference was observed between chondrocyte culture alone and chondrocyte/perichondrocyte scaffold coculture. The polyurethane matrix successfully integrated into the auricular defect and was a suitable scaffold in vitro for cartilage tissue engineering, demonstrating its potential application in auricular reconstruction. PMID:26284639

  9. [Articular cartilage regeneration using scaffold].

    PubMed

    Ishimoto, Yoshiyuki; Hattori, Koji; Ohgushi, Hajime

    2008-12-01

    The self-healing capacity of articular cartilage for repair is limited. For articular cartilage injury, several surgical techniques are used in clinical practice, namely drilling, abrasion arthroplasty, microfracture, or autologous osteochondral grafting, while various methods of autologous chondrocyte transplantation to cartilage defect sites have been reported since 1990s. In a case of chondrocyte transplantation to cartilage defect site, the use of proper scaffold is important. Currently, collagen gel or PLGA is used widely as a scaffold. PMID:19043192

  10. Estrogens, cartilage, and osteoarthritis.

    PubMed

    Richette, Pascal; Corvol, Maïté; Bardin, Thomas

    2003-08-01

    A role for estrogens in osteoarthritis is consistent with the larger increases in women than in men in the incidence and prevalence of hip, knee, and finger osteoarthritis after 50 years of age. Furthermore, hormone replacement therapy for the menopause seems to be associated with a decrease in the prevalence of symptoms and radiological alterations related to hip and knee osteoarthritis. The two estrogen receptors alpha and beta (ERalpha and Erbeta) have been identified in normal and osteoarthritic cartilage, indicating that cartilage can respond to estrogens. Finally, in vivo experiments in animals and in vitro studies have shed light on the mechanisms by which estrogens may influence chondrocyte metabolism. PMID:12951307

  11. A comparative study of acellular nerve xenografts and allografts in repairing rat facial nerve defects.

    PubMed

    Huang, Haitao; Xiao, Hongxi; Liu, Huawei; Niu, Yu; Yan, Rongzeng; Hu, Min

    2015-10-01

    Acellular nerves are composed of a basal lamina tube, which retains sufficient bioactivity to promote axon regeneration, thereby repairing peripheral nerve gaps. However, the clinical application of acellular allografts has been restricted due to its limited availability. To investigate whether xenografts, a substitute to allograft acellular nerves in abundant supply, could efficiently promote nerve regeneration, rabbit and rat acellular nerve grafts were used to reconstruct 1 cm defects in Wistar rat facial nerves. Autologous peroneal nerve grafts served as a positive control group. A total of 12 weeks following the surgical procedure, the axon number, myelinated axon number, myelin sheath thickness, and nerve conduction velocity of the rabbit and rat‑derived acellular nerve grafts were similar, whereas the fiber diameter of the rabbit‑derived acellular xenografts decreased, as compared with those of rat‑derived acellular allografts. Autografts exerted superior effects on nerve regeneration; however, no significant difference was observed between the axon number in the autograft group, as compared with the two acellular groups. These results suggested that autografts perform better than acellular nerve grafts, and chemically extracted acellular allografts and xenografts have similar effects on the regeneration of short facial nerve defects. PMID:26239906

  12. Cartilage fibrillation on the lateral tibial plateau in Liverpool necropsies.

    PubMed Central

    Meachim, G

    1976-01-01

    A study has been made of the state at necropsy of the hyaline articular cartilage of the left tibial plateaux, with particular reference to the lateral plateau, in 47 adult white Europeans (24 men; 23 women) aged 21-88 years. The surface morphology and topographical distribution of the lesions is described for the bare area of the lateral plateau and its meniscus-covered segments, and quantitative point-counting data are presented for the amount, according to age, of overt fibrillation on the bare area. A variety of cartilage lesions was encountered: macroscopically apparent ' parallel linear' minimal fibrillation; other patterns of minimal fibrillation; 'ravines'; overt fibrillation; localized incomplete defects of the cartilage; and full-thickness cartilage loss with bone exposure. Sites of superficial fraying and splitting of the hyaline articular cartilage are a normal finding on adult human tibial plateaux. Especially in younger adults, such sites are often accompanied by large areas of cartilage surface which are still intact. On the lateral plateau, the bare area and the meniscus-covered posterior segment are more susceptible to overt fibrillation than are the meniscus-covered lateral and anterior segments. In contrast to the findings in other synovial joints, the peripheral rim of the upper tibial cartilage sheet is not particularly susceptible to overt fibrillation. Tangential extension of the changes on the lateral plateau leads to widespread involvement of the bare area and the meniscus-covered posterior segment in older subjects. However, vertical progression of the changes, sufficient to give full-thickness cartilage loss with tibio-femoral bone exposure, was seen in only a minority of persons aged over 80 years. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 10 Fig. 11 Fig. 12 PMID:946428

  13. Lubrication and cartilage.

    PubMed Central

    Wright, V; Dowson, D

    1976-01-01

    Mechanisms of lubrication of human synovial joints have been analysed in terms of the operating conditions of the joint, the synovial fluid and articular cartilage. In the hip and knee during a walking cycle the load may rise up to four times body weight. In the knee on dropping one metre the load may go up to 25 time body weight. The elastic modulus of cartilage is similar to that of the synthetic rubber of a car tyre. The cartilage surface is rough and in elderly specimens the centre line average is 2-75 mum. The friction force generated in reciprocating tests shows that both cartilage and synovial fluid are important in lubrication. The viscosity-shear rate relationships of normal synovial fluid show that it is non-Newtonian. Osteoarthrosic fluid is less so and rheumatoid fluid is more nearly Newtonian. Experiments with hip joints in a pendulum machine show that fluid film lubrication obtains at some phases of joint action. Boundary lubrication prevails under certain conditions and has been examined with a reciprocating friction machine. Digestion of hyaluronate does not alter the boundary lubrication, but trypsin digestion does. Surface active substances (lauryl sulphate and cetyl 3-ammonium bromide) give a lubricating ability similar to that of synovial fluid. The effectiveness of the two substances varies with pH. Images Fig. 10 PMID:3490

  14. Chondroptosis in alkaptonuric cartilage.

    PubMed

    Millucci, Lia; Giorgetti, Giovanna; Viti, Cecilia; Ghezzi, Lorenzo; Gambassi, Silvia; Braconi, Daniela; Marzocchi, Barbara; Paffetti, Alessandro; Lupetti, Pietro; Bernardini, Giulia; Orlandini, Maurizio; Santucci, Annalisa

    2015-05-01

    Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of treatment is palliative and little is known about AKU physiopathology. Chondroptosis, a peculiar type of cell death in cartilage, has been so far reported to occur in osteoarthritis, a rheumatic disease that shares some features with AKU. In the present work, we wanted to assess if chondroptosis might also occur in AKU. Electron microscopy was used to detect the morphological changes of chondrocytes in damaged cartilage distinguishing apoptosis from its variant termed chondroptosis. We adopted histological observation together with Scanning Electron Microscopy and Transmission Electron Microscopy to evaluate morphological cell changes in AKU chondrocytes. Lipid peroxidation in AKU cartilage was detected by fluorescence microscopy. Using the above-mentioned techniques, we performed a morphological analysis and assessed that AKU chondrocytes undergo phenotypic changes and lipid oxidation, resulting in a progressive loss of articular cartilage structure and function, showing typical features of chondroptosis. To the best of our knowledge, AKU is the second chronic pathology, following osteoarthritis, where chondroptosis has been documented. Our results indicate that Golgi complex plays an important role in the apoptotic process of AKU chondrocytes and suggest a contribution of chondroptosis in AKU pathogenesis. These findings also confirm a similarity between osteoarthritis and AKU. PMID:25336110

  15. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  16. Fracture of articular cartilage.

    PubMed

    Chin-Purcell, M V; Lewis, J L

    1996-11-01

    Crack formation and propagation is a significant element of the degeneration process in articular cartilage. In order to understand this process, and separate the relative importance of structural overload and material failure, methods for measuring the fracture toughness of cartilage are needed. In this paper, two such methods are described and used to measure fracture properties of cartilage from the canine patella. A modified single edge notch (MSEN) specimen was used to measure J, and a trouser tear test was used to measure T, both measures of fracture toughness with units of kN/m. A pseudo-elastic modulus was also obtained from the MSEN test. Several potential error sources were examined, and results for the MSEN test compared with another method for measuring the fracture parameter for urethane rubber. Good agreement was found. The two test methods were used to measure properties of cartilage from the patellae of 12 canines: 4-9 specimens from each of 12 patellae, with 5 right-left pairs were tested. Values of J ranged from 0.14-1.2 kN/m. J values correlated with T and were an average of 1.7 times larger than T. A variety of failure responses was seen in the MSEN tests, consequently a grade of 0 to 3 was assigned to each test, where 0 represented a brittle-like crack with minimal opening and 3 represented plastic flow with no crack formation. The initial cracks in 12/82 specimens did not propagate and were assigned to grade 3. The method for reducing data in the MSEN test assumed pseudo-elastic response and could not be used for the grade 3 specimens. Stiffness did not correlate with J. Neither J nor T was statistically different between right-left pairs, but varied between animals. The test methods appear useful for providing a quantitative measure of fracture toughness for cartilage and other soft materials. PMID:8950659

  17. Engineering lubrication in articular cartilage.

    PubMed

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2012-04-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

  18. Engineering Lubrication in Articular Cartilage

    PubMed Central

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

  19. Comparison of toxicities of acellular pertussis vaccine with whole cell pertussis vaccine in experimental animals.

    PubMed

    Sato, Y; Sato, H

    1991-01-01

    There is no suitable animal model for pertussis encephalopathy in humans. In this study, we have compared the toxicity of acellular pertussis vaccine with whole cell pertussis vaccine in mice or guinea pigs. Two lots of acellular and two lots of whole cell vaccine produced in different countries were assayed in the test. 1. There was no statistical difference in mouse protective potency between these acellular or whole cell pertussis vaccines. 2. There were no differences in chemical ingredients between acellular and whole cell pertussis vaccines except for protein nitrogen content. The protein nitrogen content of whole cell vaccine was at least three times higher than that of the acellular product. 3. Anti-PT antibody productivity of the acellular vaccine was higher than that of the whole cell vaccine. 4. Anti-agglutinogen antibody productivity of the whole cell vaccine was higher than that of the acellular vaccine. 5. There was no pyrogenic activity with the acellular vaccine, but high pyrogenicity was seen with whole cell vaccine. 6. There was high body-weight decreasing toxicity in mice and guinea pigs by the whole cell vaccine. 7. The mice died when they received whole cell pertussis vaccine iv, but no deaths occurred in the mice which received acellular pertussis vaccine. PMID:1778317

  20. CARTILAGE CELL CLUSTERS

    PubMed Central

    Lotz, Martin K.; Otsuki, Shuhei; Grogan, Shawn P.; Sah, Robert; Terkeltaub, Robert; D’Lima, Darryl

    2010-01-01

    The formation of new cell clusters is a histological hallmark of arthritic cartilage but the biology of clusters and their role in disease are poorly understood. This is the first comprehensive review of clinical and experimental conditions associated with cluster formation. Genes and proteins that are expressed in cluster cells, the cellular origin of the clusters, mechanisms that lead to cluster formation and the role of cluster cells in pathogenesis are discussed. PMID:20506158

  1. Cartilage analysis by reflection spectroscopy

    NASA Astrophysics Data System (ADS)

    Laun, T.; Muenzer, M.; Wenzel, U.; Princz, S.; Hessling, M.

    2015-07-01

    A cartilage bioreactor with analytical functions for cartilage quality monitoring is being developed. For determining cartilage composition, reflection spectroscopy in the visible (VIS) and near infrared (NIR) spectral region is evaluated. Main goal is the determination of the most abundant cartilage compounds water, collagen I and collagen II. Therefore VIS and NIR reflection spectra of different cartilage samples of cow, pig and lamb are recorded. Due to missing analytical instrumentation for identifying the cartilage composition of these samples, typical literature concentration values are used for the development of chemometric models. In spite of these limitations the chemometric models provide good cross correlation results for the prediction of collagen I and II and water concentration based on the visible and the NIR reflection spectra.

  2. Signaling Pathways in Cartilage Repair

    PubMed Central

    Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

    2014-01-01

    In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

  3. MRI based knee cartilage assessment

    NASA Astrophysics Data System (ADS)

    Kroon, Dirk-Jan; Kowalski, Przemyslaw; Tekieli, Wojciech; Reeuwijk, Els; Saris, Daniel; Slump, Cornelis H.

    2012-03-01

    Osteoarthritis is one of the leading causes of pain and disability worldwide and a major health problem in developed countries due to the gradually aging population. Though the symptoms are easily recognized and described by a patient, it is difficult to assess the level of damage or loss of articular cartilage quantitatively. We present a novel method for fully automated knee cartilage thickness measurement and subsequent assessment of the knee joint. First, the point correspondence between a pre-segmented training bone model is obtained with use of Shape Context based non-rigid surface registration. Then, a single Active Shape Model (ASM) is used to segment both Femur and Tibia bone. The surfaces obtained are processed to extract the Bone-Cartilage Interface (BCI) points, where the proper segmentation of cartilage begins. For this purpose, the cartilage ASM is trained with cartilage edge positions expressed in 1D coordinates at the normals in the BCI points. The whole cartilage model is then constructed from the segmentations obtained in the previous step. An absolute thickness of the segmented cartilage is measured and compared to the mean of all training datasets, giving as a result the relative thickness value. The resulting cartilage structure is visualized and related to the segmented bone. In this way the condition of the cartilage is assessed over the surface. The quality of bone and cartilage segmentation is validated and the Dice's coefficients 0.92 and 0.86 for Femur and Tibia bones and 0.45 and 0.34 for respective cartilages are obtained. The clinical diagnostic relevance of the obtained thickness mapping is being evaluated retrospectively. We hope to validate it prospectively for prediction of clinical outcome the methods require improvements in accuracy and robustness.

  4. Towards Regeneration of Articular Cartilage

    PubMed Central

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  5. Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study

    PubMed Central

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E

    2016-01-01

    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson’s trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation

  6. Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study.

    PubMed

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E

    2016-01-01

    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson's trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation

  7. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  8. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair.

    PubMed

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-07-15

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  9. Advances in understanding cartilage remodeling

    PubMed Central

    Li, Yefu; Xu, Lin

    2015-01-01

    Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current “controversial” observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis. PMID:26380073

  10. Phase II trial of whole-cell pertussis vaccine vs an acellular vaccine containing agglutinogens.

    PubMed

    Miller, E; Ashworth, L A; Robinson, A; Waight, P A; Irons, L I

    1991-01-12

    An acellular pertussis vaccine containing agglutinogens 2 and 3, pertussis toxin, and filamentous haemagglutinin was developed by the Centre for Applied Microbiology and Research in the UK. 188 infants were entered into a randomised blind trial and received either the acellular or a whole-cell vaccine, combined with diphtheria and tetanus toxoids, in a 3, 5, and 8-10 month schedule. Local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine. Mean log-antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole-cell vaccine. Persistence of antibodies one year after the third dose was also better in the acellular group. PMID:1670725

  11. Use of an Acellular Regenerative Tissue Matrix Over Chronic Wounds

    PubMed Central

    Stacey, D. Heath

    2013-01-01

    Objectives: Bioengineered skin grafts, including acellular dermal matrices, may be effective in treating lower extremity and trunk wounds that are not responsive to traditional wound management. Acellular dermal wound matrix is derived from human acellular dermal wound matrix (HADWM) tissue and provides a scaffold that supports cellular repopulation and revascularization. The major structural components of the dermis are retained during processing, and a single application has been shown to help achieve wound closure. Methods: This patient case series examined the use of HADWM on lower extremity and trunk wounds in 11 patients (6 male and 5 female) with a mean age of 55 years (range: 31–83 years). Wounds were debrided 1 to 2 times, followed by placement of HADWM (range: 4–330 cm2) on wounds that varied from the dorsal surface of the foot, lower abdomen, and lower extremity to the Achilles flap. A nonadherent layer in conjunction with bacitracin was placed over HADWM. Negative pressure wound therapy (NPWT) was placed over the HADWM and initiated continuously at −125 mm Hg for 1 to 2 weeks. After the application of NPWT, HADWM was covered with various gauze dressings using mineral oil. Results: All patients completed their treatment successfully, and follow-up ranged from 1 week to 6 months. One patient experienced an infection, which resulted in partial graft loss that required replacement with HADWM and NPWT. No additional complications occurred in the other patients. Conclusions: This patient case series demonstrated successful use of HADWM and NPWT, which further supports published studies documenting HADWM success in chronic wounds. PMID:24324850

  12. Whooping cough, twenty years from acellular vaccines introduction.

    PubMed

    Greco, D; Esposito, S; Tozzi, A; Pandolfi, E; Icardi, G; Giammanco, A

    2015-01-01

    Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years. PMID:26051141

  13. Treatment of severe burn with DermACELL®, an acellular dermal matrix

    PubMed Central

    Chen, Shyi-Gen; Tzeng, Yuan-Sheng; Wang, Chih-Hsin

    2012-01-01

    For treatment of skin burn injuries, there exist several methods of treatment related to tissue regeneration, including the use of autograft skin and cryopreserved skin. However, each method has drawbacks. An alternative method for tissue regeneration is allograft acellular dermal matrix, with potential as a biocompatible scaffold for new tissue growth. One recently produced material of this type is DermACELL®, which was used in this case presentation for treating a scar resulting from second- and third-degree burns in a 33-year-old female patient. The patient presented with significant hypertrophic scarring from the elbow to the hand and with limited wrist and elbow motion. The scarring was removed, and the patient was treated with a 1:3 mesh of DermACELL. The wound was resurfaced with a split thickness skin graft, and postoperative care included application of pressure garment and silicone sheet, as well as range of motion exercise and massage. At 30 days after DermACELL application, the wound appeared well-healed with little scar formation. At 180 days post-application, the wound continued to appear healed well without significant scar formation. Additionally, the wound was supple, and the patient experienced significant improvement in range of motion. In the case presented, DermACELL appears to have been a successful method of treatment for scarring due to severe burns by preventing further scar formation and improving range of motion. PMID:23071908

  14. Acellular dermal matrices in breast reconstructions - a literature review.

    PubMed

    Skovsted Yde, Simon; Brunbjerg, Mette Eline; Damsgaard, Tine Engberg

    2016-08-01

    During the last two decades, acellular dermal matrices (ADM) have been more widely used in reconstructive procedures i.e. breast reconstructions. Several, both synthetic and biologic products derived from human, porcine and bovine tissue, have been introduced. Until this point postoperative complications for the acellular dermal matrices, as a group, have been the main focus. The purpose of this literature review is to summarize the current knowledge on the each biologic product used in breast reconstructions, including product specific complication frequencies. A systematic search of the literature was performed in the PubMed and EMBASE databases, identifying 55 relevant articles, mainly evidence level III. AlloDerm seems to be associated with severe complicating matters in the reconstructive process compared to other products. This could be due to the higher number of investigating studies relative to the others. The surgical area faces certain challenges comparing results, due to surgical variance, the data collection and follow-up. More well-defined guidelines and more high-evidence randomized studies could increase the overall level of evidence in this area. PMID:26881927

  15. Human acellular dermal wound matrix: evidence and experience.

    PubMed

    Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

    2015-12-01

    A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. PMID:24283346

  16. Characterization of cathepsins in cartilage

    PubMed Central

    Ali, S. Y.; Evans, L.; Stainthorpe, E.; Lack, C. H.

    1967-01-01

    The presence of a cathepsin B-like enzyme in rabbit ear cartilage was established by the use of the synthetic substrates benzoyl-l-arginine amide and benzoyl-dl-arginine 2-naphthylamide. This was facilitated by using a technique that permits the incubation of a fixed weight of thin (18μ) cartilage sections with an appropriate exogenous substrate. The enzymic properties of cathepsin B in cartilage have been compared with an endogenous enzyme that liberates chondromucopeptide by degrading the cartilage matrix autocatalytically at pH5. Besides being maximally active at pH4·7, these cartilage enzymes are enhanced in activity by cysteine and inhibited by arginine analogues, iodoacetamide, chloroquine and mercuric chloride. They are not inhibited by EDTA, di-isopropyl phosphorofluoridate and diethyl p-nitrophenyl phosphate. When inhibiting the release of chondromucopeptide from cartilage at pH5, the arginine-containing synthetic substrates are hydrolysed simultaneously. These enzymes also share the same heat-inactivation characteristics at various pH values, being stable at acid pH and unstable at neutral and alkaline pH. The experimental evidence indicates that a cathepsin B-like enzyme may be partly responsible for the autolytic degradation of cartilage matrix at pH5. PMID:5583997

  17. Proteomic analysis of engineered cartilage

    PubMed Central

    Pu, Xinzhu; Oxford, Julia Thom

    2016-01-01

    Summary Tissue engineering holds promise for the treatment of damaged and diseased tissues, especially for those tissues that do not undergo repair and regeneration readily in situ. Many techniques are available for cell and tissue culturing and differentiation of chondrocytes using a variety of cell types, differentiation methods, and scaffolds. In each case, it is critical to demonstrate the cellular phenotype and tissue composition, with particular attention to the extracellular matrix molecules that play a structural role and that contribute to the mechanical properties of the resulting tissue construct. Mass spectrometry provides an ideal analytical method with which to characterize the full spectrum of proteins produced by tissue engineered cartilage. Using normal cartilage tissue as a standard, tissue engineered cartilage can be optimized according to the entire proteome. Proteomic analysis is a complementary approach to biochemical, immunohistochemical, and mechanical testing of cartilage constructs. Proteomics is applicable as an analysis approach to most cartilage constructs generated from a variety of cellular sources including primary chondrocytes, mesenchymal stem cells from bone marrow, adipose tissue, induced pluripotent stem cells, and embryonic stem cells. Additionally, proteomics can be used to optimize novel scaffolds and bioreactor applications, yielding cartilage tissue with the proteomic profile of natural cartilage. PMID:26445845

  18. Microsphere-based scaffolds encapsulating chondroitin sulfate or decellularized cartilage.

    PubMed

    Gupta, Vineet; Tenny, Kevin M; Barragan, Marilyn; Berkland, Cory J; Detamore, Michael S

    2016-09-01

    Extracellular matrix materials such as decellularized cartilage (DCC) and chondroitin sulfate (CS) may be attractive chondrogenic materials for cartilage regeneration. The goal of the current study was to investigate the effects of encapsulation of DCC and CS in homogeneous microsphere-based scaffolds, and to test the hypothesis that encapsulation of these extracellular matrix materials would induce chondrogenesis of rat bone marrow stromal cells. Four different types of homogeneous scaffolds were fabricated from microspheres of poly(D,L-lactic-co-glycolic acid): Blank (poly(D,L-lactic-co-glycolic acid) only; negative control), transforming growth factor-β3 encapsulated (positive control), DCC encapsulated, and CS encapsulated. These scaffolds were then seeded with rat bone marrow stromal cells and cultured for 6 weeks. The DCC and CS encapsulation altered the morphological features of the microspheres, resulting in higher porosities in these groups. Moreover, the mechanical properties of the scaffolds were impacted due to differences in the degree of sintering, with the CS group exhibiting the highest compressive modulus. Biochemical evidence suggested a mitogenic effect of DCC and CS encapsulation on rat bone marrow stromal cells with the matrix synthesis boosted primarily by the inherently present extracellular matrix components. An important finding was that the cell seeded CS and DCC groups at week 6 had up to an order of magnitude higher glycosaminoglycan contents than their acellular counterparts. Gene expression results indicated a suppressive effect of DCC and CS encapsulation on rat bone marrow stromal cell chondrogenesis with differences in gene expression patterns existing between the DCC and CS groups. Overall, DCC and CS were easily included in microsphere-based scaffolds; however, there is a requirement to further refine their concentrations to achieve the differentiation profiles we seek in vitro. PMID:27358376

  19. Polymer Formulations for Cartilage Repair

    SciTech Connect

    Gutowska, Anna; Jasionowski, Marek; Morris, J. E.; Chrisler, William B.; An, Yuehuei H.; Mironov, V.

    2001-05-15

    Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into a defect. The best results are obtained with the use of autologus cells. However, obtaining large amounts of autologus cartilage cells causes a problem of creating a large cartilage defect in a donor site. Techniques are currently being developed to harvest a small number of cells and propagate them in vitro. It is a challenging task, however, due to the fact that ordinarily, in a cell culture on flat surfaces, chondrocytes do not maintain their in vivo phenotype and irreversibly diminish or cease the synthesis of aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.

  20. Cartilage (Bovine and Shark) (PDQ)

    MedlinePlus

    ... a treatment for cancer. There has been one randomized clinical trial of cartilage as cancer treatment published ... reported that it has little harmful effect. A randomized clinical trial studied the effect of AE-941/ ...

  1. Anti-Inflammatory Strategies in Cartilage Repair

    PubMed Central

    Zhang, Ying; Pizzute, Tyler

    2014-01-01

    Cartilage defects are normally concomitant with posttraumatic inflammation and pose a major challenge in cartilage repair. Due to the avascular nature of cartilage and its inability to surmount an inflammatory response, the cartilage is easily attacked by proinflammatory factors and oxidative stress; if left untreated, osteoarthritis may develop. Suppression of inflammation has always been a crux for cartilage repair. Pharmacological drugs have been successfully applied in cartilage repair; however, they cannot optimally work alone. This review article will summarize current pharmacological drugs and their application in cartilage repair. The development of extracellular matrix-based scaffolds and preconditioned tissue-specific stem cells will be emphasized because both of these tissue engineering components could contribute to an enhanced ability not only for cartilage regeneration but also for anti-inflammation. These strategies could be combined to boost cartilage repair under inflammatory conditions. PMID:24846478

  2. Extended Eden model reproduces growth of an acellular slime mold

    NASA Astrophysics Data System (ADS)

    Wagner, Geri; Halvorsrud, Ragnhild; Meakin, Paul

    1999-11-01

    A stochastic growth model was used to simulate the growth of the acellular slime mold Physarum polycephalum on substrates where the nutrients were confined in separate drops. Growth of Physarum on such substrates was previously studied experimentally and found to produce a range of different growth patterns [Phys. Rev. E 57, 941 (1998)]. The model represented the aging of cluster sites and differed from the original Eden model in that the occupation probability of perimeter sites depended on the time of occupation of adjacent cluster sites. This feature led to a bias in the selection of growth directions. A moderate degree of persistence was found to be crucial to reproduce the biological growth patterns under various conditions. Persistence in growth combined quick propagation in heterogeneous environments with a high probability of locating sources of nutrients.

  3. Application of acellular dermis and autograft on burns and scars.

    PubMed

    Ramos Duron, L E; Martínez Pardo, M E; Olivera Zavaleta, V; Silva Diaz, T; Reyes Frías, M L; Luna Zaragoza, D

    1999-01-01

    The cases of two patients with burns treated with dermis allograft and of one patient for lip reconstructive aesthetic filling treated with less than one mm3 of radiosterilised acellular dermis are presented. This paper emphasizes the treatment with radiosterilised dermal grafts with a permanent character so far. Hospitals, therefore, can satisfy the demand for this kind of tissue in the case of disaster and patients with serious injuries. In the cases cited, histocompatibility analysis was not required, thus having the advantage of long-time storage of the radiosterilised dermis used on these patients. Neither inflammatory reaction nor acute phase re-absorption were observed. Moreover, shrink (contract) healing was diminished. After two years, the results are still satisfactory. PMID:10853787

  4. Protection against pertussis by acellular pertussis vaccines (Takeda, Japan): household contact studies in Kawasaki City, Japan.

    PubMed

    Kato, T; Goshima, T; Nakajima, N; Kaku, H; Arimoto, Y; Hayashi, F

    1989-12-01

    To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, acellular vaccine made by Takeda Pharmaceutical Company, which contains a high level of FHA (filamentous hemagglutinin), a low level of PT (pertussis toxin) and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand, 27 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.7%). The present study revealed an efficacy rate of 93.7% for Takeda's acellular pertussis vaccine. PMID:2516396

  5. [Protection against pertussis by Japanese T type acellular pertussis vaccine: household contact study in Kawasaki City].

    PubMed

    Kato, T; Matsuyoshi, S; Goshima, T; Nakajima, N; Yamamoto, H; Arimoto, Y; Kaku, H; Hayashi, F

    1989-09-01

    To evaluate the vaccine efficacy of acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was made by a questionnaire from secondary pertussis attack through family contact in 149 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand of the siblings immunized with Takeda's acellular vaccine 27 were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.4%). The present study revealed an efficacy rate of 94.2% for the Takeda's acellular pertussis vaccine. PMID:2509597

  6. Protection against pertussis by Takeda's acellular pertussis vaccine: household contact studies in Kawasaki City, Japan.

    PubMed

    Kato, T; Kaku, H; Arimoto, Y

    1988-01-01

    To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 27 siblings (62.9%) not immunized with pertussis vaccine. On the other hand, 26 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.8%). The present study revealed an efficacy rate of 93.9% for Takeda's acellular pertussis vaccine. PMID:3078808

  7. CARTILAGE-ON-CARTILAGE VS. METAL-ON-CARTILAGE IMPACT CHARACTERISTICS AND RESPONSES

    PubMed Central

    Heiner, Anneliese D.; Smith, Abigail D.; Goetz, Jessica E.; Goreham-Voss, Curtis M.; Judd, Kyle T.; McKinley, Todd O.; Martin, James A.

    2013-01-01

    A common in vitro model for studying acute mechanical damage in cartilage is to impact an isolated osteochondral or cartilage specimen with a metallic impactor. The mechanics of a cartilage-on-cartilage (COC) impact, as encountered in vivo, are likely different than those of a metal-on-cartilage (MOC) impact. The hypothesis of this study was that impacted in vitro COC and MOC specimens would differ in their impact behavior, mechanical properties, chondrocyte viability, cell metabolism, and histologic structural damage. Osteochondral specimens were impacted with either an osteochondral plug or a metallic cylinder at the same delivered impact energy per unit area, and processed after 14 days in culture. The COC impacts resulted in about half of the impact maximum stress and a quarter of the impact maximum stress rate of change, as compared to the MOC impacts. The impacted COC specimens had smaller changes in mechanical properties, smaller decreases in chondrocyte viability, higher total proteoglycan content, and less histologic structural damage, as compared to the impacted MOC specimens. If metal-on-cartilage impact conditions are to be used for modeling of articular injuries and post-traumatic osteoarthritis, the differences between COC and MOC impacts must be kept in mind. PMID:23335281

  8. Model-based cartilage thickness measurement in the submillimeter range

    SciTech Connect

    Streekstra, G. J.; Strackee, S. D.; Maas, M.; Wee, R. ter; Venema, H. W.

    2007-09-15

    Current methods of image-based thickness measurement in thin sheet structures utilize second derivative zero crossings to locate the layer boundaries. It is generally acknowledged that the nonzero width of the point spread function (PSF) limits the accuracy of this measurement procedure. We propose a model-based method that strongly reduces PSF-induced bias by incorporating the PSF into the thickness estimation method. We estimated the bias in thickness measurements in simulated thin sheet images as obtained from second derivative zero crossings. To gain insight into the range of sheet thickness where our method is expected to yield improved results, sheet thickness was varied between 0.15 and 1.2 mm with an assumed PSF as present in the high-resolution modes of current computed tomography (CT) scanners [full width at half maximum (FWHM) 0.5-0.8 mm]. Our model-based method was evaluated in practice by measuring layer thickness from CT images of a phantom mimicking two parallel cartilage layers in an arthrography procedure. CT arthrography images of cadaver wrists were also evaluated, and thickness estimates were compared to those obtained from high-resolution anatomical sections that served as a reference. The thickness estimates from the simulated images reveal that the method based on second derivative zero crossings shows considerable bias for layers in the submillimeter range. This bias is negligible for sheet thickness larger than 1 mm, where the size of the sheet is more than twice the FWHM of the PSF but can be as large as 0.2 mm for a 0.5 mm sheet. The results of the phantom experiments show that the bias is effectively reduced by our method. The deviations from the true thickness, due to random fluctuations induced by quantum noise in the CT images, are of the order of 3% for a standard wrist imaging protocol. In the wrist the submillimeter thickness estimates from the CT arthrography images correspond within 10% to those estimated from the anatomical

  9. The use of an acellular collagen matrix in penile augmentation: A pilot study in Saudi Arabia

    PubMed Central

    Tealab, Alaa A.; Maarouf, Aref M.; Habous, Mohamed; Ralph, David J.; Abohashem, Safwat

    2013-01-01

    Objectives To assess the use of an acellular collagen matrix (Pelvicol, Bard Medical, Covington, GA, USA), a successful agent for reconstructive surgery, for enhancing penile girth. Patients and methods Between June and December 2011, 18 patients (mean age 24 years, range 19–38) had their penis augmented with Pelvicol; the mean (range) penile circumference was 9.2 (7–13) cm before treatment. They were divided into two groups; the first (10 patients) had a Pelvicol sheet of 8 × 12 cm inserted through a V–Y suprapubic incision and wrapped around the shaft in a bilayer under the dartos fascia, but not covering the urethra, with division of the suspensory ligament. The second group of eight patients had the Pelvicol inserted through a subcoronal degloving incision and placed in one layer. The penile circumference was measured at 6 and 12 months after surgery. Patient satisfaction at 1 year after surgery was assessed as ‘poor’, ‘unsatisfied’, ‘moderately satisfied’, ‘highly satisfied’, or ‘excellent’. Results The mean (range) increase in girth (circumference) was 2.8 (2–3.2) cm in group 1 and 1.7 (1.2–2) cm in group 2. In group 1, two patients were highly satisfied, four moderately satisfied and four unsatisfied; in group 2, three were moderately satisfied and five unsatisfied. Complications were common in both groups, with five patients in group 1 and three in group 2 developing severe penile oedema and ischaemic shaft ulcers. Removal of the graft was required in two patients in each group. Conclusion This pilot study shows that Pelvicol is not an ideal option for enhancing penile girth, and the method of placement did not apparently influence the result. PMID:26558077

  10. Imaging of cartilage repair procedures

    PubMed Central

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts. PMID:25114387

  11. Transcriptomic profiling of cartilage ageing.

    PubMed

    Peffers, Mandy Jayne; Liu, Xuan; Clegg, Peter David

    2014-12-01

    The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386). PMID:26484061

  12. Cartilage collagen analysis in the chondrodystrophies.

    PubMed

    Horton, W A; Chou, J W; Machado, M A

    1985-09-01

    A simple and reproducible method for analyzing small samples of cartilage collagens was developed. Following extraction with guanidine HCl, the cartilage specimens were digested directly with CNBr and the resultant peptides separated by gel-permeation high-performance liquid chromatography. Resting cartilage collagen CNBr peptide maps differed from normal in two inherited chondrodystrophies, achondrogenesis II and spondyloepiphyseal dysplasia congenita. PMID:4053564

  13. Emergence of Scaffold-free Approaches for Tissue Engineering Musculoskeletal Cartilages

    PubMed Central

    DuRaine, Grayson D.; Brown, Wendy E.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages –for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc – are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well. PMID:25331099

  14. MRI EVALUATION OF KNEE CARTILAGE

    PubMed Central

    Rodrigues, Marcelo Bordalo; Camanho, Gilberto Luís

    2015-01-01

    Through the ability of magnetic resonance imaging (MRI) to characterize soft tissue noninvasively, it has become an excellent method for evaluating cartilage. The development of new and faster methods allowed increased resolution and contrast in evaluating chondral structure, with greater diagnostic accuracy. In addition, physiological techniques for cartilage assessment that can detect early changes before the appearance of cracks and erosion have been developed. In this updating article, the various techniques for chondral assessment using knee MRI will be discussed and demonstrated. PMID:27022562

  15. Investigation of the Regenerative Capacity of an Acellular Porcine Medial Meniscus for Tissue Engineering Applications

    PubMed Central

    Ingram, Joanne; Fisher, John; Ingham, Eileen

    2011-01-01

    Previously, we have described the development of an acellular porcine meniscal scaffold. The aims of this study were to determine the immunocompatibility of the scaffold and capacity for cellular attachment and infiltration to gain insight into its potential for meniscal repair and replacement. Porcine menisci were decellularized by exposing the tissue to freeze–thaw cycles, incubation in hypotonic tris buffer, 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors, nucleases, hypertonic buffer followed by disinfection using 0.1% (v/v) peracetic, and final washing in phosphate-buffered saline. In vivo immunocompatibility was assessed after implantation of the acellular meniscal scaffold subcutaneously into galactosyltransferase knockout mice for 3 months in comparison to fresh and acellular tissue treated with α-galactosidase (negative control). The cellular infiltrates in the explants were assessed by histology and characterized using monoclonal antibodies against: CD3, CD4, CD34, F4/80, and C3c. Static culture was used to assess the potential of acellular porcine meniscal scaffold to support the attachment and infiltration of primary human dermal fibroblasts and primary porcine meniscal cells in vitro. The explants were surrounded by capsules that were more pronounced for the fresh meniscal tissue compared to the acellular tissues. Cellular infiltrates compromised mononuclear phagocytes, CD34-positive cells, and nonlabeled fibroblastic cells. T-lymphocytes were sparse in all explanted tissue types and there was no evidence of C3c deposition. The analysis revealed an absence of a specific immune response to all of the implanted tissues. Acellular porcine meniscus was shown to be capable of supporting the attachment and infiltration of primary human fibroblasts and primary porcine meniscal cells. In conclusion, acellular porcine meniscal tissue exhibits excellent immunocompatibility and potential for cellular regeneration in the longer

  16. Comparative biological activities of acellular pertussis vaccines produced by Kitasato.

    PubMed

    Watanabe, M; Izumiya, K; Sato, T; Yoshino, K; Nakagawa, N; Ohoishi, M; Hoshino, M

    1991-04-01

    The quality of 14 lots of acellular pertussis-diphtheria-tetanus (AC-PDT) vaccines manufactured by the Kitasato Institute during the period 1987-1990 were investigated. The geometric means of HSU, LPU, and BWDU were 0.078, 0.257, and 7.33 per ml respectively. The potency was higher than 14 IU per ml. These results indicated the consistency of the Kitasato AC-PDT vaccines. The antibody response to the AC-PDT vaccines was measured in primary and secondary vaccinated mice by ELISA. IgG antibody response to FHA and PT was obtained in all immunized mice (P less than 0.001) after the primary injection. In contrast, IgG antibody response to fimbriae 2 showed a significant titer rise (P less than 0.001) after the booster injection. The results indicated that the Kitasato AC-P vaccines consisted of protein, PT and FHA as the major antigens, and a little agglutinogen as the minor antigen. PMID:1798236

  17. [Experimental, clinical and immunologic assessment of acellular staphylococcal vaccine "Staphylovac"].

    PubMed

    Egorova, N B; Efremova, V N; Kurbatova, E A; Gruber, I M

    2008-01-01

    Results of experimental, clinical and immunological effects of acellular dry staphylococcal vaccine "Staphylovac" developed in Mechnikov Research Institute of Vaccines and Sera are presented. Original mildly virulent strains of Staphylococcus aureus having high immunogenicity, and intra- and interspecies protective activity against different representatives of opportunistic microflora were used for construction of the preparation. Low-toxicity and weak anapylactogenicity of the vaccine were established. In experiments on mice, guinea pigs and rabbits significant protective, antigenic and immunomodulate activity of the preparation was revealed with low sensitization of animals. Clinical trials performed in different centers showed that inclusion of vaccinotherapy in complex treatment of chronic staphylococcal infections (chronic pyodermia, lung abscess etc.) resulted in prolonged pathologic locus, decrease of number and severity of exacerbations, prolongation of remission, and complete recovery in significant number of patients. Activation of innate and adaptive immunity was revealed in the same patients. It was shown on the large group of athletes that administration of the vaccine by aerosol route prevents disruption of immunologic adaptation occurring due to excess physical activity and stress situations during competitions. PMID:19186558

  18. Spherical indentation of free-standing acellular extracellular matrix membranes.

    PubMed

    Cloonan, Aidan J; O'Donnell, Michael R; Lee, William T; Walsh, Michael T; De Barra, Eamonn; McGloughlin, Tim M

    2012-01-01

    Numerous scaffold materials have been developed for tissue engineering and regenerative medicine applications to replace or repair damaged tissues and organs. Naturally occurring scaffold materials derived from acellular xenogeneic and autologous extracellular matrix (ECM) are currently in clinical use. These biological scaffold materials possess inherent variations in mechanical properties. Spherical indentation or ball burst testing has commonly been used to evaluate ECM and harvested tissue due to its ease of use and simulation of physiological biaxial loading, but has been limited by complex material deformation profiles. An analytical methodology has been developed and applied to experimental load-deflection data of a model hyperelastic material and lyophilized ECM scaffolds. An optimum rehydration protocol was developed based on water absorption, hydration relaxation and dynamic mechanical analysis. The analytical methodology was compared with finite element simulations of the tests and excellent correlation was seen between the computed biaxial stress resultants and geometry deformations. A minimum rehydration period of 5 min at 37°C was sufficient for the evaluated multilaminated ECM materials. The proposed approach may be implemented for convenient comparative analysis of ECM materials and source tissues, process optimization or during lot release testing. PMID:21864728

  19. [Cartilage tumors : Pathology and radiomorphology].

    PubMed

    Uhl, M; Herget, G; Kurz, P

    2016-06-01

    Primary cartilage-forming tumors of the bone are frequent entities in the daily work of skeletal radiologists. This article describes the correlation of pathology and radiology in cartilage-forming skeletal tumors, in particular, enchondroma, osteochondroma, periosteal chondromas, chondroblastoma and various forms of chondrosarcoma. After reading, the radiologist should be able to deduce the different patterns of cartilage tumors on radiographs, CT, and MRI from the pathological aspects. Differentiation of enchondroma and chondrosarcoma is a frequent diagnostic challenge. Some imaging parameters, e. g., deep cortical scalloping (more than two thirds of the cortical thickness), cortical destruction, or a soft-tissue mass, are features of a sarcoma. Osteochondromas are bony protrusions with a continuous extension of bone marrow from the parent bone, the host cortical bone runs continuously from the osseous surface of the tumor into the shaft of the osteochondroma and the osteochondroma has a cartilage cap. Chondromyxoid fibromas are well-defined lytic and eccentric lesions of the metaphysis of the long bones, with nonspecific MRI findings. Chondroblastomas have a strong predilection for the epiphysis of long tubular bones and develop an intense perifocal bone marrow edema. Dedifferentiated chondrosarcomas are bimorphic lesions with a low-grade chondrogenic component and a high-grade noncartilaginous component. Most chondrogenic tumors have a predilection with regard to site and age at manifestation. PMID:27233920

  20. Femoral head cartilage disarticulation disorder

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Femoral head cartilage disarticulation disorder and necrosis is a major skeletal problem in broiler breeders since they are maintained for a long time in the farm. The etiology of this disease is not well understood. A field study was conducted to understand the basis of this metabolic disease. Six ...

  1. Animal models of cartilage repair

    PubMed Central

    Cook, J. L.; Hung, C. T.; Kuroki, K.; Stoker, A. M.; Cook, C. R.; Pfeiffer, F. M.; Sherman, S. L.; Stannard, J. P.

    2014-01-01

    Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94. PMID:24695750

  2. New techniques in articular cartilage imaging.

    PubMed

    Potter, Hollis G; Black, Brandon R; Chong, Le Roy

    2009-01-01

    Standardized magnetic resonance imaging (MRI) pulse sequences provide an accurate, reproducible assessment of cartilage morphology. Three-dimensional (3D) modeling techniques enable semiautomated models of the joint surface and thickness measurements, which may eventually prove essential in templating before partial or total joint resurfacing as well as focal cartilage repair. Quantitative MRI techniques, such as T2 mapping, T1 rho, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), provide noninvasive information about cartilage and repair tissue biochemistry. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) demonstrate information regarding the regional anisotropic variation of cartilage ultrastructure. Further research strengthening the association between quantitative MRI and cartilage material properties may predict the functional capacity of native and repaired tissue. MRI provides an essential objective assessment of cartilage regenerative procedures. PMID:19064167

  3. Effects of natural cartilaginous extracellular matrix on chondrogenic potential for cartilage cell transplantation.

    PubMed

    Yang, W; Lee, S; Jo, Y H; Lee, K M; Nemeno, J G; Nam, B M; Kim, B Y; Jang, I J; Kim, H N; Takebe, T; Lee, J I

    2014-05-01

    Autologous chondrocyte transplantation (ACT) has been established to contribute cartilage regeneration over the past years; however, many obstacles need to be overcome. Recently, newer ACT technique involves cotransplantation of chondrocytes and biomaterial. Although various proposed intelligent biomaterials exist, many of them remain insufficient and controversial. In this study, we aimed to examine the effects of natural extracellular matrix (ECM) to the proliferation rate and differentiation on the chondrocytes. We first derived a natural ECM sheet from 10-μm-thick frozen sections of porcine knee cartilages. We then cultured the chondrocytes derived from a rabbit's knee on a dish precoated with the natural ECM. Then we assessed differentiation and chondrogenic potential of the cells compared with those grown in untreated culture dishes. We characterized the gene expression of chondrogenic markers, such as collagen type II, SOX-9, and aggrecan, as well as the level of ECM protein with the use of reverse-transcription polymerase chain reaction analysis. The cells cultured with the ECM sheet showed highest chondrogenic potential and differentiation. Therefore, we can induce good chondrogenesis by with the use of a natural ECM sheet on the culture dish. The readily available and easy-to-handle thin ECM sheets create an environment that promotes efficient cartilage regeneration. Our data suggest that this natural ECM scaffold improved the chondrogenic differentiation of the cells in vitro by providing a favorable microenvironment. PMID:24815172

  4. A simple measuring device for laboratory indentation tests on cartilage.

    PubMed

    Koeller, Wolfgang; Kunow, Julius; Ostermeyer, Oliver; Stomberg, Peter; Boos, Carsten; Russlies, Martin

    2008-04-01

    Mechanical testing of articular cartilage and repair tissue enables judgment of their capacity in withstanding mechanical loading. In the past, different methods have been developed requiring a complex technical setup and extensive data analysis. Therefore, the aim of the present project was to build up a simple measuring apparatus for laboratory indentation tests. The device consists of an incremental optical displacement transducer with a sleeve bearing guided plunger and a spherical tip made of polished steel (radius: 0.75 or 1.5 mm), a sensitive load cell and a stiff frame. The indentation force results from the plunger's gravity plus the force of the spring inside the displacement transducer and levels at 0.170 N or 0.765 N. The displacement transducer is fixed to the frame via the load cell that enables one to detect the initial contact of the tip with the tissue. The load cell has a standard uncertainty of 2 mN and the displacement transducer of 1 microm. From indentation-creep tests, a "0.25-s elastic modulus" is calculated. Measurements on thin rubber sheets were carried out to determine the quality of the measuring device. Compression tests on cylinders made of these rubber sheets yielded control data, and a good agreement with the "0.25-s elastic modulus" was found. Indentation tests on cartilage at different sites of sheep femoral condyles yielded a very good repeatability of the measurement results (+/-7.5%). PMID:18979621

  5. Development of artificial articular cartilage.

    PubMed

    Oka, M; Ushio, K; Kumar, P; Ikeuchi, K; Hyon, S H; Nakamura, T; Fujita, H

    2000-01-01

    Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of

  6. Use of an acellular flowable dermal replacement scaffold on lower extremity sinus tract wounds: a retrospective series.

    PubMed

    Brigido, Stephen A; Schwartz, Edward; McCarroll, Raymond; Hardin-Young, Janet

    2009-04-01

    A novel injectable human dermal matrix has been developed for the treatment of complex diabetic sinus tract wounds. Bioengineered grafts are commercially available that have been somewhat effective in treating chronic wounds such as diabetic foot ulcers; however, these bioengineered grafts are only available in sheet form. These therapies are less effective in treating complex or irregularly shaped wounds that demonstrate tunnels or extensions into deep soft tissue. One acellular graft (GRAFTJACKET, Matrix, Wright Medical Technology, Arlington, Tennessee) that has been shown to effectively treat open wounds is also available in a micronized form (GRAFTJACKET Xpress Scaffold, Wright Medical Technology). This human dermal graft forms a flowable soft tissue scaffold that can be delivered via syringe into tunneling wounds. In this retrospective series, 12 patients with deep tunneling wounds were treated with GRAFTJACKET Xpress Scaffold and followed for 12 weeks. Complete wound healing was achieved in 10 of 12 patients within the 12-week evaluation. The average time to complete healing was 8.5 weeks, whereas the average time to depth healing was 7.8 weeks. The data from the study suggest that this injectable human dermal matrix has unique properties that allow it to facilitate healing of complex tunneling diabetic foot ulcers. The material is easy to prepare and inject into the wound, thereby preventing the necessity of extensive surgical exposure. The matrix supports neo-subcutaneous tissue formation and allows the body to rapidly repair these wounds. PMID:19825754

  7. [Pertussis vaccines: acellular versus whole cell. Perhaps a return to the past?].

    PubMed

    Cofré, José

    2015-10-01

    The resurgence of pertussis in the world and in our country has questioned the effectiveness of cellular and acellular vaccines. The reason why pertussis has not been controlled or eliminated after 70 years of implementation of the vaccination is probably multifactorial. This article, on the basis of questions and answers, describes the benefits and limitations of both cellular and acellular vaccines and suggests new strategies of vaccination in childhood. It is a fact that the currently applied vaccination does not eliminate the circulation of Bordetella pertussis in the community. Perhaps the introduction of vaccines with live B. pertussis, inhalation, will be able to eliminate the disease around the world. PMID:26633113

  8. Cartilage repair: 2013 Asian update.

    PubMed

    Hui, James H P; Goyal, Deepak; Nakamura, Norimasa; Ochi, Mitsuo

    2013-12-01

    Despite financial and regulatory hurdles, Asian scientists and clinicians have made important contributions in the area of cartilage repair. Because it is impossible to include observations on all the published articles in one review, our attempt is to highlight Asian progress in this area during recent years (2005 to the present), reviewing research development and clinical studies. In the former, our discussion of in vitro studies focuses on (1) potential sources of stem cells--such as mesenchymal stem cells (MSCs) from marrow, cord blood, synovium, and mobilized peripheral blood--which are capable of enhancing cartilage repair and (2) the use of growth factors and scaffolds with and without cells. Our discussion of animal studies attempts to summarize activities in evaluating surgical procedures and determining the route of cell administration, as well as studies on matrices and scaffolds. It ranges from the use of small animals such as rats and rabbits to larger animals like pigs and dogs. The local adherent technique, enhancement of microfracture with poly(l-lactic-co-glycolic acid) scaffold, adenovirus-mediated bone morphogenic protein (BMP) genes, and MSCs--whether they are magnetically labeled, suspended in hyaluronic acid, or immobilized with transforming growth factor-β (TGF-β)--have all been able to engineer a repair of the osteochondral defect. Although published Asian reports of clinical studies on cartilage repair are few, the findings of relevant trials are summarized in our discussion of these investigations. There has been a long history of use of laboratory-derived MSCs for cartilage repair. Recent progress has suggested the potential utility of cord blood and mobilized peripheral blood in this area, as well as more injectable bone marrow (BM)-derived stem cells. Finally, we make a few suggestions on the direction of research and development activities and the need for collaborative approaches by regulatory agencies. PMID:24286798

  9. Diode laser (980nm) cartilage reshaping

    NASA Astrophysics Data System (ADS)

    El Kharbotly, A.; El Tayeb, T.; Mostafa, Y.; Hesham, I.

    2011-03-01

    Loss of facial or ear cartilage due to trauma or surgery is a major challenge to the otolaryngologists and plastic surgeons as the complicated geometric contours are difficult to be animated. Diode laser (980 nm) has been proven effective in reshaping and maintaining the new geometric shape achieved by laser. This study focused on determining the optimum laser parameters needed for cartilage reshaping with a controlled water cooling system. Harvested animal cartilages were angulated with different degrees and irradiated with different diode laser powers (980nm, 4x8mm spot size). The cartilage specimens were maintained in a deformation angle for two hours after irradiation then released for another two hours. They were serially measured and photographed. High-power Diode laser irradiation with water cooling is a cheep and effective method for reshaping the cartilage needed for reconstruction of difficult situations in otorhinolaryngologic surgery. Key words: cartilage,diode laser (980nm), reshaping.

  10. Supporting Biomaterials for Articular Cartilage Repair

    PubMed Central

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  11. Cartilage degeneration in different human joints.

    PubMed

    Kuettner, K E; Cole, A A

    2005-02-01

    Variations among joints in the initiation and progression of degeneration may be explained, in part, by metabolic, biochemical and biomechanical differences. Compared to the cartilage in the knee joint, ankle cartilage has a higher content of proteoglycans and water, as well as an increased rate of proteoglycan turnover and synthesis, all of which are responsible for its increased stiffness and reduced permeability. Chondrocytes within ankle cartilage have a decreased response to catabolic factors such as interleukin-1 and fibronectin fragments, compared to the chondrocytes of knee cartilage. Moreover, in response to damage, ankle chondrocytes synthesize proteoglycans at a higher rate than that found in knee cartilage chondrocytes, which suggests a greater capacity for repair. In addition to the cartilages of the two joints, the underlying bones also respond differently to degenerative changes. Taken together, these metabolic, biochemical and biomechanical differences may provide protection to the ankle. PMID:15694570

  12. Izogenic cartilage transfer in rhinoplasty procedure.

    PubMed

    Yigit, Baris; Bicer, Ahmet; Aytop, Derya

    2015-01-01

    Cartilage is commonly grafted during primary and secondary rhinoplasties as a means of addressing both functional and esthetic issues. Generally, such grafts are taken from the nasal septum, but auricular conchae or ribs may serve as donor sites if needed. However, the latter often entail considerable morbidity and graft mismatch. To circumvent these drawbacks, use of implants or processed cartilage (allogenic or xenogenic in origin) has been proposed. Herein, the isogenic transfer of nasal septal cartilage between identical twins is reported. PMID:25569406

  13. Surface of articular cartilage: immunohistological studies.

    PubMed

    Duance, V C

    1983-10-01

    Using several physical techniques the surface of articular cartilage has been reported to be structurally different from the deeper layers. In this paper using immunohistochemical methods, the surface has been shown to contain a characteristically different collagen, Type I in contrast to Type II which is the major collagen of cartilage. These results support previous proposals for a surface layer, or lamina splendens, the presence of which would be of considerable importance in understanding the degradation of cartilage in arthritides. PMID:6678620

  14. Multimodal evaluation of tissue-engineered cartilage.

    PubMed

    Mansour, Joseph M; Welter, Jean F

    2013-02-01

    Tissue engineering (TE) has promise as a biological solution and a disease modifying treatment for arthritis. Although cartilage can be generated by TE, substantial inter- and intra-donor variability makes it impossible to guarantee optimal, reproducible results. TE cartilage must be able to perform the functions of native tissue, thus mechanical and biological properties approaching those of native cartilage are likely a pre-requisite for successful implantation. A quality-control assessment of these properties should be part of the implantation release criteria for TE cartilage. Release criteria should certify that selected tissue properties have reached certain target ranges, and should be predictive of the likelihood of success of an implant in vivo. Unfortunately, it is not currently known which properties are needed to establish release criteria, nor how close one has to be to the properties of native cartilage to achieve success. Achieving properties approaching those of native cartilage requires a clear understanding of the target properties and reproducible assessment methodology. Here, we review several main aspects of quality control as it applies to TE cartilage. This includes a look at known mechanical and biological properties of native cartilage, which should be the target in engineered tissues. We also present an overview of the state of the art of tissue assessment, focusing on native articular and TE cartilage. Finally, we review the arguments for developing and validating non-destructive testing methods for assessing TE products. PMID:23606823

  15. Immunogenicity and safety of a monovalent, multicomponent acellular pertussis vaccine in 15 month-6-year-old German children. Monovalent Acellular Pertussis Vaccine Study Group.

    PubMed

    Stehr, K; Heininger, U; Uhlenbusch, R; Angersbach, P; Hackell, J; Eckhardt, T

    1995-03-01

    Immunization against pertussis has been re-recommended for healthy children in Germany in 1991. In addition the former restriction of immunizing only in the first 2 years of life was abolished. In children born before 1991 immunization rates against pertussis were 15% or less. With the new recommendations physicians are now faced with an increasing demand of parents for catch-up vaccinations in these children. Since they were immunized against diphtheria and tetanus previously monovalent pertussis vaccines are needed for this indication. Therefore a monovalent, multicomponent acellular pertussis vaccine was studied in 249 German children 15 months to 6 years of age. Three doses were administered at 6-10 week intervals. Reactogenicity and antibody responses against the vaccine antigens pertussis toxin (PT), filamentous haemagglutinin (FHA), 69-kd antigen (pertactin) and fimbriae-2 (agglutinogen) were investigated. Local and systemic reactions were minimal in frequency and severity. Antibody responses against all vaccine antigens were pronounced with 93%-100% of vaccinees demonstrating at least four fold titre rises above pre-immunization after the third dose. These findings indicate that this monovalent, multicomponent acellular pertussis vaccine with excellent immunogenicity and low reactogenicity is an appropriate candidate for closing immunization gaps in older children in countries with previously low vaccination rates against pertussis. Based on the results of this study the monovalent acellular pertussis vaccine was licensed in Germany in January 1994. PMID:7758519

  16. Design and Synthesis of an Artificial Pulmonary Pleura for High Throughput Studies in Acellular Human Lungs

    PubMed Central

    Wagner, Darcy E.; Fenn, Spencer L.; Bonenfant, Nicholas R.; Marks, Elliot R.; Borg, Zachary; Saunders, Patrick; Oldinski, Rachael A.; Weiss, Daniel J.

    2015-01-01

    Whole organ decellularization of complex organs, such as lungs, presents a unique opportunity for use of acellular scaffolds for ex vivo tissue engineering or for studying cell-extracellular matrix interactions ex vivo. A growing body of literature investigating decellularizing and recellularizing rodent lungs has provided important proof of concept models and rodent lungs are readily available for high throughput studies. In contrast, comparable progress in large animal and human lungs has been impeded owing to more limited availability and difficulties in handling larger tissue. While the use of smaller segments of acellular large animal or human lungs would maximize usage from a single lung, excision of small acellular segments compromises the integrity of the pleural layer, leaving the terminal ends of blood vessels and airways exposed. We have developed a novel pleural coating using non-toxic ionically crosslinked alginate or photocrosslinked methacrylated alginate which can be applied to excised acellular lung segments, permits inflation of small segments, and significantly enhances retention of cells inoculated through cannulated airways or blood vessels. Further, photocrosslinking methacrylated alginate, using eosin Y and triethanolamine (TEOA) at 530nm wavelength, results in a mechanically stable pleural coating that permits effective cyclic 3-dimensional stretch, i.e. mechanical ventilation, of individual segments. PMID:25750684

  17. Repair of a Gingival Fenestration Using an Acellular Dermal Matrix Allograft.

    PubMed

    Breault, Lawrence G; Brentson, Raquel C; Fowler, Edward B; Bisch, Frederick C

    2016-01-01

    A case report illustrating the successful treatment of a gingival fenestration with an acellular dermal matrix (ADM) allograft. After 2½ months of healing, the ADM was completely integrated into the soft tissues of the mandibular anterior gingiva with complete resolution of the gingival fenestration, resulting in excellent gingival esthetics. PMID:26874103

  18. Acellular ostrich corneal stroma used as scaffold for construction of tissue-engineered cornea

    PubMed Central

    Liu, Xian-Ning; Zhu, Xiu-Ping; Wu, Jie; Wu, Zheng-Jie; Yin, Yong; Xiao, Xiang-Hua; Su, Xin; Kong, Bin; Pan, Shi-Yin; Yang, Hua; Cheng, Yan; An, Na; Mi, Sheng-Li

    2016-01-01

    AIM To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy (TEM) and hematoxylin and eosin (H&E) staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype. RESULTS The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process. In vitro, the methyl thiazolyl tetrazolium results revealed that extracts of the acellular ostrich corneas (AOCs) had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes. The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea (APC) transplantation. The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer. CONCLUSION We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft. PMID:27158598

  19. Effects of the decellularization method on the local stiffness of acellular lungs.

    PubMed

    Melo, Esther; Garreta, Elena; Luque, Tomas; Cortiella, Joaquin; Nichols, Joan; Navajas, Daniel; Farré, Ramon

    2014-05-01

    Lung bioengineering, a novel approach to obtain organs potentially available for transplantation, is based on decellularizing donor lungs and seeding natural scaffolds with stem cells. Various physicochemical protocols have been used to decellularize lungs, and their performance has been evaluated in terms of efficient decellularization and matrix preservation. No data are available, however, on the effect of different decellularization procedures on the local stiffness of the acellular lung. This information is important since stem cells directly sense the rigidity of the local site they are engrafting to during recellularization, and it has been shown that substrate stiffness modulates cell fate into different phenotypes. The aim of this study was to assess the effects of the decellularization procedure on the inhomogeneous local stiffness of the acellular lung on five different sites: alveolar septa, alveolar junctions, pleura, and vessels' tunica intima and tunica adventitia. Local matrix stiffness was measured by computing Young's modulus with atomic force microscopy after decellularizing the lungs of 36 healthy rats (Sprague-Dawley, male, 250-300 g) with four different protocols with/without perfusion through the lung circulatory system and using two different detergents (sodium dodecyl sulfate [SDS] and 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate [CHAPS]). The local stiffness of the acellular lung matrix significantly depended on the site within the matrix (p<0.001), ranging from ∼ 15 kPa at the alveolar septum to ∼ 60 kPa at the tunica intima. Acellular lung stiffness (p=0.003) depended significantly, albeit modestly, on the decellularization process. Whereas perfusion did not induce any significant differences in stiffness, the use of CHAPS resulted in a ∼ 35% reduction compared with SDS, the influence of the detergent being more important in the tunica intima. In conclusion, lung matrix stiffness is considerably inhomogeneous, and

  20. Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

    PubMed Central

    Korossis, Sotirios A.; Wilshaw, Stacy-Paul; Jennings, Louise M; Fisher, John; Ingham, Eileen

    2014-01-01

    Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure. PMID:24786313

  1. [Cartilage vs. temporal fascia as graft material].

    PubMed

    Dost, Philipp; Maune, Steffen

    2014-08-01

    So far, comparative studies have shown no significant audiological difference between cartilage and fascia grafts. In this retrospective study, the Turkish scientists E E Callioglu et al. examined next audiological results and morphological results after surgical cartilage and fascial tympanoplasty in patients with comparable preoperative hearing and middle ear pathology. PMID:25215384

  2. Concepts in Gene Therapy for Cartilage Repair

    PubMed Central

    Steinert, Andre F.; Nöth, Ulrich; Tuan, Rocky S.

    2009-01-01

    Summary Once articular cartilage is injured, it has a very limited capacity for self-repair. Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface. Current research offers a growing number of bioactive reagents, including proteins and nucleic acids, that may be used to augment different aspects of the repair process. As these agents are difficult to administer effectively, gene transfer approaches are being developed to provide their sustained synthesis at sites of repair. To augment regeneration of articular cartilage, therapeutic genes can be delivered to the synovium, or directly to the cartilage lesion. Gene delivery to the cells of the synovial lining is generally considered more suitable for chondroprotective approaches, based on the expression of anti-inflammatory mediators. Gene transfer targeted to cartilage defects can be achieved by either direct vector administration to cells located at or surrounding the defects, or by transplantation of genetically modified chondrogenic cells into the defect. Several studies have shown that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage, where they are expressed at therapeutically relevant levels. Furthermore, data is beginning to emerge indicating, that efficient delivery and expression of these genes is capable of influencing a repair response toward the synthesis of a more hyaline cartilage repair tissue in vivo. This review presents the current status of gene therapy for cartilage healing and highlights some of the remaining challenges. PMID:18313477

  3. Magnetic Resonance Imaging of Cartilage Repair

    PubMed Central

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  4. Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

    NASA Astrophysics Data System (ADS)

    Sitterle, Valerie B.; Roberts, David W.

    2003-06-01

    The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

  5. TGFβ Signaling in Cartilage Development and Maintenance

    PubMed Central

    Wang, Weiguang; Rigueur, Diana; Lyons, Karen M.

    2014-01-01

    Members of the transforming growth factor beta (TGFβ) superfamily of secreted factors play essential roles in nearly every aspect of cartilage formation and maintenance. However, the mechanisms by which TGFβs transduce their effects in cartilage in vivo remain poorly understood. Mutations in several TGFβ family members, their receptors, extracellular modulators, and intracellular transducers have been described, and these usually impact the development of the cartilaginous skeleton. Furthermore, genome-wide association studies have linked components of the (TGFβ) superfamily to susceptibility to osteoarthritis. This review focuses on recent discoveries from genetic studies in the mouse regarding the regulation of TGFβ signaling in developing growth plate and articular cartilage, as well as the different modes of crosstalk between canonical and noncanonical TGFβ signaling. These new insights into TGFβ signaling in cartilage may open new prospects for therapies that maintain healthy articular cartilage. PMID:24677722

  6. Cartilage tissue engineering for degenerative joint disease.

    PubMed

    Nesic, Dobrila; Whiteside, Robert; Brittberg, Mats; Wendt, David; Martin, Ivan; Mainil-Varlet, Pierre

    2006-05-20

    Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed. PMID:16574268

  7. Articular cartilage: structure and regeneration.

    PubMed

    Becerra, José; Andrades, José A; Guerado, Enrique; Zamora-Navas, Plácido; López-Puertas, José M; Reddi, A Hari

    2010-12-01

    Articular cartilage (AC) has no or very low ability of self-repair, and untreated lesions may lead to the development of osteoarthritis. One method that has been proven to result in long-term repair or isolated lesions is autologous chondrocyte transplantation. However, first generation of these cells' implantation has limitations, and introducing new effective cell sources can improve cartilage repair. AC provides a resilient and compliant articulating surface to the bones in diarthrodial joints. It protects the joint by distributing loads applied to it, so preventing potentially damaging stress concentrations on the bone. At the same time it provides a low-friction-bearing surface to enable free movement of the joint. AC may be considered as a visco- or poro-elastic fiber-composite material. Fibrils of predominantly type II collagen provide tensile reinforcing to a highly hydrated proteoglycan gel. The tissue typically comprises 70% water and it is the structuring and retention of this water by the proteoglycans and collagen that is largely responsible for the remarkable ability of the tissue to support compressive loads. PMID:20836752

  8. Correction of Asian Short Nose with Lower Lateral Cartilage Repositioning and Ear Cartilage Grafting

    PubMed Central

    Kim, Kenneth K.

    2013-01-01

    Background: Asians with short nose lack the cartilage needed to extend the length of the nose. A rhinoplasty technique using lower lateral cartilage (LLC) repositioning and ear cartilage grafting allows for sufficient nasal lengthening and nasal tip mobility in the correction of short nose in Asians. Methods: Short nose was classified into 3 subtypes: type I, II, or III. During LLC repositioning, the LLC was separated from surrounding retaining structures, except at the footplate. The LLC was approximated medially and advanced with a Medpor strut. A silicone dorsal implant was inserted to suit the newly projected nasal tip. An ear cartilage onlay graft or ear cartilage extension graft was applied to further project and enhance the nasal tip and columella. Results: Of the 854 primary rhinoplasty procedures performed on Asian patients between January 2008 and December 2011, 295 were performed on patients with short nose. LLC repositioning and ear cartilage onlay grafting were performed on 228 patients. LLC repositioning and ear cartilage extension grafting with or without ear cartilage onlay grafting were performed on 67 patients. Short nasal tip, alar retraction, and columellar retraction were corrected. Wound dehiscence with marginal necrosis occurred in 7 patients. One patient developed nasal infection. Conclusions: LLC repositioning and ear cartilage grafting aid in the correction of short nose in Asians. With LLC repositioning and ear cartilage grafting, the nasal tip can be positioned in accordance with the patient’s anatomic limits. The entire nasal tip and columella can be lengthened, while the tip maintains its mobility. PMID:25289239

  9. Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair

    PubMed Central

    Little, Christopher B.; Meeker, Clare T.; Golub, Suzanne B.; Lawlor, Kate E.; Farmer, Pamela J.; Smith, Susan M.; Fosang, Amanda J.

    2007-01-01

    Aggrecan loss from cartilage in arthritis is mediated by aggrecanases. Aggrecanases cleave aggrecan preferentially in the chondroitin sulfate–2 (CS-2) domain and secondarily at the E373↓374A bond in the interglobular domain (IGD). However, IGD cleavage may be more deleterious for cartilage biomechanics because it releases the entire CS-containing portion of aggrecan. Recent studies identifying aggrecanase-2 (ADAMTS-5) as the predominant aggrecanase in mouse cartilage have not distinguished aggrecanolysis in the IGD from aggrecanolysis in the CS-2 domain. We generated aggrecan knockin mice with a mutation that rendered only the IGD resistant to aggrecanases in order to assess the contribution of this specific cleavage to cartilage pathology. The knockin mice were viable and fertile. Aggrecanase cleavage in the aggrecan IGD was not detected in knockin mouse cartilage in situ nor following digestion with ADAMTS-5 or treatment of cartilage explant cultures with IL-1α. Blocking cleavage in the IGD not only diminished aggrecan loss and cartilage erosion in surgically induced osteoarthritis and a model of inflammatory arthritis, but appeared to stimulate cartilage repair following acute inflammation. We conclude that blocking aggrecanolysis in the aggrecan IGD alone protects against cartilage erosion and may potentiate cartilage repair. PMID:17510707

  10. Method and apparatus for cartilage reshaping by radiofrequency heating

    DOEpatents

    Wong, Brian J.; Milner, Thomas E.; Sobol, Emil N.; Keefe, Michael W.

    2003-07-08

    A method and apparatus for reshaping cartilage using radiofrequency heating. The cartilage temperature is raised sufficiently for stress relaxation to occur in the cartilage, but low enough so that significant denaturation of the cartilage does not occur. The RF electrodes may be designed to also function as molds, preses, clamps, or mandrills to deform the cartilage tissue. Changes in various properties of the cartilage associated with stress relaxation in the cartilage may be measured in order to provide the control signal to provide effective reshaping without denaturation.

  11. Mesenchymal stem cells in cartilage regeneration.

    PubMed

    Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

    2014-01-01

    Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment. PMID:25005451

  12. The bone-cartilage unit in osteoarthritis.

    PubMed

    Lories, Rik J; Luyten, Frank P

    2011-01-01

    Osteoarthritis (OA) refers to a group of mechanically-induced joint disorders to which both genetic and acquired factors contribute. Current pathophysiological concepts focus on OA as a disease of the whole joint. Within these models, the functional unit formed by the articular cartilage and the subchondral bone seems to be of particular interest. Cartilage and bone receive and dissipate the stress associated with movement and loading, and are therefore continuously challenged biomechanically. Recent data support the view that cartilage and bone can communicate over the calcified tissue barrier; vessels reach out from bone into the cartilage zone, patches of uncalcified cartilage are in contact with bone, and microcracks and fissures further facilitate transfer of molecules. Several molecular signaling pathways such as bone morphogenetic proteins and Wnts are hypothesized to have a role in OA and can activate cellular and molecular processes in both cartilage and bone cells. In addition, intracellular activation of different kinase cascades seems to be involved in the molecular crosstalk between cartilage and bone cells. Further research is required to integrate these different elements into a comprehensive approach that will increase our understanding of the disease processes in OA, and that could lead to the development of specific therapeutics or treatment strategies. PMID:21135881

  13. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible. PMID:26069647

  14. Study of laser mediated cartilage reshaping

    NASA Astrophysics Data System (ADS)

    Dobrikov, Dimitar; Avramov, Lachezar; Valkanov, Seryozha

    2005-04-01

    Cartilage is a specialized tissue, which serves as a load-bearing structure. Its main components are: 70% water, 10-20% collagen fibers, 5-10% proteoglycans, 5%-chondrocytes. When bent, cartilage exhibits its property of shape memorization. Laser radiation may be used to change the shape of cartilage by heating of mechanically deformed specimen. The high water percentage in the cartilage, which determines its mechanical properties, raises the question of whether the medium in which the sample is placed influences the process of relaxation, connected with cartilage water losses. Using Nd:YAG laser (λ=1.32 μm), cartilage samples were irradiated. The stress relaxation time, the surface temperature during irradiation and the time dependence of the backscattered light intensity (which is indication for changes in the internal stress), were compared. The shape retention was measured by comparing the curvature before and after irradiation. Overbending of specimens was done in order to achieve the required angle. The obtained data could be used for development of clinical methods for correction or transplantation of injured human cartilage due to trauma or certain diseases.

  15. Cartilage Repair and Subchondral Bone Remodeling in Response to Focal Lesions in a Mini-Pig Model: Implications for Tissue Engineering

    PubMed Central

    Fisher, Matthew B.; Belkin, Nicole S.; Milby, Andrew H.; Henning, Elizabeth A.; Bostrom, Marc; Kim, Minwook; Pfeifer, Christian; Meloni, Gregory; Dodge, George R.; Burdick, Jason A.; Schaer, Thomas P.; Steinberg, David R.

    2015-01-01

    Objective: Preclinical large animal models are essential for evaluating new tissue engineering (TE) technologies and refining surgical approaches for cartilage repair. Some preclinical animal studies, including the commonly used minipig model, have noted marked remodeling of the subchondral bone. However, the mechanisms underlying this response have not been well characterized. Thus, our objective was to compare in-vivo outcomes of chondral defects with varied injury depths and treatments. Design: Trochlear chondral defects were created in 11 Yucatan minipigs (6 months old). Groups included an untreated partial-thickness defect (PTD), an untreated full-thickness defect (FTD), and FTDs treated with microfracture, autologous cartilage transfer (FTD-ACT), or an acellular hyaluronic acid hydrogel. Six weeks after surgery, micro-computed tomography (μCT) was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. A finite element model (FEM) was developed to assess load transmission. Results: Using μCT, substantial bone remodeling was observed for all FTDs, but not for the PTD group. The best overall histological scores and greatest type II collagen staining was found for the FTD-ACT and PTD groups. The FEM confirmed that only the FTD-ACT group could initially restore appropriate transfer of compressive loads to the underlying bone. Conclusions: The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair. PMID:25318414

  16. [Surgical therapeutic possibilities of cartilage damage].

    PubMed

    Burkart, A C; Schoettle, P B; Imhoff, A B

    2001-09-01

    Therapy of cartilage damage is a frequent problem, especially in the young and active patient. For the treatment of a cartilage damage we have to consider the size of the defect, age and weight of the patient, meniscal tears, ligament instabilities and varus-/valgus-malalignment. Lavage, shaving and debridement are only sufficient for a short time and have no long term effect. Abrasio and drilling could be useful in eldery people. Microfracturing seems to be an effective alternative for small defects. The restoration of the cartilage surface with the use of autologous chondrocyte transplantation, osteochondral autograft transplantation and posterior condyle transfer seems to be an adequate treatment for younger patients. PMID:11572120

  17. Distinguishing ankle and knee articular cartilage.

    PubMed

    Cole, Ada A; Margulis, Arkady; Kuettner, Klaus E

    2003-06-01

    Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee. PMID:12911243

  18. Cartilage invasion patterns in laryngeal cancer.

    PubMed

    Gómez Serrano, Manuel; Iglesias Moreno, María Cruz; Gimeno Hernández, Jesús; Ortega Medina, Luis; Martín Villares, Cristina; Poch Broto, Joaquín

    2016-07-01

    The cartilaginous invasion determines the T and is one of the most common sources of mistake in tumor staging. Also it is of great importance when planning any therapeutic alternative. In the latest revision of the TNM classification a clear distinction is made between infiltration of cartilage without going through it, considered a T3 recently and that would be a T4 according to the previous classification, and those going through the cartilage, classified as T4a. While this classification makes the difference in depth of infiltration, it does not emphasize the extent of invasion. This paper provides a detailed description of the laryngeal cartilage tumor infiltration by whole organ serial section in which the invasion is considered both horizontal (transcartilaginous) and vertical (extent of invasion) and establishing patterns of three-dimensional infiltration of the cartilage. This is a cross-sectional study of prevalence. 275 records of patients treated for laryngeal squamous cell carcinoma between 1995 and 2000 were reviewed. The pathological processing of laryngectomy surgical specimens was performed following the method of whole organ serial section described by G. F. Tucker. The following patterns of cartilaginous infiltration were defined: (1) transcartilaginous infiltration; (2a) partial focal infiltration of the cartilage: infiltration not going through the cartilage but occupying one third or less of its extent; (2b) partial extensive infiltration of the cartilage: infiltration occupying two thirds or more of its length and (3) no cartilage infiltration: tumor in contact with the cartilage (paraglottic space) but without affecting it. 161 patients met the inclusion criteria. The most frequent tumor location was supraglottic (58 cases) followed by glottic (47). 109 patients (67.7 %) were treated with total laryngectomy. Partial surgical techniques were performed in the remaining cases. TNM tumor staging was performed according to the results of

  19. Prosthetic Breast Reconstruction With Acellular Dermal Matrices: Achieving Predictability and Reproducibility.

    PubMed

    Nahabedian, Maurice Y

    2016-05-01

    The use of acellular dermal matrices in the setting of prosthetic breast reconstruction has captured the attention of many plastic surgeons. The regenerative capacity of these materials has provided additional tissue support to the mastectomy skin flaps with the ultimate result of improving surgical and aesthetic outcomes. Despite the benefits, there remains a significant diversity with regard to outcomes with some surgeons reporting increased morbidity. The reasons for this are varied but ultimately related to differences in patient selection and surgical techniques. The purpose of this article is to provide strategies for using acellular dermal matrix to achieve success in a manner that is usually associated with outcomes that are predictable and reproducible. PMID:27579223

  20. Pioneering technique using Acellular Dermal Matrix in the rescue of a radiation ulcer

    PubMed Central

    NASEEM, S.; PATEL, A.D.; DEVALIA, H.

    2016-01-01

    Background Radiotherapy as an adjuvant to mastectomy is integral to the treatment of breast cancer, but can result in skin ulceration. Skin ulceration following radiotherapy is traditionally managed by removing the implant and allowing the skin to heal by secondary intention. Case report A 42-year-old woman underwent radiotherapy following a breast reconstruction. She developed a 2 x 3cm radiation ulcer. The ulcer was managed by removing the implant and performing capsulectomy. A Beckers 50 expander was placed and reinforced with acellular dermal matrix inferolaterally. At follow-up the patient had a good cosmetic outcome. Conclusion Post-radiation skin ulcers present a challenge to treat with no current standardised management. The use of acellular dermal matrix may present a new technique to promote healing in these testing cases. PMID:27142826

  1. Prosthetic Breast Reconstruction With Acellular Dermal Matrices: Achieving Predictability and Reproducibility

    PubMed Central

    2016-01-01

    Summary: The use of acellular dermal matrices in the setting of prosthetic breast reconstruction has captured the attention of many plastic surgeons. The regenerative capacity of these materials has provided additional tissue support to the mastectomy skin flaps with the ultimate result of improving surgical and aesthetic outcomes. Despite the benefits, there remains a significant diversity with regard to outcomes with some surgeons reporting increased morbidity. The reasons for this are varied but ultimately related to differences in patient selection and surgical techniques. The purpose of this article is to provide strategies for using acellular dermal matrix to achieve success in a manner that is usually associated with outcomes that are predictable and reproducible. PMID:27579223

  2. DermACELL: Human Acellular Dermal Matrix Allograft A Case Report.

    PubMed

    Cole, Windy E

    2016-03-01

    Diabetes often causes ulcers on the feet of diabetic patients. A 56-year-old, insulin-dependent, diabetic woman presented to the wound care center with a Wagner grade 3 ulcer of the right heel. She reported a 3-week history of ulceration with moderate drainage and odor and had a history of ulceration and osteomyelitis in the contralateral limb. Rigorous wound care, including hospitalization; surgical incision and drainage; intravenous antibiotic drug therapy; vacuum-assisted therapy; and a new room temperature, sterile, human acellular dermal matrix graft were used to heal the wound, save her limb, and restore her activities of daily living. This case presentation involves alternative treatment of a diabetic foot ulcer with this new acellular dermal matrix, DermACELL. PMID:27031550

  3. Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function.

    PubMed

    Schwarz, Silke; Elsaesser, Alexander F; Koerber, Ludwig; Goldberg-Bockhorn, Eva; Seitz, Andreas M; Bermueller, Christian; Dürselen, Lutz; Ignatius, Anita; Breiter, Roman; Rotter, Nicole

    2015-12-01

    One key point in the development of new bioimplant matrices for the reconstruction and replacement of cartilage defects is to provide an adequate microenvironment to ensure chondrocyte migration and de novo synthesis of cartilage-specific extracellular matrix (ECM). A recently developed decellularization and sterilization process maintains the three-dimensional (3D) collagen structure of native septal cartilage while increasing matrix porosity, which is considered to be crucial for cartilage tissue engineering. Human primary nasal septal chondrocytes were amplified in monolayer culture and 3D-cultured on processed porcine nasal septal cartilage scaffolds. The influence of chondrogenic growth factors on neosynthesis of ECM proteins was examined at the protein and gene expression levels. Seeding experiments demonstrated that processed xenogenic cartilage matrices provide excellent environmental properties for human nasal septal chondrocytes with respect to cell adhesion, migration into the matrix and neosynthesis of cartilage-specific ECM proteins, such as collagen type II and aggrecan. Matrix biomechanical stability indicated that the constructs retrieve full stability and function during 3D culture for up to 42 days, proportional to collagen type II and GAG production. Thus, processed xenogenic cartilage offers a suitable environment for human nasal chondrocytes and has promising potential for cartilage tissue engineering in the head and neck region. PMID:23193064

  4. Outcomes of allogenic acellular matrix therapy in treatment of diabetic foot wounds: an initial experience.

    PubMed

    Martin, Billy R; Sangalang, Melinda; Wu, Stephanie; Armstrong, David G

    2005-06-01

    The purpose of this study was to evaluate outcomes of persons with UT grade 2A neuropathic diabetic foot wounds treated with an acellular matrix. Data were abstracted for 17 consecutive patients with diabetes--76.5% males, aged 61.5 +/- 8.5 years with a mean glycated haemoglobin of 9.2 +/- 2.2% presenting for care at a large, multidisciplinary wound care centre. All patients received surgical debridement for their diabetic foot wounds and were placed on therapy consisting of a single application of an acellular matrix graft (GraftJacket; Wright Medical Technologies, Arlington, TN, USA) with dressing changes taking place weekly. Outcomes evaluated included time to complete wound closure and proportion of patients achieving wound closure in 20 weeks. Acellular matrix therapy was used as initial therapy and was sutured or stapled in place under a silicone-based non adherent dressing. Therapy was then followed by a moisture-retentive dressing until complete epithelialisation. In total, 82.4% of wounds measuring a mean 4.6 +/- 3.2 cm(2) healed in the 20-week evaluation period. For those that healed in this period, healing took place in a mean 8.9 +/- 2.7 weeks. We conclude that a regimen consisting of moist wound healing using an acellular matrix dressing may be a useful adjunct to appropriate diabetic foot ulcer care for deep, non-infected, non-ischaemic wounds. We await the completion of further trials in this area to confirm or refute this initial assessment. PMID:16722865

  5. Hertwig's epithelial root sheath cell behavior during initial acellular cementogenesis in rat molars.

    PubMed

    Yamamoto, Tsuneyuki; Yamamoto, Tomomaya; Yamada, Tamaki; Hasegawa, Tomoka; Hongo, Hiromi; Oda, Kimimitsu; Amizuka, Norio

    2014-11-01

    This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle. PMID:24859538

  6. Biomechanical evaluation of acellular collagen matrix augmented Achilles tendon repair in sheep.

    PubMed

    Song, Lin; Olsen, Raymond E; Spalazzi, Jeffrey P; Davisson, Twana

    2010-01-01

    The rate of rerupture of repaired Achilles tendon in young and athletic populations remains high despite improvement in surgical techniques, suture design, and postsurgical management. Acellular biological matrices can be used to enhance the immediate strength of repaired tendons and to serve as scaffolds for cell in-growth and constructive tissue remodeling. A number of commercially available matrices have been used clinically, albeit with varying degrees of success and failure. The disparity is likely attributable to the different physical and biochemical properties of individual matrices. In this study, we investigated the biomechanical characteristics of 2 different acellular collagen matrices, namely TissueMend and GraftJacket, using a sheep Achilles tendon repair model. Static and cyclic creep, cyclic and linear construct stiffness, maximum load to failure, and displacement at maximum load were determined at time zero. We found that the maximum load to failure, displacement, and ultimate failure mode were similar between tendons augmented with either acellular collagen matrix; however, TissueMend augmentation yielded lower creep and smaller construct elongation than did GraftJacket. The results indicated that the strength of TissueMend-augmented tendons and GraftJacket-augmented tendons was not statistically significantly different, although tendons augmented with TissueMend displayed greater stiffness, which may be clinically advantageous in the restoration of ruptured tendons. PMID:20797586

  7. Immunolocation of proteoglycans and bone-related noncollagenous glycoproteins in developing acellular cementum of rat molars.

    PubMed

    Yamamoto, T; Domon, T; Takahashi, S; Arambawatta, A K S; Wakita, M

    2004-09-01

    To elucidate the roles of proteoglycans of (PGs), bone sialoprotein (BSP), and osteopontin (OPN) in cementogenesis, their distribution was investigated in developing and established acellular cementum of rat molars by an immunoperoxidase method. To characterize PGs, antibodies against five species of glycosaminoglycans (GAGS), chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), unsulfated chondroitin (C0S), dermatan sulfate (DS), and keratan sulfate (KS) were used. Routine histological staining was also applied. With onset of dentin mineralization, the initial cementum appeared on the dentin surface as a hematoxylin-stained fibril-poor layer. Subsequently, primitive principal fibers attached to the initial cementum. As the acellular cementum containing extrinsic fibers covered the initial cementum, the intal cementum formed the cemento-dentinal junction. Following immunohistochemistry at the earliest time of cementogenesis, the initial cementum was intensely immunoreactive for C4S, C6S, C0S, BSP, and OPN. After the initial cementum was embedded, neither the cemento-dentinal junction nor the cementum was immunoreactive for any GAG species. However, the cementum was immunoreactive for any GAG species. However, the cementum and cemento-dentinal were consistently immunoreactive for BSP. Although the cemento-dentinal junction was consistently immunoreactive for OPN, the remaining cementum showed no significant immunoreactivity. Thus, initial acellular cementogenesis requires a dense accumulation of PGs, BSP, and OPN, which may be associated with the mineralization process independently of collagen fibrils and initial principal fiber attachment. PMID:15278434

  8. Preparation and characterization of an acellular bovine pericardium intended for manufacture of valve bioprostheses.

    PubMed

    Goissis, Gilberto; Giglioti, Aparecida de Fátima; Braile, Domingo Marcolino

    2011-05-01

    Major problems with biological heart valves post-implantation are associated with progressive structural deterioration and calcification attributed to glutaraldehyde processing, dead cells, and cell fragments present in the native tissue. In spite of these problems, glutaraldehyde still is the reagent of choice. The results with acellular matrix xenograft usually prepared by detergent treatment in association with enzymes are rather conflicting because while preserving mechanical properties, tissue morphology and collagen structure are process dependent. This work describes a chemical approach for the preparation of an acellular bovine pericardium matrix intended for the manufacture of heart valve bioprostheses. Cell removal was performed by an alkaline extraction in the presence of calcium salts for periods ranging from 6 to 48 h. The results showed that cell removal was achieved after 12 h, with swelling and negative charge increasing with processing time. Nevertheless, collagen fibril structure, ability to form fibrils, and stability to collagenase were progressive after 24-h processing. There was no denaturation of the collagen matrix. A process is described for the preparation of acellular bovine pericardium matrices with preserved fibril structure and morphology for the manufacture of cardiac valve bioprostheses and may be used in other applications for tissue reconstruction. PMID:21595716

  9. Nanomechanics of the Cartilage Extracellular Matrix

    NASA Astrophysics Data System (ADS)

    Han, Lin; Grodzinsky, Alan J.; Ortiz, Christine

    2011-08-01

    Cartilage is a hydrated biomacromolecular fiber composite located at the ends of long bones that enables proper joint lubrication, articulation, loading, and energy dissipation. Degradation of extracellular matrix molecular components and changes in their nanoscale structure greatly influence the macroscale behavior of the tissue and result in dysfunction with age, injury, and diseases such as osteoarthritis. Here, the application of the field of nanomechanics to cartilage is reviewed. Nanomechanics involves the measurement and prediction of nanoscale forces and displacements, intra- and intermolecular interactions, spatially varying mechanical properties, and other mechanical phenomena existing at small length scales. Experimental nanomechanics and theoretical nanomechanics have been applied to cartilage at varying levels of material complexity, e.g., nanoscale properties of intact tissue, the matrix associated with single cells, biomimetic molecular assemblies, and individual extracellular matrix biomolecules (such as aggrecan, collagen, and hyaluronan). These studies have contributed to establishing a fundamental mechanism-based understanding of native and engineered cartilage tissue function, quality, and pathology.

  10. Materials science: Like cartilage, but simpler

    NASA Astrophysics Data System (ADS)

    Ladegaard Skov, Anne

    2015-01-01

    The properties of articular cartilage, which lines bones in joints, depend partly on repulsion between components of the material. A new synthetic gel that mimics this feature has rare, direction-dependent properties. See Letter p.68

  11. Controlled-Potential Electromechanical Reshaping of Cartilage.

    PubMed

    Hunter, Bryan M; Kallick, Jeremy; Kissel, Jessica; Herzig, Maya; Manuel, Cyrus; Protsenko, Dmitri; Wong, Brian J F; Hill, Michael G

    2016-04-25

    An alternative to conventional "cut-and-sew" cartilage surgery, electromechanical reshaping (EMR) is a molecular-based modality in which an array of needle electrodes is inserted into cartilage held under mechanical deformation by a jig. Brief (ca. 2 min) application of an electrochemical potential at the water-oxidation limit results in permanent reshaping of the specimen. Highly sulfated glycosaminoglycans within the cartilage matrix provide structural rigidity to the tissue through extensive ionic-bonding networks; this matrix is highly permselective for cations. Our studies indicate that EMR results from electrochemical generation of localized, low-pH gradients within the tissue: fixed negative charges in the proteoglycan matrix are protonated, resulting in chemically induced stress relaxation of the tissue. Re-equilibration to physiological pH restores the fixed negative charges, and yields remodeled cartilage that retains a new shape approximated by the geometry of the reshaping jig. PMID:27059655

  12. Harnessing biomechanics to develop cartilage regeneration strategies.

    PubMed

    Athanasiou, Kyriacos A; Responte, Donald J; Brown, Wendy E; Hu, Jerry C

    2015-02-01

    As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of

  13. Native Chondrocyte Viability during Cartilage Lesion Progression

    PubMed Central

    Ganguly, Kumkum; McRury, Ian D.; Goodwin, Peter M.; Morgan, Roy E.; Augé, Wayne K.

    2010-01-01

    Objective: Early surgical intervention for articular cartilage disease is desirable before full-thickness lesions develop. As early intervention treatments are designed, native chondrocyte viability at the treatment site before intervention becomes an important parameter to consider. The purpose of this study is to evaluate native chondrocyte viability in a series of specimens demonstrating the progression of articular cartilage lesions to determine if the chondrocyte viability profile changes during the evolution of articular cartilage disease to the level of surface fibrillation. Design: Osteochondral specimens demonstrating various degrees of articular cartilage damage were obtained from patients undergoing knee total joint replacement. Three groups were created within a patient harvest based on visual and tactile cues commonly encountered during surgical intervention: group 1, visually and tactilely intact surfaces; group 2, visually intact, tactilely soft surfaces; and group 3, surface fibrillation. Confocal laser microscopy was performed following live/dead cell viability staining. Results: Groups 1 to 3 demonstrated viable chondrocytes in all specimens, even within the fibrillated portions of articular cartilage, with little to no evidence of dead chondrocytes. Chondrocyte viability profile in articular cartilage does not appear to change as disease lesion progresses from normal to surface fibrillation. Conclusions: Fibrillated partial-thickness articular cartilage lesions are a good therapeutic target for early intervention. These lesions retain a high profile of viable chondrocytes and are readily diagnosed by visual and tactile cues during surgery. Early intervention should be based on matrix failure rather than on more aggressive procedures that further corrupt the matrix and contribute to chondrocyte necrosis of contiguous untargeted cartilage. PMID:26069561

  14. Biomaterial scaffolds in cartilage-subchondral bone defects influencing the repair of autologous articular cartilage transplants.

    PubMed

    Fan, Wei; Wu, Chengtie; Miao, Xigeng; Liu, Gang; Saifzadeh, Siamak; Sugiyama, Sadahiro; Afara, Isaac; Crawford, Ross; Xiao, Yin

    2013-05-01

    The repair of articular cartilage typically involves the repair of cartilage-subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage-subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite-β-tricalcium phosphate (HA-TCP), poly lactic-glycolic acid (PLGA)-HA-TCP dual-layered composite scaffolds (PLGA/HA-TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA-TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA-TCP scaffolds. Furthermore, HA-TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA-TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects. PMID:22684516

  15. Cartilage homeostasis in health and rheumatic diseases

    PubMed Central

    Goldring, Mary B; Marcu, Kenneth B

    2009-01-01

    As the cellular component of articular cartilage, chondrocytes are responsible for maintaining in a low-turnover state the unique composition and organization of the matrix that was determined during embryonic and postnatal development. In joint diseases, cartilage homeostasis is disrupted by mechanisms that are driven by combinations of biological mediators that vary according to the disease process, including contributions from other joint tissues. In osteoarthritis (OA), biomechanical stimuli predominate with up-regulation of both catabolic and anabolic cytokines and recapitulation of developmental phenotypes, whereas in rheumatoid arthritis (RA), inflammation and catabolism drive cartilage loss. In vitro studies in chondrocytes have elucidated signaling pathways and transcription factors that orchestrate specific functions that promote cartilage damage in both OA and RA. Thus, understanding how the adult articular chondrocyte functions within its unique environment will aid in the development of rational strategies to protect cartilage from damage resulting from joint disease. This review will cover current knowledge about the specific cellular and biochemical mechanisms that regulate cartilage homeostasis and pathology. PMID:19519926

  16. Imaging of articular cartilage: current concepts

    PubMed Central

    RONGA, MARIO; ANGERETTI, GLORIA; FERRARO, SERGIO; DE FALCO, GIOVANNI; GENOVESE, EUGENIO A.; CHERUBINO, PAOLO

    2014-01-01

    Magnetic resonance imaging (MRI) is the gold standard method for non-invasive assessment of joint cartilage, providing information on the structure, morphology and molecular composition of this tissue. There are certain minimum requirements for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5 Tesla); the use of surface coils; and the use of T2-weighted, proton density-weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient echo (3D-FS T1W GRE) sequences. For better contrast between the different joint structures, MR arthography is a method that can highlight minimal fibrillation or fractures of the articular surface and allow evaluation of the integrity of the native cartilage-repair tissue interface. To assess the biochemical composition of cartilage and cartilage repair tissue, various techniques have been proposed for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI, etc.], collagen, and water distribution [T2 mapping, “magnetisation transfer contrast”, diffusion-weighted imaging (DWI), and so on]. Several MRI classifications have been proposed for evaluating the processes of joint degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image quality and facilitate the diagnosis of disorders of articular structures adjacent to cartilage. PMID:25606557

  17. Vitrification of intact human articular cartilage.

    PubMed

    Jomha, Nadr M; Elliott, Janet A W; Law, Garson K; Maghdoori, Babak; Forbes, J Fraser; Abazari, Alireza; Adesida, Adetola B; Laouar, Leila; Zhou, Xianpei; McGann, Locksley E

    2012-09-01

    Articular cartilage injuries do not heal and large defects result in osteoarthritis with major personal and socioeconomic costs. Osteochondral transplantation is an effective treatment for large joint defects but its use is limited by the inability to store cartilage for long periods of time. Cryopreservation/vitrification is one method to enable banking of this tissue but decades of research have been unable to successfully preserve the tissue while maintaining cartilage on its bone base - a requirement for transplantation. To address this limitation, human knee articular cartilage from total knee arthroplasty patients and deceased donors was exposed to specified concentrations of 4 different cryoprotective agents for mathematically determined periods of time at lowering temperatures. After complete exposure, the cartilage was immersed in liquid nitrogen for up to 3 months. Cell viability was 75.4 ± 12.1% determined by membrane integrity stains and confirmed with a mitochondrial assay and pellet culture documented production of sulfated glycosaminoglycans and collagen II similar to controls. This report documents successful vitrification of intact human articular cartilage on its bone base making it possible to bank this tissue indefinitely. PMID:22698720

  18. Effects of introducing cultured human chondrocytes into a human articular cartilage explant model.

    PubMed

    Secretan, Charles; Bagnall, Keith M; Jomha, Nadr M

    2010-02-01

    Articular cartilage (AC) heals poorly and effective host-tissue integration after reconstruction is a concern. We have investigated the ability of implanted chondrocytes to attach at the site of injury and to be incorporated into the decellularized host matrix adjacent to a defect in an in vitro human explant model. Human osteochondral dowels received a standardized injury, were seeded with passage 3 chondrocytes labelled with PKH 26 and compared with two control groups. All dowels were cultured in vitro, harvested at 0, 7, 14 and 28 days and assessed for chondrocyte adherence and migration into the region of decellularized tissue adjacent to the defects. Additional evaluation included cell viability, general morphology and collagen II production. Seeded chondrocytes adhered to the standardized defect and areas of lamina splendens disruption but did not migrate into the adjacent acellular region. A difference was noted in viable-cell density between the experimental group and one control group. A thin lattice-like network of matrix surrounded the seeded chondrocytes and collagen II was present. The results indicate that cultured human chondrocytes do indeed adhere to regions of AC matrix injury but do not migrate into the host tissue, despite the presence of viable cells. This human explant model is thus an effective tool for studying the interaction of implanted cells and host tissue. PMID:20012649

  19. Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

    PubMed Central

    Jungmann, Pia M.; Baum, Thomas; Bauer, Jan S.; Karampinos, Dimitrios C.; Link, Thomas M.; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J.; Woertler, Klaus; Welsch, Goetz H.

    2014-01-01

    Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair. PMID:24877139

  20. Damage Control Mechanisms in Articular Cartilage

    PubMed Central

    Martin, James A; Scherb, MB; Lembke, Lois A; Buckwalter, Joseph

    2000-01-01

    Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we

  1. Ultrastructure of rabbit semilunar cartilages.

    PubMed Central

    Ghadially, F N; Thomas, I; Yong, N; Lalonde, J M

    1978-01-01

    A light and transmission electron microscopical study of 6 to 8 months old rabbit semilunar cartilages has shown that the cells in this tissue resemble chondrocytes more than fibroblasts. The prominent organelles in these cells were rough endoplasmic reticulum and the Golgi complex. An unusual finding was the occurrence of filamentous material in Golgi sacs and vesicles, and collagen fibrils within smooth membrane-bound tubular structures, apparently within the cells. Collagen fibrils forming fibres, fibre bundles and lamellae constituted the major component of the menisci. Protein-polysaccharide particles and associated fine filaments were found in the interfibrillary matrix and in the sparse territorial matrix adjacent to the chondrocytes. Numerous immature elastic fibrils, and rare mature elastic fibres with an electorn-lucent amorphous core, were also found in the general matrix amongst the collagen fibrils. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 PMID:580431

  2. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition. PMID:26264867

  3. Cartilage-inspired superelastic ultradurable graphene aerogels prepared by the selective gluing of intersheet joints

    NASA Astrophysics Data System (ADS)

    Hong, Jin-Yong; Yun, Sol; Wie, Jeong Jae; Zhang, Xu; Dresselhaus, Mildred S.; Kong, Jing; Park, Ho Seok

    2016-06-01

    In this study, we demonstrate a cartilage-inspired superelastic and ultradurable nanocomposite strategy for the selective inclusion of viscoelastic poly(dimethylsiloxane) (PDMS) into graphene sheet junctions to create effective stress-transfer pathways within three-dimensional (3D) graphene aerogels (GAs). Inspired by the joint architectures in the human body, where small amounts of soft cartilage connect stiff (or hard) but hollow (and thus lightweight) bones, the 3D internetworked GA@PDMS achieves synergistic toughening. The resulting GA@PDMS nanocomposites exhibit fully reversible structural deformations (99.8% recovery even at a 90% compressive strain) and high compressive mechanical strength (448.2 kPa at a compressive strain of 90%) at repeated compression cycles. Owing to the combination of excellent mechanical and electrical properties, the GA@PDMS nanocomposites are used as signal transducers for strain sensors, showing very short response and recovery times (in the millisecond range) with reliable sensitivity and extreme durability. Furthermore, the proposed system is applied to electronic scales with a large detectable weight of about 4600 times greater than its own weight. Such bio-inspired cartilage architecture opens the door to fabricate new 3D multifunctional and mechanically durable nanocomposites for emerging applications, which include sensors, actuators, and flexible devices.In this study, we demonstrate a cartilage-inspired superelastic and ultradurable nanocomposite strategy for the selective inclusion of viscoelastic poly(dimethylsiloxane) (PDMS) into graphene sheet junctions to create effective stress-transfer pathways within three-dimensional (3D) graphene aerogels (GAs). Inspired by the joint architectures in the human body, where small amounts of soft cartilage connect stiff (or hard) but hollow (and thus lightweight) bones, the 3D internetworked GA@PDMS achieves synergistic toughening. The resulting GA@PDMS nanocomposites exhibit fully

  4. Articular cartilage: from formation to tissue engineering.

    PubMed

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue. PMID:26923076

  5. Interactions of Cartilage Extracellular Matrix Macromolecules.

    PubMed

    Horkay, Ferenc

    2012-12-15

    Articular cartilage is a low-friction, load-bearing tissue located at joint surfaces. The extracellular matrix (ECM) of cartilage consists of a fibrous collagen network, which is pre-stressed by the osmotic swelling pressure exerted by negatively charged proteoglycan aggregates embedded in the collagen network. The major proteoglycan is the bottlebrush shaped aggrecan, which forms complexes with linear hyaluronic acid chains. We quantify microscopic and macroscopic changes resulting from self-assembly between aggrecan and hyaluronic acid using a complementary set of physical measurements to determine structure and interactions by combining scattering techniques, including small-angle X-ray scattering, small-angle neutron scattering, and dynamic light scattering with macroscopic osmotic pressure measurements. It is demonstrated that the osmotic pressure that defines the load bearing ability of cartilage is primarily governed by the main macromolecular components (aggrecan and collagen) of the ECM. Knowledge of the interactions between the macromolecular components of cartilage ECM is essential to understand biological function and to develop successful tissue engineering strategies for cartilage repair. PMID:23997426

  6. Animal Evolution: The Hard Problem of Cartilage Origins.

    PubMed

    Brunet, Thibaut; Arendt, Detlev

    2016-07-25

    Our skeletons evolved from cartilaginous tissue, but it remains a mystery how cartilage itself first arose in evolution. Characterization of cartilage in cuttlefish and horseshoe crabs reveals surprising commonalities with chordate chondrocytes, suggesting a common evolutionary origin. PMID:27458918

  7. Florid pustular dermatitis of breast: A case report on a unusual complication from acellular dermal matrix use

    PubMed Central

    James, Justin; Jackson, Lee; Saunders, Christobel

    2016-01-01

    Introduction Idiopathic erythematous reaction of the breast (Red breast syndrome) is a known complication following breast reconstruction with acellular dermal matrix. However pustular dermatitis like presentation is not previously known. Presentation of case We present a 42-year-old lady who developed bilateral pustular dermatitis like appearance following breast reconstruction with acellular dermal matrix slings. Though surgical washout was done, both expanders and flex HD could be preserved. Discussion Acellular dermal matrix use is the only possible explanation for such a presentation and this can be considered a variant of red breast syndrome. Conclusion Pustular dermatitis like presentation can be associated with acelluar dermal matrix use and should be considered in similar clinical presentations, since this can avoid unnecessary surgical procedures. PMID:27058152

  8. Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

    PubMed Central

    Akkiraju, Hemanth; Nohe, Anja

    2016-01-01

    Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration. PMID:27347486

  9. Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.

    PubMed

    Tsai, Pei-Chin; Zhang, Zheng; Florek, Charles; Michniak-Kohn, Bozena B

    2016-01-01

    The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool. PMID:26415037

  10. The Human Umbilical Vein with Wharton's Jelly as an Allogeneic, Acellular Construct for Vocal Fold Restoration

    PubMed Central

    Rodriguez, Maritza L.; McFetridge, Peter S.

    2009-01-01

    This study investigated the potential of the decellularized human umbilical vein (HUV) as an allogeneic, acellular extracellular matrix (ECM) scaffold for engineering the vocal fold lamina propria in vitro. HUV specimens with Wharton's jelly on the abluminal surface were uniformly dissected from native umbilical cords using an automated procedure and subjected to a novel saline-based decellularization treatment for removal of potentially antigenic epitopes. Human vocal fold fibroblasts from primary culture were seeded onto the resulting acellular constructs and cultured for 21 days. The structures of decellularized and fibroblast-repopulated HUV constructs and the attachment, proliferation, and infiltration of fibroblasts were examined with light microscopy and scanning electron microscopy. Changes in the relative densities of collagen in the constructs associated with decellularization and recellularization were quantified using digital image analysis. In addition, fibroblasts infiltrating the scaffolds were released by cell recovery and quantified by counting. Viscoelastic properties of the scaffolds were measured using a linear, simple-shear rheometer at phonatory frequencies. Results showed that an acellular ECM construct with an intact three-dimensional structure of Wharton's jelly was fabricated. Vocal fold fibroblasts readily attached on the abluminal surface of the construct with high viability, with significant cellular infiltration up to approximately 600 μm deep into the construct. A significant increase in collagen expression was observed with recellularization. The elastic modulus and dynamic viscosity of the fibroblast-repopulated scaffolds were comparable to those of the human vocal fold lamina propria. These findings supported the potential of the construct as a possible surgical allograft for vocal fold restoration and reconstruction. PMID:19456236

  11. Altered function in cartilage derived mesenchymal stem cell leads to OA-related cartilage erosion

    PubMed Central

    Xia, Zenan; Ma, Pei; Wu, Nan; Su, Xinlin; Chen, Jun; Jiang, Chao; Liu, Sen; Chen, Weisheng; Ma, Bupeng; Yang, Xu; Ma, Yufen; Weng, Xisheng; Qiu, Guixing; Huang, Shishu; Wu, Zhihong

    2016-01-01

    A portion of osteoarthritis (OA) patients with total knee arthroplasty (TKA) had monocondylar destruction in medial femoral condyle, but healthy-appearant cartilage in lateral side. However, there is limited information concerning functional differences of cartilage derived mesenchymal stem cell (CMSC) between these two locations in the same donor and its possible role in the pathogenesis of OA. Cells isolated from the degraded cartilage in medial condyle and normal cartilage in lateral side from OA patients were identified with co-expressed markers CD105 and CD166 and confirmed as CMSCs by immunophenotype. The relative percentage, proliferation activity, multi-lineage differentiation potential and miRNA expression profile of CMSCs in two groups were compared by flow cytometry, CCK-8 assay, cytochemical staining, immunohistochemistry, real-time PCR and miRNA microarray analysis. Our study suggested that the percentage (10.61±6.97% vs. 18.44±9.97%, P<0.05) and proliferation rate (P<0.01) of CD105+/CD166+ CMSCs from the degraded cartilage were significantly reduced compared with those from the normal cartilage. CMSCs from the degraded cartilage also showed stronger osteogenic (P<0.05), weaker adipogenic (P<0.01), and comparable chondrogenic potential (P>0.05) during differentiation. MiR-31-5p and miR-424-5p were down regulated in CMSCs from the degraded cartilage. In conclusion, altered function such as reduced percentage and proliferation ability, as well as changes in differentiation profile of CMSC contributed to homeostasis imbalance, leading to OA-related cartilage erosion. Furthermore, regulatory networks of multiple miRNAs may be partially responsible for the dysfunction of CMSCs. PMID:27158337

  12. Induced pluripotent stem cells in cartilage repair

    PubMed Central

    Lietman, Steven A

    2016-01-01

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  13. Irradiated homologous costal cartilage for augmentation rhinoplasty

    SciTech Connect

    Lefkovits, G. )

    1990-10-01

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed.

  14. Induced pluripotent stem cells in cartilage repair.

    PubMed

    Lietman, Steven A

    2016-03-18

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  15. Current opinions on indications and algorithms for acellular dermal matrix use in primary prosthetic breast reconstruction.

    PubMed

    Vu, Michael M; Kim, John Y S

    2015-06-01

    Acellular dermal matrix (ADM) is widely used in primary prosthetic breast reconstruction. Many indications and contraindications to use ADM have been reported in the literature, and their use varies by institution and surgeon. Developing rational, tested algorithms to determine when ADM is appropriate can significantly improve surgical outcomes and reduce costs associated with ADM use. We review the important indications and contraindications, and discuss the algorithms that have been put forth so far. Further research into algorithmic decision-making for ADM use will allow optimized balancing of cost with risk and benefit. PMID:26161304

  16. Mechanisms by which acellular biologic scaffolds promote functional skeletal muscle restoration.

    PubMed

    Badylak, Stephen F; Dziki, Jenna L; Sicari, Brian M; Ambrosio, Fabrisia; Boninger, Michael L

    2016-10-01

    Acellular biologic scaffolds derived from extracellular matrix have been investigated in preclinical and clinical studies as a regenerative medicine approach for volumetric muscle loss treatment. The present manuscript provides a review of previous studies supporting the use of extracellular matrix derived biologic scaffolds for the promotion of functional skeletal muscle tissue formation that is contractile and innervated. The manuscript also identifies key mechanisms that have been associated with ECM-mediated skeletal muscle repair, and provides hypotheses as to why there have been variable outcomes, ranging from successful to unsatisfactory, associated with ECM bioscaffold implantation in the skeletal muscle injury microenvironment. PMID:27376561

  17. Shear and Compression Bioreactor for Cartilage Synthesis.

    PubMed

    Shahin, Kifah; Doran, Pauline M

    2015-01-01

    Mechanical forces, including hydrodynamic shear, hydrostatic pressure, compression, tension, and friction, can have stimulatory effects on cartilage synthesis in tissue engineering systems. Bioreactors capable of exerting forces on cells and tissue constructs within a controlled culture environment are needed to provide appropriate mechanical stimuli. In this chapter, we describe the construction, assembly, and operation of a mechanobioreactor providing simultaneous dynamic shear and compressive loading on developing cartilage tissues to mimic the rolling and squeezing action of articular joints. The device is suitable for studying the effects of mechanical treatment on stem cells and chondrocytes seeded into three-dimensional scaffolds. PMID:26445842

  18. Body Weight Independently Affects Articular Cartilage Catabolism

    PubMed Central

    Denning, W. Matt; Winward, Jason G.; Pardo, Michael Becker; Hopkins, J. Ty; Seeley, Matthew K.

    2015-01-01

    Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW) independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity). The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW), +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP) was measured immediately before (baseline) and after, and 15 and 30 minutes after the walk. Heart rate (HR) and rate of perceived exertion (RPE) were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response. Key points Walking for 30 minutes with adjustments in body weight (normal body weight, +40% and -40% body weight) significantly influences articular cartilage catabolism, measured via serum COMP concentration. Compared to baseline levels, walking with +40% body weight and normal body weight both elicited significant increases in

  19. The use of acellular dermal matrix as a scaffold for periosteum replacement.

    PubMed

    Beniker, Dan; McQuillan, David; Livesey, Stephen; Urban, Robert M; Turner, Thomas M; Blum, Barbara; Hughes, Kim; Haggard, Warren O

    2003-05-01

    Three preclinical models were used to evaluate GraftJacket Acellular Periosteum Replacement Scaffold (Wright Medical Technology, Inc, Arlington, Tenn). The studies assessed the ability of the acellular dermal matrix to repopulate with cells, revascularize, provide a protected environment for bone defect restoration, and minimize fibrous tissue infiltration. An athymic nude rat muscle implantation study demonstrated a steady increase in cellular repopulation through days 2-21. The formation of blood vessels occurred between days 7-14 in this study. Results from a porcine femoral drill hole study indicated that the scaffold material was intact and adherent to surrounding bone and allowed cellular repopulation and vascular infiltration at a 5-week time period. A preliminary porcine segmental bone defect model at a 6-week time period demonstrated the ability of the scaffold material to protect the bone defect site as revealed by new bone formation within the margins of the defect and adjacent to the scaffold. The segmental model also indicated minimal to no soft tissue invasion into the defect site. The combined studies provided preliminary evidence that the dermal membrane material may be used as a scaffold for periosteum regeneration by allowing for cellular repopulation, revascularization, and bone defect restoration. PMID:12755232

  20. A preliminary study on the effects of acellular tissue graft augmentation in acute Achilles tendon ruptures.

    PubMed

    Lee, Daniel K

    2008-01-01

    Acute Achilles tendon rupture injuries present surgical challenges because of the mechanical forces placed on this tendon. The purpose of this study was to evaluate the effectiveness of an acellular human dermal tissue matrix, GraftJacket Matrix (Wright Medical Technology, Inc., Arlington, TN), as an augmentation material in acute Achilles tendon repair. Eleven consecutive patients with acute tendon ruptures were evaluated and followed up (20-31 months). Primary repair was followed by augmentation with the graft sutured circumferentially around the tendon. Patients were placed in an early functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20-month postoperative follow-up, there have been no cases of rerupture or recurrent pain. The average return-to-activity time was 11.8 +/- 0.75 weeks. These retrospective clinical results suggest that with an acellular human dermal tissue matrix to augment acute Achilles tendon, primary repair offers a desirable return-to-activity time without any rerupture or complications. ACFAS Level of Clinical Evidence: 2c. PMID:18156058

  1. Achilles tendon repair with acellular tissue graft augmentation in neglected ruptures.

    PubMed

    Lee, Daniel K

    2007-01-01

    Neglected Achilles tendon rupture injuries present surgical challenges because of the quality and quantity of tendon tissue during repair combined with the magnitude of mechanical forces placed on this tendon. The purpose of this study was to evaluate the effects of an acellular human dermal tissue matrix, GRAFTJACKET, as an augmentation material in neglected Achilles tendon repair. Nine patients with neglected Achilles tendon ruptures were evaluated and followed up for a minimum of 20 months. Primary repair was followed by augmentation with the graft and suturing circumferentially around the tendon. Patients were placed in an early, functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20 to 30 months postoperative follow-up range, there has been no incidence of re-rupture or recurrent pain. The average return-to-activity time was 15.2 +/- 1.7 weeks. The results from this retrospective clinical series suggest that using an acellular human dermal tissue matrix to augment neglected Achilles tendon rupture primary repair offers desirable return-to-activity time points and viable surgical alternative over previously reported surgical options. PMID:17980842

  2. Aseptic versus Sterile Acellular Dermal Matrices in Breast Reconstruction: An Updated Review

    PubMed Central

    Mendenhall, Shaun D.; Neumeister, Michael W.; Cederna, Paul S.; Momoh, Adeyiza O.

    2016-01-01

    Background: As the use of acellular dermal matrices in breast reconstruction has become more commonplace and efforts are made to improve on postoperative outcomes, the method of acellular dermal matrix (ADM) processing (aseptic versus sterile) has become a subject of interest. This article provides an updated overview of the critical aspects of ADM processing in addition to application of ADMs in single- and two-stage breast reconstruction, a review of the morbidity associated with ADM use, and alternatives. Methods: A literature review was performed in PubMed identifying recent systematic reviews, meta-analyses, and head-to-head comparisons on aseptically processed ADM and sterile-processed ADM in implant-based breast reconstruction. Results: Recent meta-analyses have shown a 2- to 3-fold increase in infections and tissue expander/implant explantation rates and a 3- to 4-fold increase in seroma formation compared with non-ADM reconstruction techniques. Comparisons of aseptic and sterile ADMs in multiple studies have shown no significant difference in infection rates and equivocal findings for other specific complications such as seroma formation. Conclusions: Current evidence on the impact of processing techniques that improve ADM sterility on postoperative morbidity in implant breast reconstruction is unclear. Deficiencies of the available data highlight the need for well-designed, multicenter, randomized controlled studies that will aid in optimizing outcomes in implant-based breast reconstruction. PMID:27536502

  3. Screening for Oxidative Stress Elicited by Engineered Nanomaterials: Evaluation of Acellular DCFH Assay

    PubMed Central

    Pal, Anoop K.; Bello, Dhimiter; Budhlall, Bridgette; Rogers, Eugene; Milton, Donald K.

    2012-01-01

    The DCFH assay is commonly used for measuring free radicals generated by engineered nanomaterials (ENM), a well-established mechanism of ENM toxicity. Concerns exist over susceptibility of the DCFH assay to: assay conditions, adsorption of DCFH onto ENM, fluorescence quenching and light scattering. These effects vary in magnitude depending on ENM physiochemical properties and concentration. A rigorous evaluation of this method is still lacking. The objective was to evaluate performance of the DCFH assay for measuring ENM-induced free radicals. A series of diverse and well-characterized ENM were tested in the acellular DCFH assay. We investigated the effect of sonication conditions, dispersion media, ENM concentration, and the use of horseradish peroxidase (HRP) on the DCFH results. The acellular DCFH assay suffers from high background signals resulting from dye auto-oxidation and lacks sensitivity and robustness. DCFH oxidation is further enhanced by HRP. The number of positive ENM in the assay and their relative ranking changed as a function of experimental conditions. An inverse dose relationship was observed for several Carbon-based ENM. Overall, these findings indicate the importance of having standardized assays for evaluating ENM toxicity and highlights limitations of the DCFH assay for measuring ENM-induced free radicals. PMID:22942866

  4. Deficiency in acellular cementum and periodontal attachment in bsp null mice.

    PubMed

    Foster, B L; Soenjaya, Y; Nociti, F H; Holm, E; Zerfas, P M; Wimer, H F; Holdsworth, D W; Aubin, J E; Hunter, G K; Goldberg, H A; Somerman, M J

    2013-02-01

    Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp (-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp (-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp (-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function. PMID:23183644

  5. Sterile acellular dermal collagen as a treatment for rippling deformity of breast.

    PubMed

    Busse, Brittany; Orbay, Hakan; Sahar, David E

    2014-01-01

    Prosthetic implants are frequently used for breast augmentation and breast reconstruction following mastectomy. Unfortunately, long-term aesthetic results of prosthetic breast restoration may be hindered by complications such as rippling, capsular contracture, and implant malposition. The advent of use of acellular dermal matrices has greatly improved the outcomes of prosthetic breast reconstruction. We describe a case of rippling deformity of breast that was treated using an acellular dermal matrix product, AlloMax. The patient presented with visible rippling of bilateral prosthetic breast implants as well as significant asymmetry of the breasts after multiple excisional biopsies for right breast ductal carcinoma in situ. A 6 × 10 cm piece of AlloMax was placed on the medial aspect of each breast between the implant and the skin flap. Follow-up was performed at 1 week, 3 months, and 1 year following the procedure. The patient recovered well from the surgery and there were no complications. At her first postoperative follow-up the patient was extremely satisfied with the result. At her 3-month and 1-year follow-up she had no recurrence of her previous deformity and no new deformity. PMID:25610697

  6. Repair of lacerated anterior tibial tendon with acellular tissue graft augmentation.

    PubMed

    DiDomenico, Lawrence A; Blasko, Gregory A; Cane, Laurence; Cross, Davina J

    2012-01-01

    In the present case report, we describe the surgical repair of a complete laceration of the anterior tibial tendon using acellular human dermal tissue matrix. A 17-year-old, elite league hockey player was injured in the locker room when a teammate still clad in ice skates stepped on his bare left foot. After evaluation at a local emergency department, the patient presented to our office the next day for additional evaluation. It was determined that surgery would be performed using acellular tissue graft augmentation, followed by physical therapy. Within 7 weeks of the injury, the athlete returned to his original level of activity. At 3 years of follow-up, he was playing Division 1 hockey at the university level. We believe that augmentation of the tendon repair with the grafting material enhanced the tendon tensile strength and promoted ingrowth through vascular channels. This, combined with the patient's dedication to physical therapy, led to excellent recovery in less time than anticipated. PMID:22762944

  7. Creation and implantation of acellular rat renal ECM-based scaffolds

    PubMed Central

    Peloso, Andrea; Ferrario, Jacopo; Maiga, Benedetta; Benzoni, Ilaria; Bianco, Carolina; Citro, Antonio; Currao, Manuela; Malara, Alessandro; Gaspari, Annalisa; Balduini, Alessandra; Abelli, Massimo; Piemonti, Lorenzo; Dionigi, Paolo; Orlando, Giuseppe; Maestri, Marcello

    2015-01-01

    Abstract Kidney transplantation is the only potentially curative treatment for patient facing end-stage renal disease, and it is now routinely used. Its use is mainly limited by the supply of transplantable donor organs, which far exceeds the demand. Regenerative medicine and tissue engineering offer promising means for overcoming this shortage. In the present study, we developed and validated a protocol for producing acellular rat renal scaffolds. Left kidneys were removed from 26 male Lewis rats (weights: 250–350 g) and decellularized by means of aortic anterograde perfusion with ionic and anionic detergents (Triton X-100 1% and SDS 1%, respectively). 19 scaffolds thus obtained (and contralateral native kidneys as controls) were deeply characterized in order to evaluate the decellularization quality, the preservation of extracellular matrix components and resultant micro-angioarchitecture structure. The other 7 were transplanted into 7 recipient rats that had undergone unilateral nephrectomy. Recipients were sacrificed on post-transplantation day 7 and the scaffolds subjected to histologic studies. The dual-detergent protocol showed, with only 5 h of perfusion per organ, to obtain thoroughly decellularized renal scaffolds consisting almost exclusively of extracellular matrix. Finally the macro- and the microarchitecture of the renal parenchyma were well preserved, and the grafts were implanted with ease. Seven days after transplant, the scaffolds were morphologically intact although all vascular structures were obstructed with thrombi. Production and implantation of acellular rat renal scaffolds is a suitable platform for further studies on regenerative medicine and tissue engineering. PMID:26186418

  8. Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement

    PubMed Central

    Arciniega, J.; Wagner, L.; Prymula, R.; Sebo, P.; Isbrucker, R.; Descampe, B.; Chapsal, J.M.; Costanzo, A.; Hendriksen, C.; Hoonaker, M.; Nelson, S.; Lidster, K.; Casey, W.; Allen, D.

    2016-01-01

    The ‘International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST’ was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9 th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials. PMID:27506225

  9. Multiplex immunoassay for in vitro characterization of acellular pertussis antigens in combination vaccines.

    PubMed

    Agnolon, Valentina; Bruno, Cristina; Galletti, Bruno; Mori, Elena; Ugozzoli, Mildred; Pergola, Carlo; O'Hagan, Derek T; Baudner, Barbara C

    2016-02-17

    Vaccines characterization is required to ensure physical, chemical, and biological integrity of antigens and adjuvants. Current analytical methods mostly require complete antigen desorption from aluminum-based adjuvants and are not always suitable to distinguish individual antigens in multivalent formulations. Here, Luminex technology is proposed to improve the analytics of vaccine characterization. As proof of concept, TdaP (tetanus, diphtheria and acellular pertussis) combination, adjuvanted with aluminum hydroxide, was chosen as model formulation to quantify and determine the level of adsorption of acellular pertussis (aP) antigens onto adjuvant surface at the same time. The assay used specific antibodies bound to magnetic microspheres presenting unique digital signatures for each pertussis antigen, allowing the simultaneous recognition of respective antigens in the whole vaccine, avoiding laborious procedures for adjuvant separation. Accurate and reproducible quantification of aP antigens in TdaP vaccine has been achieved in the range 0.78-50 ng/mL, providing simultaneously information on antigen identity, quantity, and degree of adsorption to aluminum hydroxide. The current study could further be considered as a model to set up in vitro potency assays thus supporting the replacement of animal tests accordingly to the 3Rs concept. PMID:26784684

  10. Cartilage-inspired superelastic ultradurable graphene aerogels prepared by the selective gluing of intersheet joints.

    PubMed

    Hong, Jin-Yong; Yun, Sol; Wie, Jeong Jae; Zhang, Xu; Dresselhaus, Mildred S; Kong, Jing; Park, Ho Seok

    2016-07-14

    In this study, we demonstrate a cartilage-inspired superelastic and ultradurable nanocomposite strategy for the selective inclusion of viscoelastic poly(dimethylsiloxane) (PDMS) into graphene sheet junctions to create effective stress-transfer pathways within three-dimensional (3D) graphene aerogels (GAs). Inspired by the joint architectures in the human body, where small amounts of soft cartilage connect stiff (or hard) but hollow (and thus lightweight) bones, the 3D internetworked GA@PDMS achieves synergistic toughening. The resulting GA@PDMS nanocomposites exhibit fully reversible structural deformations (99.8% recovery even at a 90% compressive strain) and high compressive mechanical strength (448.2 kPa at a compressive strain of 90%) at repeated compression cycles. Owing to the combination of excellent mechanical and electrical properties, the GA@PDMS nanocomposites are used as signal transducers for strain sensors, showing very short response and recovery times (in the millisecond range) with reliable sensitivity and extreme durability. Furthermore, the proposed system is applied to electronic scales with a large detectable weight of about 4600 times greater than its own weight. Such bio-inspired cartilage architecture opens the door to fabricate new 3D multifunctional and mechanically durable nanocomposites for emerging applications, which include sensors, actuators, and flexible devices. PMID:27244686

  11. Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model.

    PubMed

    Hasegawa, Masateru; Yamato, Masayuki; Kikuchi, Akihiko; Okano, Teruo; Ishikawa, Isao

    2005-01-01

    Conventional periodontal regeneration methods remain insufficient to attain complete and reliable clinical regeneration of periodontal tissues. We have developed a new method of cell transplantation using cell sheet engineering and have applied it to this problem. The purpose of this study was to investigate the characteristics of human periodontal ligament (HPDL) cell sheets retrieved from culture on unique temperature-responsive culture dishes, and to examine whether these cell sheets can regenerate periodontal tissues. The HPDL cell sheets were examined histologically and biochemically, and also were transplanted into a mesial dehiscence model in athymic rats. HPDL cells were harvested from culture dishes as a contiguous cell sheet with abundant extracellular matrix and retained intact integrins that are susceptible to trypsin-EDTA treatment. In the animal study, periodontal ligament-like tissues that include an acellular cementum-like layer and fibrils anchoring into this layer were identified in all the athymic rats transplanted with HPDL cell sheets. This fibril anchoring highly resembles native periodontal ligament fibers; such regeneration was not observed in nontransplanted controls. These results suggest that this technique, based on the concept of cell sheet engineering, can be useful for periodontal tissue regeneration. PMID:15869425

  12. Interposition Porcine Acellular Dermal Matrix Xenograft Successful Alternative in Treatment for Massive Rotator Cuff

    PubMed Central

    Neumann, Julie; Zgonis, Miltiadis H.; Reay, Kathleen Dolores; Mayer, Stephanie W.; Boggess, Blake; Toth, Alison P.

    2016-01-01

    Objectives: Despite advances in the surgical techniques of rotator cuff repair (RCR), the management of massive rotator cuff tears in shoulders without glenohumeral arthritis poses a difficult problem for surgeons. Failure of massive rotator cuff repairs range from 20-90% at one to two years postoperatively using arthrography, ultrasound, or magnetic resonance imaging. Additionally, there are inconsistent outcomes reported with debridement alone of massive rotator cuff tears as well as limitations seen with other current methods of operative intervention including arthroplasty and tendon transfers. The purpose of this prospective, comparative study was to determine if the repair of massive rotator cuff tears using an interposition porcine acellular dermal matrix xenograft improves subjective function, pain, range of motion, and strength at greater than two years follow-up. To our knowledge, this is the largest prospective series reporting outcomes of using porcine acellular dermal matrix xenograft as an interposition graft. Methods: Thirty-seven patients (37 shoulders) with an average age of 66 years (range 51-80 years) were prospectively followed for 33 months (range 23-48) following massive RCR using porcine acellular dermal matrix interposition xenograft. Subjective outcomes were measured using the Visual Analog Scale (VAS) pain score (0-10, 0 = no pain), Modified American Shoulder and Elbow Score (M-ASES), and Short-Form12 (SF-12) scores. Preoperative and postoperative objective outcome measures included active range of motion and supraspinatus and infraspinatus manual muscle strength. Postoperative outcome measures included quantitative muscle strength using a dynamometer and static and dynamic ultrasonography to assess the integrity of the repair. Results: Average VAS pain score decreased from 4.5 to 1.1 (P<0.001). Average postoperative M-ASES was 89.23. Average postoperative SF-12 was 52.6. Mean forward flexion, external and internal rotation significantly

  13. PRP and Articular Cartilage: A Clinical Update

    PubMed Central

    Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

    2015-01-01

    The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

  14. The Elusive Path to Cartilage Regeneration

    PubMed Central

    Hunziker, Ernst B.

    2010-01-01

    Numerous attempts have been made to develop an efficacious strategy for the repair of articular cartilage. These endeavours have been undaunted, if not spurred, by the challenge of the task and by the largely disappointing outcomes in animal models. Of the strategies that have been lately applied in a clinical setting, the autologous-chondrocyte-transplantation technique is the most notorious example. This methodology, which was prematurely launched on the clinical scene, was greeted with enthusiasm and has been widely adopted. However, a recent prospective and randomized clinical trial has revealed the approach to confer no advantage over conventional microfracturing. Why is the repair of articular cartilage such a seemingly intractable problem? The root of the evil undoubtedly lies in the tissue's poor intrinsic healing capacity. But the failure of investigators to tackle the biological stumbling blocks systematically rather than empirically is hardly a less inauspicious circumstance. Moreover, it is a common misbelief that the formation of hyaline cartilage per se suffices, whereas to be durable and functionally competent, the tissue must be fully mature. An appreciation of this necessity, coupled with a thorough understanding of the postnatal development of articular cartilage, would help to steer investigators clear of biological cul-de-sacs. PMID:20882507

  15. Nanomechanics of the Cartilage Extracellular Matrix

    PubMed Central

    Han, Lin; Grodzinsky, Alan J.; Ortiz, Christine

    2012-01-01

    Cartilage is a hydrated biomacromolecular fiber composite located at the ends of long bones that enables proper joint lubrication, articulation, loading, and energy dissipation. Degradation of extracellular matrix molecular components and changes in their nanoscale structure greatly influence the macroscale behavior of the tissue and result in dysfunction with age, injury, and diseases such as osteoarthritis. Here, the application of the field of nanomechanics to cartilage is reviewed. Nanomechanics involves the measurement and prediction of nanoscale forces and displacements, intra- and intermolecular interactions, spatially varying mechanical properties, and other mechanical phenomena existing at small length scales. Experimental nanomechanics and theoretical nanomechanics have been applied to cartilage at varying levels of material complexity, e.g., nanoscale properties of intact tissue, the matrix associated with single cells, biomimetic molecular assemblies, and individual extracellular matrix biomolecules (such as aggrecan, collagen, and hyaluronan). These studies have contributed to establishing a fundamental mechanism-based understanding of native and engineered cartilage tissue function, quality, and pathology. PMID:22792042

  16. The effects of exercise on human articular cartilage

    PubMed Central

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-01-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

  17. Synoviocytes protect cartilage from the effects of injury in vitro

    PubMed Central

    2013-01-01

    Background It is well documented that osteoarthritis (OA) can develop following traumatic joint injury and is the leading cause of lameness and subsequent wastage of equine athletes. Although much research of injury induced OA has focused on cartilage, OA is a disease that affects the whole joint organ. Methods In this study, we investigated the impact of synovial cells on the progression of an OA phenotype in injured articular cartilage. Injured and control cartilage were cultured in the presence of synoviocytes extracted from normal equine synovium. Synoviocytes and cartilage were evaluated for catabolic and anabolic gene expression. The cartilage was also evaluated histologically for loss of extracellular matrix molecules, chondrocyte cell death and chondrocyte cluster formation. Results The results indicate synoviocytes exert both positive and negative effects on injured cartilage, but ultimately protect injured cartilage from progressing toward an OA phenotype. Synoviocytes cultured in the presence of injured cartilage had significantly reduced expression of aggrecanase 1 and 2 (ADAMTS4 and 5), but also had increased expression of matrix metalloproteinase (MMP) -1 and reduced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1). Injured cartilage cultured with synoviocytes had increased expression of both collagen type 2 and aggrecanase 2. Histologic examination of cartilage indicated that there was a protective effect of synoviocytes on injured cartilage by reducing the incidence of both focal cell loss and chondrocyte cluster formation, two major hallmarks of OA. Conclusions These results support the importance of evaluating more than one synovial joint tissue when investigating injury induced OA. PMID:23374282

  18. Investigations into human tracheal cartilage osseocalcineus metaplasia II. Histopathological examination of tracheal cartilages.

    PubMed

    Sośnik, Henryk; Sośnik, Katarzyna

    2009-01-01

    Different opinions in the literature about changes in tracheal cartilages were the basis for investigations concerning the types of morphological changes occurring in ageing tracheal cartilages. 5 micron thick specimens stained with haematoxylin-eosin and in selected cases using von Kossa method of 371 cartilages taken from 95 male (mean age 56.6 +/-13.4 years) and 279 cartilages from 70 female patients (mean age 64.9 +/-16 years) (p < 0.001) were the investigated material. The analysis demonstrated statistically significant cartilage type differences between men and women (p < 0.001). Chondrolysis and asbestoids were observed in 11.9% of male and 2.9% of female patients. Calcium deposits were seen in 13.2% of male and 9.7% of female patients, while cartilage ossification in 20.5% and 3.6%, respectively. The coexistence of calcium deposits and osseous metaplasia was observed in 8.6% of male and 3.9% of female patients. PMID:20072952

  19. Zn deposition at the bone cartilage interface in equine articular cartilage

    NASA Astrophysics Data System (ADS)

    Bradley, D. A.; Moger, C. J.; Winlove, C. P.

    2007-09-01

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  20. Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

    PubMed

    Muehleman, Carol; Chapman, L Dean; Kuettner, Klaus E; Rieff, Joel; Mollenhauer, Juergen A; Massuda, Koichi; Zhong, Zhong

    2003-05-01

    Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration. PMID:12704696

  1. Extracellular matrix production in vitro in cartilage tissue engineering

    PubMed Central

    2014-01-01

    Cartilage tissue engineering is arising as a technique for the repair of cartilage lesions in clinical applications. However, fibrocartilage formation weakened the mechanical functions of the articular, which compromises the clinical outcomes. Due to the low proliferation ability, dedifferentiation property and low production of cartilage-specific extracellular matrix (ECM) of the chondrocytes, the cartilage synthesis in vitro has been one of the major limitations for obtaining high-quality engineered cartilage constructs. This review discusses cells, biomaterial scaffolds and stimulating factors that can facilitate the cartilage-specific ECM production and accumulation in the in vitro culture system. Special emphasis has been put on the factors that affect the production of ECM macromolecules such as collagen type II and proteoglycans in the review, aiming at providing new strategies to improve the quality of tissue-engineered cartilage. PMID:24708713

  2. Cartilage issues in football—today's problems and tomorrow's solutions

    PubMed Central

    Mithoefer, Kai; Peterson, Lars; Zenobi-Wong, Marcy; Mandelbaum, Bert R

    2015-01-01

    Articular cartilage injury is prevalent in football players and results from chronic joint stress or acute traumatic injuries. Articular cartilage injury can often result in progressive painful impairment of joint function and limit sports participation. Management of articular cartilage injury in athletes aims to return the player to competition, and requires effective and durable joint surface restoration that resembles normal hyaline articular cartilage that can withstand the high joint stresses of football. Existing articular cartilage repair techniques can return the athlete with articular cartilage injury to high-impact sports, but treatment does not produce normal articular cartilage, and this limits the success rate and durability of current cartilage repair in athletes. Novel scientific concepts and treatment techniques that apply modern tissue engineering technologies promise further advancement in the treatment of these challenging injuries in the high demand athletic population. We review the current knowledge of cartilage injury pathophysiology, epidemiology and aetiology, and outline existing management algorithms, developing treatment options and future strategies to manage articular cartilage injuries in football players. PMID:25878075

  3. Persisting High Levels of Synovial Fluid Markers after Cartilage Repair

    PubMed Central

    Konttinen, Yrjö T.; Peterson, Lars; Lindahl, Anders; Kiviranta, Ilkka

    2008-01-01

    Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18709427

  4. WNT signaling and cartilage: of mice and men.

    PubMed

    Ma, Bin; Landman, Ellie B M; Miclea, Razvan L; Wit, Jan M; Robanus-Maandag, Els C; Post, Janine N; Karperien, Marcel

    2013-05-01

    In adult articular cartilage, the extracellular matrix is maintained by a balance between the degradation and the synthesis of matrix components. Chondrocytes that sparsely reside in the matrix and rarely proliferate are the key cellular mediators for cartilage homeostasis. There are indications for the involvement of the WNT signaling pathway in maintaining articular cartilage. Various WNTs are involved in the subsequent stages of chondrocyte differentiation during development, and deregulation of WNT signaling was observed in cartilage degeneration. Even though gene expression and protein synthesis can be activated upon injury, articular cartilage has a limited ability of self-repair and efforts to regenerate articular cartilage have so far not been successful. Because WNT signaling was found to be involved in the development and maintenance of cartilage as well as in the degeneration of cartilage, interfering with this pathway might contribute to improving cartilage regeneration. However, most of the studies on elucidating the role of WNT signaling in these processes were conducted using in vitro or in vivo animal models. Discrepancies have been found in the role of WNT signaling between chondrocytes of mouse and human origin, and extrapolation of results from mouse models to the human situation remains a challenge. Elucidation of detailed WNT signaling functions will provide knowledge to improve cartilage regeneration. PMID:23212543

  5. Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?

    PubMed Central

    Memon, A. R.; Quinlan, J. F.

    2012-01-01

    Articular cartilage (AC) injury is a common disorder. Numerous techniques have been employed to repair or regenerate the cartilage defects with varying degrees of success. Three commonly performed techniques include bone marrow stimulation, cartilage repair, and cartilage regeneration. This paper focuses on current level of evidence paying particular attention to cartilage regeneration techniques. PMID:22655202

  6. Cell sheet approach for tissue engineering and regenerative medicine.

    PubMed

    Matsuura, Katsuhisa; Utoh, Rie; Nagase, Kenichi; Okano, Teruo

    2014-09-28

    After the biotech medicine era, regenerative medicine is expected to be an advanced medicine that is capable of curing patients with difficult-to-treat diseases and physically impaired function. Our original scaffold-free cell sheet-based tissue engineering technology enables transplanted cells to be engrafted for a long time, while fully maintaining their viability. This technology has already been applied to various diseases in the clinical setting, including the cornea, esophagus, heart, periodontal ligament, and cartilage using autologous cells. Transplanted cell sheets not only replace the injured tissue and compensate for impaired function, but also deliver growth factors and cytokines in a spatiotemporal manner over a prolonged period, which leads to promotion of tissue repair. Moreover, the integration of stem cell biology and cell sheet technology with sufficient vascularization opens possibilities for fabrication of human three-dimensional vascularized dense and intact tissue grafts for regenerative medicine to parenchymal organs. PMID:24858800

  7. Significance of Epigenetic Landscape in Cartilage Regeneration from the Cartilage Development and Pathology Perspective

    PubMed Central

    Li, Jingting; Ohliger, James

    2014-01-01

    Regenerative therapies for cartilage defects have been greatly advanced by progress in both the stem cell biology and tissue engineering fields. Despite notable successes, significant barriers remain including shortage of autologous cell sources and generation of a stable chondrocyte phenotype using progenitor cells. Increasing demands for the treatment of degenerative diseases, such as osteoarthritis and rheumatoid arthritis, highlight the importance of epigenetic remodeling in cartilage regeneration. Epigenetic regulatory mechanisms, such as microRNAs, DNA methylation, and histone modifications, have been intensively studied due to their direct regulatory role on gene expression. However, a thorough understanding of the environmental factors that initiate these epigenetic events may provide greater insight into the prevention of degenerative diseases and improve the efficacy of treatments. In other words, if we could identify a specific factor from the environment and its downstream signaling events, then we could stop or retard degradation and enhance cartilage regeneration. A more operational definition of epigenetic remodeling has recently been proposed by categorizing the signals during the epigenetic process into epigenators, initiators, and maintainers. This review seeks to compile and reorganize the existing literature pertaining to epigenetic remodeling events placing emphasis on perceiving the landscape of epigenetic mechanisms during cartilage regeneration with the new operational definition, especially from the environmental factors' point of view. Progress in understanding epigenetic regulatory mechanisms could benefit cartilage regeneration and engineering on a larger scale and provide more promising therapeutic applications. PMID:24555773

  8. Analysis of friction between articular cartilage and polyvinyl alcohol hydrogel artificial cartilage.

    PubMed

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

    Many biomaterials are being used to repair damaged articular cartilage. In particular, poly vinyl alcohol hydrogel has similar mechanical properties to natural cartilage under compressive and shearing loading. Here, three-factor and two-level friction experiments and long-term tests were conducted to better evaluate its tribological properties. The friction coefficient between articular cartilage and the poly vinyl alcohol hydrogel depended primarily on the three factors of load, speed, and lubrication. When the speed increased from 10 to 20 mm/s under a load of 10 N, the friction coefficient increased from 0.12 to 0.147. When the lubricant was changed from Ringer's solution to a hyaluronic acid solution, the friction coefficient decreased to 0.084 with loads as high as 22 N. The poly vinyl alcohol hydrogel was severely damaged and lost its top surface layers, which were transferred to the articular cartilage surface. Wear was observed in the surface morphologies, which indicated the occurrence of surface adhesion of bovine cartilage. Surface fatigue and adhesive wear was the dominant wear mechanism. PMID:26970769

  9. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone.

    PubMed

    Boyde, A; Riggs, C M; Bushby, A J; McDermott, B; Pinchbeck, G L; Clegg, P D

    2011-01-01

    Arthropathy of the distal articular surfaces of the third metacarpal (Mc3) and metatarsal (Mt3) bones in the Thoroughbred racehorse (Tb) is a natural model of repetitive overload arthrosis. We describe a novel pathology that affects the articular calcified cartilage (ACC) and subchondral bone (SCB) and which is associated with hyaline articular cartilage degeneration. Parasagittal slices cut from the palmar quadrant of the distal condyles of the left Mc3/Mt3 of 39 trained Tbs euthanized for welfare reasons were imaged by point projection microradiography, and backscattered electron (BSE) scanning electron microscopy (SEM), light microscopy, and confocal scanning light microscopy. Mechanical properties were studied by nanoindentation. Data on the horses' training and racing career were also collected. Highly mineralised projections were observed extending from cracks in the ACC mineralising front into the hyaline articular cartilage (HAC) up to two-thirds the thickness of the HAC, and were associated with focal HAC surface fibrillation directly overlying their site. Nanoindentation identified this extruded matrix to be stiffer than any other mineralised phase in the specimen by a factor of two. The presence of projections was associated with a higher cartilage Mankin histology score (P<0.02) and increased amounts of gross cartilage loss pathologically on the condyle (P<0.02). Presence of projections was not significantly associated with: total number of racing seasons, age of horse, amount of earnings, number of days in training, total distance galloped in career, or presence of wear lines. PMID:21623571

  10. Tissue-Engineered Articular Cartilage Exhibits Tension-Compression Nonlinearity Reminiscent of the Native Cartilage

    PubMed Central

    Kelly, Terri-Ann N.; Roach, Brendan L.; Weidner, Zachary D.; Mackenzie-Smith, Charles R.; O'Connell, Grace D.; Lima, Eric G.; Stoker, Aaron M.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

    2013-01-01

    The tensile modulus of articular cartilage is much larger than its compressive modulus. This tension-compression nonlinearity enhances interstitial fluid pressurization and decreases the frictional coefficient. The current set of studies examines the tensile and compressive properties of cylindrical chondrocyte-seeded agarose constructs over different developmental stages through a novel method that combines osmotic loading, video microscopy, and uniaxial unconfined compression testing. This method was previously used to examine tension-compression nonlinearity in native cartilage. Engineered cartilage, cultured under free-swelling (FS) or dynamically loaded (DL) conditions, was tested in unconfined compression in hypertonic and hypotonic salt solutions. The apparent equilibrium modulus decreased with increasing salt concentration, indicating that increasing the bath solution osmolarity shielded the fixed charges within the tissue, shifting the measured moduli along the tension-compression curve and revealing the intrinsic properties of the tissue. With this method, we were able to measure the tensile (401±83 kPa for FS and 678±473 kPa for DL) and compressive (161±33 kPa for FS and 348±203 kPa for DL) moduli of the same engineered cartilage specimens. These moduli are comparable to values obtained from traditional methods, validating this technique for measuring the tensile and compressive properties of hydrogel-based constructs. This study shows that engineered cartilage exhibits tension-compression nonlinearity reminiscent of the native tissue, and that dynamic deformational loading can yield significantly higher tensile properties. PMID:23791084

  11. Engineered cartilage using primary chondrocytes cultured in a porous cartilage-derived matrix

    PubMed Central

    Cheng, Nai-Chen; Estes, Bradley T; Young, Tai-Horng; Guilak, Farshid

    2011-01-01

    Aim To investigate the cell growth, matrix accumulation and mechanical properties of neocartilage formed by human or porcine articular chondrocytes on a porous, porcine cartilage-derived matrix (CDM) for use in cartilage tissue engineering. Materials & methods We examined the physical properties, cell infiltration and matrix accumulation in different formulations of CDM and selected a CDM made of homogenized cartilage slurry as an appropriate scaffold for long-term culture of human and porcine articular chondrocytes. Results The CDM scaffold supported growth and proliferation of both human and porcine chondrocytes. Histology and immunohistochemistry showed abundant cartilage-specific macromolecule deposition at day 28. Human chondrocytes migrated throughout the CDM, showing a relatively homogeneous distribution of new tissue accumulation, whereas porcine chondrocytes tended to form a proteoglycan-rich layer primarily on the surfaces of the scaffold. Human chondrocyte-seeded scaffolds had a significantly lower aggregate modulus and hydraulic permeability at day 28. Conclusions These data show that a scaffold derived from native porcine articular cartilage can support neocartilage formation in the absence of exogenous growth factors. The overall characteristics and properties of the constructs depend on factors such as the concentration of CDM used, the porosity of the scaffold, and the species of chondrocytes. PMID:21175289

  12. Effective management of major lower extremity wounds using an acellular regenerative tissue matrix: a pilot study.

    PubMed

    Brigido, Stephen A; Boc, Steven F; Lopez, Ramon C

    2004-01-01

    Wound healing is a significant problem in orthopedics. Graftjacket tissue matrix (Wright Medical Technology, Inc, Arlington, Tenn), a novel acellular regenerative tissue matrix, has been designed to aid wound closure. A prospective, randomized study was initiated to determine the efficacy of this tissue product in wound repair compared with conventional treatment. Lower extremity wounds are refractile to healing in patients with diabetes mellitus. Therefore, researchers used diabetic foot ulcers to evaluate the efficacy of GraftJacket tissue matrix in wound repair. Only a single administration of the tissue matrix was required. After 1 month of treatment, preliminary results demonstrate that this novel tissue matrix promotes faster healing at a statistically significant rate over conventional treatment. Because wounds in this series of patients are deep and circulation around the wound is poor, the preliminary results suggest that this tissue matrix will be applicable to other types of orthopedic wounds. PMID:14763548

  13. Confocal Laser Scanning Microscopy Evaluation of an Acellular Dermis Tissue Transplant (Epiflex®)

    PubMed Central

    Hohenberger, Peter

    2012-01-01

    The structure of a biological scaffold is a major determinant of its biological characteristics and its interaction with cells. An acellular dermis tissue transplant must undergo a series of processing steps, to remove cells and genetic material and provide the sterility required for surgical use. During manufacturing and sterilization the structure and composition of tissue transplants may change. The composition of the human cell-free dermis transplant Epiflex® was investigated with specific attention paid to its structure, matrix composition, cellular content and biomechanics. We demonstrated that after processing, the structure of Epiflex remains almost unchanged with an intact collagen network and extracellular matrix (ECM) protein composition providing natural cell interactions. Although the ready to use transplant does contain some cellular and DNA debris, the processing procedure results in a total destruction of cells and active DNA which is a requirement for an immunologically inert and biologically safe substrate. Its biomechanical parameters do not change significantly during the processing. PMID:23056225

  14. Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity.

    PubMed

    Mahara, Atsushi; Somekawa, Shota; Kobayashi, Naoki; Hirano, Yoshiaki; Kimura, Yoshiharu; Fujisato, Toshiya; Yamaoka, Tetsuji

    2015-07-01

    Researchers have attempted to develop efficient antithrombogenic surfaces, and yet small-caliber artificial vascular grafts are still unavailable. Here, we demonstrate the excellent patency of tissue-engineered small-caliber long-bypass grafts measuring 20-30 cm in length and having a 2-mm inner diameter. The inner surface of an acellular ostrich carotid artery was modified with a novel heterobifunctional peptide composed of a collagen-binding region and the integrin α4β1 ligand, REDV. Six grafts were transplanted in the femoral-femoral artery crossover bypass method. Animals were observed for 20 days and received no anticoagulant medication. No thrombogenesis was observed on the luminal surface and five cases were patent. In contrast, all unmodified grafts became occluded, and severe thrombosis was observed. The vascular grafts reported here are the first successful demonstrations of short-term patency at clinically applicable sizes. PMID:25941782

  15. Gravity related behavior of the acellular slime mold Physarum polycephalum (7-IML-1)

    NASA Technical Reports Server (NTRS)

    Block, I.

    1992-01-01

    The objective of the experiment is to investigate the effect of near weightlessness on a single cell. The test object is the acellular slime mold Physarum polycephalum. This cell is composed of a network of protoplastic strands which perform rhythmic contractions in the minute range. These contractions of the strands' ectoplastic walls generate the force to drive the vigorous shuttle streaming of fluid protoplasm inside the strands (hydrostatic pressure flow). A net transport of protoplasm in one direction determines the direction of the cell's locomotion itself. In this way, gravity modifies the contraction rhythm of the strands, the streaming velocity of protoplasm in the strands, and the direction of locomotion of the whole slime mold (geotaxis). The other parts of this experiment will address the major question of how this cell, which does not possess any specialized gravireceptors, gets the information about the direction of the gravity vector. Details of the experimental setup are given.

  16. Histone Deacetylases in Cartilage Homeostasis and Osteoarthritis.

    PubMed

    Carpio, Lomeli R; Westendorf, Jennifer J

    2016-08-01

    The involvement of the epigenome in complex diseases is becoming increasingly clear and more feasible to study due to new genomic and computational technologies. Moreover, therapies altering the activities of proteins that modify and interpret the epigenome are available to treat cancers and neurological disorders. Many additional uses have been proposed for these drugs based on promising preclinical results, including in arthritis models. Understanding the effects of epigenomic drugs on the skeleton is of interest because of its importance in maintaining overall health and fitness. In this review, we summarize ongoing advancements in how one class of epigenetic modifiers, histone deacetylases (Hdacs), controls normal cartilage development and homeostasis, as well as recent work aimed at understanding the alterations in the expression and activities of these enzymes in osteoarthritis (OA). We also review recent studies utilizing Hdac inhibitors and discuss the potential therapeutic benefits and limitations of these drugs for preventing cartilage destruction in OA. PMID:27402109

  17. Cartilage restoration technique of the hip.

    PubMed

    Mardones, Rodrigo; Larrain, Catalina

    2016-04-01

    Hip cartilage lesions represent a diagnostic challenge and can be an elusive source of pain. Treatment may present difficulties due to localization and spherical form of the joint and is most commonly limited to excision, debridement, thermal chondroplasty and microfractures. This chapter will focus in new technologies to enhance the standard techniques. These new technologies are based in stem cells therapies; as intra-articular injections of expanded mesenchymal stem cells, mononuclear concentrate in a platelet-rich plasma matrix and expanded mesenchymal stem cells seeded in a collagen membrane. This review will discuss the bases, techniques and preliminary results obtained with the use of stem cells for the treatment of hip cartilage lesions. PMID:27026816

  18. Cartilage restoration technique of the hip

    PubMed Central

    Mardones, Rodrigo; Larrain, Catalina

    2016-01-01

    Hip cartilage lesions represent a diagnostic challenge and can be an elusive source of pain. Treatment may present difficulties due to localization and spherical form of the joint and is most commonly limited to excision, debridement, thermal chondroplasty and microfractures. This chapter will focus in new technologies to enhance the standard techniques. These new technologies are based in stem cells therapies; as intra-articular injections of expanded mesenchymal stem cells, mononuclear concentrate in a platelet-rich plasma matrix and expanded mesenchymal stem cells seeded in a collagen membrane. This review will discuss the bases, techniques and preliminary results obtained with the use of stem cells for the treatment of hip cartilage lesions. PMID:27026816

  19. Bioprinted Scaffolds for Cartilage Tissue Engineering.

    PubMed

    Kang, Hyun-Wook; Yoo, James J; Atala, Anthony

    2015-01-01

    Researchers are focusing on bioprinting technology as a viable option to overcome current difficulties in cartilage tissue engineering. Bioprinting enables a three-dimensional (3-D), free-form, computer-designed structure using biomaterials, biomolecules, and/or cells. The inner and outer shape of a scaffold can be controlled by this technology with great precision. Here, we introduce a hybrid bioprinting technology that is a co-printing process of multiple materials including high-strength synthetic polymer and cell-laden hydrogel. The synthetic polymer provides mechanical support for shape maintenance and load bearing, while the hydrogel provides the biological environment for artificial cartilage regeneration. This chapter introduces the procedures for printing of a 3-D scaffold using our hybrid bioprinting technology and includes the source materials for preparation of 3-D printing. PMID:26445837

  20. Noncontrast MR techniques and imaging of cartilage.

    PubMed

    Koff, Mathew F; Potter, Hollis G

    2009-05-01

    Recent advances in noncontrast MR imaging produce images with higher quality for standardized diagnostic interpretation and in many cases may obviate the need for intra-articular contrast agents. These techniques may now be applied to all joints, and are particularly efficacious in the assessment of articular cartilage. Additional specialized noncontrast sequences enable the direct quantitative assessment of articular cartilage and other joint structures, thereby providing indirect assessment of tissue health and biochemistry. T2 mapping displays local water content and collagen fibril orientation, and the method of T1 rho mapping displays the local proteoglycan content of the tissue. Ultrashort echo imaging improves the contrast of joint structures with high tissue isotropy or low water content, such as ligament, tendon, and meniscus. PMID:19361672

  1. Cartilage Injuries in the Adult Knee

    PubMed Central

    Moyad, Thomas F.

    2011-01-01

    Cartilage injuries are frequently recognized as a source of significant morbidity and pain in patients with previous knee injuries. The majority of patients who undergo routine knee arthroscopy have evidence of a chondral defect. These injuries represent a continuum of pathology from small, asymptomatic lesions to large, disabling defects affecting a major portion of one or more compartments within the knee joint. In comparison to patients with osteoarthritis, individuals with isolated chondral surface damage are often younger, significantly more active, and usually less willing to accept limitations in activities that require higher impact. At the present time, a variety of surgical procedures exist, each with their unique indications. This heterogeneity of treatment options frequently leads to uncertainty regarding which techniques, if any, are most appropriate for patients. The purpose of this review is to describe the workup and discuss the management techniques for cartilage injuries within the adult knee. PMID:26069581

  2. Ligament reconstruction with tendon interposition using an acellular dermal allograft for thumb carpometacarpal arthritis.

    PubMed

    Kokkalis, Zinon T; Zanaros, George; Sotereanos, Dean G

    2009-03-01

    Ligament reconstruction tendon interposition arthroplasty is currently the preferred technique for carpometacarpal joint arthritis of the thumb by most surgeons. Despite its efficacy, morbidity has been associated with the harvest of the flexor carpi radialis tendon. Using an allograft as material for arthroplasty, donor site morbidity is avoided. In this report, we present our surgical technique to perform ligament reconstruction tendon interposition arthroplasty using an acellular dermal matrix allograft (GraftJacket) in patients with Eaton stages II, III, and IV symptomatic first carpometacarpal arthritis.One hundred thumbs with trapeziometacarpal osteoarthritis underwent surgical treatment using GraftJacket allograft instead of the flexor carpi radialis tendon autograft. Each patient was followed for a minimum of 12 months. The surgical procedure included trapezial excision and identification of the flexor carpi radialis. The allograft was cut to create a 15-cm strip. The ligament reconstruction was performed by passing the strip around the flexor carpi radialis tendon and suturing it to the base of the thumb metacarpal base through an intramedullary drill hole. The remaining portion of the allograft was fashioned as an interposition mass (anchovy) and interposed between the scaphoid and the base of the first metacarpal.All but 1 patient experienced significant improvement in his or her pain scale rating and grip and pinch strengths. Outcomes from this study compare very favorably with those of other series. No patients experienced a foreign body reaction or infection in this series. We believe that the use of an acellular dermal allograft for both ligament reconstruction and tendon interposition provides a safe and an effective alternative technique for the treatment of advanced first carpometacarpal arthritis. PMID:19276927

  3. Physiological distal drift in rat molars contributes to acellular cementum formation.

    PubMed

    Tsuchiya, Shinobu; Tsuchiya, Masahiro; Nishioka, Takashi; Suzuki, Osamu; Sasano, Yasuyuki; Igarashi, Kaoru

    2013-08-01

    Occlusal forces may induce the physiological teeth migration in humans, but there is little direct evidence. Rat molars are known to migrate distally during aging, possibly caused by occlusal forces. The purpose of this study was to determine if a reduction in occlusion would decrease teeth migration and affect associated periodontal structures such as cementum. To reduce occlusal forces, the right upper first molar (M1) in juvenile rats was extracted. The transition of the position of upper second molar (M2) and formation of M2 cementum was followed during aging. From the cephalometric analyses, upper M2 was located more anterior compared with the original position with aging after M1 extraction. Associated with this "slowing-down" of the physiological drift, cementum thickness on distal surface, but not on mesial surface, of M2 root was significantly increased. The accumulation of alizarin red as vital stain indicative of calcification, was observed in the distal cementum of M2 root only on the side of M1 extraction. Extraction of M1 that results in less functional loading, distinctly attenuates the physiological drift only in the upper dentition. The decreased physiological drift appears to activate acellular cementum formation only on distal surface of M2 root, perhaps due to reduced mechanical stress associated with the attenuated distal drift. In conclusion, the physiological distal drift in rat molars appears to be largely driven by the occlusal force and also affects the formation of acellular cementum. These findings provide additional direct evidence for an important role of occlusal forces in tooth migration. PMID:23775928

  4. Is Sterile Better Than Aseptic? Comparing the Microbiology of Acellular Dermal Matrices

    PubMed Central

    Klein, Gabriel M.; Nasser, Ahmed E.; Phillips, Brett T.; Gersch, Robert P.; Fourman, Mitchell S.; Lilo, Sarit E.; Fritz, Jason R.; Khan, Sami U.; Dagum, Alexander B.

    2016-01-01

    Introduction: Postoperative infections are a major complication associated with tissue-expander-based breast reconstruction. The use of acellular dermal matrix (ADM) in this surgery has been identified as a potential reservoir of infection, prompting the development of sterile ADM. Although aseptic and sterile ADMs have been investigated, no study has focused on the occurrence and clinical outcome of bacterial colonization before implantation. Methods: Samples of aseptic AlloDerm, sterile Ready-To-Use AlloDerm, and AlloMax were taken before implantation. These samples were incubated in Tryptic soy broth overnight before being streaked on Trypticase soy agar, MacConkey agar, and 5% blood agar plates for culture and incubated for 48 hours. Culture results were cross-referenced with patient outcomes for 1 year postoperatively. Results: A total of 92 samples of ADM were collected from 63 patients. There were 15 cases of postoperative surgical site infection (16.3%). Only 1 sample of ADM (AlloMax) showed growth of Escherichia coli, which was likely a result of contamination. That patient did not develop any infectious sequelae. Patient outcomes showed no difference in the incidence of seroma or infection between sterile and aseptic ADMs. Conclusions: This study evaluates the microbiology of acellular dermal matrices before use in breast reconstruction. No difference was found in the preoperative bacterial load of either aseptic or sterile ADM. No significant difference was noted in infection or seroma formation. Given these results, we believe aseptic processing used on ADMs is equivalent to sterile processing in our patient cohort in terms of clinical infection and seroma occurrence postoperatively. PMID:27482500

  5. A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair.

    PubMed

    Ainola, Mari; Tomaszewski, Waclaw; Ostrowska, Barbara; Wesolowska, Ewa; Wagner, H Daniel; Swieszkowski, Wojciech; Sillat, Tarvo; Peltola, Emilia; Konttinen, Yrjö T

    2016-01-01

    The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-β3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration. PMID:26341661

  6. Chondrogenic Progenitor Cells Respond to Cartilage Injury

    PubMed Central

    Choe, Hyeonghun; Zheng, Hongjun; Yu, Yin; Jang, Keewoong; Walter, Morgan W.; Lehman, Abigail D.; Ding, Lei; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Objective Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to posttraumatic osteoarthritis. However, we observed that nonviable areas in cartilage injured by blunt impact were repopulated within 7–14 days by cells that appeared to migrate from the surrounding matrix. The aim of this study was to assess our hypothesis that the migrating cell population included chondrogenic progenitor cells that were drawn to injured cartilage by alarmins. Methods Osteochondral explants obtained from mature cattle were injured by blunt impact or scratching, resulting in localized chondrocyte death. Injured sites were serially imaged by confocal microscopy, and migrating cells were evaluated for chondrogenic progenitor characteristics. Chemotaxis assays were used to measure the responses to chemokines, injury-conditioned medium, dead cell debris, and high mobility group box chromosomal protein 1 (HMGB-1). Results Migrating cells were highly clonogenic and multipotent and expressed markers associated with chondrogenic progenitor cells. Compared with chondrocytes, these cells overexpressed genes involved in proliferation and migration and underexpressed cartilage matrix genes. They were more active than chondrocytes in chemotaxis assays and responded to cell lysates, conditioned medium, and HMGB-1. Glycyrrhizin, a chelator of HMGB-1 and a blocking antibody to receptor for advanced glycation end products (RAGE), inhibited responses to cell debris and conditioned medium and reduced the numbers of migrating cells on injured explants. Conclusion Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitor cells, in part via HMGB-1 release and RAGE-mediated chemotaxis. Their repopulation of the matrix could promote the repair of chondral damage that might otherwise contribute to progressive cartilage loss. PMID:22777600

  7. Quantitative MRI techniques of cartilage composition

    PubMed Central

    Matzat, Stephen J.; van Tiel, Jasper; Gold, Garry E.

    2013-01-01

    Due to aging populations and increasing rates of obesity in the developed world, the prevalence of osteoarthritis (OA) is continually increasing. Decreasing the societal and patient burden of this disease motivates research in prevention, early detection of OA, and novel treatment strategies against OA. One key facet of this effort is the need to track the degradation of tissues within joints, especially cartilage. Currently, conventional imaging techniques provide accurate means to detect morphological deterioration of cartilage in the later stages of OA, but these methods are not sensitive to the subtle biochemical changes during early disease stages. Novel quantitative techniques with magnetic resonance imaging (MRI) provide direct and indirect assessments of cartilage composition, and thus allow for earlier detection and tracking of OA. This review describes the most prominent quantitative MRI techniques to date—dGEMRIC, T2 mapping, T1rho mapping, and sodium imaging. Other, less-validated methods for quantifying cartilage composition are also described—Ultrashort echo time (UTE), gagCEST, and diffusion-weighted imaging (DWI). For each technique, this article discusses the proposed biochemical correlates, as well its advantages and limitations for clinical and research use. The article concludes with a detailed discussion of how the field of quantitative MRI has progressed to provide information regarding two specific patient populations through clinical research—patients with anterior cruciate ligament rupture and patients with impingement in the hip. While quantitative imaging techniques continue to rapidly evolve, specific challenges for each technique as well as challenges to clinical applications remain. PMID:23833729

  8. Nanostructured Capsules for Cartilage Tissue Engineering.

    PubMed

    Correia, Clara R; Reis, Rui L; Mano, João F

    2015-01-01

    Polymeric multilayered capsules (PMCs) have found great applicability in bioencapsulation, an evolving branch of tissue engineering and regenerative medicine. Here, we describe the production of hierarchical PMCs composed by an external multilayered membrane by layer-by-layer assembly of poly(L-lysine), alginate, and chitosan. The core of the PMCs is liquified and encapsulates human adipose stem cells and surface-functionalized collagen II-TGF-β3 poly(L-lactic acid) microparticles for cartilage tissue engineering. PMID:26445839

  9. Strategies to minimize hypertrophy in cartilage engineering and regeneration

    PubMed Central

    Chen, Song; Fu, Peiliang; Cong, Ruijun; Wu, HaiShan; Pei, Ming

    2015-01-01

    Due to a blood supply shortage, articular cartilage has a limited capacity for self-healing once damaged. Articular chondrocytes, cartilage progenitor cells, embryonic stem cells, and mesenchymal stem cells are candidate cells for cartilage regeneration. Significant current attention is paid to improving chondrogenic differentiation capacity; unfortunately, the potential chondrogenic hypertrophy of differentiated cells is largely overlooked. Consequently, the engineered tissue is actually a transient cartilage rather than a permanent one. The development of hypertrophic cartilage ends with the onset of endochondral bone formation which has inferior mechanical properties. In this review, current strategies for inhibition of chondrogenic hypertrophy are comprehensively summarized; the impact of cell source options is discussed; and potential mechanisms underlying these strategies are also categorized. This paper aims to provide guidelines for the prevention of hypertrophy in the regeneration of cartilage tissue. This knowledge may also facilitate the retardation of osteophytes in the treatment of osteoarthritis. PMID:26000333

  10. Cartilage Tissue Engineering: What Have We Learned in Practice?

    PubMed

    Doran, Pauline M

    2015-01-01

    Many technologies that underpin tissue engineering as a research field were developed with the aim of producing functional human cartilage in vitro. Much of our practical experience with three-dimensional cultures, tissue bioreactors, scaffold materials, stem cells, and differentiation protocols was gained using cartilage as a model system. Despite these advances, however, generation of engineered cartilage matrix with the composition, structure, and mechanical properties of mature articular cartilage has not yet been achieved. Currently, the major obstacles to synthesis of clinically useful cartilage constructs are our inability to control differentiation to the extent needed, and the failure of engineered and host tissues to integrate after construct implantation. The aim of this chapter is to distil from the large available body of literature the seminal approaches and experimental techniques developed for cartilage tissue engineering and to identify those specific areas requiring further research effort. PMID:26445827

  11. Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

    PubMed Central

    2015-01-01

    In this study, we investigated the molecular adhesion between the major constituents of cartilage extracellular matrix, namely, the highly negatively charged proteoglycan aggrecan and the type II/IX/XI fibrillar collagen network, in simulated physiological conditions. Colloidal force spectroscopy was applied to measure the maximum adhesion force and total adhesion energy between aggrecan end-attached spherical tips (end radius R ≈ 2.5 μm) and trypsin-treated cartilage disks with undamaged collagen networks. Studies were carried out in various aqueous solutions to reveal the physical factors that govern aggrecan–collagen adhesion. Increasing both ionic strength and [Ca2+] significantly increased adhesion, highlighting the importance of electrostatic repulsion and Ca2+-mediated ion bridging effects. In addition, we probed how partial enzymatic degradation of the collagen network, which simulates osteoarthritic conditions, affects the aggrecan–collagen interactions. Interestingly, we found a significant increase in aggrecan–collagen adhesion even when there were no detectable changes at the macro- or microscales. It is hypothesized that the aggrecan–collagen adhesion, together with aggrecan–aggrecan self-adhesion, works synergistically to determine the local molecular deformability and energy dissipation of the cartilage matrix, in turn, affecting its macroscopic tissue properties. PMID:24491174

  12. Time-dependent nanomechanics of cartilage.

    PubMed

    Han, Lin; Frank, Eliot H; Greene, Jacqueline J; Lee, Hsu-Yi; Hung, Han-Hwa K; Grodzinsky, Alan J; Ortiz, Christine

    2011-04-01

    In this study, atomic force microscopy-based dynamic oscillatory and force-relaxation indentation was employed to quantify the time-dependent nanomechanics of native (untreated) and proteoglycan (PG)-depleted cartilage disks, including indentation modulus E(ind), force-relaxation time constant τ, magnitude of dynamic complex modulus |E(∗)|, phase angle δ between force and indentation depth, storage modulus E', and loss modulus E″. At ∼2 nm dynamic deformation amplitude, |E(∗)| increased significantly with frequency from 0.22 ± 0.02 MPa (1 Hz) to 0.77 ± 0.10 MPa (316 Hz), accompanied by an increase in δ (energy dissipation). At this length scale, the energy dissipation mechanisms were deconvoluted: the dynamic frequency dependence was primarily governed by the fluid-flow-induced poroelasticity, whereas the long-time force relaxation reflected flow-independent viscoelasticity. After PG depletion, the change in the frequency response of |E(∗)| and δ was consistent with an increase in cartilage local hydraulic permeability. Although untreated disks showed only slight dynamic amplitude-dependent behavior, PG-depleted disks showed great amplitude-enhanced energy dissipation, possibly due to additional viscoelastic mechanisms. Hence, in addition to functioning as a primary determinant of cartilage compressive stiffness and hydraulic permeability, the presence of aggrecan minimized the amplitude dependence of |E(∗)| at nanometer-scale deformation. PMID:21463599

  13. Cartilage Engineering from Mesenchymal Stem Cells

    NASA Astrophysics Data System (ADS)

    Goepfert, C.; Slobodianski, A.; Schilling, A. F.; Adamietz, P.; Pörtner, R.

    Mesenchymal progenitor cells known as multipotent mesenchymal stromal cells or mesenchymal stem cells (MSC) have been isolated from various tissues. Since they are able to differentiate along the mesenchymal lineages of cartilage and bone, they are regarded as promising sources for the treatment of skeletal defects. Tissue regeneration in the adult organism and in vitro engineering of tissues is hypothesized to follow the principles of embryogenesis. The embryonic development of the skeleton has been studied extensively with respect to the regulatory mechanisms governing morphogenesis, differentiation, and tissue formation. Various concepts have been designed for engineering tissues in vitro based on these developmental principles, most of them involving regulatory molecules such as growth factors or cytokines known to be the key regulators in developmental processes. Growth factors most commonly used for in vitro cultivation of cartilage tissue belong to the fibroblast growth factor (FGF) family, the transforming growth factor-beta (TGF-β) super-family, and the insulin-like growth factor (IGF) family. In this chapter, in vivo actions of members of these growth factors described in the literature are compared with in vitro concepts of cartilage engineering making use of these growth factors.

  14. Time-Dependent Nanomechanics of Cartilage

    PubMed Central

    Han, Lin; Frank, Eliot H.; Greene, Jacqueline J.; Lee, Hsu-Yi; Hung, Han-Hwa K.; Grodzinsky, Alan J.; Ortiz, Christine

    2011-01-01

    In this study, atomic force microscopy-based dynamic oscillatory and force-relaxation indentation was employed to quantify the time-dependent nanomechanics of native (untreated) and proteoglycan (PG)-depleted cartilage disks, including indentation modulus Eind, force-relaxation time constant τ, magnitude of dynamic complex modulus |E∗|, phase angle δ between force and indentation depth, storage modulus E′, and loss modulus E″. At ∼2 nm dynamic deformation amplitude, |E∗| increased significantly with frequency from 0.22 ± 0.02 MPa (1 Hz) to 0.77 ± 0.10 MPa (316 Hz), accompanied by an increase in δ (energy dissipation). At this length scale, the energy dissipation mechanisms were deconvoluted: the dynamic frequency dependence was primarily governed by the fluid-flow-induced poroelasticity, whereas the long-time force relaxation reflected flow-independent viscoelasticity. After PG depletion, the change in the frequency response of |E∗| and δ was consistent with an increase in cartilage local hydraulic permeability. Although untreated disks showed only slight dynamic amplitude-dependent behavior, PG-depleted disks showed great amplitude-enhanced energy dissipation, possibly due to additional viscoelastic mechanisms. Hence, in addition to functioning as a primary determinant of cartilage compressive stiffness and hydraulic permeability, the presence of aggrecan minimized the amplitude dependence of |E∗| at nanometer-scale deformation. PMID:21463599

  15. Stress relaxation and cartilage shaping under laser radiation

    NASA Astrophysics Data System (ADS)

    Sobol, Emil N.; Sviridov, Alexander P.; Bagratashvili, Victor N.; Omelchenko, Alexander I.; Ovchinnikov, Yuriy M.; Shekhter, Anatoliy B.; Downes, S.; Howdle, Steven; Jones, Nicholas; Lowe, J.

    1996-05-01

    The problem of a purposeful change of the shape of cartilage is of great importance for otolaryngology, orthopaedics, and plastic surgery. In 1992 we have found a possibility of controlled shaping of cartilage under moderate laser heating. This paper presents new results in studies of that phenomenon. We have measured temperature and stress in a tissue undergoing to irradiation with a Holmium laser. Study of cartilage structure allowed us to find conditions for laser shaping without pronounced alterations in the structure of matrix.

  16. Use magnetic resonance imaging to assess articular cartilage

    PubMed Central

    Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

    2012-01-01

    Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

  17. [The early development of the articular cartilage. IV. The metamorphosing cartilage].

    PubMed

    Knese, K H

    1980-01-01

    The definite articular cartilage originate from 2 anlagen, the primordial tangential layer and the greater part including the joint bone plate from the metamorphosing cartilage. The tangential layer grow by apposition from the perichondrium. Additional the layer becomes also dilatated as a result of the growing volume of the ossification center. In this way the Lamina splendens with residues of cells may be formed. The chondrocytes resemble partly fibroblasts, in older animals possibly even tendocytes. Moreover the cells exhibit a varying different shape. Today it is impossible to interpret the polymorphism of the cells. In the primordial state, the chondrocyts are embedded in a network from thin cartilage fibrils. Later on collagen fibrils from varied thickness (up to 900 A) are formed. The fibrils run only partly parallel to each other, in general they form a network, in which they cross with a low angle. There are great local differences in the fibrillar structure by the same animal. PMID:7461420

  18. Acellularization-Induced Changes in Tensile Properties Are Organ Specific - An In-Vitro Mechanical and Structural Analysis of Porcine Soft Tissues

    PubMed Central

    Aust, Gabriela; Boldt, Andreas; Fritsch, Sebastian; Keil, Isabel; Koch, Holger; Möbius, Robert; Scheidt, Holger A.; Wagner, Martin F. X.; Hammer, Niels

    2016-01-01

    Introduction Though xenogeneic acellular scaffolds are frequently used for surgical reconstruction, knowledge of their mechanical properties is lacking. This study compared the mechanical, histological and ultrastructural properties of various native and acellular specimens. Materials and Methods Porcine esophagi, ureters and skin were tested mechanically in a native or acellular condition, focusing on the elastic modulus, ultimate tensile stress and maximum strain. The testing protocol for soft tissues was standardized, including the adaption of the tissue’s water content and partial plastination to minimize material slippage as well as templates for normed sample dimensions and precise cross-section measurements. The native and acellular tissues were compared at the microscopic and ultrastructural level with a focus on type I collagens. Results Increased elastic modulus and ultimate tensile stress values were quantified in acellular esophagi and ureters compared to the native condition. In contrast, these values were strongly decreased in the skin after acellularization. Acellularization-related decreases in maximum strain were found in all tissues. Type I collagens were well-preserved in these samples; however, clotting and a loss of cross-linking type I collagens was observed ultrastructurally. Elastins and fibronectins were preserved in the esophagi and ureters. A loss of the epidermal layer and decreased fibronectin content was present in the skin. Discussion Acellularization induces changes in the tensile properties of soft tissues. Some of these changes appear to be organ specific. Loss of cross-linking type I collagen may indicate increased mechanical strength due to decreasing transverse forces acting upon the scaffolds, whereas fibronectin loss may be related to decreased load-bearing capacity. Potentially, the alterations in tissue mechanics are linked to organ function and to the interplay of cells and the extracellular matrix, which is different in

  19. Cartilage Grown in Lab Might One Day Help Younger Arthritis Sufferers

    MedlinePlus

    ... the new study, the authors reported on laboratory tests of an artificial cartilage designed to replace the surface of the hip joint. The researchers used 3-D textile technology to create the cartilage. It "mimics natural cartilage," ...

  20. ANTI-APOPTOTIC TREATMENTS PREVENT CARTILAGE DEGRADATION AFTER ACUTE TRAUMA TO HUMAN ANKLE CARTILAGE

    PubMed Central

    Garrido, Cecilia Pascual; Hakimiyan, Arnavaz A.; Rappoport, Lev; Oegema, Theodore R.; Wimmer, Markus A.; Chubinskaya, Susan

    2009-01-01

    Objectives To investigate the effect of anti-apoptotic agents on cartilage degradation after a single impact to ankle cartilage. Design Ten human normal tali were impacted with the impulse of 1 Ns generating peak forces in the range of 600 N using a 4mm diameter indenter. Eight mm cartilage plugs contained the 4mm diameter impacted core and a 4mm adjacent ring were removed and cultured with or without P188 surfactant (8mg/ml), caspase-3 (10uM), or caspase-9 (2uM) inhibitors for 48hrs. Results were assessed in the superficial and middle-deep layers immediately after injury at day 0 and at 2, 7 and 14 days after injury by live/dead cell and Tunel assays and by histology with Safranin-O/fast green staining. Results A single impact to human articular cartilage ex vivo resulted in cell death, cartilage degeneration, and radial progression of apoptosis to the areas immediately adjacent to the impact. The P188 was more effective in preventing cell death than the inhibitors of caspases. It reduced cell death by more than 2-fold (P<0.05) in the core and by about 30% in the ring in comparison with the impacted untreated control at all time points. P188 also prevented radial expansion of apoptosis in the ring region especially in the first 7 days post impaction (7.5% Tunel-positive cells vs. 46% in the untreated control; p<0.01). Inhibitors of caspase-3 or 9 were effective in reducing cell death in the impacted core only at early time points, but were ineffective in doing so in the ring. Mankin score was significantly improved in the P188 and caspase-3 treated groups. Conclusions Early intervention with the P188 and caspase-3 inhibitor may have therapeutic potential in the treatment of cartilage defects immediately after injury. PMID:19332178

  1. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    PubMed Central

    Boisen, Julie; Malone, C. Helen; Kelly, Brent; Wagner, Richard F.

    2016-01-01

    Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin. PMID:27293916

  2. Cartilage-Specific Near-Infrared Fluorophores for Biomedical Imaging.

    PubMed

    Hyun, Hoon; Owens, Eric A; Wada, Hideyuki; Levitz, Andrew; Park, GwangLi; Park, Min Ho; Frangioni, John V; Henary, Maged; Choi, Hak Soo

    2015-07-20

    A novel class of near-infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage-specific drug development. PMID:26095685

  3. Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches.

    PubMed

    Tatman, Philip David; Gerull, William; Sweeney-Easter, Sean; Davis, Jeffrey Isaac; Gee, Albert O; Kim, Deok-Ho

    2015-12-01

    Articular cartilage is the load-bearing tissue found inside all articulating joints of the body. It vastly reduces friction and allows for smooth gliding between contacting surfaces. The structure of articular cartilage matrix and cellular composition is zonal and is important for its mechanical properties. When cartilage becomes injured through trauma or disease, it has poor intrinsic healing capabilities. The spectrum of cartilage injury ranges from isolated areas of the joint to diffuse breakdown and the clinical appearance of osteoarthritis. Current clinical treatment options remain limited in their ability to restore cartilage to its normal functional state. This review focuses on the evolution of biomaterial scaffolds that have been used for functional cartilage tissue engineering. In particular, we highlight recent developments in multiscale biofabrication approaches attempting to recapitulate the complex 3D matrix of native articular cartilage tissue. Additionally, we focus on the application of these methods to engineering each zone of cartilage and engineering full-thickness osteochondral tissues for improved clinical implantation. These methods have shown the potential to control individual cell-to-scaffold interactions and drive progenitor cell differentiation into a chondrocyte lineage. The use of these bioinspired nanoengineered scaffolds hold promise for recreation of structure and function on the whole tissue level and may represent exciting new developments for future clinical applications for cartilage injury and restoration. PMID:26200439

  4. Secondary cartilage revealed in a non-avian dinosaur embryo.

    PubMed

    Bailleul, Alida M; Hall, Brian K; Horner, John R

    2013-01-01

    The skull and jaws of extant birds possess secondary cartilage, a tissue that arises after bone formation during embryonic development at articulations, ligamentous and muscular insertions. Using histological analysis, we discovered secondary cartilage in a non-avian dinosaur embryo, Hypacrosaurus stebingeri (Ornithischia, Lambeosaurinae). This finding extends our previous report of secondary cartilage in post-hatching specimens of the same dinosaur species. It provides the first information on the ontogeny of avian and dinosaurian secondary cartilages, and further stresses their developmental similarities. Secondary cartilage was found in an embryonic dentary within a tooth socket where it is hypothesized to have arisen due to mechanical stresses generated during tooth formation. Two patterns were discerned: secondary cartilage is more restricted in location in this Hypacrosaurus embryo, than it is in Hypacrosaurus post-hatchlings; secondary cartilage occurs at far more sites in bird embryos and nestlings than in Hypacrosaurus. This suggests an increase in the number of sites of secondary cartilage during the evolution of birds. We hypothesize that secondary cartilage provided advantages in the fine manipulation of food and was selected over other types of tissues/articulations during the evolution of the highly specialized avian beak from the jaws of their dinosaurian ancestors. PMID:23418610

  5. Secondary Cartilage Revealed in a Non-Avian Dinosaur Embryo

    PubMed Central

    Bailleul, Alida M.; Hall, Brian K.; Horner, John R.

    2013-01-01

    The skull and jaws of extant birds possess secondary cartilage, a tissue that arises after bone formation during embryonic development at articulations, ligamentous and muscular insertions. Using histological analysis, we discovered secondary cartilage in a non-avian dinosaur embryo, Hypacrosaurus stebingeri (Ornithischia, Lambeosaurinae). This finding extends our previous report of secondary cartilage in post-hatching specimens of the same dinosaur species. It provides the first information on the ontogeny of avian and dinosaurian secondary cartilages, and further stresses their developmental similarities. Secondary cartilage was found in an embryonic dentary within a tooth socket where it is hypothesized to have arisen due to mechanical stresses generated during tooth formation. Two patterns were discerned: secondary cartilage is more restricted in location in this Hypacrosaurus embryo, than it is in Hypacrosaurus post-hatchlings; secondary cartilage occurs at far more sites in bird embryos and nestlings than in Hypacrosaurus. This suggests an increase in the number of sites of secondary cartilage during the evolution of birds. We hypothesize that secondary cartilage provided advantages in the fine manipulation of food and was selected over other types of tissues/articulations during the evolution of the highly specialized avian beak from the jaws of their dinosaurian ancestors. PMID:23418610

  6. Studies of the humoral factors produced by layered chondrocyte sheets.

    PubMed

    Hamahashi, K; Sato, M; Yamato, M; Kokubo, M; Mitani, G; Ito, S; Nagai, T; Ebihara, G; Kutsuna, T; Okano, T; Mochida, J

    2015-01-01

    The authors aimed to repair and regenerate articular cartilage with layered chondrocyte sheets, produced using temperature-responsive culture dishes. The purpose of this study was to investigate the humoral factors produced by layered chondrocyte sheets. Articular chondrocytes and synovial cells were harvested during total knee arthroplasty. After co-culture, the samples were divided into three groups: a monolayer, 7 day culture sheet group (group M); a triple-layered, 7 day culture sheet group (group L); and a monolayer culture group with a cell count identical to that of group L (group C). The secretion of collagen type 1 (COL1), collagen type 2 (COL2), matrix metalloproteinase-13 (MMP13), transforming growth factor-β (TGFβ), melanoma inhibitory activity (MIA) and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA). Layered chondrocyte sheets produced the most humoral factors. PGE2 expression declined over time in group C but was significantly higher in groups M and L. TGFβ expression was low in group C but was significantly higher in groups M and L (p<0.05). Our results suggest that the humoral factors produced by layered chondrocyte sheets may contribute to cartilaginous tissue repair and regeneration. PMID:23165985

  7. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes*

    PubMed Central

    ZHAO, Ming; CHEN, Zhu; LIU, Kang; WAN, Yu-qing; LI, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-01-01

    Objective: In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods: Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. Results: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). Conclusions: Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage. PMID:26537209

  8. Zika Virus Fact Sheet

    MedlinePlus

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Zika virus Fact sheet Updated 6 September 2016 Key facts ... and last for 2-7 days. Complications of Zika virus disease After a comprehensive review of evidence, there ...

  9. Structural Biology Fact Sheet

    MedlinePlus

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  10. Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration

    PubMed Central

    Wagner, Darcy E.; Bonenfant, Nicholas R.; Sokocevic, Dino; DeSarno, Michael; Borg, Zachary; Parsons, Charles; Brooks, Elice M.; Platz, Joseph; Khalpey, Zain; Hoganson, David M.; Deng, Bin; Lam, Ying Wai; Oldinski, Rachael A.; Ashikaga, Takamaru; Weiss, Daniel J.

    2014-01-01

    Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de- and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼1–3cm3) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold. PMID:24411675

  11. FT-IR Microspectroscopy of Rat Ear Cartilage

    PubMed Central

    Vidal, Benedicto de Campos; Mello, Maria Luiza S.

    2016-01-01

    Rat ear cartilage was studied using Fourier transform-infrared (FT-IR) microspectroscopy to expand the current knowledge which has been established for relatively more complex cartilage types. Comparison of the FT-IR spectra of the ear cartilage extracellular matrix (ECM) with published data on articular cartilage, collagen II and 4-chondroitin-sulfate standards, as well as of collagen type I-containing dermal collagen bundles (CBs) with collagen type II, was performed. Ear cartilage ECM glycosaminoglycans (GAGs) were revealed histochemically and as a reduction in ECM FT-IR spectral band heights (1140–820 cm-1) after testicular hyaluronidase digestion. Although ear cartilage is less complex than articular cartilage, it contains ECM components with a macromolecular orientation as revealed using polarization microscopy. Collagen type II and GAGs, which play a structural role in the stereo-arrangement of the ear cartilage, contribute to its FT-IR spectrum. Similar to articular cartilage, ear cartilage showed that proteoglycans add a contribution to the collagen amide I spectral region, a finding that does not recommend this region for collagen type II quantification purposes. In contrast to articular cartilage, the symmetric stretching vibration of –SO3- groups at 1064 cm-1 appeared under-represented in the FT-IR spectral profile of ear cartilage. Because the band corresponding to the asymmetric stretching vibration of –SO3- groups (1236–1225 cm-1) overlapped with that of amide III bands, it is not recommended for evaluation of the –SO3- contribution to the FT-IR spectrum of the ear cartilage ECM. Instead, a peak (or shoulder) at 1027–1016 cm-1 could be better considered for this intent. Amide I/amide II ratios as calculated here and data from the literature suggest that protein complexes of the ear cartilage ECM are arranged with a lower helical conformation compared to pure collagen II. The present results could motivate further studies on this tissue

  12. FT-IR Microspectroscopy of Rat Ear Cartilage.

    PubMed

    Vidal, Benedicto de Campos; Mello, Maria Luiza S

    2016-01-01

    Rat ear cartilage was studied using Fourier transform-infrared (FT-IR) microspectroscopy to expand the current knowledge which has been established for relatively more complex cartilage types. Comparison of the FT-IR spectra of the ear cartilage extracellular matrix (ECM) with published data on articular cartilage, collagen II and 4-chondroitin-sulfate standards, as well as of collagen type I-containing dermal collagen bundles (CBs) with collagen type II, was performed. Ear cartilage ECM glycosaminoglycans (GAGs) were revealed histochemically and as a reduction in ECM FT-IR spectral band heights (1140-820 cm-1) after testicular hyaluronidase digestion. Although ear cartilage is less complex than articular cartilage, it contains ECM components with a macromolecular orientation as revealed using polarization microscopy. Collagen type II and GAGs, which play a structural role in the stereo-arrangement of the ear cartilage, contribute to its FT-IR spectrum. Similar to articular cartilage, ear cartilage showed that proteoglycans add a contribution to the collagen amide I spectral region, a finding that does not recommend this region for collagen type II quantification purposes. In contrast to articular cartilage, the symmetric stretching vibration of -SO3- groups at 1064 cm-1 appeared under-represented in the FT-IR spectral profile of ear cartilage. Because the band corresponding to the asymmetric stretching vibration of -SO3- groups (1236-1225 cm-1) overlapped with that of amide III bands, it is not recommended for evaluation of the -SO3- contribution to the FT-IR spectrum of the ear cartilage ECM. Instead, a peak (or shoulder) at 1027-1016 cm-1 could be better considered for this intent. Amide I/amide II ratios as calculated here and data from the literature suggest that protein complexes of the ear cartilage ECM are arranged with a lower helical conformation compared to pure collagen II. The present results could motivate further studies on this tissue under

  13. Optical clearing of articular cartilage: a comparison of clearing agents

    NASA Astrophysics Data System (ADS)

    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  14. Human acellular dermal matrix for repair of abdominal wall defects: review of clinical experience and experimental data.

    PubMed

    Holton, Luther H; Kim, Daniel; Silverman, Ronald P; Rodriguez, Eduardo D; Singh, Navin; Goldberg, Nelson H

    2005-01-01

    The use of prosthetic mesh for the tension-free repair of incisional hernias has been shown to be more effective than primary suture repair. Unfortunately, prosthetic materials can be a suboptimal choice in a variety of clinical scenarios. In general, prosthetic materials should not be implanted into sites with known contamination or infection because they lack an endogenous vascular network and are thus incapable of clearing bacteria. This is of particular relevance to the repair of recurrent hernias, which are often refractory to repair because of indolent bacterial colonization that weakens the site and retards appropriate healing. Although fascia lata grafts and muscle flaps can be employed for tension-free hernia repairs, they carry the potential for significant donor site morbidity. Recently, a growing number of clinicians have used human acellular dermal matrix as a graft material for the tension-free repair of ventral hernias. This material has been shown to become revascularized in both animal and human subjects. Once repopulated with a vascular network, this graft material is theoretically capable of clearing bacteria, a property not found in prosthetic graft materials. Unlike autologous materials such as fascial grafts and muscle flaps, acellular dermal matrix can be used without subjecting the patient to additional morbidity in the form of donor site complications. This article presents a thorough review of the current literature, describing the properties of human acellular dermal matrix and discussing both animal and human studies of its clinical performance. In addition to the review of previously published clinical experiences, we discuss our own preliminary results with the use of acellular dermal matrix for ventral hernia repair in 46 patients. PMID:16218902

  15. Possible role of dentin matrix in region-specific deposition of cellular and acellular extrinsic fibre cementum.

    PubMed

    Takano, Yoshiro; Sakai, Hideo; Watanabe, Eiko; Ideguchi-Ohma, Noriko; Jayawardena, Chantha K; Arai, Kazumi; Asawa, Yukiyo; Nakano, Yukiko; Shuda, Yoko; Sakamoto, Yujiro; Terashima, Tatsuo

    2003-01-01

    The mechanism whereby a region-specific deposition of the two types of cementum (cellular cementum and acellular extrinsic fibre cementum) is regulated on the growing root surface was tested using bisphosphonate-affected teeth of young rats and guinea pigs. The animals were injected subcutaneously with 8 or 10 mg P x kg body weight(-1) x day(-1) of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) for 1 or 2 weeks. In rat molars, HEBP prevented mineralization of newly formed root dentin matrix and totally inhibited de novo deposition of acellular extrinsic fibre cementum. Instead, thick cellular cementum was induced on the non-mineralized root dentin surface, irrespective of the position of the root. In both animals, cellular cementum was also induced on the non-mineralized surface of root analogue dentin in HEBP-affected incisors, where only acellular extrinsic fibre cementum is deposited under normal conditions. In normal rat molars, dentin sialoprotein (DSP) was concentrated along the dentin-cellular cementum border, but not that of dentin and acellular extrinsic fibre cementum. In HEBP-affected rat incisors, DSP was shown to penetrate through the non-mineralized dentin into the surrounding tissues, but not through the mineralized portions. These data suggest that, at the site of cellular cementum formation, putative inducing factors for cellular cementum might diffuse into the periodontal space through the newly deposited mantle dentin matrix before it is mineralized. At earlier stages of root formation, mantle dentin might mineralize more promptly not to allow such diffusion. The timing of mineralization of mantle dentin matrix might be the key determinant of the types of the cementum deposited on the growing root surface. PMID:14756246

  16. Computational model for the analysis of cartilage and cartilage tissue constructs.

    PubMed

    Smith, David W; Gardiner, Bruce S; Davidson, John B; Grodzinsky, Alan J

    2016-04-01

    We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23784936

  17. Computational model for the analysis of cartilage and cartilage tissue constructs

    PubMed Central

    Smith, David W.; Gardiner, Bruce S.; Davidson, John B.; Grodzinsky, Alan J.

    2013-01-01

    We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue. PMID:23784936

  18. Deep Anterior Lamellar Keratoplasty Using Irradiated Acellular Cornea with Amniotic Membrane Transplantation for Intractable Ocular Surface Diseases

    PubMed Central

    Wee, Sung Wook; Choi, Sang Uk

    2015-01-01

    Purpose To report the clinical outcomes of deep anterior lamellar keratoplasty (DALK) when sterile gamma-irradiated acellular corneal tissues (VisionGraft) are used in combination with amniotic membrane transplantation (AMT) for intractable ocular surface diseases. Methods The medical records of fifteen patients who had DALK with AMT were retrospectively reviewed. Indications for surgery included ocular burn, bacterial keratitis, herpes simplex virus keratitis, corneal opacity with Stevens-Johnson syndrome, Mooren's ulcer, idiopathic myxoid degeneration of corneal stroma, and recurrent band keratopathy. DALK was performed using partial-thickness acellular corneal tissue and a temporary amniotic membrane patch was added at the end of the operation. Results All cases that underwent DALK with AMT became epithelialized within 2 postoperative weeks. Twelve patients showed favorable outcomes without graft rejection, corneal opacification, or neovascularization. The other three grafts developed corneal opacification and neovascularization, and required additional penetrating keratoplasty (PK). Unlike the results of previous PKs, there were no graft rejections and the graft clarity was well-maintained in these three cases for at least 8 months after PK. Conclusions DALK using sterile acellular corneal tissues in combination with AMT may be a good therapeutic strategy for treating intractable ocular surface diseases because of lowered immune rejection, fibroblast activation, and facilitation of epithelialization. Furthermore, DALK can help stabilize the ocular surface, prolong graft survival, and may allow better outcomes when combined with subsequent PK. PMID:25829823

  19. Management of failed and infected first metatarsophalangeal joint implant arthroplasty by reconstruction with an acellular dermal matrix: a case report.

    PubMed

    Khoury, Wissam E; Fahim, Ramy; Sciulli, Jessica M; Ehredt, Duane J

    2012-01-01

    Management of failed first metatarsophalangeal joint implant arthroplasty, especially in the face of infection, is an area of debate without a clear consensus. The purpose of the present report was to explore a new option of reconstructing the joint with an acellular dermal matrix substance in a single case study during a 12-month follow-up period. A staged approach that began with removal of the failed 2-component great toe implant, Koenig(®), excisional debridement of the wound with resection of the necrotic bone (proximal phalanx and distal portion of the first metatarsal bones), and culture-specific antibiosis therapy. The final stage included incorporating the acellular dermal matrix, Graftjacket(®) into the joint in an accordion-type fashion, and reconstruction of the joint capsule. Postoperative radiographs revealed a more rectus joint with some improvement in length. At 6 months postoperatively, magnetic resonance imaging revealed incorporation of the graft material into the joint. Finally, at the 1-year mark, the patient was pain free with satisfactory function at the first metatarsophalangeal joint during gait. This is the first reported case of salvaging failed and infected first metatarsophalangeal joint implant arthroplasty with incorporation of the acellular dermal matrix and provides a new option to consider in the future. PMID:22704789

  20. Evaluation of respiratory model employing conventional NIH mice to access the immunity induced by cellular and acellular pertussis vaccines.

    PubMed

    Dias, Alexandre Alves de Souza de Oliveira; Boller, Maria Aparecida Affonso; Werneck, Lúcia Maria Correa; Hirata Junior, Raphael; Mattos-Guaraldi, Ana Luíza

    2006-11-01

    The increasing number of pertussis cases reported on the last twenty years and the existence of new acellular vaccines reinforce the need of research for experimental models to assure the quality of available pertussis vaccines. In this study, allotments of whole-cell and acellular pertussis vaccines were tested through the Intranasal Challenge Model (INM) using conventional NIH mice. The results have been compared to those achieved by the "Gold standard" Intracerebral Challenge Model (ICM). In contrast to ICM, INM results did not show intralaboratorial variations. Statistical analysis by Anova and Ancova tests revealed that the INM presented reproducibility and allowed identification and separation of different products, including three-component and four-component accellular pertussis vaccines. INM revealed differences between pertussis vaccines. INM provides lower distress to the mice allowing the reduction of mice number including the possibility of using conventional mice (less expensive) under non-aseptic environment. Thus, INM may be used as an alternative method of verifying the consistence of allotment production, including acellular pertussis vaccines. PMID:17160282

  1. Characterization of chondrocyte sheets prepared using a co-culture method with temperature-responsive culture inserts.

    PubMed

    Kokubo, Mami; Sato, Masato; Yamato, Masayuki; Mitani, Genya; Kutsuna, Toshiharu; Ebihara, Goro; Okano, Teruo; Mochida, Joji

    2016-06-01

    Conventional culture methods using temperature-responsive culture dishes require 4-5 weeks to prepare layered chondrocyte sheets that can be used in articular cartilage repair and regeneration. This study investigated whether the use of synovial tissue obtained from the same joint as the chondrocyte nutritive supply source could more quickly facilitate the preparation of chondrocyte sheets. After culturing derived synoviocytes and chondrocytes together (i.e. combined culture or co-culture) on temperature-responsive inserts, chondrocyte growth was assessed and a molecular analysis of the chondrocyte sheets was performed. Transplantable tissue could be obtained more quickly using this method (average 10.5 days). Real-time polymerase chain reaction and immunostaining of the three-layer chondrocyte sheets confirmed the significant expression of genes critical to cartilage maintenance, including type II collagen (COL2), aggrecan-1 and tissue metallopeptidase inhibitor 1. However, the expression of COL1, matrix metalloproteinase 3 (MMP3), MMP13 and A-disintegrin and metalloproteinase with thrombospondin motifs 5 was suppressed. The adhesive factor fibronectin-1 (FN1) was observed in all sheet layers, whereas in sheets generated using conventional preparation methods positive FN1 immunostaining was observed only on the surface of the sheets. The results indicate that synoviocyte co-cultures provide an optimal environment for the preparation of chondrocyte sheets for tissue transplantation and are particularly beneficial for shortening the required culture period. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23868865

  2. A molecular theory of cartilage viscoelasticity.

    PubMed

    Kovach, I S

    1996-03-01

    Recent work on the subject of cartilage mechanics has begun to focus on the relationship between the microscopic structure of cartilage and its macroscopic mechanical properties (Bader et al., Biochem. Biophys. Acta, 1116 (1992) 147-154; Buschmann, PhD Thesis, Massachusetts Institute of Technology, 1992; Kovach, Biophys. Chem., 53 (1995) 181-187; Lai et al., J. Biochem. Eng., 113 (1991) 245-248; Armstrong and Mow, J. Bone Jt. Surg., 64A (1982) 88; Jackson and James, Biorheology, 19 (1982) 317-330). This paper reviews recent theoretical developments and presents a comprehensive explanation of the viscoelastic properties of cartilage in terms of molecular structure. In doing this, a closed form hybrid solution to the non-linear, cylindrical Poisson-Boltzmann equation is developed to describe the charge-dependent component of the equilibrium elasticity arising from polysaccharide charge (Benham, J. Chem. Phys., 79 (4) (1983) 1969-1973; Einevoll and Hemmer, J. Phys. Chem., 89 (1) (1988) 474-484; Fixman, J. Chem. Phys., 70 (11) (1979) 4995-5001; Ramanathan and Woodburg, J. Chem. Phys., 82 (3) (1985) 1482-1491; Wennerstrom et al., J. Chem. Phys., 76 (9) (1982) 4665-4670). This solution agrees with numerical solutions found in the literature (Buschmann, PhD Thesis, Massachusetts Institute of Technology, 1992). The charge-independent, entropic contribution to the equilibrium elasticity is explained in a manner similar to that recently presented for concentrated proteoglycan solution (Kovach, Biophys. Chem., 53 (1995) 181-187). This approach exploits a lattice model of the solution, subject to a Bragg-Williams type approximation to derive the volume dependence of polysaccharide configuration entropy (Flory, Principles of Polymer Chemistry, Cornell University Press, Ithaca, NY, 1953; Huggins, Some properties of Solutions of Long-chain Compounds, 1941, pp. 151-157; Stanley, Introduction to Phase Transitions and Critical Phenomena, Oxford University Press, Oxford, 1971

  3. Evaluation of cartilage repair and osteoarthritis with sodium MRI.

    PubMed

    Zbýň, Štefan; Mlynárik, Vladimír; Juras, Vladimir; Szomolanyi, Pavol; Trattnig, Siegfried

    2016-02-01

    The growing need for early diagnosis and higher specificity than that which can be achieved with morphological MRI is a driving force in the application of methods capable of probing the biochemical composition of cartilage tissue, such as sodium imaging. Unlike morphological imaging, sodium MRI is sensitive to even small changes in cartilage glycosaminoglycan content, which plays a key role in cartilage homeostasis. Recent advances in high- and ultrahigh-field MR systems, gradient technology, phase-array radiofrequency coils, parallel imaging approaches, MRI acquisition strategies and post-processing developments have resulted in many clinical in vivo sodium MRI studies of cartilage, even at 3 T. Sodium MRI has great promise as a non-invasive tool for cartilage evaluation. However, further hardware and software improvements are necessary to complete the translation of sodium MRI into a clinically feasible method for 3-T systems. This review is divided into three parts: (i) cartilage composition, pathology and treatment; (ii) sodium MRI; and (iii) clinical sodium MRI studies of cartilage with a focus on the evaluation of cartilage repair tissue and osteoarthritis. PMID:25810325

  4. Stem Cells and Gene Therapy for Cartilage Repair

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Berton, Alessandra; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions. PMID:22481959

  5. Crosstalk between cartilage and bone: when bone cytokines matter.

    PubMed

    Funck-Brentano, Thomas; Cohen-Solal, Martine

    2011-04-01

    The cartilage damage which characterizes osteoarthritis is often accompanied by bone lesions. Joint integrity results from the balance in the physiological interactions between bone and cartilage. Several local factors regulate the physiological remodeling of cartilage, the disequilibrium of these leading to a higher cartilage catabolism. Several cytokines secreted by bone cells can induce chondrocyte differentiation, which suggests their role in the dialogue between both cells. Accumulative in vivo evidence shows that increased bone resorption occurs at an early stage in the development of osteoarthritis and that blocking bone-resorbing cytokines prevents cartilage damage, confirming the role of bone factors in the crosstalk of both tissues. Recently, molecules of the Wnt pathway have emerged as key regulators of bone and cartilage. Activation of Wnt/βcatenin induces an imbalance in cartilage homeostasis, and agonists/antagonists of Wnt are potential candidates for this interaction. This review will summarize what is known about the contribution of bone cytokines to the physiological remodeling of cartilage and in the pathophysiology of osteoarthritis. PMID:21596615

  6. Magnetic Resonance Imaging of Cartilage Repair: A Review.

    PubMed

    Trattnig, Siegfried; Winalski, Carl S; Marlovits, Stephan; Jurvelin, Jukka S; Welsch, Goetz H; Potter, Hollis G

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  7. Remobilization does not fully restore immobilization induced articular cartilage atrophy.

    PubMed

    Haapala, J; Arokoski, J P; Hyttinen, M M; Lammi, M; Tammi, M; Kovanen, V; Helminen, H J; Kiviranta, I

    1999-05-01

    The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage. PMID:10335301

  8. Two dimensional spectral camera development for cartilage monitoring

    NASA Astrophysics Data System (ADS)

    Kuehn, A.; Graf, A.; Wenzel, U.; Princz, S.; Miller, R.; Mantz, H.; Hessling, M.

    2015-07-01

    In the joint project "BioopTiss" between the Ulm University Medical Center and Ulm University of Applied Sciences, a bioreactor is under development to grow facial cartilage by the methods of tissue engineering. In order to ensure a sufficient quality of the cartilage for implantation, the cartilage growth must be monitored continuously. Current monitoring methods destroy the cultured cartilage so that it is no longer suitable for implantation. Alternatively, it is possible to analyze the cartilage using fluorescence spectroscopy with UV light excitation. This allows a non-invasive assessment of cartilage in terms of composition and quality. The cultured cartilage tissue can reach a size of several square centimeters. For recording fluorescence spectra of every point of the cartilage sample, a highly sensitive spectral camera has been developed which allows distinguishing collagen I from collagen II non-invasively by their fluorescence. This spectral camera operates according to the computed tomography imaging spectrometry (CTIS) principle, which allows obtaining many spectra of a small area with only one snapshot.

  9. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    PubMed

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair. PMID:26559963

  10. Improvement of PHBV Scaffolds with Bioglass for Cartilage Tissue Engineering

    PubMed Central

    Li, Haiyan; Sun, Junying; Liu, Kai

    2013-01-01

    Polymer scaffold systems consisting of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) have proven to be possible matrices for the three-dimensional growth of chondrocyte cultures. However, the engineered cartilage grown on these PHBV scaffolds is currently unsatisfactory for clinical applications due to PHBV’s poor hydrophilicity, resulting in inadequate thickness and poor biomechanical properties of the engineered cartilage. It has been reported that the incorporation of Bioglass (BG) into PHBV can improve the hydrophilicity of the composites. In this study, we compared the effects of PHBV scaffolds and PHBV/BG composite scaffolds on the properties of engineered cartilage in vivo. Rabbit articular chondrocytes were seeded into PHBV scaffolds and PHBV/BG scaffolds. Short-term in vitro culture followed by long-term in vivo transplantation was performed to evaluate the difference in cartilage regeneration between the cartilage layers grown on PHBV and PHBV/BG scaffolds. The results show that the incorporation of BG into PHBV efficiently improved both the hydrophilicity of the composites and the percentage of adhered cells and promoted cell migration into the inner part the constructs. With prolonged incubation time in vivo, the chondrocyte-scaffold constructs in the PHBV/BG group formed thicker cartilage-like tissue with better biomechanical properties and a higher cartilage matrix content than the constructs in the PHBV/BG group. These results indicate that PHBV/BG scaffolds can be used to prepare better engineered cartilage than pure PHBV. PMID:23951190

  11. Combinatorial scaffold morphologies for zonal articular cartilage engineering.

    PubMed

    Steele, J A M; McCullen, S D; Callanan, A; Autefage, H; Accardi, M A; Dini, D; Stevens, M M

    2014-05-01

    Articular cartilage lesions are a particular challenge for regenerative medicine strategies as cartilage function stems from a complex depth-dependent organization. Tissue engineering scaffolds that vary in morphology and function offer a template for zone-specific cartilage extracellular matrix (ECM) production and mechanical properties. We fabricated multi-zone cartilage scaffolds by the electrostatic deposition of polymer microfibres onto particulate-templated scaffolds produced with 0.03 or 1.0mm(3) porogens. The scaffolds allowed ample space for chondrocyte ECM production within the bulk while also mimicking the structural organization and functional interface of cartilage's superficial zone. Addition of aligned fibre membranes enhanced the mechanical and surface properties of particulate-templated scaffolds. Zonal analysis of scaffolds demonstrated region-specific variations in chondrocyte number, sulfated GAG-rich ECM, and chondrocytic gene expression. Specifically, smaller porogens (0.03mm(3)) yielded significantly higher sGAG accumulation and aggrecan gene expression. Our results demonstrate that bilayered scaffolds mimic some key structural characteristics of native cartilage, support in vitro cartilage formation, and have superior features to homogeneous particulate-templated scaffolds. We propose that these scaffolds offer promise for regenerative medicine strategies to repair articular cartilage lesions. PMID:24370641

  12. Tool marks in bones and cartilage.

    PubMed

    Bonte, W

    1975-04-01

    The identification of the implement used is an important factor in the explantion of the causes of violent deaths. Hitherto existing knowledge has been almost exclusively confined to the damages to skull bones. This paper draws attention to tool marks in the area of pierced rib cartilage and considers the possibilities of their analysis. The evaluation of saw marks is further discussed on the basis of sawing experiments. Also, there are features and peculiarities which can help to solve the problems posed by criminal dismemberment. PMID:1123601

  13. New developments in osteoarthritis and cartilage biology.

    PubMed

    Poulet, Blandine; Staines, Katherine A

    2016-06-01

    Osteoarthritis (OA) is a degenerative joint disease and the most common form of arthritis. Characterised by articular cartilage loss, subchondral bone thickening and osteophyte formation, the OA joint afflicts much pain and disability. Whilst OA has been associated with many contributing factors, its underpinning molecular mechanisms are, nevertheless, not fully understood. Clinical management of OA is largely palliative and there is an ever growing need for an effective disease modifying treatment. This review discusses some of the recent progress in OA therapies in the different joint tissues affected by OA pathology. PMID:26921602

  14. Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft

    PubMed Central

    Agrawal, Vivek

    2012-01-01

    Purpose: This study presents a retrospective case series of the clinical and structural outcomes (1.5 T MRI) of arthroscopic rotator cuff repair with acellular human dermal graft reinforcement performed by a single surgeon in patients with large, massive, and previously repaired rotator cuff tears. Materials and Methods: Fourteen patients with mean anterior to posterior tear size 3.87 ± 0.99 cm (median 4 cm, range 2.5–6 cm) were enrolled in the study and were evaluated for structural integrity using a high-field (1.5 T) MRI at an average of 16.8 months after surgery. The Constant-Murley scores, the Flexilevel Scale of Shoulder Function (Flex SF), scapular plane abduction, and strength were analyzed. Results: MRI results showed that the rotator cuff repair was intact in 85.7% (12/14) of the patients studied. Two patients had a Sugaya Type IV recurrent tear (2 of 14; 14.3%), which were both less than 1 cm. The Constant score increased from a preoperative mean of 49.72 (range 13–74) to a postoperative mean of 81.07 (range 45–92) (P value = 0.009). Flexilevel Scale of Shoulder Function (Flex SF) Score normalized to a 100-point scale improved from a preoperative mean of 53.69 to a postoperative mean of 79.71 (P value = 0.003). The Pain Score improved from a preoperative mean of 7.73 to a postoperative mean of 13.57 (P value = 0.008). Scapular plane abduction improved from a preoperative mean of 113.64° to a postoperative mean of 166.43° (P value = 0.010). The strength subset score improved from a preoperative mean of 1.73 kg to a postoperative mean of 7.52 kg (P value = 0.006). Conclusions: This study presents a safe and effective technique that may help improve the healing rates of large, massive, and revision rotator cuff tears with the use of an acellular human dermal allograft. This technique demonstrated favorable structural healing rates and statistically improved functional outcomes in the near term. Level of Evidence: 4. Retrospective case series. PMID

  15. Microscale surface friction of articular cartilage in early osteoarthritis.

    PubMed

    Desrochers, Jane; Amrein, Matthias W; Matyas, John R

    2013-09-01

    Articular cartilage forms the articulating surface of long bones and facilitates energy dissipation upon loading as well as joint lubrication and wear resistance. In normal cartilage, boundary lubrication between thin films at the cartilage surface reduces friction in the absence of interstitial fluid pressurization and fluid film lubrication by synovial fluid. Inadequate boundary lubrication is associated with degenerative joint conditions such as osteoarthritis (OA), but relations between OA and surface friction, lubrication and wear in boundary lubrication are not well defined. The purpose of the present study was to measure microscale boundary mode friction of the articular cartilage surface in an in vivo experimental model to better understand changes in cartilage surface friction in early OA. Cartilage friction was measured on the articular surface by atomic force microscopy (AFM) under applied loads ranging from 0.5 to 5 μN. Microscale AFM friction analyses revealed depth dependent changes within the top-most few microns of the cartilage surface in this model of early OA. A significant increase of nearly 50% was observed in the mean engineering friction coefficient for OA cartilage at the 0.5 μN load level; no significant differences in friction coefficients were found under higher applied loads. Changes in cartilage surface morphology observed by scanning electron microscopy included cracking and roughening of the surface indicative of disruption and wear accompanied by an apparent disintegration of the thin surface lamina from the underlying matrix. Immunohistochemical staining of lubricin - an important cartilage surface boundary lubricant - did not reveal differences in spatial distribution near the cartilage surface in OA compared to controls. The increase in friction at the 0.5 μN force level is interpreted to reflect changes in the interfacial mechanics of the thin surface lamina of articular cartilage: increased friction implies reduced

  16. Stem Cell-assisted Approaches for Cartilage Tissue Engineering

    PubMed Central

    Park, In-Kyu; Cho, Chong-Su

    2010-01-01

    The regeneration of damaged articular cartilage remains challenging due to its poor intrinsic capacity for repair. Tissue engineering of articular cartilage is believed to overcome the current limitations of surgical treatment by offering functional regeneration in the defect region. Selection of proper cell sources and ECM-based scaffolds, and incorporation of growth factors or mechanical stimuli are of primary importance to successfully produce artificial cartilage for tissue repair. When designing materials for cartilage tissue engineering, biodegradability and biocompatibility are the key factors in selecting material candidates, for either synthetic or natural polymers. The unique environment of cartilage makes it suitable to use a hydrogel with high water content in the cross-linked or thermosensitive (injectable) form. Moreover, design of composite scaffolds from two polymers with complementary physicochemical and biological properties has been explored to provide residing chondrocytes with a combination of the merits that each component contributes. PMID:24855547

  17. Engineering Superficial Zone Features in Tissue Engineered Cartilage

    PubMed Central

    Chen, Tony; Hilton, Matthew J.; Brown, Edward B.; Zuscik, Michael J.; Awad, Hani A.

    2013-01-01

    A major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here we report that hydrodynamic conditions that mimic the motion-induced flow fields in between the articular surfaces in the synovial joint induce the formation of a distinct superficial layer in tissue engineered cartilage hydrogels, with enhanced production of cartilage matrix proteoglycan and type II collagen. Moreover, the flow stimulation at the surface induces the production of the surface zone protein Proteoglycan 4 (aka PRG4 or lubricin). Analysis of second harmonic generation signature of collagen in this superficial layer reveals a highly aligned fibrillar matrix that resembles the alignment pattern in native tissue's surface zone, suggesting that mimicking synovial fluid flow at the cartilage surface in hydrodynamic bioreactors could be key to creating engineered cartilage with superficial zone features. PMID:23239161

  18. Tissue Engineering of Articular Cartilage with Biomimetic Zones

    PubMed Central

    Klein, Travis J.; Malda, Jos; Sah, Robert L.

    2009-01-01

    Articular cartilage damage is a persistent and increasing problem with the aging population, and treatments to achieve biological repair or restoration remain a challenge. Cartilage tissue engineering approaches have been investigated for over 20 years, but have yet to achieve the consistency and effectiveness for widespread clinical use. One of the potential reasons for this is that the engineered tissues do not have or establish the normal zonal organization of cells and extracellular matrix that appears critical for normal tissue function. A number of approaches are being taken currently to engineer tissue that more closely mimics the organization of native articular cartilage. This review focuses on the zonal organization of native articular cartilage, strategies being used to develop such organization, the reorganization that occurs after culture or implantation, and future prospects for the tissue engineering of articular cartilage with biomimetic zones. PMID:19203206

  19. Engineering cell attachments to scaffolds in cartilage tissue engineering

    NASA Astrophysics Data System (ADS)

    Steward, Andrew J.; Liu, Yongxing; Wagner, Diane R.

    2011-04-01

    One of the challenges of tissue engineering, a promising cell-based treatment for damaged or diseased cartilage, is designing the scaffold that provides structure while the tissue regenerates. In addition to the scaffold material's biocompatibility, mechanical properties, and ease of manufacturing, scaffold interactions with the cells must also be considered. In cartilage tissue engineering, a range of scaffolds with various degrees of cell attachment have been proposed, but the attachment density and type have yet to be optimized. Several techniques have been developed to modulate cell adhesion to the scaffold. These studies suggest that the need for cell attachment in cartilage tissue engineering may vary with cell type, stage of differentiation, culture condition, and scaffold material. Further studies will elucidate the role of cell attachment in cartilage regeneration and enhance efforts to engineer cell-based cartilage therapies.

  20. Simultaneous magnetic resonance imaging and consolidation measurement of articular cartilage.

    PubMed

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M; Momot, Konstantin I

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  1. Cartilage extracellular matrix metabolism differs in serum and synovial fluid.

    PubMed

    Martin, James A; Wilkey, Andrew L; Brand, Richard A

    2002-01-01

    Most cartilage explant culture studies assume conventional serum-supplemented growth media are biologically equivalent to the natural synovial fluid which baths cartilage in vivo. Few studies have systematically compared the effects of serum versus synovial fluid in culture. To address this assumption we conducted a series of studies to determine if cartilage matrix synthesis is significantly different in serum-based versus synovial fluid-based media. Normal bovine cartilage explants were cultured in DMEM either alone or supplemented with bovine serum or bovine synovial fluid. Matrix synthesis was measured with radiolabeling techniques. We then compared responses to insulin-like growth factor I (IGF-I, a stimulator of matrix synthesis), and interleukin-1beta (IL-1beta, an inhibitor of matrix synthesis). We observed significantly lower matrix synthesis activity in synovial fluid versus serum. Caution shoud be used in extrapolating studies of cartilage grown in media supplemented with serum rather than synovial fluid. PMID:12843702

  2. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

    PubMed Central

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M.; Momot, Konstantin I.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  3. Studies on cathepsin B in human articular cartilage.

    PubMed Central

    Bayliss, M T; Ali, S Y

    1978-01-01

    The thiol proteinase cathepsin B (EC 3.4.22.1), previously called cathepsin B1, was assayed in human articular cartilage by its hydrolysis of the synthetic substrate alpha-N-benzoyl-DL-arginine 2-naphthylamide. The enzyme was activated by cysteine and EDTA and completely inhibited by iodoacetamide and HgCl2. It was also partially inhibited by whole human serum. Human osteoarthrotic cartilage had increased activity when compared with normal cartilage. Cathepsin B activity of normal cartilage was age-related, being high in juveniles and declining to low values in adult and elderly individuals. Cathepsin D and cathepsin B both exhibited a zonal variation through the cartilage depth; the surface cells appeared to contain more activity than those close to the subchondral bone. PMID:417724

  4. Stem cells and cartilage development: complexities of a simple tissue.

    PubMed

    Hollander, Anthony P; Dickinson, Sally C; Kafienah, Wael

    2010-11-01

    Cartilage is considered to be a simple tissue that should be easy to engineer because it is avascular and contains just one cell type, the chondrocyte. Despite this apparent simplicity, regenerating cartilage in a form that can function effectively after implantation in the joint has proven difficult. This may be because we have not fully appreciated the importance of different structural regions of articular cartilage or of understanding the origins of chondrocytes and how this cell population is maintained in the normal tissue. This review considers what is known about different regions of cartilage and the types of stem cells in articulating joints and emphasizes the potential importance of regeneration of the lamina splendens at the joint surface and calcified cartilage at the junction with bone for long-term survival of regenerated tissue in vivo. PMID:20882533

  5. Stem Cells and Cartilage Development: Complexities of a Simple Tissue

    PubMed Central

    Hollander, Anthony P; Dickinson, Sally C; Kafienah, Wael

    2010-01-01

    Cartilage is considered to be a simple tissue that should be easy to engineer because it is avascular and contains just one cell type, the chondrocyte. Despite this apparent simplicity, regenerating cartilage in a form that can function effectively after implantation in the joint has proven difficult. This may be because we have not fully appreciated the importance of different structural regions of articular cartilage or of understanding the origins of chondrocytes and how this cell population is maintained in the normal tissue. This review considers what is known about different regions of cartilage and the types of stem cells in articulating joints and emphasizes the potential importance of regeneration of the lamina splendens at the joint surface and calcified cartilage at the junction with bone for long-term survival of regenerated tissue in vivo. Stem Cells 2010;28:1992–1996 PMID:20882533

  6. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    PubMed Central

    Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

    2014-01-01

    Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

  7. Direct human cartilage repair using three-dimensional bioprinting technology.

    PubMed

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M G; Lotz, Martin; D'Lima, Darryl D

    2012-06-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  8. Direct Human Cartilage Repair Using Three-Dimensional Bioprinting Technology

    PubMed Central

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M.G.; Lotz, Martin

    2012-01-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  9. Multiphasic, Multistructured and Hierarchical Strategies for Cartilage Regeneration.

    PubMed

    Correia, Clara R; Reis, Rui L; Mano, João F

    2015-01-01

    Cartilage tissue is a complex nonlinear, viscoelastic, anisotropic, and multiphasic material with a very low coefficient of friction, which allows to withstand millions of cycles of joint loading over decades of wear. Upon damage, cartilage tissue has a low self-reparative capacity due to the lack of neural connections, vascularization, and a latent pool of stem/chondro-progenitor cells. Therefore, the healing of articular cartilage defects remains a significant clinical challenge, affecting millions of people worldwide. A plethora of biomaterials have been proposed to fabricate devices for cartilage regeneration, assuming a wide range of forms and structures, such as sponges, hydrogels, capsules, fibers, and microparticles. In common, the fabricated devices were designed taking in consideration that to fully achieve the regeneration of functional cartilage it is mandatory a well-orchestrated interplay of biomechanical properties, unique hierarchical structures, extracellular matrix (ECM), and bioactive factors. In fact, the main challenge in cartilage tissue engineering is to design an engineered device able to mimic the highly organized zonal architecture of articular cartilage, specifically its spatiomechanical properties and ECM composition, while inducing chondrogenesis, either by the proliferation of chondrocytes or by stimulating the chondrogenic differentiation of stem/chondro-progenitor cells. In this chapter we present the recent advances in the development of innovative and complex biomaterials that fulfill the required structural key elements for cartilage regeneration. In particular, multiphasic, multiscale, multilayered, and hierarchical strategies composed by single or multiple biomaterials combined in a well-defined structure will be addressed. Those strategies include biomimetic scaffolds mimicking the structure of articular cartilage or engineered scaffolds as models of research to fully understand the biological mechanisms that influence the

  10. Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering

    PubMed Central

    Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G.; Ching, Kuan Y.; Jonnalagadda, Umesh S.; Oreffo, Richard O. C.; Hill, Martyn

    2014-01-01

    Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects. PMID:25272195

  11. Special pattern of endochondral ossification in human laryngeal cartilages: X-ray and light-microscopic studies on thyroid cartilage.

    PubMed

    Claassen, Horst; Schicht, Martin; Sel, Saadettin; Paulsen, Friedrich

    2014-04-01

    Endochondral ossification is a process that also occurs in the skeleton of the larynx. Differences in the ossification mechanism in comparison to growth plates are not understood until now. To get deeper insights into this process, human thyroid cartilage was investigated by the use of X-rays and a series of light-microscopic stainings. A statistical analysis of mineralization was done by scanning areas of mineralized cartilage and of ossification. We detected a special mode of endochondral ossification which differs from the processes in growth plates. Thyroid cartilage ossifies very slowly and in a gender-specific manner. Compared with age-matched women, bone formation in thyroid cartilage of men is significantly higher in the age group 41-60 years. Endochondral ossification is prepared by internal changes of extracellular matrix leading to areas of asbestoid fibers with ingrowing cartilage canals. In contrast to growth plates, bone is deposited on large areas of mineralized cartilage, which appear at the rims of cartilage canals. Furthermore, primary parallel fibered bone was observed which was deposited on woven bone. The predominant bone type is cancellous bone with trabeculae, whereas compact bone with Haversian systems was seldom found. Trabeculae contain a great number of reversal and arresting lines meaning that the former were often reconstructed and that bone formation was arrested and resumed again with advancing age. It is hypothesized that throughout life trabeculae of ossified thyroid cartilage undergo adaptation to different loads due to the use of voice. PMID:24496984

  12. Poroelasticity of cartilage at the nanoscale.

    PubMed

    Nia, Hadi Tavakoli; Han, Lin; Li, Yang; Ortiz, Christine; Grodzinsky, Alan

    2011-11-01

    Atomic-force-microscopy-based oscillatory loading was used in conjunction with finite element modeling to quantify and predict the frequency-dependent mechanical properties of the superficial zone of young bovine articular cartilage at deformation amplitudes, δ, of ~15 nm; i.e., at macromolecular length scales. Using a spherical probe tip (R ~ 12.5 μm), the magnitude of the dynamic complex indentation modulus, |E*|, and phase angle, φ, between the force and tip displacement sinusoids, were measured in the frequency range f ~ 0.2-130 Hz at an offset indentation depth of δ(0) ~ 3 μm. The experimentally measured |E*| and φ corresponded well with that predicted by a fibril-reinforced poroelastic model over a three-decade frequency range. The peak frequency of phase angle, f(peak), was observed to scale linearly with the inverse square of the contact distance between probe tip and cartilage, 1/d(2), as predicted by linear poroelasticity theory. The dynamic mechanical properties were observed to be independent of the deformation amplitude in the range δ = 7-50 nm. Hence, these results suggest that poroelasticity was the dominant mechanism underlying the frequency-dependent mechanical behavior observed at these nanoscale deformations. These findings enable ongoing investigations of the nanoscale progression of matrix pathology in tissue-level disease. PMID:22067171

  13. Multicomponent T2 relaxation analysis in cartilage

    PubMed Central

    Reiter, David A.; Lin, Ping-Chang; Fishbein, Kenneth W.; Spencer, Richard G.

    2009-01-01

    MR techniques are sensitive to the initial phases of osteoarthritis, characterized by disruption of collagen and loss of proteoglycan (PG), but are of limited specificity. Here, water compartments in normal and trypsin-degraded bovine nasal cartilage were identified using a non-negative least squares multiexponential analysis of T2 relaxation. Three components were detected: T2,1 = 2.3 ms, T2,2 = 25.2 ms, and T2,3 = 96.3 ms, with fractions w1 = 6.2%, w2 = 14.5%, and w3 = 79.3%, respectively. Trypsinization resulted in increased (p<0.01) values of T2,2 = 64.2 ms and T2,3 = 149.4 ms, supporting their assignment to water compartments that are bound and loosely associated with PG, respectively. The T2 of the rapidly-relaxing component was not altered by digestion, supporting assignment to relatively immobile collagen-bound water. Relaxation data were simulated for a range of TE, number of echoes, and SNR to guide selection of acquisition parameters and assess the accuracy and precision of experimental results. Based on this, the expected experimental accuracy of measured T2’s and associated weights was within 2% and 4% respectively, with precision within 1% and 3%. These results demonstrate the potential of multiexponential T2 analysis to increase the specificity of MR characterization of cartilage. PMID:19189393

  14. Poroelasticity of Cartilage at the Nanoscale

    PubMed Central

    Nia, Hadi Tavakoli; Han, Lin; Li, Yang; Ortiz, Christine; Grodzinsky, Alan

    2011-01-01

    Atomic-force-microscopy-based oscillatory loading was used in conjunction with finite element modeling to quantify and predict the frequency-dependent mechanical properties of the superficial zone of young bovine articular cartilage at deformation amplitudes, δ, of ∼15 nm; i.e., at macromolecular length scales. Using a spherical probe tip (R ∼ 12.5 μm), the magnitude of the dynamic complex indentation modulus, |E∗|, and phase angle, ϕ, between the force and tip displacement sinusoids, were measured in the frequency range f ∼ 0.2–130 Hz at an offset indentation depth of δ0 ∼ 3 μm. The experimentally measured |E∗| and ϕ corresponded well with that predicted by a fibril-reinforced poroelastic model over a three-decade frequency range. The peak frequency of phase angle, fpeak, was observed to scale linearly with the inverse square of the contact distance between probe tip and cartilage, 1/d2, as predicted by linear poroelasticity theory. The dynamic mechanical properties were observed to be independent of the deformation amplitude in the range δ = 7–50 nm. Hence, these results suggest that poroelasticity was the dominant mechanism underlying the frequency-dependent mechanical behavior observed at these nanoscale deformations. These findings enable ongoing investigations of the nanoscale progression of matrix pathology in tissue-level disease. PMID:22067171

  15. Deformation of Nasal Septal Cartilage During Mastication

    PubMed Central

    Dayeh, Ayman A. Al; Rafferty, Katherine L.; Egbert, Mark; Herring, Susan W.

    2009-01-01

    The cartilaginous nasal septum plays a major role in structural integrity and growth of the face, but its internal location has made physiologic study difficult. By surgically implanting transducers in 10 miniature pigs (Sus scrofa), we recorded in vivo strains generated in the nasal septum during mastication and masseter stimulation. The goals were (1) to determine whether the cartilage should be considered as a vertical strut supporting the nasal cavity and preventing its collapse, or as a damper of stresses generated during mastication and (2) to shed light on the overall pattern of snout deformation during mastication. Strains were recorded simultaneously at the septo-ethmoid junction and nasofrontal suture during mastication. A third location in the anterior part of the cartilage was added during masseter stimulation and manipulation. Contraction of jaw closing muscles during mastication was accompanied by anteroposterior compressive strains (around −1,000 με) in the septo-ethmoid junction. Both the orientation and the magnitude of the strain suggest that the septum does not act as a vertical strut but may act in absorbing loads generated during mastication. The results from masseter stimulation and manipulation further suggest that the masticatory strain pattern arises from a combination of dorsal bending and/or shearing and anteroposterior compression of the snout. J. Morphol. PMID:19434723

  16. Overview of currently available Japanese acellular pertussis vaccines and future problems.

    PubMed

    Kamiya, H; Nii, R

    1988-01-01

    Acellular pertussis diphtheria, tetanus vaccine (APDT) was licensed in 1981 in Japan. This vaccine contains pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogen (AGG) as the main protective antigens. The new APDT vaccine produced by each company differs slightly in composition. There are two representative types of vaccine. One vaccine (B type) contains PT and FHA in a ratio of 1 to 1 and the other one (T type) contains PT and FHA in a ratio of 4 to 1 or 9 to 1 and also contains different amounts of AGG. We have been comparing the effectiveness of these two types of vaccine. The adverse reactions of APDT were local reactions such as redness and swelling, with a few febrile cases. No central nervous system adverse reactions were observed. The antibody protective level of this vaccine is also being investigated. After we changed from conventional vaccine to APDT, the frequency of serious adverse reactions was reduced and the number of pertussis infections also gradually decreased. This vaccine should be used for the children world-wide. PMID:3273618

  17. Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

    PubMed

    Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

    2012-01-01

    A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing. PMID:22629190

  18. Cellular Response to a Novel Fetal Acellular Collagen Matrix: Implications for Tissue Regeneration

    PubMed Central

    Rennert, Robert C.; Garg, Ravi K.; Gurtner, Geoffrey C.

    2013-01-01

    Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting. PMID:23970899

  19. Effect of dynamic seeding methods on the distribution of fibroblasts within human acellular dermis.

    PubMed

    Vitacolonna, Mario; Belharazem, Djeda; Hohenberger, Peter; Roessner, Eric D

    2015-12-01

    The purpose of this investigation was to compare different dynamic cell seeding methods regarding their seeding efficiency, homogeneity, infiltration depth and proliferation within a human acellular dermis. In addition, the growth behaviour was observed during a 12-day static in vitro culture. The dynamic methods included orbital-shaker seeding and the use of a plate centrifuge with different rotational speeds, combinations of low-pressure for matrix degassing and centrifugal seeding. Scaffolds were incubated for up to 12 days statically. Cell distribution and infiltration depth were analysed histologically at days 0, 4, 8 and 12. Seeding efficiency and cell proliferation were quantified with the MTT-assay at the same time points. Centrifugal seeding with 300g for 5 × 1 min combined with matrix degassing significantly increased the seeding efficiency and homogeneity compared to the other methods. However, following static culture, no cells were detectable after 4 days in the inner matrix zones. Furthermore, none of the degassing+centrifugation groups reached a significantly higher proliferation at day 8 compared to the reference. The use of a single dynamic method resulted in an inefficient cell seeding. We archived the highest seeding efficiency, homogeneity and infiltration depth using a combination of degassing+centrifugation at 300g for 5 × 1 min. PMID:25795264

  20. Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

    PubMed

    Lü, Wei-Dong; Wang, An-Ping; Wu, Zhong-Shi; Zhang, Ming; Hu, Tie-Hui; Lei, Guang-Yan; Hu, Ye-Rong

    2012-10-01

    This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation. PMID:22615255

  1. Brainless but Multi-Headed: Decision Making by the Acellular Slime Mould Physarum polycephalum.

    PubMed

    Beekman, Madeleine; Latty, Tanya

    2015-11-20

    Because of its peculiar biology and the ease with which it can be cultured, the acellular slime mould Physarum polycephalum has long been a model organism in a range of disciplines. Due to its macroscopic, syncytial nature, it is no surprise that it has been a favourite amongst cell biologists. Its inclusion in the experimental tool kit of behavioural ecologists is much more recent. These recent studies have certainly paid off. They have shown that, for an organism that lacks a brain or central nervous system, P. polycephalum shows rather complex behaviour. For example, it is capable of finding the shortest path through a maze, it can construct networks as efficient as those designed by humans, it can solve computationally difficult puzzles, it makes multi-objective foraging decisions, it balances its nutrient intake and it even behaves irrationally. Are the slime mould's achievements simply "cute", worthy of mentioning in passing but nothing to take too seriously? Or do they hint at the fundamental processes underlying all decision making? We will address this question after reviewing the decision-making abilities of the slime mould. PMID:26189159

  2. Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study.

    PubMed

    Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

    2016-01-01

    Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco's Modified Eagle's Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on the use of sodium hydroxide (NaOH), on samples from 28 donors. Cell viability was assessed using an MTT assay and microbiological monitoring was performed on all samples processed after each step. Two surgeons evaluated the biomechanical characteristics of grafts of increasing thickness. The effects of the different decellularization protocols were assessed by means of histological examination and immunohistochemistry, and residual DNA after decellularization was quantified using a real-time TaqMan MGB probe. Finally, we compared the results of DMEM based decellularization protocol on reticular dermis derived samples with the results of the same protocol applied on papillary dermis derived grafts. Our experimental results indicated that the use of glycerolized reticular dermis after 5 weeks of treatment with DMEM results in an HADM with good handling and biocompatibility properties. PMID:26918526

  3. Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study

    PubMed Central

    Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

    2016-01-01

    Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco’s Modified Eagle’s Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on the use of sodium hydroxide (NaOH), on samples from 28 donors. Cell viability was assessed using an MTT assay and microbiological monitoring was performed on all samples processed after each step. Two surgeons evaluated the biomechanical characteristics of grafts of increasing thickness. The effects of the different decellularization protocols were assessed by means of histological examination and immunohistochemistry, and residual DNA after decellularization was quantified using a real-time TaqMan MGB probe. Finally, we compared the results of DMEM based decellularization protocol on reticular dermis derived samples with the results of the same protocol applied on papillary dermis derived grafts. Our experimental results indicated that the use of glycerolized reticular dermis after 5 weeks of treatment with DMEM results in an HADM with good handling and biocompatibility properties. PMID:26918526

  4. Does Acellular Dermal Matrix Thickness Affect Complication Rate in Tissue Expander Based Breast Reconstruction?

    PubMed Central

    2016-01-01

    Background. While the benefits of using acellular dermal matrices (ADMs) in breast reconstruction are well described, their use has been associated with additional complications. The purpose of this study was to determine if ADM thickness affects complications in breast reconstruction. Methods. A retrospective chart review was performed including all tissue expander based breast reconstructions with AlloDerm (LifeCell, Branchburg, NJ) over 4 years. We evaluated preoperative characteristics and assessed postoperative complications including seroma, hematoma, infection, skin necrosis, and need for reintervention. We reviewed ADM thickness and time to Jackson-Pratt (JP) drain removal. Results. Fifty-five patients underwent 77 ADM-associated tissue expander based breast reconstructions, with average age of 48.1 years and average BMI of 25.9. Average ADM thickness was 1.21 mm. We found higher complication rates in the thick ADM group. Significant associations were found between smokers and skin necrosis (p < 0.0001) and seroma and prolonged JP drainage (p = 0.0004); radiated reconstructed breasts were more likely to suffer infections (p = 0.0085), and elevated BMI is a significant predictor for increased infection rate (p = 0.0037). Conclusion. We found a trend toward increased complication rates with thicker ADMs. In the future, larger prospective studies evaluating thickness may provide more information.

  5. Does Acellular Dermal Matrix Thickness Affect Complication Rate in Tissue Expander Based Breast Reconstruction?

    PubMed

    Rose, Jessica F; Zafar, Sarosh N; Ellsworth Iv, Warren A

    2016-01-01

    Background. While the benefits of using acellular dermal matrices (ADMs) in breast reconstruction are well described, their use has been associated with additional complications. The purpose of this study was to determine if ADM thickness affects complications in breast reconstruction. Methods. A retrospective chart review was performed including all tissue expander based breast reconstructions with AlloDerm (LifeCell, Branchburg, NJ) over 4 years. We evaluated preoperative characteristics and assessed postoperative complications including seroma, hematoma, infection, skin necrosis, and need for reintervention. We reviewed ADM thickness and time to Jackson-Pratt (JP) drain removal. Results. Fifty-five patients underwent 77 ADM-associated tissue expander based breast reconstructions, with average age of 48.1 years and average BMI of 25.9. Average ADM thickness was 1.21 mm. We found higher complication rates in the thick ADM group. Significant associations were found between smokers and skin necrosis (p < 0.0001) and seroma and prolonged JP drainage (p = 0.0004); radiated reconstructed breasts were more likely to suffer infections (p = 0.0085), and elevated BMI is a significant predictor for increased infection rate (p = 0.0037). Conclusion. We found a trend toward increased complication rates with thicker ADMs. In the future, larger prospective studies evaluating thickness may provide more information. PMID:27190645

  6. Acellular Dermal Matrix in Reconstructive Breast Surgery: Survey of Current Practice among Plastic Surgeons

    PubMed Central

    Ibrahim, Ahmed M. S.; Koolen, Pieter G. L.; Ashraf, Azra A.; Kim, Kuylhee; Mureau, Marc A. M.; Lee, Bernard T.

    2015-01-01

    Background: Acellular dermal matrices (ADMs) in plastic surgery have become increasingly popular particularly for breast reconstruction. Despite their advantages, questions exist regarding their association with a possible increased incidence of complications. We describe a collective experience of plastic surgeons’ use of ADMs in reconstructive breast surgery using an internet-based survey. Methods: Members of the American Society of Plastic Surgeons were recruited through voluntary, anonymous participation in an online survey. The web-based survey garnered information about participant demographics and their experience with ADM use in breast reconstruction procedures. After responses were collected, all data were anonymously processed. Results: Data were ascertained through 365 physician responses of which 99% (n = 361) completed the survey. The majority of participants were men (84.5%) between 51 and 60 years (37.4%); 84.2% used ADM in breast reconstruction, including radiated patients (79.7%). ADM use was not favored for nipple reconstruction (81.5%); 94.6% of participants used drains, and 87.8% administered antibiotics postoperatively. The most common complications were seroma (70.9%) and infection (16%), although 57.4% claimed anecdotally that overall complication rate was unchanged after incorporating ADM into their practice. High cost was a deterrent for ADM use (37.5%). Conclusions: Plastic surgeons currently use ADM in breast reconstruction for both immediate and staged procedures. Of those responding, a majority of plastic surgeons will incorporate drains and use postoperative antibiotics for more than 48 hours. PMID:25973359

  7. Three-dimensional Reconstruction of the Microstructure of Human Acellular Nerve Allograft.

    PubMed

    Zhu, Shuang; Zhu, Qingtang; Liu, Xiaolin; Yang, Weihong; Jian, Yutao; Zhou, Xiang; He, Bo; Gu, Liqiang; Yan, Liwei; Lin, Tao; Xiang, Jianping; Qi, Jian

    2016-01-01

    The exact inner 3D microstructure of the human peripheral nerve has been a mystery for decades. Therefore, it has been difficult to solve several problems regarding peripheral nerve injury and repair. We used high-resolution X-ray computed microtomography (microCT) to scan a freeze-dried human acellular nerve allograft (hANA). The microCT images were then used to reconstruct a 3D digital model, which was used to print a 3D resin model of the nerve graft. The 3D digital model of the hANA allowed visualization of all planes. The magnified 3D resin model clearly showed the nerve bundles and basement membrane tubes of the hANA. Scanning electron microscopy (SEM) was used to analyse the microstructure of the hANA. Compared to the SEM images, the microCT image clearly demonstrated the microstructure of the hANA cross section at a resolution of up to 1.2 μm. The 3D digital model of the hANA facilitates a clear and easy understanding of peripheral nerve microstructure. Furthermore, the enlarged 3D resin model duplicates the unique inner structure of each individual hANA. This is a crucial step towards achieving 3D printing of a hANA or nerve that can be used as a nerve graft. PMID:27476584

  8. Three-dimensional Reconstruction of the Microstructure of Human Acellular Nerve Allograft

    PubMed Central

    Zhu, Shuang; Zhu, Qingtang; Liu, Xiaolin; Yang, Weihong; Jian, Yutao; Zhou, Xiang; He, Bo; Gu, Liqiang; Yan, Liwei; Lin, Tao; Xiang, Jianping; Qi, Jian

    2016-01-01

    The exact inner 3D microstructure of the human peripheral nerve has been a mystery for decades. Therefore, it has been difficult to solve several problems regarding peripheral nerve injury and repair. We used high-resolution X-ray computed microtomography (microCT) to scan a freeze-dried human acellular nerve allograft (hANA). The microCT images were then used to reconstruct a 3D digital model, which was used to print a 3D resin model of the nerve graft. The 3D digital model of the hANA allowed visualization of all planes. The magnified 3D resin model clearly showed the nerve bundles and basement membrane tubes of the hANA. Scanning electron microscopy (SEM) was used to analyse the microstructure of the hANA. Compared to the SEM images, the microCT image clearly demonstrated the microstructure of the hANA cross section at a resolution of up to 1.2 μm. The 3D digital model of the hANA facilitates a clear and easy understanding of peripheral nerve microstructure. Furthermore, the enlarged 3D resin model duplicates the unique inner structure of each individual hANA. This is a crucial step towards achieving 3D printing of a hANA or nerve that can be used as a nerve graft. PMID:27476584

  9. Preparation and characterization of an advanced collagen aggregate from porcine acellular dermal matrix.

    PubMed

    Liu, Xinhua; Dan, Nianhua; Dan, Weihua

    2016-07-01

    The objective of this study was to extract and characterize an advanced collagen aggregate (Ag-col) from porcine acellular dermal matrix (pADM). Based on histological examination, scanning electron microscopy (SEM) and atomic force microscope (AFM), Ag-col was composed of the D-periodic cross-striated collagen fibrils and thick collagen fiber bundles with uneven diameters and non-orientated arrangement. Fourier transform infrared (FTIR) spectra of pADM, Ag-col and Col were similar and revealed the presence of the triple helix. Circular dichroism (CD) analysis exhibited a slightly higher content of α-helix but inappreciably less amount of random coil structure in Ag-col compared to Col. Moreover, imino acid contents of pADM, Ag-col and Col were 222.43, 218.30 and 190.01 residues/1000 residues, respectively. From zeta potential analysis, a net charge of zero was found at pH 6.45 and 6.11 for Ag-col and Col, respectively. Differential scanning calorimetry (DSC) study suggested that the Td of Ag-col was 20°C higher than that of Col as expected, and dynamic mechanical analysis (DMA) indicated that Ag-col possessed a higher storage modulus but similar loss factor compared to Col. Therefore, the collagen aggregate from pADM could serve as a better alternative source of collagens for further applications in food and biological industries. PMID:27039117

  10. Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis.

    PubMed

    Li, Zenglan; Zhang, Yan; Wang, Qi; Li, Zhengjun; Liu, Yongdong; Zhang, Songping; Zhang, Guifeng; Ma, Guanghui; Luo, Jian; Su, Zhiguo

    2016-07-25

    Development of acellular pertussis vaccine (aPV) requires purification of several components from Bordetella pertussis. While the components pertussis toxin (PT) and filamentous hemagglutinin (FHA) have been successfully purified, the third component, pertactin, proves to be a difficult target due to its very low concentration. In order to solve its purification problem, we performed the surface potential analysis with GRASP2 program. The results demonstrated that there are two major charge patches, one negative and one positive, which are located separately on this linear protein. For this special feature, we designed a dual ion exchange chromatography strategy including an anionic exchange and a cationic exchange process for separation of pertactin from the heat extract of B. pertussis. The initial anionic exchange chromatography concentrated the product from 1.7% to 14.6%, with recovery of 80%. The second cationic exchange chromatography increased the purity to 33%, with recovery of 83%. The final purification was accomplished by hydrophobic interaction chromatography, yielding a purity of 96%. The total recovery of the three columns was 61%. Characterization of the purified antigen was performed with CD, intrinsic fluorescence, HP-SEC and western-blot, showing that the purified protein kept its natural conformation and immune-reactivity. The rationally designed process proved to be feasible, and it is suitable for large-scale preparation of the third aPV component pertactin. PMID:27302339

  11. Complex ventral hernia repair with a human acellular dermal matrix and component separation: A case series

    PubMed Central

    Garcia, Alvaro; Baldoni, Anthony

    2015-01-01

    We present a case series of 19 patients requiring complex abdominal hernia repairs. Patients presented with challenging clinical histories with 95% having multiple significant comorbidities including overweight or obesity (84%), hypertension (53%), diabetes (42%), cancer (26%), and pulmonary disease (16%). The majority of patients (68%) had prior abdominal infections and 53% had at least one failed prior hernia repair. Upon examination, fascial defects averaged 282 cm2. Anterior and posterior component separation was performed with placement of a human acellular dermal mesh. Midline abdominal closure under minimal tension was achieved primarily in all cases. Post-operative complications included 2 adverse events (11%) – one pulmonary embolism and one post-operative hemorrhage requiring transfusion; 6 wound-related complications (32%), 1 seroma (5%) and 1 patient with post-operative ileus (5%). Operative intervention was not required in any of the cases and most patients made an uneventful recovery. Increased patient age and longer OR time were independently predictive of early post-operative complications. At a median 2-year follow-up, three patients had a documented hernia recurrence (16%) and one patient was deceased due to unrelated causes. Conclusion Patients at high risk for post-operative events due to comorbidities, prior abdominal infection and failed mesh repairs do well following component separation reinforced with a human bioprosthetic mesh. Anticipated post-operative complications were managed conservatively and at a median 2-year follow-up, a low rate of hernia recurrence was observed with this approach. PMID:26288732

  12. Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013.

    PubMed

    O'Halloran, Alissa C; Lu, Peng-Jun; Williams, Walter W; Ding, Helen; Meyer, Sarah A

    2016-07-01

    The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy. PMID:27372388

  13. Distinctive expression of extracellular matrix molecules at mRNA and protein levels during formation of cellular and acellular cementum in the rat.

    PubMed

    Sasano, Y; Maruya, Y; Sato, H; Zhu, J X; Takahashi, I; Mizoguchi, I; Kagayama, M

    2001-02-01

    Little is known about differential expression of extracellular matrices secreted by cementoblasts between cellular and acellular cementum. We hypothesize that cementoblasts lining acellular cementum express extracellular matrix genes differently from those lining cellular cementum, thereby forming two distinct types of extracellular matrices. To test this hypothesis, we investigated spatial and temporal gene expression of selected extracellular matrix molecules, that is type I collagen, bone sialoprotein, osteocalcin and osteopontin, during formation of both cellular and acellular cementum using in situ hybridization. In addition, their extracellularly deposited and accumulated proteins were examined immunohistochemically. The mRNA transcripts of pro-alpha1 (I) collagen were primarily localized in cementoblasts of cellular cementum and cementocytes, while those of bone sialoprotein were predominantly seen in cementoblasts lining acellular cementum. In contrast, osteocalcin was expressed by both types of cementoblasts and cementocytes and so was osteopontin but only transiently. Our immunohistochemical examination revealed that translated proteins were localized extracellularly where the genes had been expressed intracellularly. The present study demonstrated the distinctive expression of genes and proteins of the extracellular matrix molecules between cellular and acellular cementum. PMID:11432645

  14. The Functions of BMP3 in Rabbit Articular Cartilage Repair.

    PubMed

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  15. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.

    PubMed

    Glass, Katherine A; Link, Jarrett M; Brunger, Jonathan M; Moutos, Franklin T; Gersbach, Charles A; Guilak, Farshid

    2014-07-01

    The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. PMID:24767790

  16. The identification of matrix Gla protein in cartilage.

    PubMed

    Hale, J E; Fraser, J D; Price, P A

    1988-04-25

    The vitamin K-dependent bone protein matrix gamma-carboxyglutamic acid (Gla) protein (MGP) has been identified by radioimmunoassay in the guanidine extract of rat cartilage. MGP was present in all cartilages tested at levels comparable to the MGP level in bone. Western blot analysis indicated that the molecular weight of cartilage MGP is the same as bone MGP, and Northern blot analysis revealed that MGP mRNA from cartilage is the same size as the MGP mRNA from bone. The structurally related vitamin K-dependent protein bone Gla protein could not be detected in cartilage by radioimmunoassay or by Northern blot analysis. The discovery that MGP is synthesized by growth plate cartilage could provide an explanation for the excessive growth plate mineralization disorder seen in rats treated with the vitamin K antagonist warfarin and the punctate mineralization of the growth plate seen in infants whose mothers received warfarin in the first trimester of pregnancy (the fetal warfarin syndrome). Both disorders appear to be caused by the inactivation of a vitamin K-dependent mineralization inhibitor in cartilage, an inhibitor which we suggest is MGP. PMID:3258600

  17. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties

    PubMed Central

    Glass, Katherine A.; Link, Jarrett M.; Brunger, Jonathan M.; Moutos, Franklin T.; Gersbach, Charles A.; Guilak, Farshid

    2014-01-01

    The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. PMID:24767790

  18. Shark cartilage, cancer and the growing threat of pseudoscience.

    PubMed

    Ostrander, Gary K; Cheng, Keith C; Wolf, Jeffrey C; Wolfe, Marilyn J

    2004-12-01

    The promotion of crude shark cartilage extracts as a cure for cancer has contributed to at least two significant negative outcomes: a dramatic decline in shark populations and a diversion of patients from effective cancer treatments. An alleged lack of cancer in sharks constitutes a key justification for its use. Herein, both malignant and benign neoplasms of sharks and their relatives are described, including previously unreported cases from the Registry of Tumors in Lower Animals, and two sharks with two cancers each. Additional justifications for using shark cartilage are illogical extensions of the finding of antiangiogenic and anti-invasive substances in cartilage. Scientific evidence to date supports neither the efficacy of crude cartilage extracts nor the ability of effective components to reach and eradicate cancer cells. The fact that people think shark cartilage consumption can cure cancer illustrates the serious potential impacts of pseudoscience. Although components of shark cartilage may work as a cancer retardant, crude extracts are ineffective. Efficiencies of technology (e.g., fish harvesting), the power of mass media to reach the lay public, and the susceptibility of the public to pseudoscience amplifies the negative impacts of shark cartilage use. To facilitate the use of reason as the basis of public and private decision-making, the evidence-based mechanisms of evaluation used daily by the scientific community should be added to the training of media and governmental professionals. Increased use of logical, collaborative discussion will be necessary to ensure a sustainable future for man and the biosphere. PMID:15574750

  19. Human cartilage repair with a photoreactive adhesive-hydrogel composite.

    PubMed

    Sharma, Blanka; Fermanian, Sara; Gibson, Matthew; Unterman, Shimon; Herzka, Daniel A; Cascio, Brett; Coburn, Jeannine; Hui, Alexander Y; Marcus, Norman; Gold, Garry E; Elisseeff, Jennifer H

    2013-01-01

    Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects. PMID:23303605

  20. The Functions of BMP3 in Rabbit Articular Cartilage Repair

    PubMed Central

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  1. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA. PMID:19876764

  2. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    PubMed Central

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  3. Mechanical properties of normal and osteoarthritic human articular cartilage.

    PubMed

    Robinson, Dale L; Kersh, Mariana E; Walsh, Nicole C; Ackland, David C; de Steiger, Richard N; Pandy, Marcus G

    2016-08-01

    Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the

  4. Biomechanical Evaluation of Human and Porcine Auricular Cartilage

    PubMed Central

    Zopf, David A.; Flanagan, Colleen L.; Nasser, Hassan B.; Mitsak, Anna G.; Huq, Farhan S.; Rajendran, Vishnu; Green, Glenn E.; Hollister, Scott J.

    2015-01-01

    Objective The mechanical properties of normal auricular cartilage provide a benchmark against which to characterize changes in auricular structure/function due to genetic defects creating phenotypic abnormalities in collage subtypes. Such properties also provide inputs/targets for auricular reconstruction scaffold design. Several studies report the biomechanical properties for septal, costal, and articular cartilage. However, analogous data for auricular cartilage is lacking. Therefore, our aim in this study was to characterize both whole ear and auricular cartilage mechanics by mechanically testing specimens and fitting the results to nonlinear constitutive models. Study Design Mechanical testing of whole ears and auricular cartilage punch biopsies. Methods Whole human cadaveric ear and auricular cartilage punch biopsies from both porcine and human cartilage were subjected to whole ear helix down compression and quasi-static unconfined compression tests. Common hyperelastic constitutive laws (widely used to characterize soft tissue mechanics) were evaluated for their ability to represent the stress-strain behavior of auricular cartilage. Results Load displacement curves for whole ear testing exhibited compliant linear behavior until after significant displacement where nonlinear stiffening occurred. All five commonly used 2-term hyperelastic soft tissue constitutive models successfully fit both human and porcine nonlinear elastic behavior (mean R2 fit greater than 0.95). Conclusion Auricular cartilage exhibits nonlinear strain stiffening elastic behavior that is similar to other soft tissues in the body. The whole ear exhibits compliant behavior with strain stiffening at high displacement. The constants from the hyperelastic model fits provide quantitative baselines for both human and porcine (a commonly used animal model for auricular tissue engineering) auricular mechanics. PMID:25891012

  5. Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds.

    PubMed

    Rowland, Christopher R; Colucci, Lina A; Guilak, Farshid

    2016-06-01

    The native extracellular matrix of cartilage contains entrapped growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potentially attractive biomaterial for cartilage tissue engineering. A limitation to this approach is that the native cartilage extracellular matrix possesses a pore size of only a few nanometers, which inhibits cellular infiltration. Efforts to increase the pore size of cartilage-derived matrix (CDM) scaffolds dramatically attenuate their mechanical properties, which makes them susceptible to cell-mediated contraction. In previous studies, we have demonstrated that collagen crosslinking techniques are capable of preventing cell-mediated contraction in CDM disks. In the current study, we investigated the effects of CDM concentration and pore architecture on the ability of CDM scaffolds to resist cell-mediated contraction. Increasing CDM concentration significantly increased scaffold mechanical properties, which played an important role in preventing contraction, and only the highest CDM concentration (11% w/w) was able to retain the original scaffold dimensions. However, the increase in CDM concentration led to a concomitant decrease in porosity and pore size. Generating a temperature gradient during the freezing process resulted in unidirectional freezing, which aligned the formation of ice crystals during the freezing process and in turn produced aligned pores in CDM scaffolds. These aligned pores increased the pore size of CDM scaffolds at all CDM concentrations, and greatly facilitated infiltration by mesenchymal stem cells (MSCs). These methods were used to fabricate of anatomically-relevant CDM hemispheres. CDM hemispheres with aligned pores supported uniform MSC infiltration and matrix deposition. Furthermore, these CDM hemispheres retained their original architecture and did not contract, warp, curl, or splay throughout the entire 28-day culture period. These findings demonstrate that given the

  6. Perforating Thin Metal Sheets

    NASA Technical Reports Server (NTRS)

    Davidson, M. E.

    1985-01-01

    Sheets only few mils thick bonded together, punched, then debonded. Three-step process yields perforated sheets of metal. (1): Individual sheets bonded together to form laminate. (2): laminate perforated in desired geometric pattern. (3): After baking, laminate separates into individual sheets. Developed for fabricating conductive layer on blankets that collect and remove ions; however, perforated foils have other applications - as conductive surfaces on insulating materials; stiffeners and conductors in plastic laminates; reflectors in antenna dishes; supports for thermal blankets; lightweight grille cover materials; and material for mockup of components.

  7. Growing Three-Dimensional Cartilage-Cell Cultures

    NASA Technical Reports Server (NTRS)

    Spaulding, Glenn F.; Prewett, Tacey L.; Goodwin, Thomas J.

    1995-01-01

    Process for growing three-dimensional cultures of mammalian cartilage from normal mammalian cells devised. Effected using horizontal rotating bioreactor described in companion article, "Simplified Bioreactor for Growing Mammalian Cells" (MSC-22060). Bioreactor provides quiescent environment with generous supplies of nutrient and oxygen. Initiated with noncartilage cells. Artificially grown tissue resembles that in mammalian cartilage. Potential use in developing therapies for damage to cartilage by joint and back injuries and by such inflammatory diseases as arthritis and temporal-mandibular joint disease. Also used to test nonsteroid anti-inflammation medicines.

  8. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  9. Chondrosarcoma of the Laryngeal Thyroid Cartilage.

    PubMed

    Righi, Stefano; Boffano, Paolo; Pateras, Dimitrios; Chiodo, Domenico; Zanardi, Fabio; Patetta, Roberta

    2015-09-01

    Chondrosarcoma of the larynx is a rare tumor, accounting for 0.07% to 2% of all laryngeal cancers. Nevertheless, it represents the most frequent nonepithelial neoplasm of the laryngeal region.Laryngeal chondrosarcomas are usually characterized by slow growth and low metastatic potential.The exact etiopathogenesis of chondrosarcoma is still debated. Diagnosis can be difficult given the slow rate of growth and nonspecific patient symptoms at presentation.Because of its rarity, literature about laryngeal chondrosarcoma is mainly made up of case reports and small case series.Therefore, it is important to add any information regarding this pathology.The aim of this article was to present and discuss a new case of chondrosarcoma located in the thyroid cartilage in a 63-year-old woman. PMID:26267570

  10. Investigations into human tracheal cartilage osseocalcineus metaplasia IV. Morphokinesis of tracheal cartilage retrograde lesions during the process of aging.

    PubMed

    Sośnik, Henryk; Sośnik, Katarzyna

    2010-01-01

    We determined the frequency of occurrence and dynamism of the mentioned retrograde lesions. The investigated material comprised 371 cartilages collected from 95 male tracheas (mean age: 56 ± 13 years), and 279 cartilages collected from 70 female tracheas (mean age: 65.3 ± 14 years) during the process of aging. The dynamism proved non-homogenous with a visible gender difference. The empirical regression curves often crossed each other. Some of the presented curves in female patients were observed beginning two decades after that of male patients, and at lower levels. Thus, it seems hard to conclude that some processes considering tracheal cartilage morphokinesis always precede others. PMID:21290346

  11. Direct Hospital Cost of Outcome Pathways in Implant-Based Reconstruction with Acellular Dermal Matrices

    PubMed Central

    Qureshi, Ali A.; Broderick, Kristen; Funk, Susan; Reaven, Nancy; Tenenbaum, Marissa M.

    2016-01-01

    Background: Current cost data on tissue expansion followed by exchange for permanent implant (TE/I) reconstruction lack a necessary assessment of the experience of a heterogenous breast cancer patient population and their multiple outcome pathways. We extend our previous analysis to that of direct hospital cost as bundling of payments is likely to follow the changing centralization of cancer care at the hospital level. Methods: We performed a retrospective analysis (2003–2009) of TE/I reconstructions with or without an acellular dermal matrix (ADM), namely Alloderm RTM. Postreconstructive events were analyzed and organized into outcome pathways as previously described. Aggregated and normalized inpatient and outpatient hospital direct costs and physician reimbursement were generated for each outcome pathway with or without ADM. Results: Three hundred sixty-seven patients were analyzed. The average 2-year hospital direct cost per TE/I breast reconstruction patient was $11,862 in the +ADM and $12,319 in the −ADM groups (P > 0.05). Initial reconstructions were costlier in the +ADM ($6,868) than in the −ADM ($5,615) group, but the average cost of subsequent postreconstructive events within 2 years was significantly lower in +ADM ($5,176) than −ADM ($6,704) patients (P < 0.05). When a complication occurred, but reconstruction was still completed within 2 years, greater costs were incurred in the −ADM than in the +ADM group for most scenarios, leading to a net equalization of cost between study groups. Conclusion: Although direct hospital cost is an important factor for resource and fund allocation, it should not remain the sole factor when deciding to use ADM in TE/I reconstruction.

  12. Schwann-like cells seeded in acellular nerve grafts improve nerve regeneration

    PubMed Central

    2014-01-01

    Background This study evaluated whether Schwann-like cells (SLCs) induced from bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into acellular nerve grafts (ANGs) could repair nerve defects compared with nerve isografts and ANGs with BM-MSCs. Methods BM-MSCs extracted, separated and purified from the bone marrow of rats, and some of the BM-MSCs were cultured with mixed induction agents that could induce BM-MSCs into SLCs. Either SLCs or BM-MSCs were seeded onto 10-mm ANGs, and the isografts were chosen as the control. The walking-track test, tibialis anterior muscle weight measurement, electrophysiological examination, toluidine blue staining, transmission electron micrographs and immunostaining of S-100 and VEGF in these three groups were evaluated in a 10-mm rat sciatic injury-repair model. Results The walking-track test, tibialis anterior muscle weight measurement and electrophysiological examination of the sciatic nerve suggested the groups of ANGs with SLCs and isografts obtained better results than the BM-MSC group (P < 0.05). Meanwhile, the results of the SLCs and isograft groups were similar (P > 0.05). All the histomorphometric analyses (toluidine blue staining, transmission electron micrographs and immunostaining of S-100 and VEGF) showed that there were more regenerating nerve fibers in the group of ANGs with SLCs than the BM-MSCs (P < 0.05), but there was no significant difference between the SLC and isograft groups (P > 0.05). Conclusions SLCs seeded in ANGs and isografts show better functional regeneration compared with BM-MSCs seeded in ANGs. Additionally, SLCs combined with ANGs present almost the same outcome as the isografts. Therefore, SLCs with ANGs can be a good choice in nerve defect repairs. PMID:24885337

  13. A Complication Analysis of 2 Acellular Dermal Matrices in Prosthetic-based Breast Reconstruction

    PubMed Central

    Page, Eugenia K.; Hart, Alexandra; Rudderman, Randall; Carlson, Grant W.; Losken, Albert

    2016-01-01

    Background: Acellular dermal matrices (ADM) are now routine in postmastectomy prosthetic-based breast reconstruction. The goal of the current study was to compare the complications of 2 ADM products—AlloDerm and Cortiva. Methods: A retrospective analysis of prosthetic-based breast reconstruction in Atlanta, Ga., over 5 years. Inclusion criteria were the use of the ADM types (AlloDerm or Cortiva) and use of a tissue expander or implant. Statistical analysis compared group demographics, risk factors, and early complications. Results: Of the 298 breast reconstructions, 174 (58.4%) used AlloDerm and 124 (41.6%) used Cortiva. There was no difference in overall complication frequency (16 AlloDerm and 18 Cortiva; P = 0.195). Within specific categories, there was a difference in mastectomy skin flap necrosis, but, based on further regression analysis, this was attributable to differences in body mass index (P = 0.036). Furthermore, there were no differences in the rates of infection (6 AlloDerm and 5 Cortiva; P = 1.0), seroma/hematoma (9 AlloDerm and 7 Cortiva; P = 1.0), or drain duration (13.2 day AlloDerm and 14.2 day Cortiva, P = 0.2). By using a general estimating equation for binomial logistical regression, it was found that only current tobacco use (P = 0.033) was a significant predictor for a complication. Trending predictors were body mass index (P = 0.074) and age (P = 0.093). The type of matrix was not a significant predictor for any of the recorded complication (P = 0.160). Conclusions: Although AlloDerm is well established, we have shown that Cortiva has an equivalent complication frequency. Future work will focus on long-term outcome measures and histological evaluation of vascularization and integration. PMID:27536479

  14. Incidence of Seromas and Infections Using Fenestrated versus Nonfenestrated Acellular Dermal Matrix in Breast Reconstructions

    PubMed Central

    Palaia, David A.; Arthur, Karen S.; Cahan, Anthony C.

    2015-01-01

    Background: Acellular dermal matrices (ADMs) provide clinical benefits in breast reconstruction but have been associated with increased postoperative complications, most frequently seromas. Fenestration of the ADM before insertion into the reconstructed breast may reduce the incidence of postoperative complications. In this retrospective analysis, postoperative complications were assessed after breast reconstruction with or without fenestrated ADMs. Methods: Patients who underwent immediate 2-staged implant breast reconstructions using ADM at a single center were assessed. The number of reconstructed breasts was stratified by ADM fenestration status and ADM type. The incidence of seroma, infection, extrusion, and explantation, and cosmetic score, was compared within the 2 stratified groups. A multivariable regression was performed to identify independent risk factors associated with these complications and aesthetic outcome. Results: In total, data from 450 patients who had 603 breast reconstructions using either AlloDerm or FlexHD demonstrated a significantly higher incidence of seroma with nonfenestrated ADMs (20%) versus fenestrated ADMs (11%; P = 0.0098). Rates of infection and explantation, and cosmetic score, were not influenced by fenestration status. In the multivariable analysis, ADM fenestration remained a significant protective factor for seroma formation. FlexHD also yielded a lower incidence of extrusion (P = 0.0031) and a higher cosmetic score (P = 0.0466) compared with AlloDerm after adjusting for other risk factors. Conclusions: The results of this study support ADM fenestration for reduction of seroma incidence in breast reconstruction, without affecting cosmetic results. Additionally, the choice of ADM may reduce extrusion incidence and improve aesthetic outcomes. PMID:26893994

  15. Plastic Surgery and Acellular Dermal Matrix: Highlighting Trends from 1999 to 2013

    PubMed Central

    Daar, David A; Gandy, Jessica R; Clark, Emily G; Mowlds, Donald S; Paydar, Keyianoosh Z; Wirth, Garrett A

    2016-01-01

    The last decade has ushered in a rapidly expanding global discussion regarding acellular dermal matrix (ADM) applications, economic analyses, technical considerations, benefits, and risks, with recent emphasis on ADM use in breast surgery. This study aims to evaluate global trends in ADM research using bibliometric analysis. The top nine Plastic Surgery journals were determined by impact factor (IF). Each issue of the nine journals between 1999 and 2013 was accessed to compile a database of articles discussing ADM. Publications were further classified by IF, authors’ geographic location, study design, and level of evidence (LOE, I-V). Productivity index and productivity share were calculated for each region. In total, 256 ADM articles were accessed. The annual global publication volume increased significantly by 4.2 (0.87) articles per year (p<0.001), with a mean productivity index of 36.3 (59.0). The mean impact factor of the nine journals increased significantly from 0.61 (0.11) to 2.47 (0.99) from 1993 to 2013 (p<0.001). Despite this increase in the global ADM literature, the majority of research was of weaker LOE (level I: 2.29% and level II: 9.17%). USA contributed the most research (87%), followed by Asia (4.76%) and Western Europe (4.71%). USA contributed the greatest volume of research. Regarding clinical application of ADM, the majority of publications focused on ADM use in breast surgery, specifically breast reconstruction (154 articles, 60.2%). The majority of research was of lower LOE; thus, efforts should be made to strengthen the body of literature, particularly with regard to cost analysis. PMID:27579264

  16. Histologic, Molecular, and Clinical Evaluation of Explanted Breast Prostheses, Capsules, and Acellular Dermal Matrices for Bacteria

    PubMed Central

    Poppler, Louis; Cohen, Justin; Dolen, Utku Can; Schriefer, Andrew E.; Tenenbaum, Marissa M.; Deeken, Corey; Chole, Richard A.; Myckatyn, Terence M.

    2015-01-01

    Background Subclinical infections, manifest as biofilms, are considered an important cause of capsular contracture. Acellular dermal matrices (ADMs) are frequently used in revision surgery to prevent recurrent capsular contractures. Objective We sought to identify an association between capsular contracture and biofilm formation on breast prostheses, capsules, and ADMs in a tissue expander/implant (TE/I) exchange clinical paradigm. Methods Biopsies of the prosthesis, capsule, and ADM from patients (N = 26) undergoing TE/I exchange for permanent breast implant were evaluated for subclinical infection. Capsular contracture was quantified with Baker Grade and intramammary pressure. Biofilm formation was evaluated with specialized cultures, rtPCR, bacterial taxonomy, live:dead staining, and scanning electron microscopy (SEM). Collagen distribution, capsular histology, and ADM remodeling were quantified following fluorescent and light microscopy. Results Prosthetic devices were implanted from 91 to 1115 days. Intramammary pressure increased with Baker Grade. Of 26 patients evaluated, one patient had a positive culture and one patient demonstrated convincing evidence of biofilm morphology on SEM. Following PCR amplification 5 samples randomly selected for 16S rRNA gene sequencing demonstrated an abundance of suborder Micrococcineae, consistent with contamination. Conclusions Our data suggest that bacterial biofilms likely contribute to a proportion, but not all diagnosed capsular contractures. Biofilm formation does not appear to differ significantly between ADMs or capsules. While capsular contracture remains an incompletely understood but common problem in breast implant surgery, advances in imaging, diagnostic, and molecular techniques can now provide more sophisticated insights into the pathophysiology of capsular contracture. Level of Evidence PMID:26229126

  17. A New Approach to Minimize Acellular Dermal Matrix Use in Prosthesis-based Breast Reconstruction

    PubMed Central

    Hadad, Ivan; Liu, Allen S.

    2015-01-01

    Background: Acellular dermal matrices (ADMs) are often used to improve lower-pole contour, as well as allow for single-stage reconstruction, but numerous studies have shown an increased complication rate using ADM. As such, our group has developed a minimal-ADM-use technique to lower complications while effectively recreating lower-pole contour. Methods: A total of 380 postmastectomy prosthesis-based breast reconstructions were performed in 265 patients by a single surgeon. One hundred eight reconstructions were performed using the traditional ADM technique, with a large piece of ADM along the entire inferior and lateral borders. Two hundred twenty-five reconstructions were performed with the minimal-use technique, patching only the lateral area of the reconstruction. Thirty-five reconstructions were performed without the use of any ADM for high-risk reconstructions, most often in morbidly obese patients. Results: Comparing the traditional technique with the minimal-use technique, the seroma rate dropped from 3% to 0%. The rate of infection and reconstruction loss fell from 9% to 1%. Upon greatly reducing or eliminating the use of ADM use in obese patients, the seroma rate decreased from 15.4% to 5.7%, and the reconstruction loss rate decreased from 38% to 9%. Conclusions: This article describes a new surgical approach to minimize the amount of ADM necessary to create an aesthetically pleasing breast reconstruction. We believe that this approach helps avoid the complications of seroma, infection, and loss of the reconstruction. In certain obese patients, total avoidance of ADM may be the better choice. PMID:26301161

  18. Potential sites for the perception of gravity in the acellular slime mold Physarum polycephalum

    NASA Astrophysics Data System (ADS)

    Block, I.; Briegleb, W.

    Recently a gravisensitivity of the acellular slime mold Physarum polycephalum, which possesses no specialized gravireceptor, could be established by conducting experiments under simulated and under real near weightlessness. In these experiments macroplasmodia showed a modulation of their contraction rhythm followed by regulation phenomena. Until now the perception mechanism for the gravistimulus is unknown, but several findings indicate the involvement of mitochondria: A) During the impediment of respiration the Og-reaction is inhibited and the regulation is reduced. B) The response to a light stimulus and the following regulation phenomena strongly resemble the behavior during exposure to Og, the only difference is that the two reactions are directed into opposite directions. In the blue-light reaction a flavin of the mitochondrial matrix seems to be involved in the light perception. C) The contraction rhythm as well as its modulations are coupled to rhythmic changes in the levels of ATP and calcium ions, involving the mitochondria as sites of energy production and of Ca++-storage. - So the mitochondria could be the site of the regulation and they possibly are the receptor sites for the light and gravity stimuli. - Also the observation of a morphologic polarity of the slime mold's plasmodial strands has to be considered: Cross-sections reveal that the ectoplasmic wall surrounding the streaming endoplasm is much thinner on the physically lower side than on the upper side of the strand - this applies to strands lying on or hanging on a horizontal surface. So, in addition to the mitochondria, also the morphologic polarity may be involved in the perception mechanism of the observed gravisensitivity and of the recently established geotaxis. - The potential role of the nuclei and of the contractile elements in the perception of gravity is also discussed.

  19. Neoinnervation and neovascularization of acellular pericardial-derived scaffolds in myocardial infarcts.

    PubMed

    Gálvez-Montón, Carolina; Fernandez-Figueras, M Teresa; Martí, Mercè; Soler-Botija, Carolina; Roura, Santiago; Perea-Gil, Isaac; Prat-Vidal, Cristina; Llucià-Valldeperas, Aida; Raya, Ángel; Bayes-Genis, Antoni

    2015-01-01

    Engineered bioimplants for cardiac repair require functional vascularization and innervation for proper integration with the surrounding myocardium. The aim of this work was to study nerve sprouting and neovascularization in an acellular pericardial-derived scaffold used as a myocardial bioimplant. To this end, 17 swine were submitted to a myocardial infarction followed by implantation of a decellularized human pericardial-derived scaffold. After 30 days, animals were sacrificed and hearts were analyzed with hematoxylin/eosin and Masson's and Gallego's modified trichrome staining. Immunohistochemistry was carried out to detect nerve fibers within the cardiac bioimplant by using βIII tubulin and S100 labeling. Isolectin B4, smooth muscle actin, CD31, von Willebrand factor, cardiac troponin I, and elastin antibodies were used to study scaffold vascularization. Transmission electron microscopy was performed to confirm the presence of vascular and nervous ultrastructures. Left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume, end-diastolic volume, end-systolic volume, end-diastolic wall mass, and infarct size were assessed by using magnetic resonance imaging (MRI). Newly formed nerve fibers composed of several amyelinated axons as the afferent nerve endings of the heart were identified by immunohistochemistry. Additionally, neovessel formation occurred spontaneously as small and large isolectin B4-positive blood vessels within the scaffold. In summary, this study demonstrates for the first time the neoformation of vessels and nerves in cell-free cardiac scaffolds applied over infarcted tissue. Moreover, MRI analysis showed a significant improvement in LVEF (P = 0.03) and CO (P = 0.01) and a 43 % decrease in infarct size (P = 0.007). PMID:26205795

  20. Light-Activated Sealing of Acellular Nerve Allografts following Nerve Gap Injury.

    PubMed

    Fairbairn, Neil G; Ng-Glazier, Joanna; Meppelink, Amanda M; Randolph, Mark A; Valerio, Ian L; Fleming, Mark E; Kochevar, Irene E; Winograd, Jonathan M; Redmond, Robert W

    2016-07-01

    Introduction Photochemical tissue bonding (PTB) uses visible light to create sutureless, watertight bonds between two apposed tissue surfaces stained with photoactive dye. In phase 1 of this two-phase study, nerve gaps repaired with bonded isografts were superior to sutured isografts. When autograft demand exceeds supply, acellular nerve allograft (ANA) is an alternative although outcomes are typically inferior. This study assesses the efficacy of PTB when used with ANA. Methods Overall 20 male Lewis rats had 15-mm left sciatic nerve gaps repaired using ANA. ANAs were secured using epineurial suture (group 1) or PTB (group 2). Outcomes were assessed using sciatic function index (SFI), gastrocnemius muscle mass retention, and nerve histomorphometry. Historical controls from phase 1 were used to compare the performance of ANA with isograft. Statistical analysis was performed using analysis of variance and Bonferroni all-pairs comparison. Results All ANAs had signs of successful regeneration. Mean values for SFI, muscle mass retention, nerve fiber diameter, axon diameter, and myelin thickness were not significantly different between ANA + suture and ANA + PTB. On comparative analysis, ANA + suture performed significantly worse than isograft + suture from phase 1. However, ANA + PTB was statistically comparable to isograft + suture, the current standard of care. Conclusion Previously reported advantages of PTB versus suture appear to be reduced when applied to ANA. The lack of Schwann cells and neurotrophic factors may be responsible. PTB may improve ANA performance to an extent, where they are equivalent to autograft. This may have important clinical implications when injuries preclude the use of autograft. PMID:26878685

  1. Improved Peripheral Nerve Regeneration Using Acellular Nerve Allografts Loaded with Platelet-Rich Plasma

    PubMed Central

    Zheng, Canbin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping

    2014-01-01

    Acellular nerve allografts (ANAs) behave in a similar manner to autografts in supporting axonal regeneration in the repair of short peripheral nerve defects but fail in larger defects. The objective of this article is to evaluate the effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach. Autologous PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and the release of growth factors. Forty-eight Sprague–Dawley rats were randomly divided into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that PRP with a high platelet concentration exhibited a sustained release of growth factors. Twelve weeks after surgery, the autograft group displayed the highest level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a better electrophysiology response for amplitude and conduction velocity than the ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and autograft groups had higher numbers of regenerating nerve fibers. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and autograft groups showed excellent physiological outcomes in terms of the prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue-engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps nearly as well as autografts. PMID:24901030

  2. Plastic Surgery and Acellular Dermal Matrix: Highlighting Trends from 1999 to 2013.

    PubMed

    Daar, David A; Gandy, Jessica R; Clark, Emily G; Mowlds, Donald S; Paydar, Keyianoosh Z; Wirth, Garrett A

    2016-05-01

    The last decade has ushered in a rapidly expanding global discussion regarding acellular dermal matrix (ADM) applications, economic analyses, technical considerations, benefits, and risks, with recent emphasis on ADM use in breast surgery. This study aims to evaluate global trends in ADM research using bibliometric analysis. The top nine Plastic Surgery journals were determined by impact factor (IF). Each issue of the nine journals between 1999 and 2013 was accessed to compile a database of articles discussing ADM. Publications were further classified by IF, authors' geographic location, study design, and level of evidence (LOE, I-V). Productivity index and productivity share were calculated for each region. In total, 256 ADM articles were accessed. The annual global publication volume increased significantly by 4.2 (0.87) articles per year (p<0.001), with a mean productivity index of 36.3 (59.0). The mean impact factor of the nine journals increased significantly from 0.61 (0.11) to 2.47 (0.99) from 1993 to 2013 (p<0.001). Despite this increase in the global ADM literature, the majority of research was of weaker LOE (level I: 2.29% and level II: 9.17%). USA contributed the most research (87%), followed by Asia (4.76%) and Western Europe (4.71%). USA contributed the greatest volume of research. Regarding clinical application of ADM, the majority of publications focused on ADM use in breast surgery, specifically breast reconstruction (154 articles, 60.2%). The majority of research was of lower LOE; thus, efforts should be made to strengthen the body of literature, particularly with regard to cost analysis. PMID:27579264

  3. Histologic Characterization of Acellular Dermal Matrices in a Porcine Model of Tissue Expander Breast Reconstruction

    PubMed Central

    Carruthers, Christopher A.; Dearth, Christopher L.; Reing, Janet E.; Kramer, Caroline R.; Gagne, Darcy H.; Crapo, Peter M.; Garcia, Onelio; Badhwar, Amit; Scott, Jeffrey R.

    2015-01-01

    Background: Acellular dermal matrices (ADMs) have been commonly used in expander-based breast reconstruction to provide inferolateral prosthesis coverage. Although the clinical performance of these biologic scaffold materials varies depending on a number of factors, an in-depth systematic characterization of the host response is yet to be performed. The present study evaluates the biochemical composition and structure of two ADMs, AlloDerm® Regenerative Tissue Matrix and AlloMax™ Surgical Graft, and provides a comprehensive spatiotemporal characterization in a porcine model of tissue expander breast reconstruction. Methods: Each ADM was characterized with regard to thickness, permeability, donor nucleic acid content, (residual double-stranded DNA [dsDNA]), and growth factors (basic fibroblast growth factor [bFGF], vascular endothelial growth factor [VEGF], and transforming growth factor-beta 1 [TGF-β1]). Cytocompatibility was evaluated by in vitro cell culture on the ADMs. The host response was evaluated at 4 and 12 weeks at various locations within the ADMs using established metrics of the inflammatory and tissue remodeling response: cell infiltration, multinucleate giant cell formation, extent of ADM remodeling, and neovascularization. Results: AlloMax incorporated more readily with surrounding host tissue as measured by earlier and greater cell infiltration, fewer foreign body giant cells, and faster remodeling of ADM. These findings correlated with the in vitro composition and cytocompatibility analysis, which showed AlloMax to more readily support in vitro cell growth. Conclusions: AlloMax and AlloDerm demonstrated distinct remodeling characteristics in a porcine model of tissue expander breast reconstruction. PMID:24941900

  4. Ex vivo evaluation of acellular and cellular collagen-glycosaminoglycan flowable matrices.

    PubMed

    Hodgkinson, Tom; Bayat, Ardeshir

    2015-08-01

    Collagen-glycosaminoglycan flowable matrices (CGFM) are increasingly finding utility in a diversifying number of cutaneous surgical procedures. Cellular in-growth and vascularisation of CGFM remain rate-limiting steps, increasing cost and decreasing efficacy. Through in vitro and ex vivo culture methods, this study investigated the improvement of injectable CGFM by the incorporation of hyaluronan (HA) and viable human cells (primary human dermal fibroblasts (PHDFs) and bone marrow-derived mesenchymal stem cells (BM-MSCs)). Ex vivo investigations included the development and evaluation of a human cutaneous wound healing model for the comparison of dermal substitutes. Cells mixed into the Integra Flowable Wound Matrix (IFWM), a commercially available CGFM, were confirmed to be viable and proliferative through MTT assays (p  <  0.05). PHDFs proliferated with greater rapidity than BM-MSCs up to 1 week in culture (p  <  0.05), with PHDF proliferation further enhanced by HA supplementation (p  <  0.05). After scaffold mixing, gene expression was not significantly altered (qRT-PCR). PHDF and BM-MSC incorporation into ex vivo wound models significantly increased re-epithelialisation rate, with maximal effects observed for BM-MSC supplemented IFWM. HA supplementation to PHDF populated IFWM increased re-epithelialisation but had no significant effect on BM-MSC populated IFWM. In conclusion, when combined with PHDF, HA increased re-epithelialisation in IFWM. BM-MSC incorporation significantly improved re-epithelialisation in ex vivo models over acellular and PHDF populated scaffolds. Viable cell incorporation into IFWM has potential to significantly benefit wound healing in chronic and acute cutaneous injuries by allowing a point-of-care matrix to be formed from autologous or allogenic cells and bioactive molecules. PMID:26181360

  5. Root Coverage in Smokers with Acellular Dermal Matrix Graft and Enamel Matrix Derivative: A 12-Month Randomized Clinical Trial.

    PubMed

    Costa, Priscila Paganini; Alves, Luciana Bastos; Souza, Sérgio Luís; Grisi, Márcio Fernando; Palioto, Daniela Bazan; Taba, Mario; Novaes, Arthur Belém

    2016-01-01

    This study investigated whether enamel matrix derivative (EMD) contributes to root coverage of gingival recessions performed with acellular dermal matrix graft (ADMG) in smokers during a 12-month follow-up. A sample of 19 smokers presenting bilateral Miller Class I or II gingival recessions were included. Selected sites randomly received both ADMG and EMD (test) or ADMG alone (control). Probing depth, clinical attachment level, gingival recession height, keratinized tissue, and root coverage were evaluated. Mean gain in recession height (P < .05), sites with complete root coverage (P < .05), and percentage of root coverage (59.7% and 52.8%, respectively) favored the test group compared with the control group. PMID:27333010

  6. Synthesis and physicochemical characterization of a series of hemoglobin-based oxygen carriers: objective comparison between cellular and acellular types.

    PubMed

    Sakai, H; Yuasa, M; Onuma, H; Takeoka, S; Tsuchida, E

    2000-01-01

    A series of hemoglobin (Hb)-based O(2) carriers, acellular and cellular types, were synthesized and their physicochemical characteristics were compared. The acellular type includes intramolecularly cross-linked Hb (XLHb), polyoxyethylene (POE)-conjugated pyridoxalated Hb (POE-PLP-Hb), hydroxyethylstarch-conjugated Hb (HES-XLHb), and glutaraldehyde-polymerized XLHb (Poly-XLHb). The cellular type is Hb-vesicles (HbV) of which the surface is modified with POE (POE-HbV). Their particle diameters are 7 +/- 2, 22 +/- 2, 47 +/- 17, 68 +/- 24, and 224 +/- 76 nm, respectively, thus all the materials penetrate across membrane filters with 0.4 microm pore size, though only the POE-HbV cannot penetrate across the filter with 0.2 microm pore size. These characteristics of permeability are important to consider an optimal particle size in microcirculation in vivo. POE-PLP-Hb ([Hb] = 5 g/dL) showed viscosity of 6.1 cP at 332 s(-1) and colloid osmotic pressure (COP) of 70.2 Torr, which are beyond the physiological conditions (human blood, viscosity = 3-4 cP, COP = ca. 25 Torr). XLHb and Poly-XLHb showed viscosities of 1.0 and 1.5 cp, respectively, which are significantly lower than that of blood. COP of POE-HbV is regulated to 20 Torr in 5% human serum albumin (HSA). HES-XLHb and POE-HbV/HSA showed comparable viscosity with human blood. Microscopic observation of human red blood cells (RBC) after mixing blood with POE-PLP-Hb or HES-XLHb disclosed aggregates of RBC, a kind of sludge, indicating a strong interaction with RBC, which is anticipated to modify peripheral blood flow in vivo. On the other hand, XLHb and POE-HbV showed no rouleaux or aggregates of RBC. The acellular Hbs (P(50) = 14-32 Torr) have their specific O(2) affinities determined by their structures, while that of the cellular POE-HbV is regulated by coencapsulating an appropriate amount of an allosteric effector (e.g., P(50) = 18, 32 Torr). These differences in physicochemical characteristics between the acellular

  7. Combined silicone implant and cartilage grafts for augmentation rhinoplasty.

    PubMed

    Wang, Huan; Fan, Fei; You, Jianjun; Wang, Sheng

    2013-03-01

    Silicone implants are widely used in Asia for nasal dorsal augmentation. Meanwhile, autologous cartilage grafts are the most preferred materials for tip surgery. In order to minimize the drawbacks of silicone implants, combined silicone implant and cartilage grafts were introduced for augmentation rhinoplasty. In this work, augmentation rhinoplasty technique using combined silicone implant and cartilage grafts are reported. Forty-six patients underwent dorsal and tip augmentation using this technique. The outcomes were satisfactory in 45 patients. Bilateral marginal incisions were used without transcolumellar incision. By suturing the silicone nasal implant with a shield cartilage graft, a new complex was achieved. Assisted with a columellar strut either sutured to the complex or not, the new complex could provide improved dorsal height and tip projection with low complication rate in augmentation rhinoplasty. PMID:23524723

  8. Cartilage (Bovine and Shark) (PDQ®)—Patient Version

    Cancer.gov

    Expert-reviewed information summary about the use of bovine and shark cartilage as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  9. Age-associated glycopeptide pigment in human costal cartilage.

    PubMed Central

    van der Korst, J. K.; Willekens, F. L.; Lansink, A. G.; Henrichs, A. M.

    1977-01-01

    Age-associated pigmentation of human costal cartilage is caused by the accumulation of a brown water-soluble substance which can be only be extracted after proteolytic disruption of the cartilage. After isolation by gel filtration and ion exchange chromatography, the compound was identified as an acid glycopeptide. In contrast to ochronotic pigment and an artificial pigment derived by oxidation of homogentistic acid in alkaline solution, the age-associated cartilage pigment was strongly fluorescent and did not form insoluble complexes with cetylpyridinium chloride. Moreover, age-associated cartilage pigment is alkali resistant, in contrast to the ochronotic pigment. The pigment differs from lipofuscin in being strongly hydrophilic and having no affinity for fat stains. The unidentified chromophore could not be separated from the glycopeptide molecule. PMID:596418

  10. Cartilage reshaping: an overview of the state of the art

    NASA Astrophysics Data System (ADS)

    Karamzadeh, Amir M.; Sobol, Emil N.; Rasouli, Alexandre; Nelson, J. Stuart; Milner, Thomas E.; Wong, Brian J.

    2001-05-01

    The laser irradiation of cartilage results in a plastic deformation of the tissue allowing for the creation of new stable shapes. During photothermal stimulation, mechanically deformed cartilage undergoes a temperature dependent phase transition, which results in accelerated stress relaxation of the tissue matrix. Cartilage specimens thus reshaped can be used to recreate the underlying framework of structures in the head and neck. Optimization of this process has required an understanding of the biophysical processes accompanying reshaping and also determination of the laser dosimetry parameters, which maintain graft viability. Extensive in vitro, ex-vivo, and in vivo animal investigations, as well as human trials, have been conducted. This technology is now in use to correct septal deviations in an office-based setting. While the emphasis of clinical investigation has focused on septoplasty procedures, laser mediated cartilage reshaping may have application in surgical procedures involving the trachea, laryngeal framework, external ear, and nasal tip. Future directions for research and device design are discussed.

  11. Cartilage (Bovine and Shark) (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the use of bovine and shark cartilage as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  12. Endobronchial Cartilage Rupture: A Rare Cause of Lobar Collapse.

    PubMed

    Dasa, Osama; Siddiqui, Nauman; Ruzieh, Mohammed; Javaid, Toseef

    2016-01-01

    Endobronchial cartilage rupture is a rare clinical condition, which can present in patients with severe emphysema with sudden onset shortness of breath. We present a case of a 62-year-old male who presented to our emergency department with sudden onset shortness of breath. Chest X-ray showed lung hyperinflation and a right lung field vague small density. Chest Computed Tomography confirmed the presence of right middle lobe collapse. Bronchoscopy revealed partial right middle lobe atelectasis and an endobronchial cartilage rupture. Endobronchial cartilage rupture is a rare condition that can present as sudden onset shortness of breath due to lobar collapse in patients with emphysema and can be triggered by cough. Bronchoscopic findings include finding a collapsed lung lobe and a visible ruptured endobronchial cartilage. A high index of suspicion, chest imaging, and early bronchoscopy can aid in the diagnosis and help prevent complications. PMID:27525149

  13. [T-cartilage tympanoplasty for an open oval window].

    PubMed

    Helms, J; Mlynski, R; Phleps, G

    2011-08-01

    A T shaped cartilage, placed into the open oval window, functions as a stapes. The transvers part of the T prevents a too deep insertion into the vestibule. If necessary small stripes of connective tissue seal the vestibule. PMID:21850613

  14. Refining the Nasal Dorsum with Free Diced Cartilage.

    PubMed

    Hoehne, Julius; Gubisch, Wolfgang; Kreutzer, Christian; Haack, Sebastian

    2016-08-01

    Refining the nasal dorsum has become a major challenge in modern rhinoplasty as irregularities of the nasal dorsum account for a significant number of revision surgeries. In our department, free diced cartilage is now routinely applied for smoothening of the nasal dorsum. In this retrospective study, the outcomes with regard to irregularities or contour deficits of the nasal dorsum of 431 rhinoplasty cases operated by a single surgeon between July 2013 and June 2015, using free diced cartilage, are compared with 327 cases operated by the same surgeon between January 2007 and December 2008, before the introduction of the free diced cartilage technique. A decrease in early revision surgeries (i.e., revision within the 2-year period evaluated) due to dorsal irregularities or contour deficits is seen. Being a quick, easy, and highly cost-effective procedure, we feel that free diced cartilage is currently the ideal technique for refinements of the nasal dorsum. PMID:27494578

  15. A literature review of lasers and articular cartilage.

    PubMed

    Vangsness, C T; Ghaderi, B

    1993-05-01

    Articles from the English literature concerning lasers and articular cartilage were reviewed. Different experimental methods and laser systems were analyzed. Many studies lacked scientific validity. Future investigations with sound biologic foundations are recommended. PMID:8327386

  16. Three-dimensional collagen architecture in bovine articular cartilage.

    PubMed

    Jeffery, A K; Blunn, G W; Archer, C W; Bentley, G

    1991-09-01

    The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair. PMID:1894669

  17. Namaste (counterbalancing) technique: Overcoming warping in costal cartilage

    PubMed Central

    Agrawal, Kapil S.; Bachhav, Manoj; Shrotriya, Raghav

    2015-01-01

    Background: Indian noses are broader and lack projection as compared to other populations, hence very often need augmentation, that too by large volume. Costal cartilage remains the material of choice in large volume augmentations and repair of complex primary and secondary nasal deformities. One major disadvantage of costal cartilage grafts (CCG) which offsets all other advantages is the tendency to warp and become distorted over a period of time. We propose a simple technique to overcome this menace of warping. Materials and Methods: We present the data of 51 patients of rhinoplasty done using CCG with counterbalancing technique over a period of 4 years. Results: No evidence of warping was found in any patient up to a maximum follow-up period of 4 years. Conclusion: Counterbalancing is a useful technique to overcome the problem of warping. It gives liberty to utilize even unbalanced cartilage safely to provide desired shape and use the cartilage without any wastage. PMID:26424973

  18. Endobronchial Cartilage Rupture: A Rare Cause of Lobar Collapse

    PubMed Central

    Siddiqui, Nauman; Javaid, Toseef

    2016-01-01

    Endobronchial cartilage rupture is a rare clinical condition, which can present in patients with severe emphysema with sudden onset shortness of breath. We present a case of a 62-year-old male who presented to our emergency department with sudden onset shortness of breath. Chest X-ray showed lung hyperinflation and a right lung field vague small density. Chest Computed Tomography confirmed the presence of right middle lobe collapse. Bronchoscopy revealed partial right middle lobe atelectasis and an endobronchial cartilage rupture. Endobronchial cartilage rupture is a rare condition that can present as sudden onset shortness of breath due to lobar collapse in patients with emphysema and can be triggered by cough. Bronchoscopic findings include finding a collapsed lung lobe and a visible ruptured endobronchial cartilage. A high index of suspicion, chest imaging, and early bronchoscopy can aid in the diagnosis and help prevent complications. PMID:27525149

  19. Post-traumatic glenohumeral cartilage lesions: a systematic review

    PubMed Central

    Ruckstuhl, Heidi; de Bruin, Eling D; Stussi, Edgar; Vanwanseele, Benedicte

    2008-01-01

    Background Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present. Methods PubMed (MEDLINE), ScienceDirect (EMBASE, BIOBASE, BIOSIS Previews) and the COCHRANE database of systematic reviews were systematically scanned using a defined search strategy to identify relevant articles in this field of research. First selection was done based on abstracts according to specific criteria, where the methodological quality in selected full text articles was assessed by two reviewers. Agreement between raters was investigated using percentage agreement and Cohen's Kappa statistic. The traumatic events were divided into two categories: 1) acute trauma which refers to any single impact situation which directly damages the articular cartilage, and 2) chronic trauma which means cartilage lesions due to overuse or disuse of the shoulder joint. Results The agreement on data quality between the two reviewers was 93% with a Kappa value of 0.79 indicating an agreement considered to be 'substantial'. It was found that acute trauma on the shoulder causes humeral articular cartilage to disrupt from the underlying bone. The pathomechanism is said to be due to compression or shearing, which can be caused by a sudden subluxation or dislocation. However, such impact lesions are rarely reported. In the case of chronic trauma glenohumeral cartilage degeneration is a result of overuse and is associated to other shoulder joint pathologies. In these latter cases it is the rotator cuff which is injured first. This can result in instability and consequent impingement which may progress to glenohumeral cartilage damage. Conclusion The great majority of glenohumeral cartilage lesions without any bony

  20. Improved Visualization of Cartilage Canals Using Quantitative Susceptibility Mapping

    PubMed Central

    Nissi, Mikko J.; Tóth, Ferenc; Wang, Luning; Carlson, Cathy S.; Ellermann, Jutta M.

    2015-01-01

    Purpose Cartilage canal vessels are critical to the normal function of epiphyseal (growth) cartilage and damage to these vessels is demonstrated or suspected in several important developmental orthopaedic diseases. High-resolution, three-dimensional (3-D) visualization of cartilage canals has recently been demonstrated using susceptibility weighted imaging (SWI). In the present study, a quantitative susceptibility mapping (QSM) approach is evaluated for 3-D visualization of the cartilage canals. It is hypothesized that QSM post-processing improves visualization of the cartilage canals by resolving artifacts present in the standard SWI post-processing while retaining sensitivity to the cartilage canals. Methods Ex vivo distal femoral specimens from 3- and 8-week-old piglets and a 1-month-old human cadaver were scanned at 9.4 T with a 3-D gradient recalled echo sequence suitable for SWI and QSM post-processing. The human specimen and the stifle joint of a live, 3-week-old piglet also were scanned at 7.0 T. Datasets were processed using the standard SWI method and truncated k-space division QSM approach. To compare the post-processing methods, minimum/maximum intensity projections and 3-D reconstructions of the processed datasets were generated and evaluated. Results Cartilage canals were successfully visualized using both SWI and QSM approaches. The artifactual splitting of the cartilage canals that occurs due to the dipolar phase, which was present in the SWI post-processed data, was eliminated by the QSM approach. Thus, orientation-independent visualization and better localization of the cartilage canals was achieved with the QSM approach. Combination of GRE with a mask based on QSM data further improved visualization. Conclusions Improved and artifact-free 3-D visualization of the cartilage canals was demonstrated by QSM processing of the data, especially by utilizing susceptibility data as an enhancing mask. Utilizing tissue-inherent contrast, this method allows

  1. Effect of passive motion on articular cartilage in rat osteoarthritis.

    PubMed

    Qian, Jie; Liang, Jun; Wang, Yubin; Wang, Huifang

    2014-08-01

    The aim of the present study was to investigate the effect of moderate passive motion on articular cartilage in osteoarthritis (OA) caused by knee fracture. Sprague-Dawley rats (age, 8 weeks) with knee fractures were used to construct rat knee early- and middle-stage OA models. The stages were fixed for three and six weeks, with 20 rats analyzed at each stage. The experimental groups were exercised daily for 15 m/min with a specified duration. Following the completion of exercise, the effects of proper passive motion on cartilage thickness, the Mankin rating, cartilage collagen matrix, proteoglycan content and the morphological structure of the cartilage in the rat OA models were measured at the various degenerative stages caused by knee fracture. The proteoglycan content of the cartilage matrix, type II collagen fibers and the number of cartilage cells undergoing apoptosis were semiquantified. For early- and middle-stage OA, the cartilage layers in the three- or six-week experimental groups were significantly thicker and the levels of proteoglycans and type II collagen fibers in the weight-bearing area of the cartilage were significantly higher when compared with the control groups (P<0.05). In addition, the Mankin ratings were lower and ligament tension was increased when compared with the control group (P<0.05). In the early-stage OA group, significantly decreased apoptotic rates (P<0.05) were observed in the three- and six-week experimental groups, however, no significant decrease was observed in the middle-stage OA group. In the early-stage OA rats, the thickness of the cartilage layer, as well as the levels of proteoglycans and type II collagen fibers, in the six-week experimental group, were significantly higher compared with the control and three-week subgroups, and a decreased apoptotic rate was observed (P<0.05). In the six-week experimental middle-stage OA group, significant differences were observed in the content of proteoglycans and type II collagen

  2. Effect of passive motion on articular cartilage in rat osteoarthritis

    PubMed Central

    QIAN, JIE; LIANG, JUN; WANG, YUBIN; WANG, HUIFANG

    2014-01-01

    The aim of the present study was to investigate the effect of moderate passive motion on articular cartilage in osteoarthritis (OA) caused by knee fracture. Sprague-Dawley rats (age, 8 weeks) with knee fractures were used to construct rat knee early- and middle-stage OA models. The stages were fixed for three and six weeks, with 20 rats analyzed at each stage. The experimental groups were exercised daily for 15 m/min with a specified duration. Following the completion of exercise, the effects of proper passive motion on cartilage thickness, the Mankin rating, cartilage collagen matrix, proteoglycan content and the morphological structure of the cartilage in the rat OA models were measured at the various degenerative stages caused by knee fracture. The proteoglycan content of the cartilage matrix, type II collagen fibers and the number of cartilage cells undergoing apoptosis were semiquantified. For early- and middle-stage OA, the cartilage layers in the three- or six-week experimental groups were significantly thicker and the levels of proteoglycans and type II collagen fibers in the weight-bearing area of the cartilage were significantly higher when compared with the control groups (P<0.05). In addition, the Mankin ratings were lower and ligament tension was increased when compared with the control group (P<0.05). In the early-stage OA group, significantly decreased apoptotic rates (P<0.05) were observed in the three- and six-week experimental groups, however, no significant decrease was observed in the middle-stage OA group. In the early-stage OA rats, the thickness of the cartilage layer, as well as the levels of proteoglycans and type II collagen fibers, in the six-week experimental group, were significantly higher compared with the control and three-week subgroups, and a decreased apoptotic rate was observed (P<0.05). In the six-week experimental middle-stage OA group, significant differences were observed in the content of proteoglycans and type II collagen

  3. Nanomechanical phenotype of chondroadherin-null murine articular cartilage.

    PubMed

    Batista, Michael A; Nia, Hadi T; Önnerfjord, Patrik; Cox, Karen A; Ortiz, Christine; Grodzinsky, Alan J; Heinegård, Dick; Han, Lin

    2014-09-01

    Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11 weeks, 4 months and 1 year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD(-/-) cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice. PMID:24892719

  4. Reducing the morbidity involved in harvesting autogenous rib cartilage.

    PubMed

    Siegert, Ralf; Magritz, Ralph

    2009-08-01

    Although the use of autogenous cartilage is the gold standard in auricular reconstruction, its main disadvantage is the morbidity due to harvesting the cartilage. This includes postoperative pain, visible scar, and possibly asymmetry and reduced stability of the thorax. To reduce all of these drawbacks, we describe some modifications that reduce pain to a low tolerable level, hide the scar invisibly in the submammary fold in females, and induce regeneration as well reestablish stability of the rib defect. PMID:19809948

  5. Articular cartilage of the knee 3 years after ACL reconstruction

    PubMed Central

    Bae, Ji-Hoon; Hosseini, Ali; Wang, Yang; Torriani, Martin; Gill, Thomas J; Grodzinsky, Alan J

    2015-01-01

    Background and purpose T1ρ or T2 relaxation imaging has been increasingly used to evaluate the cartilage of the knee. We investigated the cartilage of ACL-reconstructed knees 3 years after surgery using T2 relaxation times. Patients and methods 10 patients with a clinically successful unilateral ACL reconstruction were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images of both knees were acquired using a 3T MRI scanner for T2 mapping of the tibiofemoral cartilage. T2 values of the superficial and deep zones of the tibiofemoral cartilage were analyzed in sub-compartmental areas and compared between the ACL-reconstructed and uninjured contralateral knees. Results Higher T2 values were observed in 1 or more sub-compartmental areas of each ACL-reconstructed knee compared to the uninjured contralateral side. Most of the T2 increases were observed at the superficial zones of the cartilage, especially at the medial compartment. At the medial compartment of the ACL-reconstructed knee, the T2 values of the femoral and tibial cartilage were increased by 3–81% compared to the uninjured contralateral side, at the superficial zones of the weight-bearing areas. T2 values in the superficial zone of the central medial femoral condyle differed between the 2 groups (p = 0.002). Interpretation The articular cartilage of ACL-reconstructed knees, although clinically satisfactory, had higher T2 values in the superficial zone of the central medial femoral condyle than in the uninjured contralateral side 3 years after surgery. Further studies are warranted to determine whether these patients would undergo cartilage degeneration over time. PMID:25854533

  6. Mechanical Properties of Porcine Cartilage After Uniform RF Heating

    PubMed Central

    Zemek, Allison J.; Protsenko, Dmitry E.; Wong, Brian J.F.

    2014-01-01

    Background and Objectives Thermally mediated modalities of cartilage reshaping utilize localized heating of cartilage combined with mechanical deformation to achieve new geometries. We sought to determine the steady state elastic modulus of thermally modified cartilage without deformation, as this provides a constraint in mechanical models of the shape change process. Study Design/Materials and Methods The main objective of this study was to characterize the steady state elastic modulus of porcine septal cartilage after uniform heating with radiofrequency (RF) to peak temperatures of 50 ± 5, 65 ± 5, and 85 ± 5°C. The cartilage was divided into three equally sized regions, designated as anterior, middle and posterior. Each region was then sectioned into two specimens with the proximal component serving as a paired control. Results The data confirm that there is high baseline variability in control steady state elastic moduli between animals. Also, the control values confirm a decreasing steady state elastic modulus from anterior to posterior. There is no statistical significance (P > 0.05) found between the elastic moduli of control and treated samples. Conclusions Although shape change and retention have been fairly well characterized, little is known about the specific relation between steady state elastic modulus of cartilage and maximum treatment temperature. We determined that the difference of steady state elastic modulus between control and treated porcine septal samples was not statistically significant after uniform heating with RF to peak temperatures of 50 ± 5, 65 ± 5, and 85 ± 5°C. Ultimately, the results of this study do not pertain to the regions of heated cartilage that are shaped to hold a new form; however, it does show that the regions that are not mechanically deformed do return to the original pre-treatment elastic modulus. This is still useful information that may be used in finite element models to predict changes in internal stress

  7. Cryoprotectant kinetic analysis of a human articular cartilage vitrification protocol.

    PubMed

    Shardt, Nadia; Al-Abbasi, Khaled K; Yu, Hana; Jomha, Nadr M; McGann, Locksley E; Elliott, Janet A W

    2016-08-01

    We recently published a protocol to vitrify human articular cartilage and a method of cryoprotectant removal in preparation for transplantation. The current study's goal was to perform a cryoprotectant kinetic analysis and theoretically shorten the procedure used to vitrify human articular cartilage. First, the loading of the cryoprotectants was modeled using Fick's law of diffusion, and this information was used to predict the kinetics of cryoprotectant efflux after the cartilage sample had been warmed. We hypothesized that diffusion coefficients obtained from the permeation of individual cryoprotectants into porcine articular cartilage could be used to provide a reasonable prediction of the cryoprotectant loading and of the combined cryoprotectant efflux from vitrified human articular cartilage. We tested this hypothesis with experimental efflux measurements. Osteochondral dowels from three patients were vitrified, and after warming, the articular cartilage was immersed in 3 mL X-VIVO at 4 °C in two consecutive solutions, each for 24 h, with the solution osmolality recorded at various times. Measured equilibrium values agreed with theoretical values within a maximum of 15% for all three samples. The results showed that diffusion coefficients for individual cryoprotectants determined from experiments with 2-mm thick porcine cartilage can be used to approximate the rate of efflux of the combined cryoprotectants from vitrified human articular cartilage of similar thickness. Finally, Fick's law of diffusion was used in a computational optimization to shorten the protocol with the constraint of maintaining the theoretical minimum cryoprotectant concentration needed to achieve vitrification. The learning provided by this study will enable future improvements in tissue vitrification. PMID:27221520

  8. Quantitative spatially resolved measurements of mass transfer through laryngeal cartilage.

    PubMed

    Macpherson, J V; O'Hare, D; Unwin, P R; Winlove, C P

    1997-11-01

    The scanning electrochemical microscope (SECM) is a scanned probe microscope that uses the response of a mobile ultramicroelectrode (UME) tip to determine the reactivity, topography, and mass transport characteristics of interfaces with high spatial resolution. SECM strategies for measuring the rates of solute diffusion and convection through samples of cartilage, using amperometric UMEs, are outlined. The methods are used to determine the diffusion coefficients of oxygen and ruthenium(III) hexamine [Ru(NH3)6(3+)] in laryngeal cartilage. The diffusion coefficient of oxygen in cartilage is found to be approximately 50% of that in aqueous electrolyte solution, assuming a partition coefficient of unity for oxygen between cartilage and aqueous solution. In contrast, diffusion of Ru(NH3)6(3+) within the cartilage sample cannot be detected on the SECM timescale, suggesting a diffusion coefficient at least two orders of magnitude lower than that in solution, given a measured partition coefficient for Ru(NH3)6(3+) between cartilage and aqueous solution, Kp = [Ru(NH3)6(3+)]cartilage/[RU(NH3)6(3+)]solution = 3.4 +/- 0.1. Rates of Ru(NH3)6(3+) osmotically driven convective transport across cartilage samples are imaged at high spatial resolution by monitoring the current response of a scanning UME, with an osmotic pressure of approximately 0.75 atm across the slice. A model is outlined that enables the current response to be related to the local flux. By determining the topography of the sample from the current response with no applied osmotic pressure, local transport rates can be correlated with topographical features of the sample surface, at much higher spatial resolution than has previously been achieved. PMID:9370471

  9. Quantitative spatially resolved measurements of mass transfer through laryngeal cartilage.

    PubMed Central

    Macpherson, J V; O'Hare, D; Unwin, P R; Winlove, C P

    1997-01-01

    The scanning electrochemical microscope (SECM) is a scanned probe microscope that uses the response of a mobile ultramicroelectrode (UME) tip to determine the reactivity, topography, and mass transport characteristics of interfaces with high spatial resolution. SECM strategies for measuring the rates of solute diffusion and convection through samples of cartilage, using amperometric UMEs, are outlined. The methods are used to determine the diffusion coefficients of oxygen and ruthenium(III) hexamine [Ru(NH3)6(3+)] in laryngeal cartilage. The diffusion coefficient of oxygen in cartilage is found to be approximately 50% of that in aqueous electrolyte solution, assuming a partition coefficient of unity for oxygen between cartilage and aqueous solution. In contrast, diffusion of Ru(NH3)6(3+) within the cartilage sample cannot be detected on the SECM timescale, suggesting a diffusion coefficient at least two orders of magnitude lower than that in solution, given a measured partition coefficient for Ru(NH3)6(3+) between cartilage and aqueous solution, Kp = [Ru(NH3)6(3+)]cartilage/[RU(NH3)6(3+)]solution = 3.4 +/- 0.1. Rates of Ru(NH3)6(3+) osmotically driven convective transport across cartilage samples are imaged at high spatial resolution by monitoring the current response of a scanning UME, with an osmotic pressure of approximately 0.75 atm across the slice. A model is outlined that enables the current response to be related to the local flux. By determining the topography of the sample from the current response with no applied osmotic pressure, local transport rates can be correlated with topographical features of the sample surface, at much higher spatial resolution than has previously been achieved. Images FIGURE 6 FIGURE 7 FIGURE 8 PMID:9370471

  10. Rapid isolation of intact, viable fetal cartilage models

    SciTech Connect

    Schmidt, R.R.; Chepenik, K.P.; Paynton, B.V.; Cotler, J.M.

    1982-04-01

    A rapid procedure is described for the isolation of viable, intact, femoral cartilage models (humeri and femora) obtained from pregnant rats on the 18th day of gestation. Viability of these models is demonstrated in an in vitro system where the incorporation of /sup 35/S-sulfate was linear with time of incubation and with numbers of cartilage models utilized. Treatment of cartilage models with ice-cold trichloroacetic acid and a boiling water bath prior to incubation with radiolabel, reduced the amount of radioactivity incorporated to 1.3% of that observed for models incubated by routine procedures. Furthermore, digestion of cartilage model homogenates with protease yielded a supernatant from which 51% to 57% of the radioactivity was precipitated as GAG. This method may also be used to isolate fetal cartilage models as early as the 16th day of gestation. with this system, specific biochemical parameters of mammalian fetal chondrogenesis may be surveyed in normally and abnormally developing fetal cartilage free of surrounding soft tissue.

  11. In Vitro Engineering of High Modulus Cartilage-Like Constructs

    PubMed Central

    Seedhom, Bahaa B.; Carey, Duane O.; Bulpitt, Andy J.; Treanor, Darren E.; Kirkham, Jennifer

    2016-01-01

    To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted. PMID:26850081

  12. Hydrogels for the Repair of Articular Cartilage Defects

    PubMed Central

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

    The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID:21510824

  13. The Role of Interstitial Fluid Pressurization in Articular Cartilage Lubrication

    PubMed Central

    Ateshian, Gerard A.

    2009-01-01

    Over the last two decades, considerable progress has been reported in the field of cartilage mechanics that impacts our understanding of the role of interstitial fluid pressurization on cartilage lubrication. Theoretical and experimental studies have demonstrated that the interstitial fluid of cartilage pressurizes considerably under loading, potentially supporting most of the applied load under various transient or steady-state conditions. The fraction of the total load supported by fluid pressurization has been called the fluid load support. Experimental studies have demonstrated that the friction coefficient of cartilage correlates negatively with this variable, achieving remarkably low values when the fluid load support is greatest. A theoretical framework that embodies this relationship has been validated against experiments, predicting and explaining various outcomes, and demonstrating that a low friction coefficient can be maintained for prolonged loading durations under normal physiological function. This paper reviews salient aspects of this topic, as well as its implications for improving our understanding of boundary lubrication by molecular species in synovial fluid and the cartilage superficial zone. Effects of cartilage degeneration on its frictional response are also reviewed. PMID:19464689

  14. Validity of echographic evaluation of cartilage in gonarthrosis. Preliminary report.

    PubMed

    Martino, F; Ettorre, G C; Angelelli, G; Macarini, L; Patella, V; Moretti, B; D'Amore, M; Cantatore, F P

    1993-06-01

    We studied an echographic technique by which precise reproducible measurements of articular cartilage thickness of the knee is possible. Two groups of individuals were studied: a group of 18 patients with gonarthrosis and a control group of 10 normal individuals. The group of 18 patients with gonarthrosis was studied by ultrasound (US) before knee prosthesis surgery. The cartilage thickness was measured within the weight-bearing area. US re-evaluation and histological measurements were made on the pathological specimen following the operation. Results of pre- and post-operative US data were compared with histological data. A good correlation between these measurements was found [P(t) > 10%]. In order to have comparative reference values of the articular cartilage within the weight-bearing area of the femoral trochlea a group of 10 control subjects was also studied with US as above. We found that the articular cartilage thickness of the femoral trochlea in the weight-bearing area has a mean of 2.2 +/- 0.3 mm for the lateral condyle and 2.3 +/- 0.2 mm for the medial condyle. The intra-observer and inter-observer difference in measurements was evaluated with Student's t-test. Our data demonstrate that US measurements of articular cartilage thickness of femoral condyles is a sensitive and reproducible technique which permits early diagnosis and management of knee arthropathy as well as quantification of cartilage damage. PMID:8358975

  15. Matrix Disruptions, Growth, and Degradation of Cartilage with Impaired Sulfation*

    PubMed Central

    Mertz, Edward L.; Facchini, Marcella; Pham, Anna T.; Gualeni, Benedetta; De Leonardis, Fabio; Rossi, Antonio; Forlino, Antonella

    2012-01-01

    Diastrophic dysplasia (DTD) is an incurable recessive chondrodysplasia caused by mutations in the SLC26A2 transporter responsible for sulfate uptake by chondrocytes. The mutations cause undersulfation of glycosaminoglycans in cartilage. Studies of dtd mice with a knock-in Slc26a2 mutation showed an unusual progression of the disorder: net undersulfation is mild and normalizing with age, but the articular cartilage degrades with age and bones develop abnormally. To understand underlying mechanisms, we studied newborn dtd mice. We developed, verified and used high-definition infrared hyperspectral imaging of cartilage sections at physiological conditions, to quantify collagen and its orientation, noncollagenous proteins, and chondroitin chains, and their sulfation with 6-μm spatial resolution and without labeling. We found that chondroitin sulfation across the proximal femur cartilage varied dramatically in dtd, but not in the wild type. Corresponding undersulfation of dtd was mild in most regions, but strong in narrow articular and growth plate regions crucial for bone development. This undersulfation correlated with the chondroitin synthesis rate measured via radioactive sulfate incorporation, explaining the sulfation normalization with age. Collagen orientation was reduced, and the reduction correlated with chondroitin undersulfation. Such disorientation involved the layer of collagen covering the articular surface and protecting cartilage from degradation. Malformation of this layer may contribute to the degradation progression with age and to collagen and proteoglycan depletion from the articular region, which we observed in mice already at birth. The results provide clues to in vivo sulfation, DTD treatment, and cartilage growth. PMID:22556422

  16. The Role of Sirtuins in Cartilage Homeostasis and Osteoarthritis.

    PubMed

    Dvir-Ginzberg, Mona; Mobasheri, Ali; Kumar, Ashok

    2016-07-01

    The past decade has witnessed many advances in the understanding of sirtuin biology and related regulatory circuits supporting the capacity of these proteins to serve as energy-sensing molecules that contribute to healthspan in various tissues, including articular cartilage. Hence, there has been a significant increase in new investigations that aim to elucidate the mechanisms of sirtuin function and their roles in cartilage biology, skeletal development, and pathologies such as osteoarthritis (OA), rheumatoid arthritis (RA), and intervertebral disc degeneration (IVD). The majority of the work carried out to date has focused on SIRT1, although SIRT6 has more recently become a focus of some investigations. In vivo work with transgenic mice has shown that Sirt1 and Sirt6 are essential for maintaining cartilage homeostasis and that the use of sirtuin-activating molecules such as resveratrol may have beneficial effects on cartilage anabolism. Current thinking is that SIRT1 exerts positive effects on cartilage by encouraging chondrocyte survival, especially under stress conditions, which may provide a mechanism supporting the use of sirtuin small-molecule activators (STACS) for future therapeutic interventions in OA and other degenerative pathologies of joints, especially those that involve articular cartilage. PMID:27289467

  17. Does vitamin D affect femoral cartilage thickness? An ultrasonographic study.

    PubMed

    Malas, Fevziye Unsal; Kara, Murat; Aktekin, Lale; Ersöz, Murat; Ozçakar, Levent

    2014-09-01

    This study aims to investigate the association between vitamin D levels and distal femoral cartilage thickness in healthy subjects. Eighty patients who were admitted to our outpatient clinic between May and July 2013 were classified into three subgroups according to their 25-OH vitamin D levels of <10, 10-20, and ≥20 ng/mL. Distal femoral cartilage thickness was measured from the midpoints of the right medial condyle (RMC), right lateral condyle (RLC), right intercondylar area (RIA), left medial condyle (LMC), left lateral condyle (LLC), and left intercondylar area (LIA) by using musculoskeletal ultrasound (US). The group with severe vitamin D deficiency (<10 ng/mL) had thinner femoral cartilage thickness at LMC (p = 0.005). Positive correlations were determined only between vitamin D levels and US measurements in the severe vitamin D deficiency group at RLC (r = 444, p = 0.020), LMC (r = 357, p = 0.067), and LLC (r = 568, p = 0.002). Low levels of vitamin D seem to affect the femoral cartilage thickness, adversely. Further studies are necessary to ascertain the clinical relevance of this change in cartilage thickness and whether vitamin D supplementation can reverse the cartilage thinning process or the allied clinical symptoms in the course of knee osteoarthritis. PMID:24221506

  18. Colonies in engineered articular cartilage express superior differentiation.

    PubMed

    Selvaratnam, L; Abd Rahim, S; Kamarul, T; Chan, K Y; Sureshan, S; Penafort, R; Ng, C L L

    2005-07-01

    In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans. PMID:16381284

  19. In Vitro Engineering of High Modulus Cartilage-Like Constructs.

    PubMed

    Finlay, Scott; Seedhom, Bahaa B; Carey, Duane O; Bulpitt, Andy J; Treanor, Darren E; Kirkham, Jennifer

    2016-04-01

    To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted. PMID:26850081

  20. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    SciTech Connect

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-07-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net /sup 35/SO/sub 4/-labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage.

  1. CCN1 Regulates Chondrocyte Maturation and Cartilage Development

    PubMed Central

    Zhang, Yongchun; Sheu, Tzong-jen; Hoak, Donna; Shen, Jie; Hilton, Matthew J; Zuscik, Michael J; Jonason, Jennifer H; O’Keefe, Regis J

    2016-01-01

    WNT/β-CATENIN signaling is involved in multiple aspects of skeletal development, including chondrocyte differentiation and maturation. Although the functions of β-CATENIN in chondrocytes have been extensively investigated through gain-of-function and loss-of-function mouse models, the precise downstream effectors through which β-CATENIN regulates these processes are not well defined. Here, we report that the matricellular protein, CCN1, is induced by WNT/β-CATENIN signaling in chondrocytes. Specifically, we found that β-CATENIN signaling promotes CCN1 expression in isolated primary sternal chondrocytes and both embryonic and postnatal cartilage. Additionally, we show that, in vitro, CCN1 overexpression promotes chondrocyte maturation, whereas inhibition of endogenous CCN1 function inhibits maturation. To explore the role of CCN1 on cartilage development and homeostasis in vivo, we generated a novel transgenic mouse model for conditional Ccn1 overexpression and show that cartilage-specific CCN1 overexpression leads to chondrodysplasia during development and cartilage degeneration in adult mice. Finally, we demonstrate that CCN1 expression increases in mouse knee joint tissues after meniscal/ligamentous injury (MLI) and in human cartilage after meniscal tear. Collectively, our data suggest that CCN1 is an important regulator of chondrocyte maturation during cartilage development and homeostasis. PMID:26363286

  2. [Molecular mechanisms of cartilage formation and chondrocyte maturation].

    PubMed

    Tamamura, Yoshihiro; Iwamoto, Masahiro

    2004-07-01

    Cartilage plays multiple roles in vertebrate animals. In an embryonic stage and early postnatal life, cartilage is important not only as a structural support of early embryo but also as a template of endochondral bone. In a later postnatal life, cartilage provides smooth joint movement and tissue elasticity. A number of critical signaling molecules that regulate cartilage formation and chondrocytes maturation in endochondral bone formation have been identified to date. The interplay of those important molecules is also actively studied. However, several fundamental questions still remain unsolved. What signal initiates mesenchymal cell condensation? Does condensation enough to make cells competent for BMP-induced chondrogenesis? Is there chondrocyte stem cell in cartilage? Likewise, it is not known which factor triggers chondrocytes maturation. In this review article, we summarized the action of several key factors including BMP, hedgehog, PTHrP, and Wnt in condensation, chondrogenenic differentiation and maturation of chondrocytes. Towards further understanding of above fundamental questions, this review article also tried to propose future direction of cartilage biology research. PMID:15577071

  3. Characterization of neopeptides in equine articular cartilage degradation.

    PubMed

    Peffers, Mandy Jayne; Thornton, David James; Clegg, Peter David

    2016-01-01

    Osteoarthritis is characterized by a loss of extracellular matrix that leads to cartilage degradation and joint space narrowing. Specific proteases, including the aggrecanases ADAMTS-4 and matrix metalloproteinase 3, are important in initiating and promoting cartilage degradation in osteoarthritis. This study investigated protease-specific and disease-specific cleavage patterns of particular extracellular matrix proteins by comparing new peptide fragments, neopeptides, in specific exogenous protease-driven digestion of a crude cartilage proteoglycan extract and an in-vitro model of early osteoarthritis. Additionally, equine cartilage explants were treated with interleukin-1 and the media collected. Proteolytic cleavage products following trypsin digestion were then identified using tandem mass spectrometry. Complete sequences of proteolytically cleaved neopeptides were determined for the major cartilage proteoglycans aggrecan, biglycan, decorin, fibromodulin plus cartilage oligomeric matrix protein. The generation of neopeptides varied with enzyme specificity; however, some peptides were common to all samples. Previous known and novel cleavage sites were identifies. The identification of novel peptide fragments provides a platform for the development of antibodies that could assist in the identification of biomarkers for osteoarthritis (OA), as well as the identification of basic biochemical processes underlying OA. PMID:26124002

  4. CCN1 Regulates Chondrocyte Maturation and Cartilage Development.

    PubMed

    Zhang, Yongchun; Sheu, Tzong-Jen; Hoak, Donna; Shen, Jie; Hilton, Matthew J; Zuscik, Michael J; Jonason, Jennifer H; O'Keefe, Regis J

    2016-03-01

    WNT/β-CATENIN signaling is involved in multiple aspects of skeletal development, including chondrocyte differentiation and maturation. Although the functions of β-CATENIN in chondrocytes have been extensively investigated through gain-of-function and loss-of-function mouse models, the precise downstream effectors through which β-CATENIN regulates these processes are not well defined. Here, we report that the matricellular protein, CCN1, is induced by WNT/β-CATENIN signaling in chondrocytes. Specifically, we found that β-CATENIN signaling promotes CCN1 expression in isolated primary sternal chondrocytes and both embryonic and postnatal cartilage. Additionally, we show that, in vitro, CCN1 overexpression promotes chondrocyte maturation, whereas inhibition of endogenous CCN1 function inhibits maturation. To explore the role of CCN1 on cartilage development and homeostasis in vivo, we generated a novel transgenic mouse model for conditional Ccn1 overexpression and show that cartilage-specific CCN1 overexpression leads to chondrodysplasia during development and cartilage degeneration in adult mice. Finally, we demonstrate that CCN1 expression increases in mouse knee joint tissues after meniscal/ligamentous injury (MLI) and in human cartilage after meniscal tear. Collectively, our data suggest that CCN1 is an important regulator of chondrocyte maturation during cartilage development and homeostasis. © 2015 American Society for Bone and Mineral Research. PMID:26363286

  5. The Role of miRNAs in Cartilage Homeostasis

    PubMed Central

    Li, Yong Ping; Wei, Xiao Chun; Li1, Peng Cu; Chen, Chun Wei; Wang, Xiao Hu; Jiao, Qiang; Wang, Dong Ming; Wei, Fang Yuan; Zhang, Jian Zhong; Wei, Lei

    2015-01-01

    Osteoarthritis (OA) is an age-related disease with poorly understood pathogenesis. Recent studies have demonstrated that miRNA might play a key role in OA initiation and development. We reviewed recent publications and elucidated the connection between miRNA and OA cartilage anabolic and catabolic signals, including four signaling pathways: TGF-β/Smads and BMPs signaling, associated with cartilage anabolism; and MAPK and NF-KB signaling, associated with cartilage catabolism. We also explored the relationships with MMP, ADAMTS and NOS (NitricOxide Synthases) families, as well as with the catabolic cytokines IL-1 and TNF-α. The potential role of miRNAs in biological processes such as cartilage degeneration, chondrocyte proliferation, and differentiation is discussed. Collective evidence indicates that miRNAs play a critical role in cartilage degeneration. These findings will aid in understanding the molecular network that governs articular cartilage homeostasis and in to elucidate the role of miRNA in the pathogenesis of OA. PMID:27019614

  6. Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

    PubMed Central

    Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

    2014-01-01

    Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

  7. Image processing techniques for noise removal, enhancement and segmentation of cartilage OCT images

    NASA Astrophysics Data System (ADS)

    Rogowska, Jadwiga; Brezinski, Mark E.

    2002-02-01

    Osteoarthritis, whose hallmark is the progressive loss of joint cartilage, is a major cause of morbidity worldwide. Recently, optical coherence tomography (OCT) has demonstrated considerable promise for the assessment of articular cartilage. Among the most important parameters to be assessed is cartilage width. However, detection of the bone cartilage interface is critical for the assessment of cartilage width. At present, the quantitative evaluations of cartilage thickness are being done using manual tracing of cartilage-bone borders. Since data is being obtained near video rate with OCT, automated identification of the bone-cartilage interface is critical. In order to automate the process of boundary detection on OCT images, there is a need for developing new image processing techniques. In this paper we describe the image processing techniques for speckle removal, image enhancement and segmentation of cartilage OCT images. In particular, this paper focuses on rabbit cartilage since this is an important animal model for testing both chondroprotective agents and cartilage repair techniques. In this study, a variety of techniques were examined. Ultimately, by combining an adaptive filtering technique with edge detection (vertical gradient, Sobel edge detection), cartilage edges can be detected. The procedure requires several steps and can be automated. Once the cartilage edges are outlined, the cartilage thickness can be measured.

  8. Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage

    PubMed Central

    2014-01-01

    Introduction Cartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Methods The distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance. Results Young, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected. Conclusions MALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved. PMID:24886698

  9. An in situ hybridization study of perlecan, DMP1, and MEPE in developing condylar cartilage of the fetal mouse mandible and limb bud cartilage.

    PubMed

    Fujikawa, K; Yokohama-Tamaki, T; Morita, T; Baba, O; Qin, C; Shibata, S

    2015-01-01

    The main purpose of this in situ hybridization study was to investigate mRNA expression of three bone/cartilage matrix components (perlecan, DMP1, and MEPE) in developing primary (tibial) and secondary (condylar) cartilage. Perlecan mRNA expression was first detected in newly formed chondrocytes in tibial cartilage at E13.0, but this expression decreased in hypertrophic chondrocytes at E14.0. In contrast, at E15.0, perlecan mRNA was first detected in the newly formed chondrocytes of condylar cartilage; these chondrocytes had characteristics of hypertrophic chondrocytes, which confirmed the previous observation that progenitor cells of developing secondary cartilage rapidly differentiate into hypertrophic chondrocytes. DMP1 mRNA was detected in many chondrocytes within the lower hypertrophic cell zone in tibial cartilage at E14.0. In contrast, DMP1 mRNA expression was only transiently detected in a few chondrocytes of condylar cartilage at E15.0. Thus, DMP1 may be less important in the developing condylar cartilage than in the tibial cartilage. Another purpose of this study was to test the hypothesis that MEPE may be a useful marker molecule for cartilage. MEPE mRNA was not detected in any chondrocytes in either tibial or condylar cartilage; however, MEPE immunoreactivity was detected throughout the cartilage matrix. Western immunoblot analysis demonstrated that MEPE antibody recognized two bands, one of 67 kDa and another of 59 kDa, in cartilage-derived samples. Thus MEPE protein may gradually accumulate in the cartilage, even though mRNA expression levels were below the limits of detection of in situ hybridization. Ultimately, we could not designate MEPE as a marker molecule for cartilage, and would modify our original hypothesis. PMID:26428891

  10. An In Situ Hybridization Study of Perlecan, DMP1, and MEPE in Developing Condylar Cartilage of the Fetal Mouse Mandible and Limb Bud Cartilage

    PubMed Central

    Fujikawa, K.; Yokohama-Tamaki, T.; Morita, T.; Baba, O.; Qin, C.; Shibata, S.

    2015-01-01

    The main purpose of this in situ hybridization study was to investigate mRNA expression of three bone/cartilage matrix components (perlecan, DMP1, and MEPE) in developing primary (tibial) and secondary (condylar) cartilage. Perlecan mRNA expression was first detected in newly formed chondrocytes in tibial cartilage at E13.0, but this expression decreased in hypertrophic chondrocytes at E14.0. In contrast, at E15.0, perlecan mRNA was first detected in the newly formed chondrocytes of condylar cartilage; these chondrocytes had characteristics of hypertrophic chondrocytes, which confirmed the previous observation that progenitor cells of developing secondary cartilage rapidly differentiate into hypertrophic chondrocytes. DMP1 mRNA was detected in many chondrocytes within the lower hypertrophic cell zone in tibial cartilage at E14.0. In contrast, DMP1 mRNA expression was only transiently detected in a few chondrocytes of condylar cartilage at E15.0. Thus, DMP1 may be less important in the developing condylar cartilage than in the tibial cartilage. Another purpose of this study was to test the hypothesis that MEPE may be a useful marker molecule for cartilage. MEPE mRNA was not detected in any chondrocytes in either tibial or condylar cartilage; however, MEPE immunoreactivity was detected throughout the cartilage matrix. Western immunoblot analysis demonstrated that MEPE antibody recognized two bands, one of 67 kDa and another of 59 kDa, in cartilage-derived samples. Thus MEPE protein may gradually accumulate in the cartilage, even though mRNA expression levels were below the limits of detection of in situ hybridization. Ultimately, we could not designate MEPE as a marker molecule for cartilage, and would modify our original hypothesis. PMID:26428891

  11. Anomalous NMR Relaxation in Cartilage Matrix Components and Native Cartilage: Fractional-Order Models

    PubMed Central

    Magin, Richard L.; Li, Weiguo; Velasco, M. Pilar; Trujillo, Juan; Reiter, David A.; Morgenstern, Ashley; Spencer, Richard G.

    2011-01-01

    We present a fractional-order extension of the Bloch equations to describe anomalous NMR relaxation phenomena (T1 and T2). The model has solutions in the form of Mittag-Leffler and stretched exponential functions that generalize conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex, heterogeneous materials. Here, we apply these fractional-order T1 and T2 relaxation models to experiments performed at 9.4 and 11.7 Tesla on type I collagen gels, chondroitin sulfate mixtures, and to bovine nasal cartilage (BNC), a largely isotropic and homogeneous form of cartilage. The results show that the fractional-order analysis captures important features of NMR relaxation that are typically described by multi-exponential decay models. We find that the T2 relaxation of BNC can be described in a unique way by a single fractional-order parameter (α), in contrast to the lack of uniqueness of multi-exponential fits in the realistic setting of a finite signal-to-noise ratio. No anomalous behavior of T1 was observed in BNC. In the single-component gels, for T2 measurements, increasing the concentration of the largest components of cartilage matrix, collagen and chondroitin sulfate, results in a decrease in α, reflecting a more restricted aqueous environment. The quality of the curve fits obtained using Mittag-Leffler and stretched exponential functions are in some cases superior to those obtained using mono- and bi-exponential models. In both gels and BNC, α appears to account for microstructural complexity in the setting of an altered distribution of relaxation times. This work suggests the utility of fractional-order models to describe T2 NMR relaxation processes in biological tissues. PMID:21498095

  12. Anomalous NMR relaxation in cartilage matrix components and native cartilage: fractional-order models.

    PubMed

    Magin, Richard L; Li, Weiguo; Pilar Velasco, M; Trujillo, Juan; Reiter, David A; Morgenstern, Ashley; Spencer, Richard G

    2011-06-01

    We present a fractional-order extension of the Bloch equations to describe anomalous NMR relaxation phenomena (T(1) and T(2)). The model has solutions in the form of Mittag-Leffler and stretched exponential functions that generalize conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex, heterogeneous materials. Here, we apply these fractional-order T(1) and T(2) relaxation models to experiments performed at 9.4 and 11.7 Tesla on type I collagen gels, chondroitin sulfate mixtures, and to bovine nasal cartilage (BNC), a largely isotropic and homogeneous form of cartilage. The results show that the fractional-order analysis captures important features of NMR relaxation that are typically described by multi-exponential decay models. We find that the T(2) relaxation of BNC can be described in a unique way by a single fractional-order parameter (α), in contrast to the lack of uniqueness of multi-exponential fits in the realistic setting of a finite signal-to-noise ratio. No anomalous behavior of T(1) was observed in BNC. In the single-component gels, for T(2) measurements, increasing the concentration of the largest components of cartilage matrix, collagen and chondroitin sulfate, results in a decrease in α, reflecting a more restricted aqueous environment. The quality of the curve fits obtained using Mittag-Leffler and stretched exponential functions are in some cases superior to those obtained using mono- and bi-exponential models. In both gels and BNC, α appears to account for micro-structural complexity in the setting of an altered distribution of relaxation times. This work suggests the utility of fractional-order models to describe T(2) NMR relaxation processes in biological tissues. PMID:21498095

  13. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

    NASA Astrophysics Data System (ADS)

    Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

    2011-12-01

    We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

  14. The initial attachment of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis in rat molars.

    PubMed

    Yamamoto, T; Domon, T; Takahashi, S; Islam, M N; Suzuki, R

    2001-03-01

    To elucidate the initial attachment mechanism of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis, developing rat molars were observed by light microscopy and scanning electron microscopy combined with NaOH maceration. The NaOH maceration was used to observe details of the positional association of cemental and dentinal fibrils during cementogenesis. An initial hematoxylin stained, cementum layer began to form on the root dentin surface with the first dentin mineralization in both acellular and cellular cementogenesis. The initial attachment of cemental fibrils to the dentin surface also began at this point. At the initial attachment the intermingling of cemental and dentinal fibrils occurred only in places. With advanced cementogenesis the initial cementum layer became the fibril-poor cemento-dentinal junction. This suggests that cemental fibrils attach on the initial cementum layer, and not directly on dentinal fibrils, so that the layer results in the fibril-poor cemento-dentinal junction. The present study suggests that an intervening adhesive is necessary for the cemento-dentinal attachment at any stage of cementogenesis in rat molars. PMID:11325058

  15. Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies.

    PubMed

    De Carlo, E; Baiguera, S; Conconi, M T; Vigolo, S; Grandi, C; Lora, S; Martini, C; Maffei, P; Tamagno, G; Vettor, R; Sicolo, N; Parnigotto, P P

    2010-02-01

    Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin- and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion. PMID:20043127

  16. Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket.

    PubMed

    Cho, Won-Kyung; Jung, Su-Kyung; Paik, Ji-Sun; Yang, Suk-Woo

    2016-07-01

    Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 ± 37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball. PMID:27258711

  17. In Vivo Confocal Microscopic Observation of Lamellar Corneal Transplantation in the Rabbit Using Xenogenic Acellular Corneal Scaffolds as a Substitute

    PubMed Central

    Feng, Yun; Wang, Wei

    2015-01-01

    Background: The limiting factor to corneal transplantation is the availability of donors. Research has suggested that xenogenic acellular corneal scaffolds (XACS) may be a possible alternative to transplantation. This study aimed to investigate the viability of performing lamellar corneal transplantation (LCT) in rabbits using canine XACS. Methods: Fresh dog corneas were decellularized by serial digestion, and LCT was performed on rabbit eyes using xenogeneic decellularized corneal matrix. Cellular and morphological changes were observed by slit-lamp, light, and scanning electron microscopy at 7, 30 and 90 days postoperatively. Immunocytochemical staining for specific markers such as keratin 3, vimentin and MUC5AC, was used to identify cells in the graft. Results: Decellularized xenogenic corneal matrix remained transparent for about 1-month after LCT. The recipient cells were able to survive and proliferate into the grafts. Three months after transplantation, grafts had merged with host tissue, and graft epithelialization and vascularization had occurred. Corneal nerve fibers were able to grow into the graft in rabbits transplanted with XACS. Conclusions: Xenogenic acellular corneal scaffolds can maintain the transparency of corneal grafts about 1-month and permit growth of cells and nerve fibers, and is, therefore, a potential substitute or carrier for a replacement cornea. PMID:25836615

  18. Silicon sheet technologies

    SciTech Connect

    Ciszek, T.F.

    1982-09-01

    A classification of silicon sheet growth methods by meniscus geometry permits them to be discussed in three groups: short meniscus techniques, high meniscus techniques, and extended meniscus or large solid/liquid interface area techniques. A second parameter, meniscus shaper interaction with the liquid silicon, is also instrumental in determining the characteristics of the various sheet processes. The current status of each process is discussed in the context of meniscus geometry and shaper/melt interaction. One aspect of sheet growth, surface area generation rate, is quantitatively compared with combined ingot growth and wafering surface area generation rates.

  19. Microcomponent sheet architecture

    DOEpatents

    Wegeng, R.S.; Drost, M.K..; McDonald, C.E.

    1997-03-18

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation. 14 figs.

  20. Microcomponent sheet architecture

    DOEpatents

    Wegeng, Robert S.; Drost, M. Kevin; McDonald, Carolyn E.

    1997-01-01

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.

  1. Potential regulation of cartilage metabolism in osteoarthritis by fibronectin fragments.

    PubMed

    Homandberg, G A

    1999-10-15

    There are few candidates for biochemical pathways that either initiate or amplify catabolic processes involved in osteoarthritis (OA). Perhaps, one of the most likely sources for such pathways may be within the extracellular matrix itself. This review focuses on an example of how specific degradation products of the extracellular matrix of cartilage, produced during proteolytic damage, have the potential to enhance OA-like processes. In this example, these products can induce or activate other factors, such as catabolic cytokines, that amplify the damage. The damage, in turn, enhances levels of the degradation products themselves, as in a positive feedback loop. Since these products are derived from the cartilage matrix, they could be considered barometers of the health of the cartilage that signal to the chondrocyte, through outside to inside signaling, the health or status of the surrounding matrix. The best example and most characterized system is that of fragments of the matrix protein, fibronectin (Fn), although as discussed later, other recently discovered fragment systems may also have the potential to regulate cartilage metabolism. In the case of Fn fragments (Fn-fs), the Fn-fs enhance levels of catabolic cytokines as in OA and, thus, are potentially earlier damage mediators than catabolic cytokines. The Fn-fs up-regulate matrix metalloproteinase (MMP) expression, significantly enhance degradation and loss of proteoglycan (PG) from cartilage and temporarily suppress PG synthesis, all events observed in OA. However, this Fn-f system may be involved in normal cartilage homeostasis as well. For example, low concentrations of Fn-fs enhance anabolic activities and could play a role in normal homeostasis. This system may also be involved in not only amplifying damage but also coupling damage to repair. For example, high concentrations of Fn-fs that might arise in OA temporarily offset the anabolic response of lower Fn-f concentrations and cause short

  2. Validation of cartilage thickness calculations using indentation analysis.

    PubMed

    Koff, Matthew F; Chong, Le Roy; Virtue, Patrick; Chen, Dan; Wang, Xioanan; Wright, Timothy; Potter, Hollis G

    2010-04-01

    Different methods have been used to cross-validate cartilage thickness measurements from magnetic resonance images (MRIs); however, a majority of these methods rely on interpolated data points, regional mean and/or maximal thickness, or surface mean thickness for data analysis. Furthermore, the accuracy of MRI cartilage thickness measurements from commercially available software packages has not necessarily been validated and may lead to an under- or overestimation of cartilage thickness. The goal of this study was to perform a matching point-to-point validation of indirect cartilage thickness calculations using a magnetic resonance (MR) image data set with direct cartilage thickness measurements using biomechanical indentation testing at the same anatomical locations. Seven bovine distal femoral condyles were prepared and a novel phantom filled with dilute gadolinium solution was rigidly attached to each specimen. High resolution MR images were acquired, and thickness indentation analysis of the cartilage was performed immediately after scanning. Segmentation of the MR data and cartilage thickness calculation was performed using semi-automated software. Registration of MR and indentation data was performed using the fluid filled phantom. The inter- and intra-examiner differences of the measurements were also determined. A total of 105 paired MRI-indentation thickness data points were analyzed, and a significant correlation between them was found (r=0.88, p<0.0001). The mean difference (+/-std. dev.) between measurement techniques was 0.00+/-0.23 mm, with Bland-Altman limits of agreement of 0.45 mm and -0.46 mm. The intra- and inter-examiner measurement differences were 0.03+/-0.22 mm and 0.05+/-0.24 mm, respectively. This study validated cartilage thickness measurements from MR images with thickness measurements from indentation by using a novel phantom to register the image-based and laboratory-based data sets. The accuracy of the measurements was comparable to

  3. Use of acellular dermal replacement in reconstruction of nonhealing lower extremity wounds.

    PubMed

    Kahn, Steven Alexander; Beers, Ryan J; Lentz, Christopher W

    2011-01-01

    Dermal templates are well established in the treatment of burn wounds and acute nonburn wounds. However, the literature regarding their use for reconstruction of chronic, nonhealing wounds is limited. This study describes a series of patients with chronic wounds reconstructed with a commercially available bilayer, acellular dermal replacement (ADR) containing a collagen-glycosaminoglycan dermal template and a silicone outer layer. A retrospective review was performed of 10 patients treated for chronic wounds with ADR and negative pressure dressing followed by split-thickness skin graft between July 2006 and January 2009. Data collected included age, gender, comorbidities, medications, wound type or location, wound size, the number of applications of ADR, the amount of ADR applied (in square centimeter), the amount of time between ADR placement and grafting, complications, need for reoperation, and percentage of graft take after 5 and 14 days. The mean age of study subjects was 44 years. All patients in the study had comorbidities that interfere with wound healing and were treated for lower extremity wounds (four to legs, five to ankles, and one to foot). The wounds had a variety of causative factors including venostasis ulcers (6, 60%), trauma in diabetic patients (2, 20%), brown recluse bite (1, 10%), and a wound caused from purpura fulminans (1, 10%). The average wound size and amount of ADR applied was 162±182 cm². Each patient required only one application of ADR. The average time between ADR placement and skin grafting was 36.5 days. The mean percentage of graft take at 5 days was 89.55%, 14 days was 90%, and 21 days was 87.3%. Only two patients required regrafting, and one of these grafts was lost because of patient noncompliance. ADR can be used successfully in the treatment of chronic wounds. ADR provides direct wound coverage and can conform to a variety of anatomical sites. This study demonstrates that the use of ADR in treating chronic wounds results

  4. Correlation between Focal Nodular Low Signal Changes in Hoffa's Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

    PubMed Central

    Ng, Wuey Min

    2016-01-01

    Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa's fat pad adjacent to anterior femoral cartilage of the knee (FNMHF) and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA) sagittal and axial images of the B1 and C1 region (described later) of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p = 0.00) between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%). Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory. PMID:27213085

  5. Abnormal mandibular growth and the condylar cartilage.

    PubMed

    Pirttiniemi, Pertti; Peltomäki, Timo; Müller, Lukas; Luder, Hans U

    2009-02-01

    Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their often disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritis (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage. PMID:19164410

  6. The pathology of cartilage in chondrodysplasias.

    PubMed

    Hwang, W S; Tock, E P; Tan, K L; Tan, L K

    1979-01-01

    The pathology of four types of chondrodysplasias, viz., type II achondrogenesis, thanatophoric dwarfism, Saldino-Noonan syndrome, and chondrodysplasia punctata were studied. In each of these disorders, cells with features similar to the chief and dark chondrocytes of normal hyaline cartilage were seen to be altered in different ways. There was a total absence of chief cells in type II achondrogenesis. All the chondrocytes present were of one variety at different states of maturation, with the fully matured cell having features of dark chondrocytes. The absence of chief cells was associated with marked diminution of interlacunar matrix and failure of growth plate development. The chief chondrocytes in thanatophoric dwarfism appeared diminished in number. They were probably abnormal functionally as evident by their lack of cytoplasmic vacuolation and the formation of thick, occasionally branched collagen in the matrix. The growth plate was stunted and poorly developed. Striking changes involving the dark cells were noted in Saldino-Noonan syndrome, where unusually elongated dark cells were found in groups within abnormal cystic spaces. The chief cells were large and contained abnormal cytoplasmic filaments. There was no formation of a growth plate. In chondrodysplasia punctata, the chief cells were enlarged and abnormally vacuolated. The matrix showed excessive aggregates of coarse granular material. In addition, there were focal accumulations of highly abnormal chief and dark cells with abnormal matrix which contained increased amount of keratan sulphate and culminated in spotty calcification. PMID:469631

  7. Nasal reconstruction with articulated irradiated rib cartilage

    SciTech Connect

    Murakami, C.S.; Cook, T.A.; Guida, R.A. )

    1991-03-01

    Nasal structural reconstruction is a formidable task in cases where there is loss of support to both the nasal dorsum and tip. A multitude of surgical approaches and materials have been used for the correction of the saddle-nose deformity with varying degrees of success. Articulated irradiated rib cartilage inserted through an external rhinoplasty approach was used to reconstruct nasal deformities in 18 patients over a 6-year period. Simultaneous use of a midline forehead flap to reconstruct the overlying soft tissue was required in four cases. Follow-up ranged from 1 to 6 years (mean, 2.8 years). Results were rewarding in most cases with marked improvement in nasal support and airway. Revision and/or replacement secondary to trauma or warping of the graft was required in four cases. None of the patients exhibited infection, extrusion, or noticeable resorption. A description of the surgical technique, review of all the cases, and recommendation for continued use of this graft material are discussed.

  8. Knee cartilage defect: marrow stimulating techniques.

    PubMed

    Mirza, M Zain; Swenson, Richard D; Lynch, Scott A

    2015-12-01

    Painful chondral defects of the knee are very difficult problems. The incidence of these lesions in the general population is not known since there is likely a high rate of asymptomatic lesions. The rate of lesions found during arthroscopic exam is highly variable, with reports ranging from 11 to 72 % Aroen (Aroen Am J Sports Med 32: 211-5, 2004); Curl(Arthroscopy13: 456-60, 1997); Figueroa(Arthroscopy 23(3):312-5, 2007;); Hjelle(Arthroscopy 18: 730-4, 2002). Examples of current attempts at cartilage restoration include marrow stimulating techniques, ostochondral autografts, osteochondral allografts, and autologous chondrocyte transplantation. Current research in marrow stimulating techniques has been focused on enhancing and guiding the biology of microfracture and other traditional techniques. Modern advances in stem cell biology and biotechnology have provided many avenues for exploration. The purpose of this work is to review current techniques in marrow stimulating techniques as it relates to chondral damage of the knee. PMID:26411978

  9. Noninvasive determination of knee cartilage deformation during jumping.

    PubMed

    Filipovic, Nenad; Vulovic, Radun; Peulic, Aleksandar; Radakovic, Radivoje; Kosanic, Djordje; Ristic, Branko

    2009-01-01

    The purpose of this investigation was to use a combination of image processing, force measurements and finite element modeling to calculate deformation of the knee cartilage during jumping. Professional athletes performed jumps analyzed using a force plate and high-speed video camera system. Image processing was performed on each frame of video using a color recognition algorithm. A simplified mass-spring-damper model was utilized for determination of global force and moment on the knee. Custom software for fitting the coupling characteristics was created. Simulated results were used as input data for the finite element calculation of cartilage deformation in the athlete's knee. Computer simulation data was compared with the average experimental ground reaction forces. The results show the three-dimensional mechanical deformation distribution inside the cartilage volume. A combination of the image recognition technology, force plate measurements and the finite element cartilage deformation in the knee may be used in the future as an effective noninvasive tool for prediction of injury during jumping. Key pointsEven there are many existing mathematical models of force distribution during running or jumping (Liu et al, 1998), to our knowledge there is no interdisciplinary approach where imaging processing, finite element modeling and experimental force plate system are employed.The aim is to explore noninvasive deformation in the knee cartilage during athlete's jumping on the force plate.An original image algorithms and software were developed as well as complex mathematical models using high-performance computational power of finite element modeling together with one-dimensional dynamics model.The initial results showed cartilage deformation in the knee and future research will be focused on the methodology and more precisely determination of the stress and strain distribution in the knee cartilage during training phase of sportsman. PMID:24149600

  10. Incidence of knee cartilage surgery in Norway, 2008–2011

    PubMed Central

    Engen, Cathrine Nørstad; Årøen, Asbjørn; Engebretsen, Lars

    2015-01-01

    Objective A systematic and long-term data collection on the treatment of focal cartilage defects (FCDs) of the knee is needed. This can be achieved through the foundation of a National Knee Cartilage Defect Registry. The aim of this study was to establish the nationwide burden of knee cartilage surgery, defined as knee surgery in patients with an FCD. We also aimed to identify any geographical differences in incidence rates, patient demographics or trends within this type of surgery. Setting A population-based study with retrospective identification of patients undergoing knee cartilage surgery in Norway through a mandatory public health database from 2008 to 2011. Participants We identified all patients undergoing cartilage surgery, or other knee surgery in patients with an FCD. All eligible surgeries were assessed for inclusion on the basis of certain types of ICD-10 and NOMESKO Classification of Surgical Procedures codes. Primary and secondary outcome measures The variables were diagnostic and surgical codes, geographic location of the performing hospital, age and sex of the patients. Yearly incidence and incidence rates were calculated. Age-adjusted incidences for risk ratios and ORs between geographical areas were also calculated. Results A total of 10 830 cases of knee cartilage surgery were identified, with slight but significant decreases from 2008 to 2011 (p<0.0003). The national incidence rate was 56/100 000 inhabitants and varied between regions, counties and hospitals. More than 50% of the procedures were palliative and nearly 400 yearly procedures were reparative or restorative. Conclusions Knee cartilage surgery is common in Norway, counting 2500 annual cases with an age-adjusted incidence rate of 68.8/100 000 inhabitants. There are significant geographical variations in incidence and trends of surgery and in trends between public and private hospitals. We suggest that a national surveillance system would be beneficial for the future evaluation

  11. Investigations into human tracheal cartilage osseocalcineus metaplasia. I. Radiographic findings.

    PubMed

    Sośnik, H; Sośnik, K

    2008-05-01

    Osseocalcineus metaplasia (OCM) of the tracheal cartilages is well known, but no exact data are available relating it to age and sex. To resolve this problem we analysed tracheal teleradiograms of 99 female (age: 0.4-92; x = 59.98 +/- +/- 22.75 years) and 110 male patients (age: 0-83; x = 53.53 +/- 19.95 years). As the first step we estimated the percentage of trachea that had complete lesions, those that had trace lesions and those that were unchanged in relation to the patient's age and sex. Secondly we determined the extent and growth of developing lesions during the process of ageing. Data were collected for all the cartilages, with two cartilages with trace lesions considered to be of similar value to one cartilage with complete remodelling. This enabled us to determine the correlation coefficient for changed cartilages and patient age and also the dynamism of OCM in the trachea examined. The chi2 and Student's t tests were used in determining the mean differences between subgroups. The lesions referred to above occurred in 66.35% of men and in 33.33% of women and correlated with age (r = 0.93, p < 0.001 in men, and r = 0.27, p < 0.01 in women). Total remodelling of the OCM occurred in the oldest age group, when both sexes were taken into consideration, while cartilages with trace changes were detected in the younger group of patients. The lowest mean patient age was observed in the group without tracheal changes. Osseocalcineus metaplasia of the tracheal cartilages was conditioned by patient age and sex. In male patients it occurred twice as often as in females. Until the age of 50 it occurred as much as nine times as often, while after this age it occurred only twice as often as in female patients. PMID:18521814

  12. Transient Hypoxia Improves Matrix Properties in Tissue Engineered Cartilage

    PubMed Central

    Yodmuang, Supansa; Gadjanski, Ivana; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Adult articular cartilage is a hypoxic tissue, with oxygen tension ranging from <10% at the cartilage surface to <1% in the deepest layers. In addition to spatial gradients, cartilage development is also associated with temporal changes in oxygen tension. However, a vast majority of cartilage tissue engineering protocols involves cultivation of chondrocytes or their progenitors under ambient oxygen concentration (21% O2), that is, significantly above physiological levels in either developing or adult cartilage. Our study was designed to test the hypothesis that transient hypoxia followed by normoxic conditions results in improved quality of engineered cartilaginous ECM. To this end, we systematically compared the effects of normoxia (21% O2 for 28 days), hypoxia (5% O2 for 28 days) and transient hypoxia—reoxygenation (5% O2 for 7 days and 21% O2 for 21 days) on the matrix composition and expression of the chondrogenic genes in cartilage constructs engineered in vitro. We demonstrated that reoxygenation had the most effect on the expression of cartilaginous genes including COL2A1, ACAN, and SOX9 and increased tissue concentrations of amounts of glycosaminoglycans and type II collagen. The equilibrium Young’s moduli of tissues grown under transient hypoxia (510.01 ± 28.15 kPa) and under normoxic conditions (417.60 ± 68.46 kPa) were significantly higher than those measured under hypoxic conditions (279.61 ± 20.52 kPa). These data suggest that the cultivation protocols utilizing transient hypoxia with reoxygenation have high potential for efficient cartilage tissue engineering, but need further optimization in order to achieve higher mechanical functionality of engineered constructs. PMID:23203946

  13. Avian Fact Sheet

    SciTech Connect

    NWCC Wildlife Work Group

    2004-12-01

    OAK-B135 After conducting four national research meetings, producing a document guiding research: Metrics and Methods for Determining or Monitoring Potential Impacts on Birds at Existing and Proposed Wind Energy Sites, 1999, and another paper, Avian Collisions with Wind Turbines: A Summary of Existing Studies and Comparisons to Other Sources of Avian Collision Mortality in the United States, 2001, the subcommittee recognized a need to summarize in a short fact sheet what is known about avian-wind interaction and what questions remain. This fact sheet attempts to summarize in lay terms the result of extensive discussion about avian-wind interaction on land. This fact sheet does not address research conducted on offshore development. This fact sheet is not intended as a conclusion on the subject; rather, it is a summary as of Fall/Winter 2002.

  14. Cerebral Aneurysms Fact Sheet

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS Cerebral Aneurysms Fact Sheet See a list of all NINDS ... I get more information? What is a cerebral aneurysm? A cerebral aneurysm (also known as an intracranial ...

  15. Sheet electron beam tester

    NASA Astrophysics Data System (ADS)

    Spear, Alexander Grenbeaux

    The DARPA HiFIVE project uses a pulsed electron sheet beam gun to power a traveling wave tube amplifier operating at 220 GHz. Presented is a method for characterizing the high current density 0.1 mm by 1 mm sheet electron beam. A tungsten tipped probe was scanned through the cross section of the sheet electron beam inside of a vacuum vessel. The probe was controlled with sub-micron precision using stepper motors and LabView computer control while boxcar averaging hardware sampled the pulsed beam. Matlab algorithms were used to interpret the data, calculate beam dimensions and current density, and create 2-dimensional cross section images. Full characterization of two separate HiFIVE sheet electron guns was accomplished and is also presented.

  16. Global ice sheet modeling

    SciTech Connect

    Hughes, T.J.; Fastook, J.L.

    1994-05-01

    The University of Maine conducted this study for Pacific Northwest Laboratory (PNL) as part of a global climate modeling task for site characterization of the potential nuclear waste respository site at Yucca Mountain, NV. The purpose of the study was to develop a global ice sheet dynamics model that will forecast the three-dimensional configuration of global ice sheets for specific climate change scenarios. The objective of the third (final) year of the work was to produce ice sheet data for glaciation scenarios covering the next 100,000 years. This was accomplished using both the map-plane and flowband solutions of our time-dependent, finite-element gridpoint model. The theory and equations used to develop the ice sheet models are presented. Three future scenarios were simulated by the model and results are discussed.

  17. Polarised light sheet tomography.

    PubMed

    Reidt, Sascha L; O'Brien, Daniel J; Wood, Kenneth; MacDonald, Michael P

    2016-05-16

    The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets. PMID:27409945

  18. Energy information sheets

    SciTech Connect

    1995-07-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  19. Biodiesel Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2014-06-01

    This fact sheet provides a brief introduction to biodiesel, including a discussion of biodiesel blends, which blends are best for which vehicles, where to buy biodiesel, how biodiesel compares to diesel fuel in terms of performance, how biodiesel performs in cold weather, whether biodiesel use will plug vehicle filters, how long-term biodiesel use may affect engines, biodiesel fuel standards, and whether biodiesel burns cleaner than diesel fuel. The fact sheet also dismisses the use of vegetable oil as a motor fuel.

  20. Current sheet model

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The model of a rectenna based on the current sheet equivalency of a large planar array is described. The model is mathematically characterized by expression for the fraction of the incident plane wave that is reflected from the sheet. The model is conceptually justified for normal incidence by comparing it to the waveguide model in which evanescent modes, present as beyond and cutoff, correspond to the near field components which become negligible at any significant distance from the antenna array.

  1. Clinical Outcomes for Breast Cancer Patients Undergoing Mastectomy and Reconstruction with Use of DermACELL, a Sterile, Room Temperature Acellular Dermal Matrix

    PubMed Central

    Vashi, Christopher

    2014-01-01

    Background. Decellularized human skin has been used in a variety of medical applications, primarily involving soft tissue reconstruction, wound healing, and tendon augmentation. Theoretically, decellularization removes potentially immunogenic material and provides a clean scaffold for cellular and vascular in growth. The use of acellular dermal matrix in two-stage postmastectomy breast reconstruction is described. Methods. Ten consecutive breast cancer patients were treated with mastectomies and immediate reconstruction from August to November 2011. There were 8 bilateral and 1 unilateral mastectomies for a total of 17 breasts, with one exclusion for chronic tobacco use. Reconstruction included the use of a new 6 × 16 cm sterile, room temperature acellular dermal matrix patch (DermACELL) soaked in a cefazolin bath. Results. Of the 17 breasts, 15 reconstructions were completed; 14 of them with expander to implant sequence and acellular dermal matrix. Histological analysis of biopsies obtained during trimming of the matrix at the second stage appeared nonremarkable with evidence of normal healing, cellularity, and vascular infiltration. Conclusion. Postoperative observations showed that this cellular dermal matrix appears to be an appropriate adjunct to reconstruction with expanders. This acellular dermal matrix appeared to work well with all patients, even those receiving postoperative chemotherapy, postoperative radiation, prednisone, or warfarin sodium. PMID:24738030

  2. An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology.

    PubMed

    Klika, Václav; Gaffney, Eamonn A; Chen, Ying-Chun; Brown, Cameron P

    2016-09-01

    There is a long history of mathematical and computational modelling with the objective of understanding the mechanisms governing cartilage׳s remarkable mechanical performance. Nonetheless, despite sophisticated modelling development, simulations of cartilage have consistently lagged behind structural knowledge and thus the relationship between structure and function in cartilage is not fully understood. However, in the most recent generation of studies, there is an emerging confluence between our structural knowledge and the structure represented in cartilage modelling. This raises the prospect of further refinement in our understanding of cartilage function and also the initiation of an engineering-level understanding for how structural degradation and ageing relates to cartilage dysfunction and pathology, as well as informing the potential design of prospective interventions. Aimed at researchers entering the field of cartilage modelling, we thus review the basic principles of cartilage models, discussing the underlying physics and assumptions in relatively simple settings, whilst presenting the derivation of relatively parsimonious multiphase cartilage models consistent with our discussions. We proceed to consider modern developments that start aligning the structure captured in the models with observed complexities. This emphasises the challenges associated with constitutive relations, boundary conditions, parameter estimation and validation in cartilage modelling programmes. Consequently, we further detail how both experimental interrogations and modelling developments can be utilised to investigate and reduce such difficulties before summarising how cartilage modelling initiatives may improve our understanding of cartilage ageing, pathology and intervention. PMID:27195911

  3. Optical coherence tomography enables accurate measurement of equine cartilage thickness for determination of speed of sound.

    PubMed

    Puhakka, Pia H; Te Moller, Nikae C R; Tanska, Petri; Saarakkala, Simo; Tiitu, Virpi; Korhonen, Rami K; Brommer, Harold; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha

    2016-08-01

    Background and purpose - Arthroscopic estimation of articular cartilage thickness is important for scoring of lesion severity, and measurement of cartilage speed of sound (SOS)-a sensitive index of changes in cartilage composition. We investigated the accuracy of optical coherence tomography (OCT) in measurements of cartilage thickness and determined SOS by combining OCT thickness and ultrasound (US) time-of-flight (TOF) measurements. Material and methods - Cartilage thickness measurements from OCT and microscopy images of 94 equine osteochondral samples were compared. Then, SOS in cartilage was determined using simultaneous OCT thickness and US TOF measurements. SOS was then compared with the compositional, structural, and mechanical properties of cartilage. Results - Measurements of non-calcified cartilage thickness using OCT and microscopy were significantly correlated (ρ = 0.92; p < 0.001). With calcified cartilage included, the correlation was ρ = 0.85 (p < 0.001). The mean cartilage SOS (1,636 m/s) was in agreement with the literature. However, SOS and the other properties of cartilage lacked any statistically significant correlation. Interpretation - OCT can give an accurate measurement of articular cartilage thickness. Although SOS measurements lacked accuracy in thin equine cartilage, the concept of SOS measurement using OCT appears promising. PMID:27164159

  4. Preliminary investigation of intrinsic UV fluorescence spectroscopic changes associated with proteolytic digestion of bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Lewis, William; Padilla-Martinez, Juan-Pablo; Ortega-Martinez, Antonio; Franco, Walfre

    2016-03-01

    Degradation and destruction of articular cartilage is the etiology of osteoarthritis (OA), an entity second only to cardiovascular disease as a cause of disability in the United States. Joint mechanics and cartilage biochemistry are believed to play a role in OA; an optical tool to detect structural and chemical changes in articular cartilage might offer benefit for its early detection and treatment. The objective of the present study was to identify the spectral changes in intrinsic ultraviolet (UV) fluorescence of cartilage that occur after proteolytic digestion of cartilage. Bovine articular cartilage samples were incubated in varying concentrations of collagenase ranging from 10ug/mL up to 5mg/mL for 18 hours at 37°C, a model of OA. Pre- and post-incubation measurements were taken of the UV excitation-emission spectrum of each cartilage sample. Mechanical tests were performed to determine the pre- and post-digestion force/displacement ratio associated with indentation of each sample. Spectral changes in intrinsic cartilage fluorescence and stiffness of the cartilage were associated with proteolytic digestion. In particular, changes in the relative intensity of fluorescence peaks associated with pentosidine crosslinks (330 nm excitation, 390 nm emission) and tryptophan (290 nm excitation, 340 nm emission) were found to correlate with different degrees of cartilage digestion and cartilage stiffness. In principle, it may be possible to use UV fluorescence spectral data for early detection of damage to articular cartilage, and as a surrogate measure for cartilage stiffness.

  5. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

    PubMed

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  6. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics

    PubMed Central

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L.

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  7. Protease inhibitors decrease rabbit cartilage degradation after meniscectomy

    SciTech Connect

    Caputo, C.B.; Sygowski, L.A.; Patton, S.P.; Wolanin, D.J.; Shaw, A.; Roberts, R.A.; DiPasquale, G.

    1988-01-01

    In vitro proteoglycan (PG) synthesis and release were measured on cartilage removed from rabbit knees within 1 week of meniscectomy. Three days following partial lateral meniscectomy, 72% of the femurs and 82% of the tibias had visible ulcers. Cartilage from the weight-bearing areas incorporated 2.0-2.9 times more /sup 35/S-sulfate in vitro than cartilage from the opposite, unoperated knees. /sup 3/H-thymidine incorporation was 2.5-3.4 times higher for surgical than control groups. /sup 35/S-sulfate incorporation by the surgical group was inhibited by 22% in the presence of 10(-4) M U24522, an inhibitor of rabbit chondrocyte metalloprotease (CMP). /sup 3/H-thymidine incorporation by the surgical group was inhibited by 28% by 10(-4) M U24522. In vitro PG release from cartilage removed 2 days after surgery was 1.6-3.7 times higher for the surgical than the control group. PG release by the surgical group after 22 h of incubation was reduced to the control level by three CMP inhibitors, U24278, U24279, and U24522. PG release by cartilage from the nonsurgical group was also reduced by these compounds at 22 h. These results suggest that both the anabolic and catabolic processes that are stimulated by surgery can be isolated in vitro and that CMP may be involved in the catabolic process.

  8. Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

    PubMed Central

    Zhen, Gehau; Cao, Xu

    2014-01-01

    Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

  9. Matrilin-3 Role in Cartilage Development and Osteoarthritis

    PubMed Central

    Muttigi, Manjunatha S.; Han, Inbo; Park, Hun-Kuk; Park, Hansoo; Lee, Soo-Hong

    2016-01-01

    The extracellular matrix (ECM) of cartilage performs essential functions in differentiation and chondroprogenitor cell maintenance during development and regeneration. Here, we discuss the vital role of matrilin-3, an ECM protein involved in cartilage development and potential osteoarthritis pathomechanisms. As an adaptor protein, matrilin-3 binds to collagen IX to form a filamentous network around cells. Matrilin-3 is an essential component during cartilage development and ossification. In addition, it interacts directly or indirectly with transforming growth factor β (TGF-β), and bone morphogenetic protein 2 (BMP2) eventually regulates chondrocyte proliferation and hypertrophic differentiation. Interestingly, matrilin-3 increases interleukin receptor antagonists (IL-Ra) in chondrocytes, suggesting its role in the suppression of IL-1β-mediated inflammatory action. Matrilin-3 downregulates the expression of matrix-degrading enzymes, such as a disintegrin metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5, matrix metalloproteinase 13 (MMP13), and collagen X, a hypertrophy marker during development and inflammatory conditions. Matrilin-3 essentially enhances collagen II and aggrecan expression, which are required to maintain the tensile strength and elasticity of cartilage, respectively. Interestingly, despite these attributes, matrilin-3 induces osteoarthritis-associated markers in chondrocytes in a concentration-dependent manner. Existing data provide insights into the critical role of matrilin-3 in inflammation, matrix degradation, and matrix formation in cartilage development and osteoarthritis. PMID:27104523

  10. Quantitative proteomic profiling of human articular cartilage degradation in osteoarthritis.

    PubMed

    Lourido, Lucía; Calamia, Valentina; Mateos, Jesús; Fernández-Puente, Patricia; Fernández-Tajes, Juan; Blanco, Francisco J; Ruiz-Romero, Cristina

    2014-12-01

    Osteoarthritis (OA) is the most common rheumatic pathology and is characterized primarily by articular cartilage degradation. Despite its high prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. Therefore, new diagnostic and monitoring tests for OA are urgently needed, which would also promote the development of alternative therapeutic strategies. In the present study, we have performed an iTRAQ-based quantitative proteomic analysis of secretomes from healthy human articular cartilage explants, comparing their protein profile to those from unwounded (early disease) and wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed us to identify a panel of 76 proteins that are distinctively released by the diseased tissue. Clustering analysis allowed the classification of proteins according to their different profile of release from cartilage. Among these proteins, the altered release of osteoprotegerin (decreased in OA) and periostin (increased in OA), both involved in bone remodelling processes, was verified in further analyses. Moreover, periostin was also increased in the synovial fluid of OA patients. Altogether, the present work provides a novel insight into the mechanisms of human cartilage degradation and a number of new cartilage-characteristic proteins with possible biomarker value for early diagnosis and prognosis of OA. PMID:25383958

  11. Strategies for Controlled Delivery of Biologics for Cartilage Repair

    PubMed Central

    Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

  12. A High Throughput Mechanical Screening Device for Cartilage Tissue Engineering

    PubMed Central

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Greg R.; Cosgrove, Brian D.; Dodge, George R.; Mauck, Robert L.

    2014-01-01

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying ‘hits’, or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput. PMID:24275442

  13. Stem cells for tissue engineering of articular cartilage.

    PubMed

    Gao, J; Yao, J Q; Caplan, A I

    2007-07-01

    Articular cartilage injuries are one of the most common disorders in the musculo-skeletal system. Injured cartilage tissue cannot spontaneously heal and, if not treated, can lead to osteoarthritis of the affected joints. Although a variety of procedures are being employed to repair cartilage damage, methods that result in consistent durable repair tissue are not yet available. Tissue engineering is a recently developed science that merges the fields of cell biology, engineering, material science, and surgery to regenerate new functional tissue. Three critical components in tissue engineering of cartilage are as follows: first, sufficient cell numbers within the defect, such as chondrocytes or multipotent stem cells capable of differentiating into chondrocytes; second, access to growth and differentiation factors that modulate these cells to differentiate through the chondrogenic lineage; third, a cell carrier or matrix that fills the defect, delivers the appropriate cells, and supports cell proliferation and differentiation. Stem cells that exist in the embyro or in adult somatic tissues are able to renew themselves through cell division without changing their phenotype and are able to differentiate into multiple lineages including the chondrogenic lineage under certain physiological or experimental conditions. Here the application of stem cells as a cell source for cartilage tissue engineering is reviewed. PMID:17822146

  14. Endoscopic laser reshaping of rabbit tracheal cartilage: preliminary investigations

    NASA Astrophysics Data System (ADS)

    Tsang, Walter; Lam, Anthony; Protsenko, Dmitry; Wong, Brian J.

    2005-04-01

    Background: Tracheal cartilage deformities due to trauma, prolonged endotracheal intubation or infection are difficult to correct. Current treatment options such as dilation, laser ablation, stent placement, and segmental resection are only temporary or carry significant risks. The objectives of this project were to design and test a laser activated endotracheal stent system that can actively modify the geometry of tracheal cartilage, leading to permanent retention of a new and desirable tracheal geometry. Methods: Ex vivo rabbit tracheal cartilage (simulating human neonate trachea) were irradiated with an Er: Glass laser, (λ= 1.54um, 0.5W-2.5W, 1 sec to 5 sec). Shape change and gross thermal injury were assessed visually to determine the best laser power parameters for reshaping. A rigid endoscopic telescope and hollow bronchoscope were used to record endoscopic images. The stent was constructed from nitinol wire, shaped into a zigzag configuration. An ex vivo testing apparatus was also constructed. Results: The best laser power parameter to produce shape change was 1 W for 6-7 seconds. At this setting, there was significant shape change with only minimal thermal injury to the tracheal mucosa, as assessed by visual inspection. The bronchoscopy system functioned adequately during testing in the ex vivo testing apparatus. Conclusion: We have successfully designed instrumentation and created the capability to endoscopically reshape tracheal cartilage in an ex vivo rabbit model. The results obtained in ex vivo tracheal cartilage indicated that reshaping using Er: Glass laser can be accomplished.

  15. 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. PMID:26319778

  16. Physical mechanisms underlying the strain-rate-dependent mechanical behavior of kangaroo shoulder cartilage

    NASA Astrophysics Data System (ADS)

    Thibbotuwawa, Namal; Oloyede, Adekunle; Li, Tong; Singh, Sanjleena; Senadeera, Wijitha; Gu, YuanTong

    2015-09-01

    Due to anatomical and biomechanical similarities to human shoulder, kangaroo was chosen as a model to study shoulder cartilage. Comprehensive enzymatic degradation and indentation tests were applied on kangaroo shoulder cartilage to study mechanisms underlying its strain-rate-dependent mechanical behavior. We report that superficial collagen plays a more significant role than proteoglycans in facilitating strain-rate-dependent behavior of the kangaroo shoulder cartilage. By comparing the mechanical properties of degraded and normal cartilages, it was noted that proteoglycan and collagen degradation significantly compromised strain-rate-dependent mechanical behavior of the cartilage. Superficial collagen contributed equally to the tissue behavior at all strain-rates. This is different to the studies reported on knee cartilage and confirms the importance of superficial collagen on shoulder cartilage mechanical behavior. A porohyperelastic numerical model also indicated that collagen disruption would lead to faster damage of the shoulder cartilage than when proteoglycans are depleted.

  17. Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications.

    PubMed

    Yan, Le-Ping; Wang, Ying-Jun; Ren, Li; Wu, Gang; Caridade, Sofia G; Fan, Jia-Bing; Wang, Ling-Yun; Ji, Pei-Hong; Oliveira, Joaquim M; Oliveira, João T; Mano, João F; Reis, Rui L

    2010-11-01

    In this study, genipin-cross-linked collagen/chitosan biodegradable porous scaffolds were prepared for articular cartilage regeneration. The influence of chitosan amount and genipin concentration on the scaffolds physicochemical properties was evaluated. The morphologies of the scaffolds were characterized by scanning electron microscope (SEM) and cross-linking degree was investigated by ninhydrin assay. Additionally, the mechanical properties of the scaffolds were assessed under dynamic compression. To study the swelling ratio and the biostability of the collagen/chitosan scaffold, in vitro tests were also carried out by immersion of the scaffolds in PBS solution or digestion in collagenase, respectively. The results showed that the morphologies of the scaffolds underwent a fiber-like to a sheet-like structural transition by increasing chitosan amount. Genipin cross-linking remarkably changed the morphologies and pore sizes of the scaffolds when chitosan amount was less than 25%. Either by increasing the chitosan ratio or performing cross-linking treatment, the swelling ratio of the scaffolds can be tailored. The ninhydrin assay demonstrated that the addition of chitosan could obviously increase the cross-linking efficiency. The degradation studies indicated that genipin cross-linking can effectively enhance the biostability of the scaffolds. The biocompatibility of the scaffolds was evaluated by culturing rabbit chondrocytes in vitro. This study demonstrated that a good viability of the chondrocytes seeded on the scaffold was achieved. The SEM analysis has revealed that the chondrocytes adhered well to the surface of the scaffolds and contacted each other. These results suggest that the genipin-cross-linked collagen/chitosan matrix may be a promising formulation for articular cartilage scaffolding. PMID:20648541

  18. [Research progress of cell sheet technology and its applications in tissue engineering and regenerative medicine].

    PubMed

    Ma, Dongyang; Ren, Liling; Mao, Tianqiu

    2014-10-01

    Cell sheet engineering is an important technology to harvest the cultured cells in the form of confluent monolayers using a continuous culture method and a physical approach. Avoiding the use of enzymes, expended cells can be harvested together with endogenous extracellular matrix, cell-matrix contacts, and cell-cell contacts. With high efficiency of cell loading ability and without using exogenous scaffolds, cell sheet engineering has several advantages over traditional tissue engineering methods. In this article, we give an overview on cell sheet technology about its applications in the filed of tissue regeneration, including the construction of soft tissues (corneal, mucous membrane, myocardium, blood vessel, pancreas islet, liver, bladder and skin) and hard tissues (bone, cartilage and tooth root). This techonoly is promising to provide a novel strategy for the development of tissue engineering and regenerative medicine. And further works should be carried out on the operability of this technology and its feasibility to construct thick tissues. PMID:25764743

  19. Electromechanical response of articular cartilage in indentation--considerations on the determination of cartilage properties during arthroscopy.

    PubMed

    Li, L P; Herzog, W

    2005-04-01

    A finite element formulation of streaming potentials in articular cartilage was incorporated into a fibril-reinforced model using the commercial software ABAQUS. This model was subsequently used to simulate interactions between an arthroscopic probe and articular cartilage in a knee joint. Fibril reinforcement was found to account for large fluid pressure at considerable strain rates, as has been observed in un-confined compression. Furthermore, specific electromechanical responses were associated with specific changes in tissue properties that occur with cartilage degeneration. For example, the strong strain-rate dependence of the load response was only observed when the collagen network was intact. Therefore, it is possible to use data measured during arthroscopy to evaluate the degree of cartilage degeneration and the source causing changed properties. However, practical problems, such as the difficulty of controlling the speed of the hand-held probe, may greatly reduce the reliability of such evaluations. The fibril-reinforced electromechanical model revealed that high-speed transient responses were associated with the collagen network, and equilibrium response was primarily determined by proteoglycan matrix. The results presented here may be useful in the application of arthroscopic tools for evaluating cartilage degeneration, for the proper interpretation of data, and for the optimization of data collection during arthroscopy. PMID:16154872

  20. The amphoteric effect on friction between the bovine cartilage/cartilage surfaces under slightly sheared hydration lubrication mode.

    PubMed

    Pawlak, Zenon; Gadomski, Adam; Sojka, Michal; Urbaniak, Wieslaw; Bełdowski, Piotr

    2016-10-01

    The amphoteric effect on the friction between the bovine cartilage/cartilage contacts has been found to be highly sensitive to the pH of an aqueous solution. The cartilage surface was characterized using a combination of the pH, wettability, as well as the interfacial energy and friction coefficient testing methods to support lamellar-repulsive mechanism of hydration lubrication. It has been confirmed experimentally that phospholipidic multi-bilayers are essentially described as lamellar frictionless lubricants protecting the surface of the joints against wear. At the hydrophilicity limit, the low friction would then be due to (a) lamellar slippage of bilayers and (b) a short-range (nanometer-scale) repulsion between the interfaces of negatively charged (PO4(-)) cartilage surfaces, and in addition, contribution of the extracellular matrix (ECM) collagen fibers, hyaluronate, proteoglycans aggregates (PGs), glycoprotein termed lubricin and finally, lamellar PLs phases. In this paper we demonstrate experimentally that the pH sensitivity of cartilage to friction provides a novel concept in joint lubrication on charged surfaces. PMID:27395038

  1. Wnt/β-catenin signaling of cartilage canal and osteochondral junction chondrocytes and full thickness cartilage in early equine osteochondrosis.

    PubMed

    Kinsley, Marc A; Semevolos, Stacy A; Duesterdieck-Zellmer, Katja F

    2015-10-01

    The objective of this study was to elucidate gene and protein expression of Wnt signaling molecules in chondrocytes of foals having early osteochondrosis (OC) versus normal controls. The hypothesis was that increased expression of components of Wnt signaling pathway in osteochondral junction (OCJ) and cartilage canal (CC) chondrocytes would be found in early OC when compared to controls. Paraffin-embedded osteochondral samples (7 OC, 8 normal) and cDNA from whole cartilage (7 OC, 10 normal) and chondrocytes surrounding cartilage canals and osteochondral junctions captured with laser capture microdissection (4 OC, 6 normal) were obtained from femoropatellar joints of 17 immature horses. Equine-specific Wnt signaling molecule mRNA expression levels were evaluated by two-step real-time qPCR. Spatial tissue protein expression of β-catenin, Wnt-11, Wnt-4, and Dkk-1 was determined by immunohistochemistry. There was significantly decreased Wnt-11 and increased β-catenin, Wnt-5b, Dkk-1, Lrp6, Wif-1, Axin1, and SC-PEP gene expression in early OC cartilage canal chondrocytes compared to controls. There was also significantly increased β-catenin gene expression in early OC osteochondral junction chondrocytes compared to controls. Based on this study, abundant gene expression differences in OC chondrocytes surrounding cartilage canals suggest pathways associated with catabolism and inhibition of chondrocyte maturation are targeted in early OC pathogenesis. PMID:25676127

  2. Chemical Pretreatment of Growth Plate Cartilage Increases Immunofluorescence Sensitivity

    PubMed Central

    Ahrens, Molly J.; Dudley, Andrew T.

    2011-01-01

    Immunofluorescence detection of proteins in growth plate cartilage is often unsuccessful because of innate autofluorescence, fixative-induced fluorescence, and dense cartilage matrix, which can inhibit antibody penetration. To overcome these limitations, the authors have tested various chemical pretreatments, including the autofluorescence quencher sodium borohydride, the antigen retrieval method of boiling sodium citrate, sugar-degrading enzymes (hyaluronidase, heparinase, and chondroitinase), and the proteolytic enzyme protease XXIV. Here the authors show that, in most cases, background fluorescence in cartilage is the primary obstacle to high-quality imaging. Blocking intrinsic fluorescence of the specimen in combination with specific pretreatments allows visualization using antibodies that previously did not generate a robust signal in the growth plate. Each antibody requires a specific combination of chemical pretreatments that must be empirically determined to achieve optimal staining levels. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. PMID:21411811

  3. Gene Transfer Strategies to Promote Chondrogenesis and Cartilage Regeneration.

    PubMed

    Im, Gun-Il

    2016-04-01

    Gene transfer has been used experimentally to promote chondrogenesis and cartilage regeneration. While it is controversial to apply gene therapy for nonlethal conditions such as cartilage defect, there is a possibility that the transfer of therapeutic transgenes may dramatically increase the effectiveness of cell therapy and reduce the quantity of cells that are needed to regenerate cartilage. Single or combination of growth factors and transcription factors has been transferred to mesenchymal stem cells or articular chondrocytes using both nonviral and viral approaches. The current challenge for the clinical applications of genetically modified cells is ensuring the safety of gene therapy while guaranteeing effectiveness. Viral gene delivery methods have been mainstays currently with enhanced safety features being recently refined. On the other hand, efficiency has been greatly improved in nonviral delivery. This review summarizes the history and recent update on the gene transfer to enhance chondrogenesis from stem cells or articular chondrocytes. PMID:26414246

  4. Evaluation of Automated Volumetric Cartilage Quantification for Hip Preservation Surgery.

    PubMed

    Ramme, Austin J; Guss, Michael S; Vira, Shaleen; Vigdorchik, Jonathan M; Newe, Axel; Raithel, Esther; Chang, Gregory

    2016-01-01

    Automating the process of femoroacetabular cartilage identification from magnetic resonance imaging (MRI) images has important implications to guiding clinical care by providing a temporal metric that allows for optimizing the timing for joint preservation surgery. In this paper, we evaluate a new automated cartilage segmentation method using a time trial, segmented volume comparison, overlap metrics, and Euclidean distance mapping. We report interrater overlap metrics using the true fast imaging with steady-state precession MRI sequence of 0.874, 0.546, and 0.704 for the total overlap, union overlap, and mean overlap, respectively. This method was 3.28× faster than manual segmentation. This technique provides clinicians with volumetric cartilage information that is useful for optimizing the timing for joint preservation procedures. PMID:26377376

  5. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration

    NASA Astrophysics Data System (ADS)

    Wang, Dong-An; Varghese, Shyni; Sharma, Blanka; Strehin, Iossif; Fermanian, Sara; Gorham, Justin; Fairbrother, D. Howard; Cascio, Brett; Elisseeff, Jennifer H.

    2007-05-01

    A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functionality and long-term performance of the tissue. Here, we use the biopolymer chondroitin sulphate (CS), one of the major components of cartilage extracellular matrix, to develop a novel bioadhesive that is readily applied and acts quickly. CS was chemically functionalized with methacrylate and aldehyde groups on the polysaccharide backbone to chemically bridge biomaterials and tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with and without cells) bonded to articular cartilage defects. In in vitro and in vivo functional studies this approach led to mechanical stability of the hydrogel and tissue repair in cartilage defects.

  6. Treatment of articular cartilage lesions of the knee

    PubMed Central

    Falah, Mazen; Nierenberg, Gabreil; Soudry, Michael; Hayden, Morris

    2010-01-01

    Treatment of articular cartilage lesions in the knee remains a challenge for the practising orthopaedic surgeon. A wide range of options are currently practised, ranging from conservative measures through various types of operations and, recently, use of growth factors and emerging gene therapy techniques. The end result of these methods is usually a fibrous repair tissue (fibrocartilage), which lacks the biomechanical characteristics of hyaline cartilage that are necessary to withstand the compressive forces distributed across the knee. The fibrocartilage generally deteriorates over time, resulting in a return of the original symptoms and occasionally reported progression to osteoarthritis. Our purpose in this study was to review the aetiology, pathogenesis and treatment options for articular cartilage lesions of the knee. At present, autologous cell therapies, growth factor techniques and biomaterials offer more promising avenues of research to find clinical answers. PMID:20162416

  7. Imaging Strategies for Assessing Cartilage Composition in Osteoarthritis

    PubMed Central

    Matzat, Stephen J.; Kogan, Feliks; Fong, Grant W.; Gold, Garry E.

    2015-01-01

    Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues before advanced damage has occurred. This is particularly relevant for damage to articular cartilage because this soft tissue lacks the capacity to repair itself following major damage and is essential to proper joint function. While conventional magnetic resonance imaging (MRI) provides sufficient contrast to visualize articular cartilage morphology, more advanced imaging strategies are necessary for understanding the underlying biochemical composition of cartilage that begins to break down in the earliest stages of OA. This review discusses the biochemical basis and the advantages and disadvantages associated with each of these techniques. Recent implementations for these techniques are touched upon, and future considerations for improving the research and clinical power of these imaging technologies are also discussed. PMID:25218737

  8. Ultrasonographic Measurement of the Femoral Cartilage Thickness in Hemiparetic Patients after Stroke

    ERIC Educational Resources Information Center

    Tunc, Hakan; Oken, Oznur; Kara, Murat; Tiftik, Tulay; Dogu, Beril; Unlu, Zeliha; Ozcakar, Levent

    2012-01-01

    The aim of the study was to evaluate the femoral cartilage thicknesses of hemiparetic patients after stroke using musculoskeletal ultrasonography and to determine whether there is any correlation between cartilage thicknesses and the clinical characteristics of the patients. Femoral cartilage thicknesses of both knees were measured in 87 (33…

  9. Nasal reconstruction with autologous rib cartilage: a 43-year follow-up.

    PubMed

    Horton, C E; Matthews, M S

    1992-01-01

    Autogenous costal cartilage has long been a popular material for nasal augmentation. The history of autogenous cartilage transplantation is reviewed. Two patients are presented who underwent nasal augmentation with autologous costal cartilage with a 43-year follow-up on each patient. PMID:1727245

  10. Tibiofemoral cartilage contact biomechanics in patients after reconstruction of a ruptured anterior cruciate ligament.

    PubMed

    Hosseini, Ali; Van de Velde, Samuel; Gill, Thomas J; Li, Guoan

    2012-11-01

    We investigated the in vivo cartilage contact biomechanics of the tibiofemoral joint in patients after reconstruction of a ruptured anterior cruciate ligament (ACL). A dual fluoroscopic and MR imaging technique was used to investigate the cartilage contact biomechanics of the tibiofemoral joint during in vivo weight-bearing flexion of the knee in eight patients 6 months following clinically successful reconstruction of an acute isolated ACL rupture. The location of tibiofemoral cartilage contact, size of the contact area, cartilage thickness at the contact area, and magnitude of the cartilage contact deformation of the ACL-reconstructed knees were compared with those previously measured in intact (contralateral) knees and ACL-deficient knees of the same subjects. Contact biomechanics of the tibiofemoral cartilage after ACL reconstruction were similar to those measured in intact knees. However, at lower flexion, the abnormal posterior and lateral shift of cartilage contact location to smaller regions of thinner tibial cartilage that has been described in ACL-deficient knees persisted in ACL-reconstructed knees, resulting in an increase of the magnitude of cartilage contact deformation at those flexion angles. Reconstruction of the ACL restored some of the in vivo cartilage contact biomechanics of the tibiofemoral joint to normal. Clinically, recovering anterior knee stability might be insufficient to prevent post-operative cartilage degeneration due to lack of restoration of in vivo cartilage contact biomechanics. PMID:22528687

  11. Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly (ethylene glycol) diacrylate scaffold

    PubMed Central

    Musumeci, G.; Loreto, C.; Carnazza, M.L.; Coppolino, F.; Cardile, V.; Leonardi, R.

    2011-01-01

    Osteoarthritis (OA) is characterized by degenerative changes within joints that involved quantitative and/or qualitative alterations of cartilage and synovial fluid lubricin, a mucinous glycoprotein secreted by synovial fibroblasts and chondrocytes. Modern therapeutic methods, including tissue-engineering techniques, have been used to treat mechanical damage of the articular cartilage but to date there is no specific and effective treatment. This study aimed at investigating lubricin immunohistochemical expression in cartilage explant from normal and OA patients and in cartilage constructions formed by Poly (ethylene glycol) (PEG) based hydrogels (PEG-DA) encapsulated OA chondrocytes. The expression levels of lubricin were studied by immunohistochemistry: i) in tissue explanted from OA and normal human cartilage; ii) in chondrocytes encapsulated in hydrogel PEGDA from OA and normal human cartilage. Moreover, immunocytochemical and western blot analysis were performed in monolayer cells from OA and normal cartilage. The results showed an increased expression of lubricin in explanted tissue and in monolayer cells from normal cartilage, and a decreased expression of lubricin in OA cartilage. The chondrocytes from OA cartilage after 5 weeks of culture in hydrogels (PEGDA) showed an increased expression of lubricin compared with the control cartilage. The present study demonstrated that OA chondrocytes encapsulated in PEGDA, grown in the scaffold and were able to restore lubricin biosynthesis. Thus our results suggest the possibility of applying autologous cell transplantation in conjunction with scaffold materials for repairing cartilage lesions in patients with OA to reduce at least the progression of the disease. PMID:22073377

  12. Analysis of cartilage-polydioxanone foil composite grafts.

    PubMed

    Kim, James H; Wong, Brian

    2013-12-01

    This study presents an analytical investigation into the mechanical behavior of a cartilage-polydioxanone (PDS) plate composite grafts. Numerical methods are used to provide a first-order, numerical model of the flexural stiffness of a cartilage-PDS graft. Flexural stiffness is a measure of resistance to bending and is inversely related to the amount of deformation a structure may experience when subjected to bending forces. The cartilage-PDS graft was modeled as a single composite beam. Using Bernoulli-Euler beam theory, a closed form equation for the theoretical flexural stiffness of the composite graft was developed. A parametric analysis was performed to see how the flexural properties of the composite model changed with varying thicknesses of PDS foil. The stiffness of the cartilage-PDS composite using 0.15-mm-thick PDS was four times higher than cartilage alone. The composite with a 0.5-mm-thick PDS graft was only 1.7 times stiffer than the composite with the 0.15-mm-thick PDS graft. Although a thicker graft material will yield higher flexural stiffness for the composite, the relationship between composite stiffness and PDS thickness is nonlinear. After a critical point, increments in graft thickness produce gradually smaller improvements in flexural stiffness. The small increase in stiffness when using the thicker PDS foils versus the 0.15 mm PDS foil may not be worth the potential complications (prolonged foreign body reaction, reduction in nutrient diffusion to cartilage) of using thicker artificial grafts. PMID:24327249

  13. Mechanical Impact Induces Cartilage Degradation via Mitogen Activated Protein Kinases

    PubMed Central

    Ding, Lei; Heying, Emily; Nicholson, Nathan; Stroud, Nicolas J.; Homandberg, Gene A.; Guo, Danping; Buckwalter, Joseph A.; Martin, James A.

    2010-01-01

    Objective To determine the activation of MAP kinases in and around cartilage subjected to mechanical damage and to determine the effects of their inhibitors on impaction induced chondrocyte death and cartilage degeneration. Design The phosphorylation of MAP kinases was examined with confocal microscopy and immunoblotting. The effects of MAP kinase inhibitors on impaction-induced chondrocyte death and proteoglycan loss were determined with fluorescent microscopy and DMMB assay. The expression of catabolic genes at mRNA levels was examined with quantitative real time PCR. Results Early p38 activation was detected at 20 min and 1 hr post-impaction. At 24 hr, enhanced phosphorylation of p38 and ERK1/2 was visualized in chondrocytes from in and around impact sites. The phosphorylation of p38 was increased by 3.0-fold in impact sites and 3.3-fold in adjacent cartilage. The phosphorylation of ERK-1 was increased by 5.8-fold in impact zone and 5.4-fold in adjacent cartilage; the phosphorylation of ERK-2 increased by 4.0-fold in impacted zone and 3.6-fold in adjacent cartilage. Furthermore, the blocking of p38 pathway did not inhibit impaction-induced ERK activation. The inhibition of p38 or ERK pathway significantly reduced injury-related chondrocyte death and proteoglycan losses. Quantative Real-time PCR analysis revealed that blunt impaction significantly up-regulated MMP-13, TNF-α, and ADAMTS-5 expression. Conclusion These findings implicate p38 and ERK MAPKs in the post injury spread of cartilage degeneration and suggest that the risk of PTOA following joint trauma could be decreased by blocking their activities, which might be involved in up-regulating expressions of MMP-13, ADAMTS-5, and TNF-α. PMID:20813194

  14. MOLECULAR RESURFACING OF CARTILAGE WITH PROTEOGLYCAN 4 (PRG4)

    PubMed Central

    Chawla, Kanika; Ham, Hyun Ok; Nguyen, Trung; Messersmith, Phillip B.

    2010-01-01

    Early loss of proteoglycan 4 (PRG4), a lubricating glycoprotein implicated in boundary lubrication, from the cartilage surface has been associated with degeneration of cartilage and early onset of osteoarthritis. Viscosupplementation with hyaluronic acid and other macromolecules has been proposed as a treatment of osteoarthritis, however efficacy of viscosupplementation is variable and may be influenced by the short residence time of lubricant in the knee joint after injection. Recent studies have demonstrated the use of aldehyde (CHO) modified extracellular matrix proteins for targeted adherence to a biological tissue surface. We hypothesized that CHO could be exploited to enhance binding of lubricating proteoglycans to the surface of PRG4 depleted cartilage. The objective of this study was to determine the feasibility of molecular resurfacing of cartilage with aldehyde modified PRG4. PRG4 was chemically functionalized with aldehyde (PRG4-CHO), and aldehyde plus Oregon Green (OG) fluorophore (PRG4-OG-CHO) to allow for differentiation of endogenous and exogenous PRG4. Cartilage disks depleted of native PRG4 were then treated with solutions of PRG4, PRG4-CHO, or PRG4-OG-CHO and then assayed for the presence of PRG4 by immunohistochemistry, ELISA, and fluorescence imaging. Repletion of cartilage surfaces was significantly enhanced with the inclusion of CHO compared to repletion with unmodified PRG4. These findings suggest a generalized approach that may be used for molecular resurfacing of tissue surfaces with PRG4 and other lubricating biomolecules, perhaps leading in the future to a convenient method for overcoming loss of lubrication during the early stages of osteoarthritis. PMID:20338268

  15. The cell mediated and humoral immune response to vaccination with acellular and whole cell pertussis vaccine in adult humans.

    PubMed

    Petersen, J W; Ibsen, P H; Bentzon, M W; Capiau, C; Heron, I

    1991-10-01

    The cell mediated immune response (CMI) against pertussis antigens following vaccination with the traditional Danish whole cell pertussis vaccine (WC-P) and the Japanese acellular pertussis vaccine (A-PV) JNIH-3 was studied in four adult human volunteers. Vaccination with the A-PV induced an in vitro proliferative response of peripheral blood lymphocytes to pertussis toxin (PT) subunits S2-S4, S3-S4 and S5 and the filamentous hemagglutinin (FHA), and a better serological response to native PT, detoxified PT (dPT) and FHA than the WC-PV. The induced CMI and serological response were followed over a period of 17 weeks, and were not seen to decline during this period. Further, an in vitro proliferative response to Bordetella pertussis agglutinogen 2 and 3 were demonstrated using lymphocytes from recently and not-so-recently pertussis-vaccinated adults. PMID:1797049

  16. Coverage of gingival recession defects using acellular dermal matrix allograft with or without beta-tricalcium phosphate.

    PubMed

    Okubo, Nobuki; Fujita, Takahisa; Ishii, Yoshihito; Ota, Mikio; Shibukawa, Yoshihiro; Yamada, Satoru

    2013-01-01

    The aim of this study was to investigate the effect of beta-tricalcium phosphate (β-TCP) particles in combination with acellular dermal matrix (ADM) allograft in gingival recession. Experimental gingival recession defects were created in beagle dogs and randomly assigned to one of the following groups: ADM, ADM + β-TCP, or coronally positioned flap (CPF; control). Tissues were histologically examined at 4, 8, or 16 weeks following treatment. A greater thickness of gingiva was observed at the sites treated in both the ADM + β-TCP and ADM groups than in the CPF group. The ADM + β-TCP group showed a statistically significant increase in both new bone and cementum formations compared to the ADM group. The results suggest that the combination of β-TCP and ADM is more effective in promoting new bone and cementum formations than ADM graft alone. PMID:21862508

  17. Use of Double Layer of Acellular Dermal Matrix and Modified Tunnel Technique to Treat Multiple Adjacent Gingival Recession Defects.

    PubMed

    Mahn, Douglas H

    2016-09-01

    The goal of connective tissue grafting is to cover exposed root surfaces with gingival tissues that are stable and have a natural appearance. The use of an acellular dermal matrix (ADM) has been shown to be a successful alternative to the palatal connective tissue graft. Use of a double layer of an ADM has been shown to have stable results for 1 year. Tunnel grafting techniques can yield root coverage with a natural appearing soft-tissue architecture. The purpose of this case report is to demonstrate the use of a modified tunnel technique and a double layer of ADM in the treatment of multiple adjacent gingival recession defects. Treated teeth were found to have root coverage and natural soft-tissue contours that were stable at 20 months. PMID:27606567

  18. Magnetic resonance imaging of hip joint cartilage and labrum

    PubMed Central

    Zilkens, Christoph; Miese, Falk; Jäger, Marcus; Bittersohl, Bernd; Krauspe, Rüdiger

    2011-01-01

    Hip joint instability and impingement are the most common biomechanical risk factors that put the hip joint at risk to develop premature osteoarthritis. Several surgical procedures like periacetabular osteotomy for hip dysplasia or hip arthroscopy or safe surgical hip dislocation for femoroacetabular impingement aim at restoring the hip anatomy. However, the success of joint preserving surgical procedures is limited by the amount of pre-existing cartilage damage. Biochemically sensitive MRI techniques like delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) might help to monitor the effect of surgical or non-surgical procedures in the effort to halt or even reverse joint damage. PMID:22053256

  19. Mechanism of laser-induced stress relaxation in cartilage

    NASA Astrophysics Data System (ADS)

    Sobol, Emil N.; Sviridov, Alexander P.; Omelchenko, Alexander I.; Bagratashvili, Victor N.; Bagratashvili, Nodar V.; Popov, Vladimir K.

    1997-06-01

    The paper presents theoretical and experimental results allowing to discuss and understand the mechanism of stress relaxation and reshaping of cartilage under laser radiation. A carbon dioxide and a Holmium laser was used for treatment of rabbits and human cartilage. We measured temperature, stress, amplitude of oscillation by free and forced vibration, internal friction, and light scattering in the course of laser irradiation. Using experimental data and theoretical modeling of heat and mass transfer in cartilaginous tissue we estimated the values of transformation heat, diffusion coefficients and energy activation for water movement.

  20. High-Resolution Methods for Diagnosing Cartilage Damage In Vivo.

    PubMed

    Novakofski, Kira D; Pownder, Sarah L; Koff, Matthew F; Williams, Rebecca M; Potter, Hollis G; Fortier, Lisa A

    2016-01-01

    Advances in current clinical modalities, including magnetic resonance imaging and computed tomography, allow for earlier diagnoses of cartilage damage that could mitigate progression to osteoarthritis. However, current imaging modalities do not detect submicrometer damage. Developments in in vivo or arthroscopic techniques, including optical coherence tomography, ultrasonography, bioelectricity including streaming potential measurement, noninvasive electroarthrography, and multiphoton microscopy can detect damage at an earlier time point, but they are limited by a lack of penetration and the ability to assess an entire joint. This article reviews current advancements in clinical and developing modalities that can aid in the early diagnosis of cartilage injury and facilitate studies of interventional therapeutics. PMID:26958316

  1. Proteases involved in cartilage matrix degradation in osteoarthritis

    PubMed Central

    Troeberg, Linda; Nagase, Hideaki

    2011-01-01

    Osteoarthritis is a common joint disease for which there are currently no disease-modifying drugs available. Degradation of the cartilage extracellular matrix is a central feature of the disease and is widely though to be mediated by proteinases that degrade structural components of the matrix, primarily aggrecan and collagen. Studies on transgenic mice have confirmed the central role of Adamalysin with Thrombospondin Motifs 5 (ADAMTS-5) in aggrecan degradation, and the collagenolytic matrix metalloproteinase MMP-13 in collagen degradation. This review discusses recent advances in current understanding of the mechanisms regulating expression of these key enzymes, as well as reviewing the roles of other proteinases in cartilage destruction. PMID:21777704

  2. Acellular porcine corneal matrix as a carrier scaffold for cultivating human corneal epithelial cells and fibroblasts in vitro

    PubMed Central

    Zhang, Ju; Zhang, Can-Wei; Du, Li-Qun; Wu, Xin-Yi

    2016-01-01

    AIM To investigate the feasibility of corneal anterior lamellar reconstruction with human corneal epithelial cells and fibroblasts, and an acellular porcine cornea matrix (APCM) in vitro. METHODS The scaffold was prepared from fresh porcine corneas which were treated with 0.5% sodium dodecyl sulfate (SDS) solution and the complete removal of corneal cells was confirmed by hematoxylin-eosin (HE) staining and 4′, 6-diamidino-2-phenylindole (DAPI) staining. Human corneal fibroblasts and epithelial cells were cultured with leaching liquid extracted from APCM, and then cell proliferative ability was evaluated by MTT assay. To construct a human corneal anterior lamellar replacement, corneal fibroblasts were injected into the APCM and cultured for 3d, followed by culturing corneal epithelial cells on the stroma construction surface for another 10d. The corneal replacement was analyzed by HE staining, and immunofluorescence staining. RESULTS Histological examination indicated that there were no cells in the APCM by HE staining, and DAPI staining did not detect any residual DNA. The leaching liquid from APCM had little influence on the proliferation ability of human corneal fibroblasts and epithelial cells. At 10d, a continuous 3 to 5 layers of human corneal epithelial cells covering the surface of the APCM was observed, and the injected corneal fibroblasts distributed within the scaffold. The phenotype of the construction was similar to normal human corneas, with high expression of cytokeratin 12 in the epithelial cell layer and high expression of vimentin in the stroma. CONCLUSION Corneal anterior lamellar replacement can be reconstructed in vitro by cultivating human corneal epithelial cells and fibroblasts with an acellular porcine cornea matrix. This laid the foundation for the further transplantation in vivo. PMID:26949602

  3. Bi-linear mechanical property determination of acellular human patellar tendon grafts for use in anterior cruciate ligament replacement.

    PubMed

    Herbert, Anthony; Brown, Christopher; Rooney, Paul; Kearney, John; Ingham, Eileen; Fisher, John

    2016-06-14

    Anterior cruciate ligament rupture is rising in its prevalence amongst the young and those with physically active lifestyles. Acellular human patellar tendon (PT) grafts offer a promising restoration solution, returning knee joint stability and overcoming some of the current disadvantages of autologous or allogeneic grafts. However, it is necessary to ensure that the decellularisation bio-processes involved do not cause structural changes in the microstructure of the tendon tissue that may adversely affect the mechanical properties, particularly with respect to the physiological range of loading. Sixteen cadaveric human PT grafts were sourced and processed from eight donors, with full ethical approval and consent for use in research. Eight specimens were allocated for decellularisation, while the remaining eight contralateral specimens were used as native controls. Testing consisted of 12 preconditioning cycles followed by uniaxial extension until failure occurred. Stress-strain data was then fitted to a bi-linear model using least squares regression by a custom-written Matlab script. The elastic moduli for the toe region and linear region of each specimen were determined, in addition to the transition point co-ordinates and strain energy density for increasing strain. No significant differences were found between groups for all of the parameters investigated. Hence, the shape and magnitude of the stress-strain profile was found to be the same for both groups throughout loading. The results of this study indicated that decellularisation appeared to have no effect on the material properties of human PT grafts under quasistatic conditions. Therefore, acellular human PT grafts can offer a viable additional solution for ACL replacement compared to current autologous and allogeneic treatment options. PMID:27063250

  4. [iPS cells for the generation of cartilage and for regenerative medicine and disease modeling of cartilage diseases].

    PubMed

    Tsumaki, Noriyuki

    2016-04-01

    The development of induced pluripotent stem cells(iPSCs)has enabled the acquisition of patient-specific chondrocytes by converting somatic cells, such as dermal fibroblasts or blood cells, from patients to iPSCs and then differentiating them toward chondrocytes. We can further generate cartilage tissue from iPSC-derived chondrocytes. Studies on iPSC-derived chondrocytes/cartilage for the regeneration of articular cartilage injury are ongoing. These studies will in the future use autologous iPSCs and allogenic iPSCs from an iPSC stock prepared from donor cells. Drug discovery research for related diseases such as skeletal dysplasia is also being conducted. PMID:27013630

  5. Energy information sheets

    SciTech Connect

    Not Available

    1993-12-02

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the general public. Written for the general public, the EIA publication Energy Information Sheets was developed to provide information on various aspects of fuel production, prices, consumption and capability. The information contained herein pertains to energy data as of December 1991. Additional information on related subject matter can be found in other EIA publications as referenced at the end of each sheet.

  6. Associations between the properties of the cartilage matrix and findings from quantitative MRI in human osteoarthritic cartilage of the knee

    PubMed Central

    Wei, Bo; Du, Xiaotao; Liu, Jun; Mao, Fengyong; Zhang, Xiang; Liu, Shuai; Xu, Yan; Zang, Fengchao; Wang, Liming

    2015-01-01

    The aim of this study was to investigate the associations between the properties of the cartilage matrix and the results of T2 mapping and delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) in human knee osteoarthritic cartilage. Osteochondral samples were harvested from the middle part of the femoral condyle and tibial plateaus of 20 patients with knee osteoarthritis (OA) during total knee arthroplasty. Sagittal T2 mapping, T1pre, and T1Gd were performed using 7.0T magnetic resonance imaging (MRI). Gycosaminoglycan (GAG) distribution was evaluated by OARSI, collagen anisotropy was assessed by polarized light microscopy (PLM), and biochemical analyses measured water, GAG, and collagen content. Associations between properties of the cartilage matrix and T2 and ΔR1 (1/T1Gd-1/T1pre) values were explored using correlation analysis. T2 and ΔR1 values were significantly correlated with the degree of cartilage degeneration (OARSI grade; Ρ = 0.53 and 0.77). T2 values were significantly correlated with water content (r = 0.69; P < 0.001), GAG content (r = -0.43; P < 0.001), and PLM grade (r = 0.47; P < 0.001), but not with collagen content (r = -0.02; P = 0.110). ΔR1 values were significantly correlated with GAG content (r = -0.84; P < 0.001) and PLM grade (r = 0.41; P < 0.001). Taken together, T2 mapping and dGEMRIC results were correlated with the properties of the cartilage matrix in human knee osteoarthritic cartilage. Combination T2 mapping and dGEMRIC represents a potential non-invasive monitoring technique to detect the progress of knee OA. PMID:26097577

  7. Investigations into human tracheal cartilage osseocalcineus metaplasia III. ventro-dorsal measurement of the thickness of human tracheal cartilages.

    PubMed

    Sośnik, Henryk; Sośnik, Katarzyna

    2010-01-01

    The aim of the study was to verify the hypothesis that osseocalcineus metaplasia present in the tracheal cartilage is conditioned by its thickness. The study group comprised 78 male tracheas (age ranging between 19 and 84 years, mean = 56.5 years ±12.6 years), and 69 female tracheas (age ranging between 18 and 90 years, mean = 65.3 ±14 years). Tracheal transverse segments (every 4 cm) were collected for histopathological examinations from organs fixed in 10% formalin solution. Typical paraffin specimens, 5 μm thick, were measured in the horizontal position using the ocular micrometer (10 : 100 Zeiss) and Semiplan 3.2/0.10 objective. Differences between mean patient group and subgroup values were statistically verified. P = 0.05 was considered as statistically significant. Osseocalcineus metaplasia occurred 2.5-fold more often in male patients, in spite of the higher mean age of female patients (p < 0.001). The average male cartilage thickness was 50.32 ±7.94 × 10⁻² cm, while that of female patients was 38.44 ±4.44 × 10⁻² cm (p < 0.001). The average height of male patients (168.63 ±27.14 cm) was significantly higher in comparison to female patients (157.2 ±5.78 cm) (p < 0.001). The thickness of tracheal cartilages in men was significantly greater in metaplastic tracheas than in tracheas without metaplasia, as well as in changed cartilages as compared to unchanged ones in the same trachea. Considering both genders, the thickness of tracheal cartilages positively correlated with patient age (men: +0.44; p < 0.001; women: +0.293; p < 0.014), whereas height did not correlate with cartilage thickness. PMID:20924990

  8. Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee Cartilage Attenuates the Degeneration of Articular Cartilage in Adult Mice

    PubMed Central

    Weng, Tujun; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Wen, Xuan; Du, Xiaolan; Chen, Qian; Deng, Chuxia; Chen, Di; Chen, Lin

    2013-01-01

    Objective Fibroblast growth factor (FGF) family members are involved in the regulation of articular cartilage homeostasis. The aim of this study was to investigate the function of FGF receptor 1 (FGFR-1) in the development of osteoarthritis (OA) and its underlying mechanisms. Methods FGFR-1 was deleted from the articular chondrocytes of adult mice in a cartilage-specific and tamoxifen-inducible manner. Two OA models (aging-associated spontaneous OA, and destabilization-induced OA), as well as an antigen-induced arthritis (AIA) model, were established and tested in Fgfr1-deficient and wild-type (WT) mice. Alterations in cartilage structure and the loss of proteoglycan were assessed in the knee joints of mice of either genotype, using these 3 arthritis models. Primary chondrocytes were isolated and the expression of key regulatory molecules was assessed quantitatively. In addition, the effect of an FGFR-1 inhibitor on human articular chondrocytes was examined. Results The gross morphologic features of Fgfr1-deficient mice were comparable with those of WT mice at both the postnatal and adult stages. The articular cartilage of 12-month-old Fgfr1-deficient mice displayed greater aggrecan staining compared to 12-month-old WT mice. Fgfr1 deficiency conferred resistance to the proteoglycan loss induced by AIA and attenuated the development of cartilage destruction after surgically induced destabilization of the knee joint. The chondroprotective effect of FGFR-1 inhibition was largely associated with decreased expression of matrix metalloproteinase 13 (MMP-13) and up-regulation of FGFR-3 in mouse and human articular chondrocytes. Conclusion Disruption of FGFR-1 in adult mouse articular chondrocytes inhibits the progression of cartilage degeneration. Down-regulation of MMP-13 expression and up-regulation of FGFR-3 levels may contribute to the phenotypic changes observed in Fgfr1-deficient mice. PMID:22833219

  9. 5. Historic American Buildings Survey Taken from drawing sheet, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey Taken from drawing sheet, SHEET #21, Showing the house as restored since Survey. (Dormer windows omitted as not authentic) - Samuel des Marest House, River Road, New Milford, Bergen County, NJ

  10. 71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLEARCHED DAM: STRESS SHEET, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLE-ARCHED DAM: STRESS SHEET, SHEET 3; DECEMBER 20, 1918. Littlerock Water District files. - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  11. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    PubMed Central

    Wang, Zhifa; Li, Zhijin; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-01-01

    To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration. PMID:26848656

  12. Quick Information Sheets. 1988.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    The Trace Center gathers and organizes information on communication, control, and computer access for handicapped individuals. The information is disseminated in the form of brief sheets describing print, nonprint, and organizational resources and listing addresses and telephone numbers for ordering or for additional information. This compilation…

  13. Quick Information Sheets.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    This compilation of "Trace Quick Sheets" provides descriptions, prices, and ordering information for products and services that assist with communication, control, and computer access for disabled individuals. Product descriptions or product sources are included for: adaptive toys and toy modifications; head pointers, light pointers, and…

  14. Insulation Fact Sheet.

    ERIC Educational Resources Information Center

    Conservation and Renewable Energy Inquiry and Referral Service (DOE), Silver Spring, MD.

    Heating and cooling account for 50-70% of the energy consumed in the average American home. Heating water accounts for another 20%. A poorly insulated home loses much of this energy, causing drafty rooms and high energy bills. This fact sheet discusses how to determine if your home needs more insulation, the additional thermal resistance (called…

  15. Ethanol Myths Fact Sheet

    SciTech Connect

    2009-10-27

    Ethanol is a clean, renewable fuel that is helping to reduce our nation’s dependence on oil and can offer additional economic and environmental benefits in the future. This fact sheet is intended to address some common misconceptions about this important alternative fuel.

  16. GED Testing Fact Sheet

    ERIC Educational Resources Information Center

    GED Testing Service, 2009

    2009-01-01

    This GED Testing fact sheet provides information on: (1) GED[R] Tests; (2) Versions and Editions of the GED Tests; (3) Earning a Credential; (4) GED Testing Service[R]; (5) History of the GED Tests; (6) Who Accepts the GED Credential; (7) Public/Private Partnership of GEDTS; (8) Renowned GED Credential Recipients; (9) GED Testing Numbers for 2008;…

  17. Algal Biofuels Fact Sheet

    SciTech Connect

    2009-10-27

    This fact sheet provides information on algal biofuels, which are generating considerable interest around the world. They may represent a sustainable pathway for helping to meet the U.S. biofuel production targets set by the Energy Independence and Security Act of 2007.

  18. Youth Demographics. Fact Sheet

    ERIC Educational Resources Information Center

    Lopez, Mark Hugo; Marcelo, Karlo Barrios

    2006-01-01

    This fact sheet compares the numbers of 18-25 year-old residents and citizens by gender, race, ethnicity, geographic distribution, marital status, military status, unemployment, educational attainment, and assesses population trends from 1968-2006. It explores such demographic characteristics of young people using data from the March Annual…

  19. Ethanol Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  20. Reading Recovery. [Fact Sheets].

    ERIC Educational Resources Information Center

    Reading Recovery Council of North America, Columbus, OH.

    This set of 10 fact sheets (each 2 to 4 pages long) addresses aspects of Reading Recovery, a program that helps children to be proficient readers and writers by the end of the first grade. It discusses the basic facts of Reading Recovery; Reading Recovery for Spanish literacy; Reading Recovery lessons; Reading Recovery professional development;…

  1. Rubella - Fact Sheet for Parents

    MedlinePlus

    ... this page: About CDC.gov . Redirect for the Rubella fact sheet page. The current fact sheet can ... http://www.cdc.gov/vaccines/parents/diseases/child/rubella.html Print page Share Compartir File Formats Help: ...

  2. A SINGLE BLUNT IMPACT ON CARTILAGE PROMOTES FIBRONECTIN FRAGMENTATION AND UPREGULATES CARTILAGE DEGRADING STROMELYSIN-1/MATRIX METALLOPROTEINASE-3 IN A BOVINE EX-VIVO MODEL

    PubMed Central

    Ding, Lei; Guo, Danping; Homandberg, Gene A.; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Post-traumatic osteoarthritis (PTOA) is characterized by progressive cartilage degeneration in injured joints. Since fibronectin fragments (Fn-fs) degrade cartilage mainly through up-regulating matrix metalloproteinases (MMPs) and pro-inflammatory cytokines, we hypothesized that Fn-fs play a key role in PTOA by promoting chondrolysis in and around injured cartilage. To test this hypothesis, we profiled the catabolic events focusing on fibronectin fragmentation and proteinase expression in bovine osteochondral explants following a single blunt impact on cartilage with a drop tower device which created partial-thickness tissue damage. Injured and control explants were cultured for up to 14 days. The presence of Fn-fs, MMPs (-1, -3, -13), ADAMTS-5 in culture media and in cartilage was determined with immunoblotting. The daily proteoglycan (PG) depletion of cartilage matrix was assessed with DMMB assay. The effect of explant-conditioned media on chondrocytes was also examined with immunoblotting. Impacted cartilage released significantly higher amount of native Fn, three chondrolytic Fn-fs and PG than non-impacted controls did. Those increases coincided with up-regulation of MMP-3 both in conditioned media and in impacted cartilage. These findings support our hypothesis that PTOA may be propelled by Fn-fs which act as catabolic mediators through up-regulating cartilage-damaging proteinases. PMID:24610678

  3. CD59 mediates cartilage patterning during spontaneous tail regeneration.

    PubMed

    Bai, Xue; Wang, Yingjie; Man, Lili; Zhang, Qing; Sun, Cheng; Hu, Wen; Liu, Yan; Liu, Mei; Gu, Xiaosong; Wang, Yongjun

    2015-01-01

    The regeneration-competent adult animals have ability to regenerate their lost complex appendages with a near-perfect replica, owing to the positional identity acquired by the progenitor cells in the blastema, i.e. the blastemal cells. CD59, a CD59/Ly6 family member, has been identified as a regulator of positional identity in the tail blastemal cells of Gekko japonicus. To determine whether this function of CD59 is unique to the regenerative amniote(s) and how CD59 mediates PD axis patterning during tail regeneration, we examined its protective role on the complement-mediated cell lysis and intervened CD59 expression in the tail blastemal cells using an in vivo model of adenovirus transfection. Our data revealed that gecko CD59 was able to inhibit complement-mediated cell lysis. Meanwhile, CD59 functioned on positional identity through expression in cartilage precursor cells. Intervening positional identity by overexpression or siRNA knockdown of CD59 resulted in abnormal cartilaginous cone patterning due to the decreased differentiation of blastemal cells to cartilage precursor cells. The cartilage formation-related genes were found to be under the regulation of CD59. These results indicate that CD59, an evolutionarily transitional molecule linking immune and regenerative regulation, affects tail regeneration by mediating cartilage patterning. PMID:26238652

  4. Tibial dyschondroplasia associated proteomic changes in chicken growth plate cartilage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tibial dyschondroplasia (TD) is a poultry leg problem that affects the proximal growth plate of tibia preventing its transition to bone. To understand the disease-induced proteomic changes we compared the protein extracts of cartilage from normal and TD- affected growth plates. TD was induced by fe...

  5. Vascularization of engineered cartilage constructs in a mouse model.

    PubMed

    Burghartz, Marc; Gehrke, Thomas; Storck, Katharina; Staudenmaier, Rainer; Mandlik, Veronika; Schurr, Christian; Hoang, Nguyen; Hagen, Rudolf; Kleinsasser, Norbert

    2015-02-01

    Tissue engineering of cartilage tissue offers a promising method for reconstructing ear, nose, larynx and trachea defects. However, a lack of sufficient nutrient supply to cartilage constructs limits this procedure. Only a few animal models exist to vascularize the seeded scaffolds. In this study, polycaprolactone (PCL)-based polyurethane scaffolds are seeded with 1 × 10(6) human cartilage cells and implanted in the right hind leg of a nude mouse using an arteriovenous flow-through vessel loop for angiogenesis for the first 3 weeks. Equally seeded scaffolds but without access to a vessel loop served as controls. After 3 weeks, a transposition of the vascularized scaffolds into the groin of the nude mouse was performed. Constructs (verum and controls) were explanted 1 and 6 weeks after transposition. Constructs with implanted vessels were well vascularized. The amount of cells increased in vascularized constructs compared to the controls but at the same time noticeably less extracellular matrix was produced. This mouse model provides critical answers to important questions concerning the vascularization of engineered tissue, which offers a viable option for repairing defects, especially when the desired amount of autologous cartilage or other tissues is not available and the nutritive situation at the implantation site is poor. PMID:25381568

  6. Arthroscopic Allograft Cartilage Transfer for Osteochondral Defects of the Talus

    PubMed Central

    Min, Kyong S.; Ryan, Paul M.

    2015-01-01

    Arthroscopic treatment of osteochondral defects is well established but has had mixed results in larger lesions and revision operations. Particulated allograft cartilage transfer may provide an arthroscopic option for lesions that would otherwise have been treated through open approaches or osteotomies. The procedure is performed under noninvasive distraction with standard arthroscopic portals. PMID:26052496

  7. Mesenchymal stromal cells for cartilage repair in osteoarthritis.

    PubMed

    Mamidi, M K; Das, A K; Zakaria, Z; Bhonde, R

    2016-08-01

    Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials. PMID:26973328

  8. Effects of Bone Morphogenic Proteins on Engineered Cartilage

    NASA Technical Reports Server (NTRS)

    Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

    2007-01-01

    A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

  9. Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis

    PubMed Central

    Xu, Lingxiao; Peng, Qiuyue; Xuan, Wenhua; Feng, Xiaoke; Zhang, Miaojia; Tan, Wenfeng; Xue, Meilang

    2016-01-01

    We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA. PMID:27433031

  10. Endodermal Wnt signaling is required for tracheal cartilage formation

    PubMed Central

    Snowball, John; Ambalavanan, Manoj; Whitsett, Jeffrey; Sinner, Debora

    2015-01-01

    Tracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal-bronchial cartilaginous rings. The normal dorsal-ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wlsf/f;ShhCre/+ tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation. PMID:26093309

  11. Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

    PubMed

    Xu, Lingxiao; Peng, Qiuyue; Xuan, Wenhua; Feng, Xiaoke; Kong, Xiangqing; Zhang, Miaojia; Tan, Wenfeng; Xue, Meilang; Wang, Fang

    2016-01-01

    We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA. PMID:27433031

  12. Syndecan-4 in intervertebral disc and cartilage: Saint or synner?

    PubMed

    Binch, Abbie L A; Shapiro, Irving M; Risbud, Makarand V

    2016-01-01

    The ECM of the intervertebral disc and articular cartilage contains a highly organised network of collagens and proteoglycans which resist compressive forces applied to these tissues. A pathological hallmark of the intervertebral disc is the imbalance between production of anabolic and catabolic factors by the resident cells. This process is thought to be mediated by pro-inflammatory cytokines, predominantly TNF-α and IL-1β, which upregulate expression of matrix degrading enzymes such as MMPs and ADAMTSs. This imbalance ultimately results in tissue degeneration causing failure of the biomechanical function of the tissues. A similar cascade of events is thought to occur in articular cartilage during development of osteoarthritis. Within these skeletal tissues a small, cell surface heparan sulphate proteoglycan; syndecan-4 (SDC4) has been implicated in maintaining physiological functions. However in the degenerating niche of the intervertebral disc and cartilage, dysregulated activities of this molecule may exacerbate pathological changes. Studies in recent years have elucidated a role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS-5 function and MMP3 expression. Discourse presented in this review highlights the potential of SDC4 as a possible therapeutic target in slowing the progression of ECM degradation in both degenerative disc disease and osteoarthritis. PMID:26796346

  13. Cartilage Transplants Hold Promise for Chal