The junction between hyaline cartilage and engineered cartilage in rabbits.

PubMed

Komura, Makoto; Komura, Hiroko; Otani, Yushi; Kanamori, Yutaka; Iwanaka, Tadashi; Hoshi, Kazuto; Tsuyoshi, Takato; Tabata, Yasuhiko

2013-06-01

Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. Controlled, prospecive study. In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

Optical properties of costal cartilage and their variation in the process of non-destructive action of laser radiation with the wavelength 1.56 μm

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

Yuzhakov, A V; Sviridov, A P; Shcherbakov, E M

2014-01-31

The optical properties of costal cartilage and their variation under the action of laser radiation with the wavelength 1.56 μm are studied. The laser action regime corresponds to that used for changing the cartilage shape. The dynamics of the passed scattered laser radiation was studied by means of the optical fibre system, and the optical properties of the cartilage tissue (on the basis of Monte Carlo modelling of light propagation) – using the setup with two integrating spheres. Under the influence of radiation, the characteristics of which corresponded to those used for the cartilage shape correction, no essential changes inmore » the optical parameters were found. The results obtained in the course of studying the dynamics of optical signals in the process of costal cartilage irradiation can be used for developing control systems, providing the safety and efficiency of laser medical technologies. (biophotonics)« less

Characteristics and time-dependence of cut marks and blunt force fractures on costal cartilages: an experimental study.

PubMed

Spagnoli, Laura; Amadasi, Alberto; Frustaci, Michela; Mazzarelli, Debora; Porta, Davide; Cattaneo, Cristina

2016-03-01

The distinction between cut marks and blunt force injuries on costal cartilages is a crucial issue in the forensic field. Moreover, a correct distinction may further be complicated by decomposition, so the need arises to investigate the distinctive features of lesions on cartilage and their changes over time. This study aimed to assess the stereomicroscopic features of cut marks (performed with six different knives) and blunt fractures (performed with a hammer and by means of manual bending) on 48 fragments of human costal cartilages. Moreover, in order to simulate decomposition, the cut and fractured surfaces were checked with stereomicroscopy and through casts after 1 and 2 days, 1 week, and 1, 2 and 4 months of drying in ambient air. In fresh samples, for single and unique cuts, striations were observed in between 44 and 88% of cases when non-serrated blades were used, and between 77 and 88% for serrated blades; in the case of "repeated" (back and forth movement) cuts, striations were detected in between 56 and 89% of cases for non-serrated blades, and between 66 and 100% for serrated blades. After only 1 week of decomposition the detection rates fell to percentages of between 28 and 39% for serrated blades and between 17 and 33% for non-serrated blades. Blunt force injuries showed non-specific characteristics, which, if properly assessed, may lead to a reliable distinction between different cut marks in fresh samples. The most evident alterations of the structure of the cartilage occurred in the first week of decomposition in ambient air. After one week of drying, the characteristics of cut marks were almost undetectable, thereby making it extremely challenging to distinguish between cut marks, blunt force fractures and taphonomic effects. The study represents a contribution to the correct assessment and distinction of cut marks and blunt force injuries on cartilages, providing a glimpse on the modifications such lesions may undergo with decomposition.

Computer-aided design and rapid prototyping-assisted contouring of costal cartilage graft for facial reconstructive surgery.

PubMed

Lee, Shu Jin; Lee, Heow Pueh; Tse, Kwong Ming; Cheong, Ee Cherk; Lim, Siak Piang

2012-06-01

Complex 3-D defects of the facial skeleton are difficult to reconstruct with freehand carving of autogenous bone grafts. Onlay bone grafts are hard to carve and are associated with imprecise graft-bone interface contact and bony resorption. Autologous cartilage is well established in ear reconstruction as it is easy to carve and is associated with minimal resorption. In the present study, we aimed to reconstruct the hypoplastic orbitozygomatic region in a patient with left hemifacial microsomia using computer-aided design and rapid prototyping to facilitate costal cartilage carving and grafting. A three-step process of (1) 3-D reconstruction of the computed tomographic image, (2) mirroring the facial skeleton, and (3) modeling and rapid prototyping of the left orbitozygomaticomalar region and reconstruction template was performed. The template aided in donor site selection and extracorporeal contouring of the rib cartilage graft to allow for an accurate fit of the graft to the bony model prior to final fixation in the patient. We are able to refine the existing computer-aided design and rapid prototyping methods to allow for extracorporeal contouring of grafts and present rib cartilage as a good alternative to bone for autologous reconstruction.

Health-related quality-of-life assessment and surgical outcomes for auricular reconstruction using autologous costal cartilage.

PubMed

Soukup, Benjamin; Mashhadi, Syed A; Bulstrode, Neil W

2012-03-01

This study aims to assess the health-related quality-of-life benefit following auricular reconstruction using autologous costal cartilage in children. In addition, key aspects of the surgical reconstruction are assessed. After auricular reconstruction, patients completed two questionnaires. The first was a postinterventional health-related quality-of-life assessment tool, the Glasgow Benefit Inventory. A score of 0 signifies no change in health-related quality-of-life, +100 indicates maximal improvement, and -100 indicates maximal negative impact. The second questionnaire assessed surgical outcomes in auricular reconstruction across three areas: facial integration, aesthetic auricular units, and costal reconstruction. These were recorded on a five-point ordinal scale and are presented as mean scores of a total of 5. The mean total Glasgow Benefit Inventory score was 48.1; significant improvements were seen in all three Glasgow Benefit Inventory subscales (p < 0.0001). A mean integration score of 3.8 and a mean aesthetic auricular unit reconstruction score of 3.4 were recorded. Skin color matching (4.3) of the ear was most successfully reconstructed and auricular cartilage reconstruction scored lowest (3.5). Of the aesthetic units, the helix scored highest (3.6) and the tragus/antitragus scored lowest (3.3). Donor-site reconstruction scored 3.9. Correlation analysis revealed that higher reconstruction scores are associated with a greater health-related quality-of-life gain (r = 0.5). Ninety-six percent of patients would recommend the procedure to a friend. Auricular reconstruction with autologous cartilage results in significant improvements in health-related quality-of-life. In addition, better surgical outcomes lead to a greater improvement in health-related quality-of-life. Comparatively poorer reconstructed areas of the ear were identified so that surgical techniques may be improved. Therapeutic, IV.

Management of chest deformity caused by microtia reconstruction: Comparison of autogenous diced cartilage versus cadaver cartilage graft partial filling techniques.

PubMed

Go, Ju Young; Kang, Bo Young; Hwang, Jin Hee; Oh, Kap Sung

2017-01-01

Efforts to prevent chest wall deformity after costal cartilage graft are ongoing. In this study, we introduce a new method to prevent donor site deformation using irradiated cadaver cartilage (ICC) and compare this method to the autogenous diced cartilage (ADC) technique. Forty-two pediatric patients comprised the ADC group (n = 24) and the ICC group (n = 18). After harvesting costal cartilage, the empty perichondrial space was filled with autologous diced cartilage in the ADC group and cadaver cartilage in the ICC group. Digital photographs and rib cartilage three-dimensional computed tomography (CT) data were analyzed to compare the preventive effect of donor site deformity. We compared the pre- and postoperative costal cartilage volumes using 3D-CT and graded the volumes (grade I: 0%-25%, grade II: 25%-50%, grade III: 50%-75%, and grade IV: 75%-100%). The average follow-up period was 20 and 24 months in the ADC and ICC groups, respectively. Grade IV maintenance of previous costal cartilage volume was evident postoperatively in 22% of patients in the ADC group and 82% of patients in the ICC group. Intercostal space narrowing and chest wall depression were less in the ICC group. There were no complications or severe resorption of cadaver cartilage. ICC support transected costal ring and prevented stability loss by acting as a spacer. The ICC technique is more effective in preventing intercostal space narrowing and chest wall depression than the ADC technique. Samsung Medical Center Institution Review Board, Unique protocol ID: 2009-10-006-008. This study is also registered on PRS (ClinicalTrials.gov Record 2009-10-006). Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Dorsal Augmentation with Homologous Rib.

PubMed

Kridel, Russell W H; Sturm, Angela K

2017-04-01

Dorsal augmentation grafts are used to reconstruct and raise the nasal dorsum in patients with dorsal saddling due to trauma, infection, or previous nasal surgery, as well as in patients with a narrow, congenitally low, and/or wide dorsum. Alloplastic implants and various biomaterials are available for grafting, each with advantages and disadvantages. Although autologous septal cartilage is a preferable and often convenient source of cartilage, it is frequently not sufficient for large volume dorsal augmentation, nor is it available in patients who have had septoplasty, infection, previous rhinoplasty with grafting, or significant trauma. Ear cartilage may be used but it is difficult to make homogenous and smooth, and dorsal irregularities can be seen in the long term especially in thin-skinned patients. For these reasons, we frequently use irradiated costal cartilage from tissue banks as our grafting source, thereby eliminating the morbidity of harvesting the patient's own rib. Proper surgical techniques, the use of antibiotics, and proper sculpting and placement of the cartilage limits complications such as warping, resorption, infection, and extrusion. Irradiated homograft costal cartilage grafts have been used successfully in large numbers of patients with long-term follow-up with low complication rates and serve as a welcome alternative to harvesting a patient's rib cartilage. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cartilage grafting in nasal reconstruction.

PubMed

Immerman, Sara; White, W Matthew; Constantinides, Minas

2011-02-01

Nasal reconstruction after resection for cutaneous malignancies poses a unique challenge to facial plastic surgeons. The nose, a unique 3-D structure, not only must remain functional but also be aesthetically pleasing to patients. A complete understanding of all the layers of the nose and knowledge of available cartilage grafting material is necessary. Autogenous material, namely septal, auricular, and costal cartilage, is the most favored material in a free cartilage graft or a composite cartilage graft. All types of material have advantages and disadvantages that should guide the most appropriate selection to maximize the functional and cosmetic outcomes for patients. Copyright © 2011 Elsevier Inc. All rights reserved.

[Modified two-stage surgery for total auriculoplasty with autogenous rib cartilage].

PubMed

Zhang, Zheng-wen; Kang, Shen-song; Xie, Feng; Ma, Teng-xiao; Li, Lei; Zhai, Hong-feng; Chou, Hai-yan; Li, Hao; Zhong, Ai-mei; Zhang, Dong-yi

2011-09-01

To introduce a modified surgery for total auriculoplasty and the experience in one hundred and forty-six cases (155 ears). The procedure was a two-stage operation. The first stage involved fabrication and grafting of a costal cartilage framework. A U-shaped skin incision was made on the posterior edge of the lobule and the remnant ear cartilage was removed completely. The area for the insertion of the cartilage framework was undermined. Skin flaps were sutured after insertion of the cartilage framework. The second-stage surgery was usually performed six months after the first-stage operation. The reconstructed auricle was elevated, and a costal cartilage block was fixed to the posterior part of the auricle. A temporoparietal fascia flap was then used to cover the costal cartilage block. Finally, the posterior aspect of the projected auricle was covered with a spit-thickness skin graft. The incisions healed in one hundred and forty-one patients (150 ears) after the first stage operation. Partial necrosis of the postauricular flap was observed in five cases (5 ears) after the first stage operation, but no exposure or absorption of the cartilage took place. The skin grafts survived in one hundred and thirty-nine cases (147 ears) after the second-stage surgery. Partial necrosis of the skin graft was observed in seven cases (8 ears), but healed after one-week of dressing changes. Ninety-four cases (97 ears) were followed up, but fifty-two cases (58 ears) were lost to follow up. The follow-up at six months to two years showed satisfactory contour and projection of the constructed ears. This two-stage surgery is simple and ideal for auricloplasty with few complications.

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.

Transplantation of rib cartilage reshaped with 1.56 μm laser radiation in rabbits

NASA Astrophysics Data System (ADS)

Sobol, E.; Baum, O.; Alexandrovskaya, Yu.; Shekhter, A.; Selezneva, L.; Svistuskin, V.

2017-02-01

As cartilage is an ideal natural material for transplantation, its use in the ENT surgery is limited by a difficulty to get proper shape of cartilage implants. Aim of the work is to make ring-shaped cartilage implants, to check their stability after laser reshaping and to perform transplantation into rabbits in vivo. We experimented with costal cartilages of 1-2 mm in thickness obtained from 3rd and 4rd ribs of a rabbit. 1.56 μm laser (Arcuo Medical Inc.) was used for cartilage reshaping. The laser settings were established taking into account anisotropy of cartilage structure for different orientation of the implants. The reshaped cartilage implants were surgically sewn to rib cartilages of the other rabbits. The rabbits were slaughtered in 3.5-4 months after surgery. The results have shown that (1) all reshaped implants kept circular form, and (2) the implants were adhered to the native rabbit cartilage sites (3) pronounced signs of regeneration in the intermediate zones were observed. The prospects of the cartilage implants use in larynx stenosis surgery are discussed.

Satisfactory surgical option for cartilage graft absorption in microtia reconstruction.

PubMed

Han, So-Eun; Oh, Kap Sung

2016-04-01

We routinely perform auricular elevation at least 6 months after implantation of framework in microtia reconstruction using costal cartilage. However, in a few cases, cartilage graft absorption has occurred, which has led to contour irregularity with unfavorable long-term results. In the present study, we recount the details of using additional rib cartilage augmentation to achieve an accentuated contour in cartilage graft absorption cases. The cartilage graft absorption was defined as contour irregularity or cartilage graft deformation as evaluated by the surgeon and patient. Depending on the extent of cartilage graft absorption, another rib cartilage framework was added to the previously implanted framework, targeting the absorption area. We used banked cartilage or harvested new cartilage based on three-dimensional rib computed tomography. Additional recontouring of framework was conducted in eight patients who were examined for cartilage graft absorption from 1.5 to 5 years after implantation of the framework. Four patients received additional rib cartilage augmentation and tissue expander insertion simultaneously prior to auricular elevation. Two patients underwent auricular elevation simultaneously. In another two patients, additional rib cartilage augmentation was performed before auricular elevation. The mean follow-up period was 18 months, and in all cases reconstructive results were acceptable. Although further follow-up evaluation is required, additional rib cartilage augmentation is an attractive surgical option for cartilage graft absorption cases. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

[Costal chondrosarcoma. 4 cases].

PubMed

Ben M'rad, S; el Hammami, S; Merai, S; Kamoun, N; Horchani, H; Ben Miled, K; Kilani, T; Djenayah, F

1999-09-04

Tumors of the rib cage are uncommon and malignant in 29% of the cases. Chondrosarcoma predominates, accounting for 40% of all cases of malignant costal tumors. Four patients (3 women, 1 man, mean age 28.2 years) were hospitalized for costal chondrosarcoma. Pain and tumefaction dominated the clinical presentation. Calcifications suggested the diagnosis in 3 cases. Curative surgery was performed in all cases. Postoperative radiotherapy was unable to improve prognosis in 2 patients. Chondrosarcoma of the ribs is characterized by a strong potential for invasive extension. Diagnosis is suspected on the basis of imaging findings and confirmed at pathology. Surgery is required. Chemotherapy and radiotherapy do not improve prognosis significantly.

Reconstruction of partially amputated external ear with costal cartilage graft: case report.

PubMed

Brunelli, A; Bottini, D J; Cervelli, V; Cervelli, G; Grimaldi, M

2004-06-01

Many causes are responsible for secondary anomalies of the outer ear, such as: car accidents, sport- or work-related accidents, assaults, bites from animals or humans, benign or malignant tumours, burns and the effects of surgical interventions of the ear (plastic surgery on the ear or attempts at correction of primary malformations of the ear). The anatomical complexity of the ear makes its reconstruction particularly complicated with post-operative results that are often disappointing. The Authors describe their experience in the reconstruction of a partially amputated outer ear following a dog bite. The therapeutic protocol required various surgical stages. Initially, a cutaneous expander was applied at the level of the mastoid in order to ensure a sufficient quantity of local skin. The second stage was to remove cartilage from the ribs, followed by construction of a cartilaginous model of the ear and its insertion into the subcutaneous mastoid region after removal of the cutaneous expander and any residual ear cartilage. The last stage was to separate the neo-formed outer ear from the mastoid skin with the insertion of a cartilage graft to the posterior region of the reconstructed ear. This graft was covered by the occipital fascia rotated at 180 degrees and by a skin graft removed from the pubis. The postoperative result was satisfactory with recuperation of a good aesthetic appearance of the ear. Aim of the present report is to describe the surgical technique employed in the reconstruction of secondary anomalies of the ear and to highlight errors committed during this procedure. These considerations have allowed us to stress some fundamental elements in the reconstruction of the ear. In particular, the watershed was the awareness that we had to create a cartilaginous model that respected, as far as possible, the anatomy of the outer ear with all its ridges, trenches and cavities. This as well as ensuring a sufficient quantity of local skin in order to cover

Laser-induced modification of structure and shape of cartilage in otolaryngology and orthopaedics

NASA Astrophysics Data System (ADS)

Sobol', E. N.; Baum, O. I.; Omel'chenko, A. I.; Soshnikova, Yu. M.; Yuzhakov, A. V.; Kas'yanenko, E. M.; Tokareva, A. V.; Baskov, A. V.; Svistushkin, V. M.; Selezneva, L. V.; Shekhter, A. B.

2017-11-01

We present the results of basic research in laser modification of tissues in otolaryngology (correcting the shape of nasal septum and larynx cartilages), cosmetology (correcting ear and nose shape), orthopaedics and spinal surgery (treatment of diseases of spine disc and joints). The physical processes and mechanisms of laser-induced relaxation of stresses and regeneration of tissues are considered. New results of studies in this fast-developing field of laser surgery are presented, in particular, the results of laser correction of costal cartilage shape in the process of making implants for the treatment of larynx stenosis and controlled regeneration of the hyaline articular cartilage. Presented at the Fundamentals of Laser Assisted Micro- and Nanotechnologies (FLAMN-2016) International Symposium (Pushkin, Leningrad oblast, 27 June to 1 July 2016).

The Cartilage Warp Prevention Suture.

PubMed

Guyuron, Bahman; Wang, Derek Z; Kurlander, David E

2018-06-01

Costal cartilage graft warping can challenge rhinoplasty surgeons and compromise outcomes. We propose a technique, the "warp control suture," for eliminating cartilage warp and examine outcomes in a pilot group. The warp control suture is performed in the following manner: Harvested cartilage is cut to the desired shape and immersed in saline to induce warping. A 4-0 or 5-0 PDS suture, depending the thickness of the cartilage, is passed from convex to concave then concave to convex side several times about 5-6 mm apart, finally tying the suture on the convex side with sufficient tension to straighten the cartilage. First an ex vivo experiment was performed in 10 specimens from 10 different patients. Excess cartilage was sutured and returned to saline for a minimum of 15 min and then assessed for warping compared to cartilage cut in the identical shape also soaked in saline. Then, charts of nine subsequent patients who received the warp control suture on 16 cartilage grafts by the senior author (BG) were retrospectively reviewed. Inclusion of study subjects required at least 6 months of follow-up with standard rhinoplasty photographs. Postoperative complications and evidence of warping were recorded. In the ex vivo experiment, none of the 10 segments demonstrated warping after replacement in saline, whereas all the matching segments demonstrated significant additional warping. Clinically, no postoperative warping was observed in any of the nine patients at least 6 months postoperatively. One case of minor infection was observed in an area away from the graft and treated with antibiotics. No warping or other complications were noted. The warp control suture technique presented here effectively straightens warped cartilage graft and prevents additional warping. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online

Comparison of the Surgical Outcomes of Dorsal Augmentation Using Expanded Polytetrafluoroethylene or Autologous Costal Cartilage.

PubMed

Joo, Yeon Hee; Jang, Yong Ju

2016-09-01

Dorsal augmentation material includes alloplastic implants and autologous tissues. However, there has been no comparison to date of dorsal augmentation using different materials performed by the same surgeon. To compare the aesthetic outcomes and complications of dorsal augmentation using expanded polytetrafluoroethylene (ePTFE) and autologous costal cartilage (ACC) in rhinoplasty. A retrospective review of the medical records of 244 patients who underwent dorsal augmentation performed by the same surgeon at the Asan Medical Center using ePTFE or ACC from March 1, 2003, through September 31, 2015. Patient demographics and surgical procedures were analyzed. The aesthetic outcomes were scored from 1 (worst) to 4 (best) by 3 otolaryngologists. Changes in dorsal height and radix height were measured by comparing preoperative and postoperative profile views. Postoperative complications were also evaluated. A total of 244 patients who underwent augmentation rhinoplasty were reviewed in this study, including 141 men (57.8%) and 103 women (42.2%). The ePTFE group included 176 patients, and the ACC group comprised 68 patients. In the ePTFE and ACC groups, 96 patients (54.5%) and 45 patients (66.2%) were male, respectively. The patient ages ranged from 11 to 69 years, with a mean (SD) age of 30.3 (11.49) years in the ePTFE group and 36.04 (12.65) years in the ACC group. The mean (SD) aesthetic outcome scores were comparable between the 2 groups: 2.99 (0.05) in the ePTFE group and 2.99 (0.06) in the ACC group (P = .93). The change of dorsal (2.64% in ePTFE group and 5.82% in ACC group) and radix (3.62% in ePTFE group and 3.77% in ACC group) heights were significantly increased after augmentation in both groups (P < .001) even though the dorsal height of the ACC group after augmentation showed a significantly greater increase compared to the ePTFE group (P < .001). However, the complication rate was significantly higher in the ACC group: 4.0% in ePTFE group and

Composite cervical skin and cartilage flap provides a novel large airway substitute after long-segment tracheal resection.

PubMed

Fabre, Dominique; Singhal, Sunil; De Montpreville, Vincent; Decante, Benoit; Mussot, Sacha; Chataigner, Olivier; Mercier, Olaf; Kolb, Frederic; Dartevelle, Philippe G; Fadel, Elie

2009-07-01

Airway replacement after long-segment tracheal resection for benign and malignant disease remains a challenging problem because of the lack of a substitute conduit. Ideally, an airway substitute should be well vascularized, rigid, and autologous to avoid infections, airway stenosis, and the need for immunosuppression. We report the development of an autologous tracheal substitute for long-segment tracheal resection that satisfies these criteria and demonstrates excellent short-term functional results in a large-animal study. Twelve adult pigs underwent long-segment (6 cm, 60% of total length) tracheal resection. Autologous costal cartilage strips measuring 6 cm x 2 mm were harvested from the chest wall and inserted at regular 0.5-cm intervals between dermal layers of a cervical skin flap. The neotrachea was then scaffolded by rotating the composite cartilage skin flap around a silicone stent measuring 6 cm in length and 1.4 cm in diameter. The neotrachea replaced the long segment of tracheal resection, and the donor flap site was closed with a double-Z plasty. Animals were killed at 1 week (group I, n = 4), 2 weeks (group II, n = 4), and 5 weeks (group III, n = 4). In group III the stent was removed 1 week before death. Viability of the neotrachea was monitored by means of daily flexible bronchoscopy and histologic examination at autopsy. Long-term morbidity and mortality were determined by monitoring weight gain, respiratory distress, and survival. There was no mortality during the study period. Weight gain was appropriate in all animals. Daily bronchoscopy and postmortem histologic evaluation confirmed excellent viability of the neotrachea. There was no evidence of suture-line dehiscence. Five animals had distal granulomas that were removed by using rigid bronchoscopy. In group III 1 animal had tracheomalacia, which was successfully managed by means of insertion of a silicon stent. Airway reconstruction with autologous cervical skin flaps scaffolded with costal

The costal skeleton of the Regourdou 1 Neandertal.

PubMed

Gómez-Olivencia, Asier; Holliday, Trenton; Madelaine, Stéphane; Couture-Veschambre, Christine; Maureille, Bruno

2018-02-26

The morphology and size of the Neandertal thorax is a subject of growing interest due to its link to general aspects of body size and shape, including physiological aspects related to bioenergetics and activity budgets. However, the number of well-preserved adult Neandertal costal remains is still low. The recent finding of new additional costal remains from the Regourdou 1 (R1) skeleton has rendered this skeleton as one of the most complete Neandertal costal skeletons with a minimum of 18 ribs represented, five of which are complete or virtually complete. Here we describe for the first time all the rib remains from R1 and compare them to a large modern Euroamerican male sample as well as to other published Neandertal individuals. The costal skeleton of this individual shows significant metric and morphological differences from our modern human male comparative sample. The perceived differences include: dorsoventrally large 1st and 2nd ribs, 3rd ribs with a very closed dorsal curvature and large maximum diameters at the posterior angle, a large tubercle-iliocostal line distance in the 4th rib, thick shafts at the dorsal end of its 6th ribs, thick mid-shafts of the 8th ribs, large articular tubercles at the 9th ribs, and thick shafts of the 11th and 12th ribs. Here we also describe a new mesosternal fragment: the left lateral half of sternebral segments 4 and 5. This portion reveals that the mesosternum of R1 had a sternal foramen in its inferiormost preserved sternal segment and supports previous estimation of the total length of this mesosternum. The new costal remains from R1 support the view that Neandertals, when compared with modern humans, show a significantly different thorax, consistent with differences found in other anatomical regions such as the vertebral column and pelvis. Copyright © 2018 Elsevier Ltd. All rights reserved.

BioCartilage Improves Cartilage Repair Compared With Microfracture Alone in an Equine Model of Full-Thickness Cartilage Loss.

PubMed

Fortier, Lisa A; Chapman, Hannah S; Pownder, Sarah L; Roller, Brandon L; Cross, Jessica A; Cook, James L; Cole, Brian J

2016-09-01

was significantly shorter (better) in the superficial region of BioCartilage-treated distal defects compared with MFx (P = .05). There were no significant differences between BioCartilage and MFx on micro-CT analysis. BioCartilage with PRP safely improved cartilage repair compared with MFx alone in an equine model of articular cartilage defects up to 13 months after implantation. The 1-year results of BioCartilage + PRP suggest that homologous allograft tissue provides a safe and effective augmentation of traditional MFx. © 2016 The Author(s).

Pectoralis major fascia in rhinoplasty.

PubMed

Xavier, Rui

2015-06-01

Fascia is frequently used in rhinoplasty, for several different purposes. The deep temporalis fascia is most often chosen, though harvesting this fascia requires a separate surgical field that adds surgical time to the procedure and morbidity to the patient. In augmentation rhinoplasty cases as well as in many revision rhinoplasty cases, costal cartilage may be required. In these cases, when costal cartilage is harvested from the 5(th) to 7(th) ribs, pectoralis major fascia is in the surgical field and must be incised to provide access to the costal cartilage. Pectoralis major fascia is similar to the deep temporalis fascia, sharing many physical and histological characteristics with it. Pectoralis major fascia can be harvested from the same surgical field as costal cartilage and used in the nose whenever autologous costal cartilage is harvested, thus precluding the need for a separate surgical field for fascia harvest. The surgical technique for harvesting pectoralis major fascia is demonstrated, and two clinical cases of patients in whom this fascia was harvested and used in the nose are presented. Pectoralis major fascia may be considered an alternative option for use in rhinoplasty cases whenever autologous costal cartilage is used. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Technical innovations in ear reconstruction using a skin expander with autogenous cartilage grafts.

PubMed

Dashan, Yu; Haiyue, Jiang; Qinghua, Yang; Bo, Pan; Lin, Lin; Tailing, Wang; Yanmei, Wang; Xiao, Qin; Hongxing, Zhuang

2008-01-01

Pioneers such as Tanzer and Brent have established the foundations of microtia reconstruction using an autogenous costal cartilage framework. The framework and its skin coverage are the two limiting factors in ear reconstruction. At the present time autogenous rib cartilage and mastoid skin are still first choice materials for most surgeons. They have the combined advantages of well-matched texture and colour. To reconstruct a symmetrical, accurate, prominent auricle and minimise as much as possible the chest wall deformity caused by rib cartilage harvesting, we set out to improve our techniques for cartilaginous framework definition and to use the remnant ear to enhance the projection of the reconstructed ear. Since 2000, 342 cases (366 ears) were treated using our current techniques. Data pertaining to complications were recorded. Final results were assessed a minimum of 1 year postoperatively. The follow-up period ranged from 1 to 6 years. Most of the patients with microtia were satisfied with the results of their ear reconstruction. In conclusion, our techniques help to reduce the quantity of rib cartilage needed to fabricate ear framework and minimise chest wall deformity. The frameworks are accurate, prominent and stable. Reconstructed ears are similar in colour and appearance to the normal side. Our innovations are practical and reliable for microtia reconstruction using skin expanders in combination with a sculpted autogenous rib cartilage framework.

Thoracoscopic cartilage resection with partial perichondrium preservation in unilateral pectus carinatum: preliminary results.

PubMed

Varela, Patricio; Torre, Michele

2011-01-01

Although minimally invasive repair of pectus excavatum has gained worldwide acceptance, treatment of pectus carinatum is mostly performed with open procedures. Different minimally invasive alternatives have been proposed in the last few years, including subpectoral CO(2) dissection and intrathoracic compression (Abramson technique), or conservative procedures, as dynamic compression system. Recently, another surgical technique has been proposed for the treatment of unilateral pectus carinatum, consisting of a thoracoscopic approach and multiple cartilage incisions. The aim of this work is to present our modification to this approach. We have modified this technique by introducing complete cartilage resection of all anomalous costal cartilages, performed thoracoscopically. Three thoracoscopic ports were used. Cartilage is removed progressively using a rongeur and preserving the anterior perichondrium. We have performed this technique in 4 patients during the last year. Follow-up ranged from 6 to 14 months. No intraoperative or postoperative complications were observed. The results, assessed by the patients themselves, were good in 2 cases, quite good in one, and fair in the first patient of our series, who was reoperated using a classical open approach. Pain was well controlled without the need of an epidural catheter. Thoracoscopic cartilage resection with perichondrium preservation can be considered as feasible alternative for the treatment of unilateral pectus carinatum. Copyright © 2011 Elsevier Inc. All rights reserved.

Treatment outcomes of saddle nose correction.

PubMed

Hyun, Sang Min; Jang, Yong Ju

2013-01-01

Many valuable classification schemes for saddle nose have been suggested that integrate clinical deformity and treatment; however, there is no consensus regarding the most suitable classification and surgical method for saddle nose correction. To present clinical characteristics and treatment outcome of saddle nose deformity and to propose a modified classification system to better characterize the variety of different saddle nose deformities. The retrospective study included 91 patients who underwent rhinoplasty for correction of saddle nose from April 1, 2003, through December 31, 2011, with a minimum follow-up of 8 months. Saddle nose was classified into 4 types according to a modified classification. Aesthetic outcomes were classified as excellent, good, fair, or poor. Patients underwent minor cosmetic concealment by dorsal augmentation (n = 8) or major septal reconstruction combined with dorsal augmentation (n = 83). Autologous costal cartilages were used in 40 patients (44%), and homologous costal cartilages were used in 5 patients (6%). According to postoperative assessment, 29 patients had excellent, 42 patients had good, 18 patients had fair, and 2 patients had poor aesthetic outcomes. No statistical difference in surgical outcome according to saddle nose classification was observed. Eight patients underwent revision rhinoplasty, owing to recurrence of saddle, wound infection, or warping of the costal cartilage for dorsal augmentation. We introduce a modified saddle nose classification scheme that is simpler and better able to characterize different deformities. Among 91 patients with saddle nose, 20 (22%) had unsuccessful outcomes (fair or poor) and 8 (9%) underwent subsequent revision rhinoplasty. Thus, management of saddle nose deformities remains challenging. 4.

Injection of Compressed Diced Cartilage in the Correction of Secondary and Primary Rhinoplasty: A New Technique with 12 Years' Experience.

PubMed

Erol, O Onur

2017-11-01

There are instances where small or large pockets are filled with diced cartilage in the nose, without use of wrapping materials. For this purpose, 1-cc commercial syringes were used. The obtained results were partial and incomplete. For better and improved results, the author designed new syringes, with two different sizes, which compress the diced cartilage for injection. The author presents his experience accrued over the past 12 years with 2366 primary, 749 secondary, 67 cleft lip and nose, and a total of 3182 rhinoplasties, using his new syringe design, which compresses diced cartilage and injects the diced cartilages as a conglutinate mass, simulating carved costal cartilage, but a malleable one. In 3125 patients, the take of cartilage graft was complete (98.2 percent) and a smooth surface was obtained, giving them a natural appearance. In 21 patients (0.65 percent), there was partial resorption of cartilage. Correction was performed with touch-up surgery by reinjection of a small amount of diced cartilage. In 36 patients (1.13 percent), there was overcorrection that, 1 year later, was treated by simple rasping. Compared with diced cartilage wrapped with Surgicel or fascia, the amount of injected cartilage graft is predictable because it consists purely of cartilage. The injected diced cartilage, because it is compressed and becomes a conglutinated mass, resembles a wood chip and simulates carved cartilage. It is superior to carved cartilage in that it is moldable, time saving, and gives a good result with no late show or warping. The injection takes only a few minutes.

Rib Diced Cartilage-Fascia Grafting in Dorsal Nasal Reconstruction: A Randomized Clinical Trial of Wrapping With Rectus Muscle Fascia vs Deep Temporal Fascia.

PubMed

As'adi, Kamran; Salehi, Seyed Hamid; Shoar, Saeed

2014-08-01

Rib cartilage is an abundant source for cartilage grafts when significant dorsal nasal augmentation or structural support is indicated. Diced cartilage wrapped in fascia was developed to counteract warping, visibility, and displacement of rib cartilage as a dorsal solid graft. The technique for wrapping diced cartilage has evolved during the past several years. The authors compared 2 distinct fascial sleeves for wrapping rib diced cartilage in the treatment of patients who required major dorsal nasal augmentation. Thirty-six patients who planned to undergo major dorsal nasal reconstruction with diced costal rib cartilage were assigned randomly to 1 of 2 groups: the intervention group, which received grafts wrapped with rectus muscle fascia from the rib cartilage harvesting site, or the control group, which received deep temporal fascia harvested separately. Outcomes were compared between the groups. Patients in the intervention group had significantly shorter operating times, significantly higher average satisfaction scores, and significantly shorter postoperative hospital stays than did patients in the control group. Harvesting rectus muscle fascia for wrapping diced rib cartilage is a feasible and reliable technique in dorsal nasal reconstruction surgery. It is associated with favorable outcomes and a high level of patient satisfaction. 4. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

Incidence and Imaging Findings of Costal Cartilage Fractures in Patients with Blunt Chest Trauma: A Retrospective Review of 1461 Consecutive Whole-Body CT Examinations for Trauma.

PubMed

Nummela, Mari T; Bensch, Frank V; Pyhältö, Tuomo T; Koskinen, Seppo K

2018-02-01

Purpose To assess the incidence of costal cartilage (CC) fractures in whole-body computed tomographic (CT) examinations for blunt trauma and to evaluate distribution of CC fractures, concomitant injuries, mechanism of injury, accuracy of reporting, and the effect on 30-day mortality. Materials and Methods Institutional review board approval was obtained for this retrospective study. All whole-body CT examinations for blunt trauma over 36 months were reviewed retrospectively and chest trauma CT studies were evaluated by a second reader. Of 1461 patients who underwent a whole-body CT examination, 39% (574 of 1461) had signs of thoracic injuries (men, 74.0% [425 of 574]; mean age, 46.6 years; women, 26.0% [149 of 574]; mean age, 48.9 years). χ 2 and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Interobserver agreement was calculated by using Cohen kappa values. Results A total of 114 patients (men, 86.8% [99 of 114]; mean age, 48.6 years; women, 13.2% [15 of 114]; mean age, 45.1 years) had 221 CC fractures. The incidence was 7.8% (114 of 1461) in all whole-body CT examinations and 19.9% (114 of 574) in patients with thoracic trauma. Cartilage of rib 7 (21.3%, 47 of 221) was most commonly injured. Bilateral multiple consecutive rib fractures occurred in 36% (41 of 114) versus 14% (64 of 460) in other patients with chest trauma (OR, 3.48; 95% CI: 2.18, 5.53; P < .0001). Hepatic injuries were more common in patients with chest trauma with CC fractures (13%, 15 of 114) versus patients with chest trauma without CC fractures (4%, 18 of 460) (OR, 3.72; 95% CI: 1.81, 7.64; P = .0001), as well as aortic injuries (n = 4 vs n = 0; P = .0015; OR, unavailable). Kappa value for interobserver agreement in detecting CC fractures was 0.65 (substantial agreement). CC fractures were documented in 39.5% (45 of 114) of primary reports. The 30-day mortality of patients with CC fractures was 7.02% (eight of 114) versus 4.78% (22 of 460) of other patients with chest

Reconstruction following traumatic partial amputation of the ear.

PubMed

Pearl, Robert A; Sabbagh, Walid

2011-02-01

Reconstruction following traumatic amputation of the external ear remains a unique challenge to the plastic surgeon. The authors report a series of ear reconstructions with autologous costal cartilage in patients following traumatic partial amputation of the ear. Technical points regarding the carving of the cartilage framework and methods of skin coverage are discussed. Fifty partial ear reconstructions with autologous costal cartilage were performed over a 4-year period. All patients had suffered previous traumatic amputation of part of the external auricle due to bite injuries (n = 36), road traffic accidents (n = 6), burns (n = 5), or torture (n = 3). A two-stage technique of reconstruction with autologous cartilage graft was used based on Nagata's adaptations of Brent's original technique. In nine cases, skin shortage or extensive scarring required preoperative tissue expansion (n = 4) or a temporoparietal fascial flap (n = 5) to provide adequate coverage of the cartilage framework. Forty-seven patients had a successful surgical outcome without complication. Two patients developed small areas of skin necrosis resulting in exposure of the cartilage framework. These healed with conservative management with minor loss of definition. One case of wound infection resulted in significant loss of definition of the construct, which required a further surgical procedure with additional costal cartilage graft. Reconstruction of the external ear with autologous costal cartilage following traumatic amputation can produce high-quality auricles consistently and is becoming the treatment of choice for such injuries, given access to a specialist center with exposure to a high volume of cases.

Nipple Reconstruction with Dorsal Skin Provides Better Projection than Reconstruction with Abdominal or Breast Skin with Cartilage Grafting.

PubMed

Mihara, Runa; Mori, Hiroki; Okazaki, Mutsumi

2017-02-01

Nipple projection of a modified C-V flap with or without costal cartilage was compared on abdominal, breast, and dorsal skin. A total of 81 patients and 85 sites were studied. The nipple was reconstructed secondarily using a modified C-V flap. Patients were classified by breast mound skin into five groups: dorsal skin without cartilage (group A, n = 18); abdominal skin without cartilage (group B, n = 6); abdominal skin with cartilage (group C, n = 26); breast skin without cartilage (group D, n = 20); and breast skin with cartilage (group E, n = 15). Complications and nipple projection were evaluated over a mean follow-up of 18.5 months; there were no significant differences among the five groups. Minor flap necrosis occurred in 10/18, 0/6, 4/26, 1/20, and 2/15 of groups A, B, C, D, and E, respectively; the percentage was higher in group A than in group D. The average projection maintenance rate (postoperative nipple projection to V flap width) was 76.5, 50.1, 56.1, 46.1, and 52.3% for groups A, B, C, D, and E, respectively; the value in group A was higher than in all other groups. Despite more minor necrosis, the nipple reconstructed with dorsal skin maintained better projection than the nipple reconstructed with abdominal skin or breast skin combined with a cartilage graft. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A3 online Instructions to Authors. www.springer.com/00266 .

Placement of trans-sternal wires according to an ellipsoid pressure vessel model of sternal forces.

PubMed

Casha, Aaron R; Manché, Alex; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Schembri-Wismayer, Pierre; Sant, Zdenka; Gatt, Ruben; Grima, Joseph N

2012-03-01

Dehiscence of median sternotomy wounds remains a clinical problem. Wall forces in thin-walled pressure vessels can be calculated by membrane stress theory. An ellipsoid pressure vessel model of sternal forces is presented together with its application for optimal wire placement in the sternum. Sternal forces were calculated by computational simulation using an ellipsoid chest wall model. Sternal forces were correlated with different sternal thicknesses and radio-density as measured by computerized tomography (CT) scans of the sternum. A comparison of alternative placement of trans-sternal wires located either at the levels of the costal cartilages or the intercostal spaces was made. The ellipsoid pressure vessel model shows that higher levels of stress are operative at increasing chest diameter (P < 0.001). CT scans show that the thickness of the sternal body is on average 3 mm and 30% thicker (P < 0.001) and 53% more radio-dense (P < 0.001) at the costal cartilage levels when compared with adjacent intercostal spaces. This results in a decrease of average sternal stress from 438 kPa at the intercostal space level to 338 kPa at the costal cartilage level (P = 0.003). Biomechanical modelling suggests that placement of trans-sternal wires at the thicker bone and more radio-dense level of the costal cartilages will result in reduced stress.

Articular soft tissue anatomy of the archosaur hip joint: Structural homology and functional implications.

PubMed

Tsai, Henry P; Holliday, Casey M

2015-06-01

Archosaurs evolved a wide diversity of locomotor postures, body sizes, and hip joint morphologies. The two extant archosaurs clades (birds and crocodylians) possess highly divergent hip joint morphologies, and the homologies and functions of their articular soft tissues, such as ligaments, cartilage, and tendons, are poorly understood. Reconstructing joint anatomy and function of extinct vertebrates is critical to understanding their posture, locomotor behavior, ecology, and evolution. However, the lack of soft tissues in fossil taxa makes accurate inferences of joint function difficult. Here, we describe the soft tissue anatomies and their osteological correlates in the hip joint of archosaurs and their sauropsid outgroups, and infer structural homology across the extant taxa. A comparative sample of 35 species of birds, crocodylians, lepidosaurs, and turtles ranging from hatchling to skeletally mature adult were studied using dissection, imaging, and histology. Birds and crocodylians possess topologically and histologically consistent articular soft tissues in their hip joints. Epiphyseal cartilages, fibrocartilages, and ligaments leave consistent osteological correlates. The archosaur acetabulum possesses distinct labrum and antitrochanter structures on the supraacetabulum. The ligamentum capitis femoris consists of distinct pubic- and ischial attachments, and is homologous with the ventral capsular ligament of lepidosaurs. The proximal femur has a hyaline cartilage core attached to the metaphysis via a fibrocartilaginous sleeve. This study provides new insight into soft tissue structures and their osteological correlates (e.g., the antitrochanter, the fovea capitis, and the metaphyseal collar) in the archosaur hip joint. The topological arrangement of fibro- and hyaline cartilage may provide mechanical support for the chondroepiphysis. The osteological correlates identified here will inform systematic and functional analyses of archosaur hindlimb evolution and

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

Dingman, R.O.; Grabb, W.C.

Use of preserved cartilage homografts in restoring contour to defects of the supporting structures of the face is described and illustrated. Adequate sterilization of contaminated cartilage is effected by Co/sup 60/ gamma irradiation for 15 hr using 3,000,000 rep. The cartilage is then stored in saline at room temperature. No pathologic organisms were cultured from a series of 70 cases in which Co/sup 60/sterilized cartilage was used. Experiments in dogs, with direct measurement and inspection of 38 grafts implanted in the rectus sheath and on the pericranium, 2-12 months after transplantation, revealed that canine costal cartilage sterilized in merthiosaline gavemore » 33.3% complete and 33.3% partial absorption, while irradiated cartilage stored in saline gave 27.8% complete and 5.5% partial absorption. Clinical evaluation of 30 patients examined from 7 months to 31/2 yr postoperatively revealed evidence of absorption only in two grafts. Techniques of preparing, sterilizing by irradiation, and storing of human costal cartilage are described. (TCO)« less

Use of a plastic eraser for ear reconstruction training.

PubMed

Erdogan, Basar; Morioka, Daichi; Hamada, Taishi; Kusano, Taro; Win, Khin Malar

2018-01-01

Microtia reconstruction is a challenging procedure, especially in developing nations. The most complex part is learning how to fabricate a framework from costal cartilage. We herein propose a training regimen for ear reconstruction with the use of a plastic eraser. The texture of a plastic eraser made from polyvinyl chloride is similar to that of human costal cartilage. The first step of the training is carving out the sixth through eighth rib cartilages from a block of plastic eraser. The second step is a fabrication of the framework from plastic rib cartilages, referring to a template from the intact auricle. As plastic erasers are inexpensive and universally available, inexperienced surgeons can repeatedly perform this framework training. Following several of these training sessions in developing nations, the co-authors and local surgeons successfully performed their microtia reconstructions in a reasonable operative time. This realistic carving model allows surgeons to gain experience before performing an actual ear reconstruction, even in resource-constrained circumstances.

Cartilage extracellular matrix as a biomaterial for cartilage regeneration.

PubMed

Kiyotake, Emi A; Beck, Emily C; Detamore, Michael S

2016-11-01

The extracellular matrix (ECM) of various tissues possesses the model characteristics that biomaterials for tissue engineering strive to mimic; however, owing to the intricate hierarchical nature of the ECM, it has yet to be fully characterized and synthetically fabricated. Cartilage repair remains a challenge because the intrinsic properties that enable its durability and long-lasting function also impede regeneration. In the last decade, cartilage ECM has emerged as a promising biomaterial for regenerating cartilage, partly because of its potentially chondroinductive nature. As this research area of cartilage matrix-based biomaterials emerged, investigators facing similar challenges consequently developed convergent solutions in constructing robust and bioactive scaffolds. This review discusses the challenges, emerging trends, and future directions of cartilage ECM scaffolds, including a comparison between two different forms of cartilage matrix: decellularized cartilage (DCC) and devitalized cartilage (DVC). To overcome the low permeability of cartilage matrix, physical fragmentation greatly enhances decellularization, although the process itself may reduce the chondroinductivity of fabricated scaffolds. The less complex processing of a scaffold composed of DVC, which has not been decellularized, appears to have translational advantages and potential chondroinductive and mechanical advantages over DCC, without detrimental immunogenicity, to ultimately enhance cartilage repair in a clinically relevant way. © 2016 New York Academy of Sciences.

Which cartilage is regenerated, hyaline cartilage or fibrocartilage? Non-invasive ultrasonic evaluation of tissue-engineered cartilage.

PubMed

Hattori, K; Takakura, Y; Ohgushi, H; Habata, T; Uematsu, K; Takenaka, M; Ikeuchi, K

2004-09-01

To investigate ultrasonic evaluation methods for detecting whether the repair tissue is hyaline cartilage or fibrocartilage in new cartilage regeneration therapy. We examined four experimental rabbit models: a spontaneous repair model (group S), a large cartilage defect model (group L), a periosteal graft model (group P) and a tissue-engineered cartilage regeneration model (group T). From the resulting ultrasonic evaluation, we used %MM (the maximum magnitude of the measurement area divided by that of the intact cartilage) as a quantitative index of cartilage regeneration. The results of the ultrasonic evaluation were compared with the histological findings and histological score. The %MM values were 61.1 +/- 16.5% in group S, 29.8 +/- 15.1% in group L, 36.3 +/- 18.3% in group P and 76.5 +/- 18.7% in group T. The results showed a strong similarity to the histological scoring. The ultrasonic examination showed that all the hyaline-like cartilage in groups S and T had a high %MM (more than 60%). Therefore, we could define the borderline between the two types of regenerated cartilage by the %MM.

The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

PubMed Central

Sutherland, Amanda J.; Converse, Gabriel L.; Hopkins, Richard A.; Detamore, Michael S.

2014-01-01

Cartilage matrix is a particularly promising acellular material for cartilage regeneration given the evidence supporting its chondroinductive character. The ‘raw materials’ of cartilage matrix can serve as building blocks and signals for enhanced tissue regeneration. These matrices can be created by chemical or physical methods: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods when combined with physical methods are particularly effective in fully decellularizing such materials. Critical endpoints include no detectable residual DNA or immunogenic antigens. It is important to first delineate between the sources of the cartilage matrix, i.e., derived from matrix produced by cells in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, i.e., decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell derived matrix (DCCM), and devitalized cell derived matrix (DVCM). Delivery of cartilage matrix may be a straightforward approach without the need for additional cells or growth factors. Without additional biological additives, cartilage matrix may be attractive from a regulatory and commercialization standpoint. Source and delivery method are important considerations for clinical translation. Only one currently marketed cartilage matrix medical device is decellularized, although trends in filed patents suggest additional decellularized products may be available in the future. To choose the most relevant source and processing for cartilage matrix, qualifying testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of raw materials, and immunogenic properties of the product. PMID:25044502

Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

PubMed

Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

2014-05-01

Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

ESTABLISHING A LIVE CARTILAGE-ON-CARTILAGE INTERFACE FOR TRIBOLOGICAL TESTING.

PubMed

Trevino, Robert L; Stoia, Jonathan; Laurent, Michel P; Pacione, Carol A; Chubinskaya, Susan; Wimmer, Markus A

2017-03-01

Mechano-biochemical wear encompasses the tribological interplay between biological and mechanical mechanisms responsible for cartilage wear and degradation. The aim of this study was to develop and start validating a novel tribological testing system, which better resembles the natural joint environment through incorporating a live cartilage-on-cartilage articulating interface, joint specific kinematics, and the application of controlled mechanical stimuli for the measurement of biological responses in order to study the mechano-biochemical wear of cartilage. The study entailed two parts. In Part 1, the novel testing rig was used to compare two bearing systems: (a) cartilage articulating against cartilage (CoC) and (b) metal articulating against cartilage (MoC). The clinically relevant MoC, which is also a common tribological interface for evaluating cartilage wear, should produce more wear to agree with clinical observations. In Part II, the novel testing system was used to determine how wear is affected by tissue viability in live and dead CoC articulations. For both parts, bovine cartilage explants were harvested and tribologically tested for three consecutive days. Wear was defined as release of glycosaminoglycans into the media and as evaluation of the tissue structure. For Part I, we found that the live CoC articulation did not cause damage to the cartilage, to the extent of being comparable to the free swelling controls, whereas the MoC articulation caused decreased cell viability, extracellular matrix disruption, and increased wear when compared to CoC, and consistent with clinical data. These results provided confidence that this novel testing system will be adequate to screen new biomaterials for articulation against cartilage, such as in hemiarthroplasty. For Part II, the live and dead cartilage articulation yielded similar wear as determined by the release of proteoglycans and aggrecan fragments, suggesting that keeping the cartilage alive may not be

Effect of upper costal and costo-diaphragmatic breathing types on electromyographic activity of respiratory muscles.

PubMed

Celhay, Isabel; Cordova, Rosa; Miralles, Rodolfo; Meza, Francisco; Erices, Pia; Barrientos, Camilo; Valenzuela, Saúl

2015-04-01

To compare electromyographic (EMG) activity in young-adult subjects with different breathing types. This study included 50 healthy male subjects with complete natural dentition, and no history of orofacial pain or craniomandibular-cervical-spinal disorders. Subjects were classified into two groups: upper costal breathing type, and costo-diaphragmatic breathing. Bipolar surface electrodes were located on sternocleidomastoid, diaphragm, external intercostal, and latissimus dorsi muscles. Electromyographic activity was recorded during the following tasks: (1) normal quiet breathing; (2) speaking the word 'Mississippi'; (3) swallowing saliva; and (4) forced deep breathing. Sternocleidomastoid and latissimus dorsi EMG activity was not significantly different between breathing types, whereas diaphragm and external intercostal EMG activity was significantly higher in the upper costal than costo-diaphragmatic breathing type in all tasks (P<0·05; Wilcoxon signed rank-sum test). Diaphragm and external intercostal EMG activity suggests that there could be differences in motor unit recruitment strategies depending on the breathing type.

Full-Thickness Reconstruction with Pedicle Flap and Diced Homologous Cartilage Over the Pericardium Complicated. Cardiac Arrest

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

Rees, Thomas D.

1961-01-01

Successful repair by plastic surgery of nonhealing ulceration of the chest wall, induced by radiotherapy for breast cancer, is described. Reconstruction of the chest wali defect by pedicle flap coverage was carried out. Radiation injury extended through the entire thickness of the chest wall and osteoradionecrosis of the ribs was present. Reconstruction with thoracoabdominal tube was considered to be the best technique, so a 4- by 9-in. tube pedicle was constructed. The underlying donor wound of the pedicle was covered with a split- thickness skin graft. Healing was without incident, and approximates 3 weeks after formation, the inferior end ofmore » this tube pedicle was migrated to the left epigastrium as an intermediate step. Healing was uncomplicated, and the lateral attachment of the pedicle was partially severed. Three weeks later, resection of all avascular tissue along with portions of the fourth and fifth ribs was carried out. This created a full-thickness chest wall defect measuring 4 by 8 in., with the anterior surface of the pericardial sac exposed in the wound. The end of the abdominal tube pedicle was elevated from its bed, rotated into position, and sutured to the healthy margins of the chest wall defect. The exposed subcutaneous fat of the undersurface of the pedicle was placed in juxtaposition to the pericardium. A split-thickness skin graft was cut from the skin of the left thigh and draped over the pedicle flap donor wound. All sutured wounds healed per primum and the entire skin graft survived. The inferior inset of the tube pedicle was cut free and the pedicle flap was tailored into position 6 weeks later. The patient was discharged from the hospital in good condition and engaged in normal activities. An attempt was made to provide protection for the heart beneath the pedicle inset by introduction of diced homologous cartilage grafts, just beneath the skin of the pedicle flap. This healed with the formation of a thick fibrocartilaginous

Cytoskeleton in trichomonads: I. Immunological and biochemical comparative study of costal proteins in the genus Tritrichomonas.

PubMed

Viscogliosi, E; Brugerolle, G

1993-05-28

Proteins of the whole cytoskeleton fraction obtained by Triton X-100 action on several Tritrichomonas species have been analyzed by gel electrophoresis. In addition to tubulins, several major protein components with molecular weights between 100 and 150 kDa were separated and presumably represent costal proteins. The partial purification of the costae from the whole cytoskeleton fraction of Tritrichomonas foetus treated with 0.3 M KI confirmed the presence of costal proteins in the 100-150 kDa zone. Costa fibres could be solubilized in 8 M urea. These characteristics indicate that costal proteins may represent a novel class of striated root proteins. A library of 7 monoclonal antibodies (MAbs) raised in mice immunized with the whole cytoskeleton fraction of Tritrichomonas foetus labelled the costa by immunofluorescence and recognize five polypeptides at 135,127,114, 88 and 47 kDa by immunoblotting. Two of these MAbs cross-react by immunofluorescence and immunoblotting with the three other Tritrichomonas species tested, i.e. T. mobilensis, T. augusta, T. muris. However, these 7 MAbs do not show immunological cross-reactivity with other trichomonad genera indicating that the costae are not identical in their biochemical composition; this corresponds to the differences observed in their respective fine structure. Nonetheless, a polyclonal antibody produced against the 118 kDa protein of the costa of Trichomonas vaginalis also labels a 118 kDa protein and the costa by IF in Tritrichomonas species indicating common epitopes. Copyright © 1993 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Reconstruction of Punitive Ear Amputations in Uganda: A Unique Surgical Burden of Disease.

PubMed

Dusseldorp, Joseph; Hodges, Andrew; Patel, Anup; Marchac, Alexandre; Firmin, Françoise

2015-06-01

Over the course of 12 months, a plastic surgical team from Paris, France, undertook 2 intensive ear reconstruction missions with plastic surgeons from the CoRSU Rehabilitation Hospital in Uganda. A cohort of over 30 adult women was assessed having been subjected to ear amputations by members of the Lords Resistance Army in Northern Uganda in the 1990s. The patients were identified, mobilized, and transferred to Kampala for surgery by a charitable arm of the Watoto Church, known as Living Hope. The surgical team performed 15 ear reconstruction cases during the first 1-week mission and 16 ear reconstruction cases during the second 1-week mission. All cases were reconstructed successfully using the 2-stage autologous auricular reconstruction method advocated by the senior author (FF). Local skin was used to cover the costal cartilage framework in the first stage without need for temporo-parietal fascial flaps. Technical challenges included the older age of patients and ossified costal cartilage, high prevalence of HIV positivity, bilateral amputation, and difficulty of surgical follow-up. The main modifications to standard practice were routine pre-op testing of the costal cartilage, pre-op viral load and CD4 count screening in HIV-positive patients, simultaneous bilateral first-stage ear reconstruction, prolonged hospital stay, and implementation of routine surgical counting procedures.

Stereomicroscopic evaluation of the joint cartilage and bone tissue in osteoporosis

NASA Astrophysics Data System (ADS)

Vasile, Liliana; Torok, Rodica; Deleanu, Bogdan; Marchese, Cristian; Valeanu, Adina; Bodea, Rodica

2012-06-01

Aim of the study. Assessment by stereomicroscopy of the severity of lesions in osteoporotic bone at both sexes and to correlate micro-and macro-bone fracture due to low bone density values with the disease evolution. Material and method: The study material consists of fragments of bone from the femoral head, vertebral bone, costal and iliac crest biopsy obtained from patients aged over 70 years, female and male, treated in the County Hospital of Timisoara, Department of Orthopedics. For the purpose of studying the samples in stereomicroscopy and trough polarized light it has been used the Olympus Microscope SZ ×7 and an Olympus camera with 2,5 × digital zoom and a 3× optical zoom in the Vest Politechnic Univesity. Results and discussions: Subchondral bone presents osteolysis associated with a osteoporotic bone transformation. Pseudocystic chondrolisis was noted in the osteoarticular cartilage, in addition with areas of hemorrhagic postfractural necrosis. The osteoporotic bone exhibits ischemic necrosis and focal hemorrhagic necrosis adjacent fracture. Microporosity pattern of the bone observed by stereomicroscopy correspond to the spongy bone osteoporosis images. Morphometry of the bone spiculi reveals length of 154.88 and 498.32 μ. In men we found a greater thickness of bone trabeculi compared with bone texture porosity in women. The subchondral bone supports and fulfills an important role in transmitting forces from the overlying articular cartilage inducing the bone resorbtion. The femoral head fracture may be the final event of many accumulated bone microcracks. Conclusions: Bone fragility depends not only of the spongy bone but also of the cortical bone properties. Osteolysis produced by loss of balance in the process of remodeling in favor of bone resorption leads to the thinning of the subchondral bone at both sexes.

Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilage.

PubMed

Kreuz, P C; Gentili, C; Samans, B; Martinelli, D; Krüger, J P; Mittelmeier, W; Endres, M; Cancedda, R; Kaps, C

2013-12-01

Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

PubMed

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

PubMed

White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

2006-11-01

To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

Engineering Cartilage

MedlinePlus

... Research Matters NIH Research Matters March 3, 2014 Engineering Cartilage Artistic rendering of human stem cells on ... situations has been a major goal in tissue engineering. Cartilage contains water, collagen, proteoglycans, and chondrocytes. Collagens ...

Current status of grafts and implants in rhinoplasty: Part II. Homologous grafts and allogenic implants.

PubMed

Sajjadian, Ali; Naghshineh, Nima; Rubinstein, Roee

2010-03-01

After reading this article, the participant should be able to: 1. Understand the challenges in restoring volume and structural integrity in rhinoplasty. 2. Identify the appropriate uses of various homologous grafts and allogenic implants in reconstruction, including: (a) freeze-dried acellular allogenic cadaveric dermis grafts, (b) irradiated cartilage grafts, (c) hydroxyapatite mineral matrix, (d) silicone implants, (e) high-density polyethylene implants, (f) polytetrafluoroethylene implants, and (g) injectable filler materials. 3. Identify the advantages and disadvantages of each of these biomaterials. 4. Understand the specific techniques that may aid in the use these grafts or implants. This review specifically addresses the use of homologous grafts and allogenic implants in rhinoplasty. It is important to stress that autologous materials remain the preferred graft material for use in rhinoplasty, owing to their high biocompatibility and low risk of infection and extrusion. However, concerns of donor-site morbidity, graft availability, and graft resorption have motivated the development and use of homologous and allogenic implants.

Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

PubMed

Ishitobi, Hiroyuki; Sanada, Yohei; Kato, Yoshio; Ikuta, Yasunari; Shibata, Sachi; Yamasaki, Satoshi; Lotz, Martin K; Matsubara, Kiminori; Miyaki, Shigeru; Adachi, Nobuo

2018-04-17

Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties reduce expression of mediators of OA pathogenesis and OA severity in animal models. Among the signaling pathways that control cellular protective mechanisms against oxygen radical damage is heme oxygenase-1 (HO-1). We recently report HO-1 reduced OA severity in a mouse model. This led to the hypothesis that compounds that increase HO-1 expression have therapeutic potential in OA. Carnosic acid (CA), a natural diterpene with oxidant activity, is prevents cartilage degeneration though induction of HO-1. CA induced HO-1 and miR-140 expression in human articular chondrocytes, and cartilage degeneration was attenuated by CA treatment. Induced HO-1 by CA was in part associated with downregulation via miR-140 binding to 3'UTR of BTB and CNC homology 1 (BACH1). These findings suggest that CA attenuates cartilage degradation through HO-1 upregulation and has potential as a supplement for OA prevention. Copyright © 2018 Elsevier B.V. All rights reserved.

Knee cartilage extraction and bone-cartilage interface analysis from 3D MRI data sets

NASA Astrophysics Data System (ADS)

Tamez-Pena, Jose G.; Barbu-McInnis, Monica; Totterman, Saara

2004-05-01

This works presents a robust methodology for the analysis of the knee joint cartilage and the knee bone-cartilage interface from fused MRI sets. The proposed approach starts by fusing a set of two 3D MR images the knee. Although the proposed method is not pulse sequence dependent, the first sequence should be programmed to achieve good contrast between bone and cartilage. The recommended second pulse sequence is one that maximizes the contrast between cartilage and surrounding soft tissues. Once both pulse sequences are fused, the proposed bone-cartilage analysis is done in four major steps. First, an unsupervised segmentation algorithm is used to extract the femur, the tibia, and the patella. Second, a knowledge based feature extraction algorithm is used to extract the femoral, tibia and patellar cartilages. Third, a trained user corrects cartilage miss-classifications done by the automated extracted cartilage. Finally, the final segmentation is the revisited using an unsupervised MAP voxel relaxation algorithm. This final segmentation has the property that includes the extracted bone tissue as well as all the cartilage tissue. This is an improvement over previous approaches where only the cartilage was segmented. Furthermore, this approach yields very reproducible segmentation results in a set of scan-rescan experiments. When these segmentations were coupled with a partial volume compensated surface extraction algorithm the volume, area, thickness measurements shows precisions around 2.6%

Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

PubMed

Nguyen, Christelle; Bazin, Dominique; Daudon, Michel; Chatron-Colliet, Aurore; Hannouche, Didier; Bianchi, Arnaud; Côme, Dominique; So, Alexander; Busso, Nathalie; Busso, Nathalie; Lioté, Frédéric; Ea, Hang-Korng

2013-01-01

Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was

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

[Preliminary results in the correction of the pectus excavatum with the Acastello modified Welch technique].

PubMed

Lorenzo, G R; Gutiérrez Dueñas, J M; Ardela, E; Martín Pinto, F

2011-10-01

Congenital malformations of the chest wall are a heterogeneous group of diseases affecting the costal cartilage, ribs, sternum, scapula and clavicle. The pectus excavatum is characterized by a posterior depression of the sternum. Acastello-Welch technique consists in a partial resection of the costal cartilages adding some bars or plates unilaterally fixed to the sternum in each hemithorax. From October 2008 to March 2011 we evaluated 108 patients with congenital malformations of the chest wall. Forty-seven patients (44%) had a pectus excavatum and 12 were treated with Acastello-Welch technique. There were no intraoperative complications. After a mean follow up of 27 months, correction of the deformity was very satisfactory both objective and subjective for patients. The Welch thoracoplasty modified by Acastello is a good option for the correction of the pectus excavatum associating little morbidity and good esthetic outcomes.

New insights on basivenal sclerites using 3D tools and homology of wing veins in Odonatoptera (Insecta).

PubMed

Jacquelin, Lauriane; Desutter-Grandcolas, Laure; Chintauan-Marquier, Ioana; Boistel, Renaud; Zheng, Daran; Prokop, Jakub; Nel, André

2018-01-10

Being implied in flight, mimetism, communication, and protection, the insect wings were crucial organs for the mega diversification of this clade. Despite several attempts, the problem of wing evolution remains unresolved because the basal parts of the veins essential for vein identification are hidden in the basivenal sclerites. The homologies between wing characters thus cannot be accurately verified, while they are of primary importance to solve long-standing problems, such as the monophyly of the Palaeoptera, viz. Odonatoptera, Panephemeroptera, and Palaeozoic Palaeodictyopterida mainly known by their wings. Hitherto the tools to homologize venation were suffering several cases of exceptions, rendering them unreliable. Here we reconstruct the odonatopteran venation using fossils and a new 3D imaging tool, resulting congruent with the concept of Riek and Kukalová-Peck, with important novelties, viz. median anterior vein fused to radius and radius posterior nearly as convex as radius anterior (putative synapomorphies of Odonatoptera); subcostal anterior (ScA) fused to costal vein and most basal primary antenodal crossvein being a modified posterior branch of ScA (putative synapomorphies of Palaeoptera). These findings may reveal critical for future analyses of the relationships between fossil and extant Palaeoptera, helping to solve the evolutionary history of the insects as a whole.

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

Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

PubMed

Wang, L; Lazebnik, M; Detamore, M S

2009-03-01

To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.

PubMed

Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied

2016-11-01

Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (p<0.03). Estimates of g(r) for the cells and matrix against the dipole distances, r, have been plotted. This plot showed that the chondrocytes and the matrix were neither dispersed nor clustered in the two study groups. Application of design-based stereological methods and also evaluation of spatial arrangement of the cartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Autologous engineering of cartilage

PubMed Central

Emans, Pieter J.; van Rhijn, Lodewijk W.; Welting, Tim J. M.; Cremers, Andy; Wijnands, Nina; Spaapen, Frank; Voncken, J. Willem; Shastri, V. Prasad

2010-01-01

Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O’Driscoll score of 11 (versus 4 for controls). An “on demand” autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage. PMID:20133690

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.

[Morphological and functional cartilage imaging].

PubMed

Rehnitz, C; Weber, M-A

2014-06-01

Excellent morphological imaging of cartilage is now possible and allows the detection of subtle cartilage pathologies. Besides the standard 2D sequences, a multitude of 3D sequences are available for high-resolution cartilage imaging. The first part therefore deals with modern possibilities of morphological imaging. The second part deals with functional cartilage imaging with which it is possible to detect changes in cartilage composition and thus early osteoarthritis as well as to monitor biochemical changes after therapeutic interventions. Validated techniques such as delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping as well the latest techniques, such as the glycosaminoglycan chemical exchange-dependent saturation transfer (gagCEST) technique will be discussed.

[Morphological and functional cartilage imaging].

PubMed

Rehnitz, C; Weber, M-A

2015-04-01

Excellent morphological imaging of cartilage is now possible and allows the detection of subtle cartilage pathologies. Besides the standard 2D sequences, a multitude of 3D sequences are available for high-resolution cartilage imaging. The first part therefore deals with modern possibilities of morphological imaging. The second part deals with functional cartilage imaging with which it is possible to detect changes in cartilage composition and thus early osteoarthritis as well as to monitor biochemical changes after therapeutic interventions. Validated techniques such as delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping as well the latest techniques, such as the glycosaminoglycan chemical exchange-dependent saturation transfer (gagCEST) technique will be discussed.

Locating articular cartilage in MR images

NASA Astrophysics Data System (ADS)

Folkesson, Jenny; Dam, Erik; Pettersen, Paola; Olsen, Ole F.; Nielsen, Mads; Christiansen, Claus

2005-04-01

Accurate computation of the thickness of the articular cartilage is of great importance when diagnosing and monitoring the progress of joint diseases such as osteoarthritis. A fully automated cartilage assessment method is preferable compared to methods using manual interaction in order to avoid inter- and intra-observer variability. As a first step in the cartilage assessment, we present an automatic method for locating articular cartilage in knee MRI using supervised learning. The next step will be to fit a variable shape model to the cartilage, initiated at the location found using the method presented in this paper. From the model, disease markers will be extracted for the quantitative evaluation of the cartilage. The cartilage is located using an ANN-classifier, where every voxel is classified as cartilage or non-cartilage based on prior knowledge of the cartilage structure. The classifier is tested using leave-one-out-evaluation, and we found the average sensitivity and specificity to be 91.0% and 99.4%, respectively. The center of mass calculated from voxels classified as cartilage are similar to the corresponding values calculated from manual segmentations, which confirms that this method can find a good initial position for a shape model.

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.

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.

Magnetically targeted delivery through cartilage

NASA Astrophysics Data System (ADS)

Jafari, Sahar; Mair, Lamar O.; Chowdhury, Sagar; Nacev, Alek; Hilaman, Ryan; Stepanov, Pavel; Baker-McKee, James; Ijanaten, Said; Koudelka, Christian; English, Bradley; Malik, Pulkit; Weinberg, Irving N.

2018-05-01

In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

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

Irradiated homologous tarsal plate banking: A new alternative in eyelid reconstruction. Part I. Technique and animal research

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

Jordan, D.R.; Tse, D.T.; Anderson, R.L.

1990-01-01

Reconstruction of full thickness eyelid defects requires the correction of both posterior lamella (tarsus, conjunctiva) and anterior lamella (skin, muscle). Tarsal substitutes including banked sclera, nasal cartilage, ear cartilage, and periosteum can be beneficial for posterior lamellar repair, while anterior lamellar replacement, including skin grafts, pedicle flaps, advancement flaps, etc., is important to cover the posterior reconstructed portion. At times, due to extensive tissue loss, the eyelid reconstruction can be particularly challenging. We have found an alternative posterior lamellar reconstructive technique utilizing irradiated homologous tarsal plate that can be particularly useful in selected cases of severe tissue loss. The experimentalmore » surgical procedure in monkeys and the histological fate of the implanted tarsus is described in Part I, and followed in Part II by our experience with this tissue in six human patients.« less

Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration

PubMed Central

Jiang, Yangzi; Cai, Youzhi; Zhang, Wei; Yin, Zi; Hu, Changchang; Tong, Tong; Lu, Ping; Zhang, Shufang; Neculai, Dante

2016-01-01

Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. Significance Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown

Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration.

PubMed

Jiang, Yangzi; Cai, Youzhi; Zhang, Wei; Yin, Zi; Hu, Changchang; Tong, Tong; Lu, Ping; Zhang, Shufang; Neculai, Dante; Tuan, Rocky S; Ouyang, Hong Wei

2016-06-01

Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6-13 cm(2)) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown to

Developmental evidence for serial homology of the vertebrate jaw and gill arch skeleton

PubMed Central

Gillis, J. Andrew; Modrell, Melinda S.; Baker, Clare V. H.

2013-01-01

Gegenbaur’s classical hypothesis of jaw-gill arch serial homology is widely cited, but remains unsupported by either paleontological evidence (e.g. a series of fossils reflecting the stepwise transformation of a gill arch into a jaw) or developmental genetic data (e.g. shared molecular mechanisms underlying segment identity in the mandibular, hyoid and gill arch endoskeletons). Here we show that nested expression of Dlx genes – the “Dlx code” that specifies upper and lower jaw identity in mammals and teleosts – is a primitive feature of the mandibular, hyoid and gill arches of jawed vertebrates. Using fate-mapping techniques, we demonstrate that the principal dorsal and ventral endoskeletal segments of the jaw, hyoid and gill arches of the skate Leucoraja erinacea derive from molecularly equivalent mesenchymal domains of combinatorial Dlx gene expression. Our data suggest that vertebrate jaw, hyoid and gill arch cartilages are serially homologous, and were primitively patterned dorsoventrally by a common Dlx blueprint. PMID:23385581

Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test.

PubMed

Yu, Fang Fang; Lin, Xia Lu; Yang, Lei; Liu, Huan; Wang, Xi; Fang, Hua; Lammi, ZMikko J; Guo, Xiong

2017-11-01

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Long-Term In Vivo Electromechanical Reshaping for Auricular Reconstruction in the New Zealand White Rabbit Model

PubMed Central

Badran, Karam W.; Manuel, Cyrus T.; Loy, Anthony Chin; Conderman, Christian; Yau, Yuk Yee; Lin, Jennifer; Tjoa, Tjoson; Su, Erica; Protsenko, Dmitriy; Wong, Brian J. F.

2016-01-01

Objectives/Hypothesis To demonstrate the dosimetry effect of electromechanical reshaping (EMR) on cartilage shape change, structural integrity, cellular viability, and remodeling of grafts in an in vivo long-term animal model. Study Design Animal study. Methods A subperichondrial cartilaginous defect was created within the base of the pinna of 31 New Zealand white rabbits. Autologous costal cartilage grafts were electromechanically reshaped to resemble the rabbit auricular base framework and mechanically secured into the pinna base defect. Forty-nine costal cartilage specimens (four control and 45 experimental) successfully underwent EMR using a paired set of voltage-time combinations and survived for 6 or 12 weeks. Shape change was measured, and specimens were analyzed using digital imaging, tissue histology, and confocal microscopy with LIVE-DEAD viability assays. Results Shape change was proportional to charge transfer in all experimental specimens (P <.01) and increased with voltage. All experimental specimens contoured to the auricular base. Focal cartilage degeneration and fibrosis was observed where needle electrodes were inserted, ranging from 2.2 to 3.9 mm. The response to injury increased with increasing charge transfer and survival duration. Conclusions EMR results in appropriate shape change in cartilage grafts with chondrocyte injury highly localized. These studies suggest that elements of auricular reconstruction may be feasible using EMR. Extended survival periods and further optimization of voltage-time pairs are necessary to evaluate the long-term effects and shape-change potential of EMR. PMID:25779479

Evolutionary Transformation of the Palmaris Longus Muscle in Flying Squirrels (Pteromyini: Sciuridae): An Anatomical Consideration of the Origin of the Uniquely Specialized Styliform Cartilage.

PubMed

Kawashima, Tomokazu; Thorington, Richard W; Bohaska, Paula W; Sato, Fumi

2017-02-01

A long-standing issue in squirrel evolution and development is the origin of the styliform cartilage of flying squirrels, which extends laterally from the carpus to support the gliding membrane (patagium). Because the styliform cartilage is one of the uniquely specialized structures permitting gliding locomotion, the knowledge of its origin and surrounding transformation is key for understanding their aerodynamic evolution. The developmental study that would definitely answer this question would be difficult due to the rarity of embryological material. Instead, anatomical examinations have suggested two major hypotheses on the homology of the styliform cartilage: the pisiform bone of other mammals, or an additional carpal structure, such as the ulnar sesamoid of some of the other mammals or the hypothenar cartilage of the non-gliding squirrels. To test these hypotheses, a detailed examination of the anatomy of the carpus of gliding and non-gliding squirrels, and the colugo were undertaken. Based on physical and virtual dissections of the carpus, this study showed that both the pisiform bone and styliform cartilage were present in flying squirrels. This finding is further supported by demonstration that a "true Palmaris longus," with innervation typical for this muscle, inserts on the styliform cartilage. Taken together, our osteological, muscular, and neurological results suggest that the styliform cartilage was transformed in flying squirrels from an initially superficial and ulnar-derived anlagen into its current form. Anat Rec, 300:340-352, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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. Copyright © 2012 John Wiley & Sons, Ltd.

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

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

Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

PubMed

Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

2015-04-01

To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

[Current overview of cartilage regeneration procedures].

PubMed

Schenker, H; Wild, M; Rath, B; Tingart, M; Driessen, A; Quack, V; Betsch, M

2017-11-01

Cartilage is an avascular, alymphatic and non-innervated tissue with limited intrinsic repair potential. The high prevalence of cartilage defects and their tremendous clinical importance are a challenge for all treating physicians. This article provides the reader with an overview about current cartilage treatment options and their clinical outcome. Microfracture is still considered the gold standard in the treatment of small cartilage lesions. Small osteochondral defects can be effectively treated with the autologous osteochondral transplantation system. Larger cartilage defects are successfully treated by autologous membrane-induced chondrogenesis (AMIC) or by membrane-assisted autologous chondrocyte implantation (MACI). Despite limitations of current cartilage repair strategies, such procedures can result in short- and mid-term clinical improvement of the patients. Further developments and clinical studies are necessary to improve the long-term outcome following cartilage repair.

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.

Laser-induced regeneration of cartilage

NASA Astrophysics Data System (ADS)

Sobol, Emil; Shekhter, Anatoly; Guller, Anna; Baum, Olga; Baskov, Andrey

2011-08-01

Laser radiation provides a means to control the fields of temperature and thermo mechanical stress, mass transfer, and modification of fine structure of the cartilage matrix. The aim of this outlook paper is to review physical and biological aspects of laser-induced regeneration of cartilage and to discuss the possibilities and prospects of its clinical applications. The problems and the pathways of tissue regeneration, the types and features of cartilage will be introduced first. Then we will review various actual and prospective approaches for cartilage repair; consider possible mechanisms of laser-induced regeneration. Finally, we present the results in laser regeneration of joints and spine disks cartilages and discuss some future applications of lasers in regenerative medicine.

Two stage ear/microtia reconstruction using costal cartilage.

PubMed

Balaji, S M

2015-01-01

Reconstruction of Grade III microtia is a challenging entity in maxillofacial esthetic rehabilitation. Several advocacies and philosophies exist in this field. The aim of the manuscript is to present a single South Indian Experience with Ear reconstruction among South Indian Population. Retrospective analysis of unilateral Grade III microtia reconstruction was performed. Using a set of predefined inclusion and exclusion criteria, the population was selected. Outcome measures in terms of the ear size, auriculocephalic angle, and the conchal depth were measured in the reconstructed and normal side. Descriptive statistics is presented. Twenty-four patients formed the study group and had undergone the classical two-stage reconstruction in a similar fashion. The mean ear size in normal side was 65.8 ± 2.8 mm whereas on the reconstructed side, it was 61.3 ± 5.8 mm. The center's technique achieved above 75% similarity as that of the other normal ear. The mean auriculocephalic angle was 44.6 ± 5.2° whereas for the surgically reconstructed ear, it was 41.9 ± 2.6°. Overall, in these patients, we achieved a 79.94% similarity of auriculocephalic angle in the reconstructed ear as compared to the normal auricle. The conchal depth was 19.2 ± 2.1 mm and 16.6 ± 1.9 mm for normal and reconstructed ear, respectively. In terms of conchal depth, the present study group showed an achievement of 82.88% of accuracy even after a prolonged follow-up. The center employs a classic two stage reconstruction with a customized prosthesis that helps to avoid the loss of projection geometry and minimizes adhesion, infection, and early loss of structural stability.

New trends in articular cartilage repair.

PubMed

Cucchiarini, Magali; Henrionnet, Christel; Mainard, Didier; Pinzano, Astrid; Madry, Henning

2015-12-01

Damage to the articular cartilage is an important, prevalent, and unsolved clinical issue for the orthopaedic surgeon. This review summarizes innovative basic research approaches that may improve the current understanding of cartilage repair processes and lead to novel therapeutic options. In this regard, new aspects of cartilage tissue engineering with a focus on the choice of the best-suited cell source are presented. The importance of non-destructive cartilage imaging is highlighted with the recent availability of adapted experimental tools such as Second Harmonic Generation (SHG) imaging. Novel insights into cartilage pathophysiology based on the involvement of the infrapatellar fat pad in osteoarthritis are also described. Also, recombinant adeno-associated viral vectors are discussed as clinically adapted, efficient tools for potential gene-based medicines in a variety of articular cartilage disorders. Taken as a whole, such advances in basic research in diverse fields of articular cartilage repair may lead to the development of improved therapies in the clinics for an improved, effective treatment of cartilage lesions in a close future.

The cranial cartilages of teleosts and their classification.

PubMed

Benjamin, M

1990-04-01

The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes.

[The three-dimensional simulation of arytenoid cartilage movement].

PubMed

Zhang, Jun; Wang, Xuefeng

2011-08-01

Exploring the characteristics of arytenoid cartilage movement. Using Pro/ENGINEER (Pro/E) software, the cricoid cartilage, arytenoid cartilage and vocal cords were simulated to the three-dimensional reconstruction, by analyzing the trajectory of arytenoid cartilage in the joint surface from the cricoid cartilage and arytenoid cartilage composition. The 3D animation simulation showed the normal movement patterns of the vocal cords and the characteristics of vocal cords movement in occasion of arytenoid cartilage dislocation vividly. The three-dimensional model has clinical significance for arytenoid cartilage movement disorders.

Enhanced cartilage repair in 'healer' mice-New leads in the search for better clinical options for cartilage repair.

PubMed

Fitzgerald, Jamie

2017-02-01

Adult articular cartilage has a poor capacity to undergo intrinsic repair. Current strategies for the repair of large cartilage defects are generally unsatisfactory because the restored cartilage does not have the same resistance to biomechanical loading as authentic articular cartilage and degrades over time. Recently, an exciting new research direction, focused on intrinsic cartilage regeneration rather than fibrous repair by external means, has emerged. This review explores the new findings in this rapidly moving field as they relate to the clinical goal of restoration of structurally robust, stable and non-fibrous articular cartilage following injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Cartilage and meniscal T2 relaxation time as non-invasive biomarker for knee osteoarthritis and cartilage repair procedures

PubMed Central

Baum, T.; Joseph, G.B.; Karampinos, D.C.; Jungmann, P.M.; Link, T.M.; Bauer, J.S.

2014-01-01

SUMMARY Objective The purpose of this work was to review the current literature on cartilage and meniscal T2 relaxation time. Methods Electronic searches in PubMed were performed to identify relevant studies about T2 relaxation time measurements as non-invasive biomarker for knee osteoarthritis (OA) and cartilage repair procedures. Results Initial osteoarthritic changes include proteoglycan loss, deterioration of the collagen network, and increased water content within the articular cartilage and menisci. T2 relaxation time measurements are affected by these pathophysiological processes. It was demonstrated that cartilage and meniscal T2 relaxation time values were significantly increased in subjects with compared to those without radiographic OA and focal knee lesions, respectively. Subjects with OA risk factors such as overweight/obesity showed significantly greater cartilage T2 values than normal controls. Elevated cartilage and meniscal T2 relaxation times were found in subjects with vs without knee pain. Increased cartilage T2 at baseline predicted morphologic degeneration in the cartilage, meniscus, and bone marrow over 3 years. Furthermore, cartilage repair tissue could be non-invasively assessed by using T2 mapping. Reproducibility errors for T2 measurements were reported to be smaller than the T2 differences in healthy and diseased cartilage indicating that T2 relaxation time may be a reliable discriminatory biomarker. Conclusions Cartilage and meniscal T2 mapping may be suitable as non-invasive biomarker to diagnose early stages of knee OA and to monitor therapy of OA. PMID:23896316

Multiple myeloma involving the cricoid cartilage.

PubMed

Floré, B; Hermans, R

2013-01-01

We present the case of a man with dyspnea due to a mass in the cricoid cartilage that turns out to be an extramedullary plasmocytoma. Although the patient has a history of multiple myeloma, the disease only rarely affects the cricoid cartilage. Other subglottic lesions possibly involving the cricoid cartilage are squamous cell carcinoma, chondroma, chondrosarcoma and metastasis. The imaging characteristics suggesting extramedullary plasmocytoma arising from the cricoid consist of thinning and expansion of the cartilage laminae without mucosal lesions nor soft tissue mass adjacent to the cricoid cartilage. The patient was successfully treated with radiation therapy and peroral steroids.

Genetics Home Reference: cartilage-hair hypoplasia

MedlinePlus

... Twitter Home Health Conditions Cartilage-hair hypoplasia Cartilage-hair hypoplasia Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Cartilage-hair hypoplasia is a disorder of bone growth characterized ...

Articulation of Native Cartilage Against Different Femoral Component Materials. Oxidized Zirconium Damages Cartilage Less Than Cobalt-Chrome.

PubMed

Vanlommel, Jan; De Corte, Ronny; Luyckx, Jean Philippe; Anderson, Melissa; Labey, Luc; Bellemans, Johan

2017-01-01

Oxidized zirconium (OxZr) is produced by thermally driven oxidization creating an oxidized surface with the properties of a ceramic at the top of the Zr metal substrate. OxZr is much harder and has a lower coefficient of friction than cobalt-chrome (CoCr), both leading to better wear characteristics. We evaluated and compared damage to the cartilage of porcine patella plugs, articulating against OxZr vs CoCr. Our hypothesis was that, owing to its better wear properties, OxZr would damage cartilage less than CoCr. If this is true, OxZr might be a better material for the femoral component during total knee arthroplasty if the patella is not resurfaced. Twenty-one plugs from porcine patellae were prepared and tested in a reciprocating pin-on-disk machine while lubricated with bovine serum and under a constant load. Three different configurations were tested: cartilage-cartilage as the control group, cartilage-OxZr, and cartilage-CoCr. Macroscopic appearance, cartilage thickness, and the modified Mankin score were evaluated after 400,000 wear cycles. The control group showed statistically significant less damage than plugs articulating against both other materials. Cartilage plugs articulating against OxZr were statistically significantly less damaged than those articulating against CoCr. Although replacing cartilage by an implant always leads to deterioration of the cartilage counterface, OxZr results in less damage than CoCr. The use of OxZr might thus be preferable to CoCr in case of total knee arthroplasty without patella resurfacing. Copyright © 2016 Elsevier Inc. All rights reserved.

The cranial cartilages of teleosts and their classification.

PubMed Central

Benjamin, M

1990-01-01

The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 24 Fig. 25 Fig. 26 Fig. 27 PMID:2384333

Free Diced Cartilage: A New Application of Diced Cartilage Grafts in Primary and Secondary Rhinoplasty.

PubMed

Kreutzer, Christian; Hoehne, Julius; Gubisch, Wolfgang; Rezaeian, Farid; Haack, Sebastian

2017-09-01

Irregularities or deformities of the nasal dorsum after hump reduction account for a significant number of revision rhinoplasties. The authors therefore developed a technique of meticulously dicing and exactly placing free diced cartilage grafts, harvested from septum, rib, or ear cartilage. The cartilage paste is used for smoothening, augmentation, or camouflaging of the nasal dorsum in primary or revision rhinoplasties. A retrospective analysis of multisurgeon consecutive open approach rhinoplasties from January to December of 2014 was conducted at a single center. The authors compared the outcome of three different techniques to augment or cover the nasal dorsum after an observation period of 7 months. In group I, 325 patients with free diced cartilage grafts as the only onlay were included. In group II, consisting of 73 patients, the dorsal onlay was either fascia alone or in combination with free diced cartilage grafts. Forty-eight patients in group III received a dorsal augmentation with the classic diced cartilage in fascia technique. Four hundred forty-six patients undergoing primary and secondary rhinoplasties in which one of the above-mentioned diced cartilage techniques was used were included in the study. The authors found revision rates for dorsal irregularities within the 7-month postoperative observation period of 5.2, 8.2, and 25 percent for groups I, II, and III, respectively. The authors' findings strongly support their clinical experience that the free diced cartilage graft technique presents an effective and easily reproducible method for camouflage and augmentation in aesthetic and reconstructive rhinoplasty.

Functional cartilage MRI T2 mapping: evaluating the effect of age and training on knee cartilage response to running.

PubMed

Mosher, T J; Liu, Y; Torok, C M

2010-03-01

To characterize effects of age and physical activity level on cartilage thickness and T2 response immediately after running. Institutional review board approval was obtained and all subjects provided informed consent prior to study participation. Cartilage thickness and magnetic resonance imaging (MRI) T2 values of 22 marathon runners and 15 sedentary controls were compared before and after 30 min of running. Runner and control groups were stratified by ageor=46 years. Multi-echo [(Time to Repetition (TR)/Time to Echo (TE) 1500 ms/9-109 ms)] MR images obtained using a 3.0 T scanner were used to calculate thickness and T2 values from the central femoral and tibial cartilage. Baseline cartilage T2 values, and change in cartilage thickness and T2 values after running were compared between the four groups using one-way analysis of variance (ANOVA). After running MRI T2 values decreased in superficial femoral (2 ms-4 ms) and tibial (1 ms-3 ms) cartilage along with a decrease in cartilage thickness: (femoral: 4%-8%, tibial: 0%-12%). Smaller decrease in cartilage T2 values were observed in the middle zone of cartilage, and no change was observed in the deepest layer. There was no difference cartilage deformation or T2 response to running as a function of age or level of physical activity. Running results in a measurable decrease in cartilage thickness and MRI T2 values of superficial cartilage consistent with greater compressibility of the superficial cartilage layer. Age and level of physical activity did not alter the T2 response to running. Copyright 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

Optical properties of nasal septum cartilage

NASA Astrophysics Data System (ADS)

Bagratashvili, Nodar V.; Sviridov, Alexander P.; Sobol, Emil N.; Kitai, Moishe S.

1998-05-01

Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission Tt, total reflection Rt, and on-axis transmission Ta for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated Tt, Rt and Ta values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

Comparisons of Auricular Cartilage Tissues from Different Species.

PubMed

Chiu, Loraine L Y; Giardini-Rosa, Renata; Weber, Joanna F; Cushing, Sharon L; Waldman, Stephen D

2017-12-01

Tissue engineering of auricular cartilage has great potential in providing readily available materials for reconstructive surgeries. As the field of tissue engineering moves forward to developing human tissues, there needs to be an interspecies comparison of the native auricular cartilage in order to determine a suitable animal model to assess the performance of engineered auricular cartilage in vivo. Here, we performed interspecies comparisons of auricular cartilage by comparing tissue microstructure, protein localization, biochemical composition, and mechanical properties of auricular cartilage tissues from rat, rabbit, pig, cow, and human. Human, pig, and cow auricular cartilage have smaller lacunae compared to rat and rabbit cartilage ( P < .05). Despite differences in tissue microstructure, human auricular cartilage has similar biochemical composition to both rat and rabbit. Auricular cartilage from pig and cow, alternatively, display significantly higher glycosaminoglycan and collagen contents compared to human, rat, and rabbit ( P < .05). The mechanical properties of human auricular cartilage were comparable to that of all 4 animal species. This is the first study that compares the microstructural, biochemical, and mechanical properties of auricular cartilage from different species. This study showed that different experimental animal models of human auricular cartilage may be suitable in different cases.

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

Sliced Costochondral Chip Grafts in Posttraumatic Enophthalmos Correction.

PubMed

Kim, Tae-Hoon; Park, Ie-Hyon; Hong, Sa-Hyeok; Eun, Seok-Chan

2017-03-01

Posttraumatic enophthalmos is a relatively common problem following orbitozygomatic fractures. However, inadequate long-term results are frequently observed due to the difficulty of performing intraoperative fine adjustments to soft-tissue volume and orbital size and gradual absorption of some grafted materials. Here, the authors describe an efficient method of enophthalmos correction using sliced costochondral bone and cartilage combination grafts. From 2005 to 2011, the authors corrected enophthalmos in 12 patients using sliced costochondral grafts. The mean follow-up period was 13 months. For costochondral graft harvest, an approximately 5-cm skin incision was made directly above the seventh costal cartilage, the perichondrium was peeled back, and a small piece of rib bone and costal cartilage was harvested from the anterior part of the seventh rib bone and cartilage and cut into 2-mm-thick slices. A subciliary and/or transcaruncular incision was made in the affected side eyelid to expose the operating field, subperiosteal dissection was performed in the orbit and orbital floor. The cartilage chips were gradually grafted onto the dissected areas from the posterior orbit. Aesthetically satisfactory results were obtained in all patients. No complications in the donor area were observed. Furthermore, no patients experienced a recurrence or deterioration of diplopia over the follow-up period. One patient experienced temporary high intraocular pressure, which spontaneously resolved with medication and eye drops. The costochondral graft is adequate for the reconstruction of the fracture, easy to obtain, easily adaptable to the orbital walls, and has minimal morbidity at the donor site.

Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development

PubMed Central

Kohn, Anat; Dong, Yufeng; Mirando, Anthony J.; Jesse, Alana M.; Honjo, Tasuku; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.

2012-01-01

The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination of Notch signaling specifically within developing and committed chondrocytes, or a determination of whether cartilage and bone formation are regulated via RBPjκ-dependent or -independent Notch signaling mechanisms. To develop a complete understanding of Notch signaling during cartilage and bone development we generated and compared general Notch gain-of-function (Rosa-NICDf/+), RBPjκ-deficient (Rbpjκf/f), and RBPjκ-deficient Notch gain-of-function (Rosa-NICDf/+;Rbpjκf/f) conditional mutant mice, where activation or deletion of floxed alleles were specifically targeted to mesenchymal progenitors (Prx1Cre) or committed chondrocytes (inducible Col2CreERT2). These data demonstrate, for the first time, that Notch regulation of chondrocyte maturation is solely mediated via the RBPjκ-dependent pathway, and that the perichodrium or osteogenic lineage probably influences chondrocyte terminal maturation and turnover of the cartilage matrix. Our study further identifies the cartilage-specific RBPjκ-independent pathway as crucial for the proper regulation of chondrocyte proliferation, survival and columnar chondrocyte organization. Unexpectedly, the RBPjκ-independent Notch pathway was also identified as an important long-range cell non-autonomous regulator of perichondral bone formation and an important cartilage-derived signal required for coordinating chondrocyte and osteoblast differentiation during endochondral bone development. Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development. PMID:22354840

The effect of magnesium ion concentration on the fibrocartilage regeneration potential of goat costal chondrocytes.

PubMed

Hagandora, Catherine K; Tudares, Mauro A; Almarza, Alejandro J

2012-03-01

Magnesium has recently been explored as a potential biomaterial for degradable orthopedic implants but its effect on fibrocartilage remains unknown. The objective of this study was to assess the effect of high concentrations of magnesium ions on the matrix production of goat costal fibrochondrocytes in vitro. Cells were cultured using a scaffoldless approach with media containing magnesium chloride (MgCl(2)) or magnesium sulfate (MgSO(4)) at concentrations of 20, 50, and 100 mM in addition to the baseline magnesium concentration of 0.8 mM MgSO(4). At 4 weeks, there were no significant differences in compressive tangent modulus and total matrix production between constructs cultured in 20 mM Mg(2+) and the 0.8 mM Mg(2+) control (435 ± 47 kPa). There was a significant decrease in compressive tangent modulus compared to the 0.8 mM Mg(2+) constructs in the 50 mM MgCl(2) and MgSO(4) groups, while the 100 mM groups were not mechanically testable (p < 0.05). The collagen and glycosaminoglycan (GAG) content of the 50 and 100 mM MgCl(2) and MgSO(4) constructs was significantly lower than the control (6.9 ± 0.5% and 16.5 ± 1.3% per dry weight, respectively) (p < 0.05). The results show that goat costal fibrochondrocytes exhibit a high degree of resiliency to magnesium ion concentrations up to 20 mM in vitro.

Transcriptomic signatures in cartilage ageing

PubMed Central

2013-01-01

Introduction Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. Methods RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P < 0.05, expression ratios ± 1.4 log2 fold-change). Ingenuity pathway analysis enabled networks, functional analyses and canonical pathways from differentially expressed genes to be determined. Results In total, the expression of 396 transcribed elements including mRNAs, small noncoding RNAs, pseudogenes, and a single microRNA was significantly different in old compared with young cartilage (± 1.4 log2 fold-change, P < 0.05). Of these, 93 were at higher levels in the older cartilage and 303 were at lower levels in the older cartilage. There was an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage derived from older donors compared with young donors. In addition, there was a reduction in Wnt signalling in ageing cartilage. Conclusion There was an age-related dysregulation of matrix, anabolic and catabolic

Piercing the upper ear: a simple infection, a difficult reconstruction.

PubMed

Cicchetti, S; Skillman, J; Gault, D T

2002-04-01

Piercing the upper ear to retain jewellery is now commonplace. When infection ensues, devastating chondritis leads to collapse of the ear. To our knowledge, the surgical reconstruction of post-piercing deformities has not been documented in the literature. We present five such cases referred for autogenous-tissue ear reconstruction. In four of these, the destroyed segments of ear cartilage were replaced with a carved costal-cartilage framework. One patient declined surgery. The importance of preventing infection is stressed. Copyright 2002 The British Association of Plastic Surgeons.

Morphogenesis of the second pharyngeal arch cartilage (Reichert's cartilage) in human embryos

PubMed Central

Rodríguez-Vázquez, J F; Mérida-Velasco, J R; Verdugo-López, S; Sánchez-Montesinos, I; Mérida-Velasco, J A

2006-01-01

This study was performed on 50 human embryos and fetuses between 7 and 17 weeks of development. Reichert's cartilage is formed in the second pharyngeal arch in two segments. The longer cranial or styloid segment is continuous with the otic capsule; its inferior end is angulated and is situated very close to the oropharynx. The smaller caudal segment is in contact with the body and greater horn of the hyoid cartilaginous structure. No cartilage forms between these segments. The persistent angulation of the inferior end of the cranial or styloid segment of Reichert's cartilage and its important neurovascular relationships may help explain the symptomatology of Eagle's syndrome. PMID:16441562

Upregulation of lipocalin-2 (LCN2) in osteoarthritic cartilage is not necessary for cartilage destruction in mice.

PubMed

Choi, W-S; Chun, J-S

2017-03-01

Lipocalin-2 (LCN2) is a recently characterized adipokine that is upregulated in chondrocytes treated with pro-inflammatory mediators and in the synovial fluid of osteoarthritis (OA) patients. Here, we explored the in vivo functions of LCN2 in OA cartilage destruction in mice. The expression levels of LCN2 were determined at the mRNA and protein levels in primary cultured mouse chondrocytes and in human and mouse OA cartilage. Experimental OA was induced in wild-type (WT) or Lcn2-knockout (KO) mice by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing hypoxia-inducible factor (HIF)-2α (Ad-Epas1), ZIP8 (Ad-Zip8), or LCN2 (Ad-Lcn2). The effect of LCN2 overexpression on the cartilage of WT mice was examined by IA injection of Ad-Lcn2. LCN2 mRNA levels in chondrocytes were markedly increased by the pro-inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), and by previously identified catabolic regulators of OA, such as HIF-2α and components of the zinc-ZIP8-MTF1 axis. LCN2 protein levels were also markedly increased in human OA cartilage and cartilage from various experimental mouse models of OA. However, overexpression of LCN2 in chondrocytes did not modulate the expression of cartilage matrix molecules or matrix-degrading enzymes. Furthermore, LCN2 overexpression in mouse cartilage via IA injection of Ad-Lcn2 did not cause OA pathogenesis, and Lcn2 KO mice showed no alteration in DMM-induced OA cartilage destruction. Our observations collectively suggest that upregulation of LCN2 in OA cartilage is not sufficient or necessary for OA cartilage destruction in mice. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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.

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

PubMed Central

Johns, D.E.; Athanasiou, K.A.

2010-01-01

Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

Functional analysis of CTRP3/cartducin in Meckel's cartilage and developing condylar cartilage in the fetal mouse mandible

PubMed Central

Yokohama-Tamaki, Tamaki; Maeda, Takashi; Tanaka, Tetsuya S; Shibata, Shunichi

2011-01-01

CTRP3/cartducin, a novel C1q family protein, is expressed in proliferating chondrocytes in the growth plate and has an important role in regulating the growth of both chondrogenic precursors and chondrocytes in vitro. We examined the expression of CTRP3/cartducin mRNA in Meckel's cartilage and in condylar cartilage of the fetal mouse mandible. Based on in situ hybridization studies, CTRP3/cartducin mRNA was not expressed in the anlagen of Meckel's cartilage at embryonic day (E)11.5, but it was strongly expressed in Meckel's cartilage at E14.0, and then reduced in the hypertrophic chondrocytes at E16.0. CTRP3/cartducin mRNA was not expressed in the condylar anlagen at E14.0, but was expressed in the upper part of newly formed condylar cartilage at E15.0. At E16.0, CTRP3/cartducin mRNA was expressed from the polymorphic cell zone to the upper part of the hypertrophic cell zone, but was reduced in the lower part of the hypertrophic cell zone. CTRP3/cartducin-antisense oligodeoxynucleotide (AS-ODN) treatment of Meckel's cartilage and condylar anlagen from E14.0 using an organ culture system indicated that, after 4-day culture, CTRP3/cartducin abrogation induced curvature deformation of Meckel's cartilage with loss of the perichondrium and new cartilage formation. Aggrecan, type I collagen, and tenascin-C were simultaneously immunostained in this newly formed cartilage, indicating possible transformation from the perichondrium into cartilage. Further, addition of recombinant mouse CTRP3/cartducin protein to the organ culture medium with AS-ODN tended to reverse the deformation. These results suggest a novel function for CTRP3/cartducin in maintaining the perichondrium. Moreover, AS-ODN induced a deformation of the shape, loss of the perichondrium/fibrous cell zone, and disorder of the distinct architecture of zones in the mandibular condylar cartilage. Additionally, AS-ODN-treated condylar cartilage showed reduced levels of mRNA expression of aggrecan, collagen types I

Cartilage Health in Knees Treated with Metal Resurfacing Implants or Untreated Focal Cartilage Lesions: A Preclinical Study in Sheep.

PubMed

Martinez-Carranza, Nicolas; Hultenby, Kjell; Lagerstedt, Anne Sofie; Schupbach, Peter; Berg, Hans E

2017-07-01

Background Full-depth cartilage lesions do not heal and the long-term clinical outcome is uncertain. In the symptomatic middle-aged (35-60 years) patient, treatment with metal implants has been proposed. However, the cartilage health surrounding these implants has not been thoroughly studied. Our objective was to evaluate the health of cartilage opposing and adjacent to metal resurfacing implants. Methods The medial femoral condyle was operated in 9 sheep bilaterally. A metallic resurfacing metallic implant was immediately inserted into an artificially created 7.5 mm defect while on the contralateral knee the defect was left untreated. Euthanasia was performed at 6 months. Six animals, of similar age and study duration, from a previous study were used for comparison in the evaluation of cartilage health adjacent to the implant. Cartilage damage to joint surfaces within the knee, cartilage repair of the defect, and cartilage adjacent to the implant was evaluated macroscopically and microscopically. Results Six animals available for evaluation of cartilage health within the knee showed a varying degree of cartilage damage with no statistical difference between defects treated with implants or left untreated ( P = 0.51; 95% CI -3.7 to 6.5). The cartilage adjacent to the implant (score 0-14; where 14 indicates no damage) remained healthy in these 6 animals showing promising results (averaged 10.5; range 9-11.5, SD 0.95). Cartilage defects did not heal in any case. Conclusion Treatment of a critical size focal lesion with a metal implant is a viable alternative treatment.

Non-Contact Evaluation for Articular Cartilage Using Ultrasound

NASA Astrophysics Data System (ADS)

Mori, Koji; Nakagawa, Yasuaki; Kuroki, Hiroshi; Nakashima, Keisuke; Ikeuchi, Ken; Mine, Takatomo; Nakamura, Takashi; Kawai, Shinya; Saito, Takashi

In orthopedic field, various new treatments of articular cartilage defect, for example autogenous osteochondral grafts, have been developed. With the spread of these treatments, orthopedists began to focus on the mechanical properties of recovered articular cartilage. The quantitative evaluation of articular cartilage before and after these treatments gives orthopedists the important information to improve these treatments and develop new treatments. We have been investigating the non-contact ultrasonic evaluation for articular cartilage under arthroscopy. In this paper, it was hypothesized that the ultrasonic evaluation depended on the collagen fiber in cartilage. The enzymatically degradation of collagen fiber in cartilage surface was performed. The effect of the degradation on sound velocity, attenuation coefficient and signal intensity, which is the index of cartilage stiffness calculated from the proposed method, was measured. The numerical analysis was performed to clear the relation between the cartilage character and ultrasonic parameters. Experimental and numerical results suggest that the present method can be expanded the sensitive evaluation for cartilage disease in clinical field.

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

The effects of exercise on human articular cartilage.

PubMed

Eckstein, F; Hudelmaier, M; Putz, R

2006-04-01

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.

An update on auricular reconstruction: three major auricular malformations of microtia, prominent ear and cryptotia.

PubMed

Park, Chul; Yoo, Yeon-Sik; Hong, Sung-Taek

2010-12-01

Microtia, prominent ear, and cryptotia are the most common types of auricular malformations. This review provides updated information on these types of reconstructions, in addition to recalling previously accepted surgical methods. Autogenous costal cartilage is still considered as an ideal material for framework fabrication in microtia reconstruction. Many surgeons have adopted the Nagata approach, the Brent approach, or variations of the two, in their work. With these employed techniques, auricles reconstructed by experienced surgeons have proven to be aesthetically promising. However, with regards to the harvesting of the costal cartilage, the underdevelopment of the chest wall donor site, alopecia of the scalp, and scarring of the postauricular-mastoid region are still considered problematic aspects of these approaches. Some articles have described attempts to solve these problems, whereas some experiments in cartilage production using tissue engineering techniques have shown promise in their initial stages of development.It is generally accepted that prominent ears should be corrected through a combination of sculpting and suture techniques, according to the individual shape and the quality of the ear prominence.Most of the cryptotia malformations show not only embedded upper auricles, but also associated adhesions of the upper auricular cartilage. Their correction should therefore resolve both deformities. A number of articles highlighting clinical experiences with auricular reconstructions for microtia, prominent ear, and cryptotia have been included in this review. We believe that the information synthesized here will become a basis for further development of auricular reconstruction techniques.

Thickness Distribution of Glenohumeral Joint Cartilage.

PubMed

Schleich, Christoph; Bittersohl, Bernd; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Kircher, Jörn

2017-04-01

High-resolution 3-dimensional cartilage-specific magnetic resonance imaging (MRI) was performed at 3 T to test the following hypotheses: (1) there is a nonuniform cartilage thickness distribution both on the proximal humerus and on the glenoid surface and (2) the glenohumeral joint as a combined system is congruent with the level of the joint cartilage surface without substantial radial mismatch. Inclusion of 38 volunteers (19 females, mean age 24.34 ± 2.22 years; range 21-29 years) in a prospective study. Measurements of: cartilage thickness in 3 regions and 3 zones; radius of both circles (glenoid and humeral cartilage) for congruency calculation using 3-T MRI with 3-dimensional dual-echo steady-state sequence with water excitation. A homogenous mean cartilage thickness (1.2-1.5 mm) and slightly higher values for the glenoidal articulating surface radii both in the mid-paracoronar section (2.4 vs. 2.1 cm, P < 0.001) and in the mid-paraaxial section (2.4 vs. 2.1 cm, P < 0.001) compared with the humeral side were observed. The concept of a radial mismatch between the humeral head and the glenoid in healthy human subjects can be confirmed. This study provides normative data for the comparison of joint cartilage changes at the shoulder for future studies.

Polymer Formulations for Cartilage Repair

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

Gutowska, Anna; Jasionowski, Marek; Morris, J. E.

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 ofmore » aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.« less

Cartilage repair in the degenerative ageing knee

PubMed Central

Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James

2016-01-01

Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738

Laser surface modification of decellularized extracellular cartilage matrix for cartilage tissue engineering.

PubMed

Goldberg-Bockhorn, Eva; Schwarz, Silke; Subedi, Rachana; Elsässer, Alexander; Riepl, Ricarda; Walther, Paul; Körber, Ludwig; Breiter, Roman; Stock, Karl; Rotter, Nicole

2018-02-01

The implantation of autologous cartilage as the gold standard operative procedure for the reconstruction of cartilage defects in the head and neck region unfortunately implicates a variety of negative effects at the donor site. Tissue-engineered cartilage appears to be a promising alternative. However, due to the complex requirements, the optimal material is yet to be determined. As demonstrated previously, decellularized porcine cartilage (DECM) might be a good option to engineer vital cartilage. As the dense structure of DECM limits cellular infiltration, we investigated surface modifications of the scaffolds by carbon dioxide (CO 2 ) and Er:YAG laser application to facilitate the migration of chondrocytes inside the scaffold. After laser treatment, the scaffolds were seeded with human nasal septal chondrocytes and analyzed with respect to cell migration and formation of new extracellular matrix proteins. Histology, immunohistochemistry, SEM, and TEM examination revealed an increase of the scaffolds' surface area with proliferation of cell numbers on the scaffolds for both laser types. The lack of cytotoxic effects was demonstrated by standard cytotoxicity testing. However, a thermal denaturation area seemed to hinder the migration of the chondrocytes inside the scaffolds, even more so after CO 2 laser treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further modifications of the laser adjustments or the use of alternative laser systems might be advantageous for surface enlargement and to facilitate migration of chondrocytes into the scaffold in one step.

Assessing Cartilage Biomechanical Properties: Techniques for Evaluating the Functional Performance of Cartilage in Health and Disease.

PubMed

Lakin, Benjamin A; Snyder, Brian D; Grinstaff, Mark W

2017-06-21

Osteoarthritis (OA) affects millions of people and results in weakened hyaline cartilage due to overloading. During joint articulation, hyaline cartilage must withstand high loads while maintaining low friction to prevent wear and tissue loss. Thus, cartilage compressive stiffness and the coefficient of friction are important indicators of the tissue's functional performance. These mechanical properties are often measured ex vivo using mechanical testing regimens, but arthroscopic handheld probes (e.g., for indentation testing, ultrasound, and optical coherence tomography) and noninvasive imaging modalities (e.g., magnetic resonance imaging and computed tomography) provide opportunities for either direct or indirect in vivo assessment of cartilage mechanical properties. In this review, we examine the application of these techniques for evaluating cartilage, with a focus on measuring mechanical properties for early-stage OA diagnosis. For each approach, we discuss the advantages, disadvantages, current and potential clinical utility, and promising technological improvement.

Cartilage proteoglycans inhibit fibronectin-mediated adhesion

NASA Astrophysics Data System (ADS)

Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

1981-09-01

Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

Cartilage.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1984-01-01

Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

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

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

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.

Current state of cartilage tissue engineering

PubMed Central

Tuli, Richard; Li, Wan-Ju; Tuan, Rocky S

2003-01-01

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering. PMID:12932283

Hyaline cartilage degenerates after autologous osteochondral transplantation.

PubMed

Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

2004-11-01

Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

Thickness Distribution of Glenohumeral Joint Cartilage

PubMed Central

Schleich, Christoph; Bittersohl, Bernd; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Kircher, Jörn

2016-01-01

High-resolution 3-dimensional cartilage-specific magnetic resonance imaging (MRI) was performed at 3 T to test the following hypotheses: (1) there is a nonuniform cartilage thickness distribution both on the proximal humerus and on the glenoid surface and (2) the glenohumeral joint as a combined system is congruent with the level of the joint cartilage surface without substantial radial mismatch. Inclusion of 38 volunteers (19 females, mean age 24.34 ± 2.22 years; range 21-29 years) in a prospective study. Measurements of: cartilage thickness in 3 regions and 3 zones; radius of both circles (glenoid and humeral cartilage) for congruency calculation using 3-T MRI with 3-dimensional dual-echo steady-state sequence with water excitation. A homogenous mean cartilage thickness (1.2-1.5 mm) and slightly higher values for the glenoidal articulating surface radii both in the mid-paracoronar section (2.4 vs. 2.1 cm, P < 0.001) and in the mid-paraaxial section (2.4 vs. 2.1 cm, P < 0.001) compared with the humeral side were observed. The concept of a radial mismatch between the humeral head and the glenoid in healthy human subjects can be confirmed. This study provides normative data for the comparison of joint cartilage changes at the shoulder for future studies. PMID:28345405

NMR Studies of Cartilage Dynamics, Diffusion, Degradation

NASA Astrophysics Data System (ADS)

Huster, Daniel; Schiller, Jurgen; Naji, Lama; Kaufmann Jorn; Arnold, Klaus

An increasing number of people is suffering from rheumatic diseases, and, therefore, methods of early diagnosis of joint degeneration are urgently required. For their establishment, however, an improved knowledge about the molecular organisation of cartilage would be helpful. Cartilage consists of three main components: Water, collagen and chondroitin sulfate (CS) that is (together with further polysaccharides and proteins) a major constituent of the proteoglycans of cartilage. 1H and 13C MAS (magic-angle spinning) NMR (nuclear magnetic resonance) opened new perspectives for the study of the macromolecular components in cartilage. We have primarily studied the mobilities of CS and collagen in bovine nasal and pig articular cartilage (that differ significantly in their collagen/polysaccharide content) by measuring 13C NMR relaxation times as well as the corresponding 13C CP (cross polarisation) MAS NMR spectra. These data clearly indicate that the mobility of cartilage macromolecules is broadly distributed from almost completely rigid (collagen) to highly mobile (polysaccharides), which lends cartilage its mechanical strength and shock-absorbing properties.

MRI of articular cartilage at microscopic resolution

PubMed Central

Xia, Y.

2013-01-01

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative. PMID:23610697

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.

Evaluation of focal cartilage lesions of the knee using MRI T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC).

PubMed

Årøen, Asbjørn; Brøgger, Helga; Røtterud, Jan Harald; Sivertsen, Einar Andreas; Engebretsen, Lars; Risberg, May Arna

2016-02-11

Assessment of degenerative changes of the cartilage is important in knee cartilage repair surgery. Magnetic Resonance Imaging (MRI) T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) are able to detect early degenerative changes. The hypothesis of the study was that cartilage surrounding a focal cartilage lesion in the knee does not possess degenerative changes. Twenty-eight consecutive patients included in a randomized controlled trial on cartilage repair were evaluated using MRI T2 mapping and dGEMRIC before cartilage treatment was initiated. Inclusion was based on disabling knee problems (Lysholm score of ≤ 75) due to an arthroscopically verified focal femoral condyle cartilage lesion. Furthermore, no major malalignments or knee ligament injuries were accepted. Mean patient age was 33 ± 9.6 years, and the mean duration of knee symptoms was 49 ± 60 months. The MRI T2 mapping and the dGEMRIC measurements were performed at three standardized regions of interest (ROIs) at the medial and lateral femoral condyle, avoiding the cartilage lesion The MRI T2 mapping of the cartilage did not demonstrate significant differences between condyles with or without cartilage lesions. The dGEMRIC results did not show significantly lower values of the affected condyle compared with the opposite condyle and the contra-lateral knee in any of the ROIs. The intraclass correlation coefficient (ICC) of the dGEMRIC readings was 0.882. The MRI T2 mapping and the dGEMRIC confirmed the arthroscopic findings that normal articular cartilage surrounded the cartilage lesion, reflecting normal variation in articular cartilage quality. NCT00885729 , registered April 17 2009.

Peptide-Based Materials for Cartilage Tissue Regeneration.

PubMed

Hastar, Nurcan; Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

2017-01-01

Cartilaginous tissue requires structural and metabolic support after traumatic or chronic injuries because of its limited capacity for regeneration. However, current techniques for cartilage regeneration are either invasive or ineffective for long-term repair. Developing alternative approaches to regenerate cartilage tissue is needed. Therefore, versatile scaffolds formed by biomaterials are promising tools for cartilage regeneration. Bioactive scaffolds further enhance the utility in a broad range of applications including the treatment of major cartilage defects. This chapter provides an overview of cartilage tissue, tissue defects, and the methods used for regeneration, with emphasis on peptide scaffold materials that can be used to supplement or replace current medical treatment options.

Permanence of diced cartilage, bone dust and diced cartilage/bone dust mixture in experimental design in twelve weeks.

PubMed

Islamoglu, Kemal; Dikici, Mustafa Bahadir; Ozgentas, Halil Ege

2006-09-01

Bone dust and diced cartilage are used for contour restoration because their minimal donor site morbidity. The purpose of this study is to investigate permanence of bone dust, diced cartilage and bone dust/diced cartilage mixture in rabbits over 12 weeks. New Zealand white rabbits were used for this study. There were three groups in the study: Group I: 1 mL bone dust. Group II: 1 mL diced cartilage. Group III: 0.5 mL bone dust + 0.5 mL diced cartilage mixture. They were placed into subcutaneous tissue of rabbits and removed 12 weeks later. The mean volumes of groups were 0.23 +/- 0.08 mL in group I, 0.60 +/- 0.12 mL in group II and 0.36 +/- 0.10 mL in group III. The differences between groups were found statistically significant. In conclusion, diced cartilage was found more reliable than bone dust aspect of preserving its volume for a long period in this study.

The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

PubMed

Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

2017-10-01

Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST Study

PubMed Central

Crema, Michel D.; Felson, David T.; Roemer, Frank W.; Wang, Ke; Marra, Monica D.; Nevitt, Michael C.; Lynch, John A.; Torner, James; Lewis, Cora E.; Guermazi, Ali

2012-01-01

Objective To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI). Methods The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders. Results Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]). Conclusion Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA. PMID:23178289

Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.

PubMed

Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

2013-07-01

Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013

Growth factor expression in cartilage wound healing: temporal and spatial immunolocalization in a rabbit auricular cartilage wound model.

PubMed

Bos, P K; van Osch, G J; Frenz, D A; Verhaar, J A; Verwoerd-Verhoef, H L

2001-05-01

The ability of cartilage to regenerate following injury is limited, potentially leading to osteoarthritis. Integrative cartilage repair, necessary for durable restoration of cartilage lesions, can be regarded as a wound healing process. Little is known about the effects of growth factors regulating acute cartilage wound healing in vivo. In this study the temporal expression patterns of growth factors and proteoglycan content in cartilage wound edges in vivo were studied. Cartilage wounds were created in rabbit ear cartilage using a 6 mm biopsy punch. Specimens were subsequently harvested 1, 3, 7, 14 and 28 days after surgery. Paraffin sections were thionin stained to visualize proteoglycan loss and replacement. Immunohistochemical staining of TGFbeta1, TGFbeta3, IGF-1, IGF-II and FGF-2 was used to define growth factor expression at the cartilage wound sites. Almost no effect of cartilage wounding was observed one day after surgery. A decrease of proteoglycan content, with a maximal loss at day 7, and a subsequent restoration was observed at the wound edges. Growth factor expression increased simultaneously. Maximal immunostaining for IGF1, IGFII, FGF2 and TGF-beta3 was observed at day 7, followed by a gradual decrease. Increased expression of TGFbeta1 lasted from day 3 until day 14. We have demonstrated the ability of chondrocytes to increase growth factor expression and to restore the rapid decrease in proteoglycan content in the initial phase following acute wounding. A temporal increase in intracellular growth factor expression suggests an autocrine and/or paracrine metabolic stimulation, which can be regarded a sign of chondrocytes repair capacity. Copyright 2001 OsteoArthritis Research Society International.

Advances and Prospects in Stem Cells for Cartilage Regeneration

PubMed Central

Wang, Mingjie; Yuan, Zhiguo; Ma, Ning; Hao, Chunxiang; Guo, Weimin; Zou, Gengyi; Zhang, Yu; Chen, Mingxue; Gao, Shuang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Lu, Shibi

2017-01-01

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed. PMID:28246531

Biological aspects of tissue-engineered cartilage.

PubMed

Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

2018-04-01

Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

PubMed

Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

2018-02-01

Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

PubMed

Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

2014-06-18

After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.

PubMed

Bos, P K; Verhaar, J A N; van Osch, G J V M

2006-01-01

Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, FGF2 and IGF1 was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.

Nano Scale Mechanical Analysis of Biomaterials Using Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Dutta, Diganta

The atomic force microscope (AFM) is a probe-based microscope that uses nanoscale and structural imaging where high resolution is desired. AFM has also been used in mechanical, electrical, and thermal engineering applications. This unique technique provides vital local material properties like the modulus of elasticity, hardness, surface potential, Hamaker constant, and the surface charge density from force versus displacement curve. Therefore, AFM was used to measure both the diameter and mechanical properties of the collagen nanostraws in human costal cartilage. Human costal cartilage forms a bridge between the sternum and bony ribs. The chest wall of some humans is deformed due to defective costal cartilage. However, costal cartilage is less studied compared to load bearing cartilage. Results show that there is a difference between chemical fixation and non-chemical fixation treatments. Our findings imply that the patients' chest wall is mechanically weak and protein deposition is abnormal. This may impact the nanostraws' ability to facilitate fluid flow between the ribs and the sternum. At present, AFM is the only tool for imaging cells' ultra-structure at the nanometer scale because cells are not homogeneous. The first layer of the cell is called the cell membrane, and the layer under it is made of the cytoskeleton. Cancerous cells are different from normal cells in term of cell growth, mechanical properties, and ultra-structure. Here, force is measured with very high sensitivity and this is accomplished with highly sensitive probes such as a nano-probe. We performed experiments to determine ultra-structural differences that emerge when such cancerous cells are subject to treatments such as with drugs and electric pulses. Jurkat cells are cancerous cells. These cells were pulsed at different conditions. Pulsed and non-pulsed Jurkat cell ultra-structures were investigated at the nano meter scale using AFM. Jurkat cell mechanical properties were measured under

A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage in an experimental animal model of cartilage repair.

PubMed

Bonadio, Marcelo B; Friedman, James M; Sennett, Mackenzie L; Mauck, Robert L; Dodge, George R; Madry, Henning

2017-12-01

This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella (n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach.

Articular cartilage tissue engineering: the role of signaling molecules

PubMed Central

Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

2017-01-01

Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

Functional peptides for cartilage repair and regeneration

PubMed Central

Liu, Qisong; Jia, Zhaofeng; Duan, Li; Xiong, Jianyi; Wang, Daping; Ding, Yue

2018-01-01

Cartilage repair after degeneration or trauma continues to be a challenge both in the clinic and for scientific research due to the limited regenerative capacity of this tissue. Cartilage tissue engineering, involving a combination of cells, scaffolds, and growth factors, is increasingly used in cartilage regeneration. Due to their ease of synthesis, robustness, tunable size, availability of functional groups, and activity, peptides have emerged as the molecules with the most potential in drug development. A number of peptides have been engineered to regenerate cartilage by acting as scaffolds, functional molecules, or both. In this paper, we will summarize the application of peptides in cartilage tissue engineering and discuss additional possibilities for peptides in this field. PMID:29511444

Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Hede, Kris Chadwick; Lind, Martin

2016-06-01

Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups

Three-step orbitofacial reconstruction after extended total maxillectomy using free RAM flap and expanded cervicofacial flap with cartilage grafts.

PubMed

Kajikawa, Akiyoshi; Ueda, Kazuki; Katsuragi, Yoko; Hirose, Taro; Asai, Emiko

2010-10-01

Facial defect after an extended total maxillectomy is one of the most difficult deformities to reconstruct aesthetically, because the defect is not only large but also three-dimensional. Although free-flap reconstruction is useful, the patchwork-like scar, bad colour match and poor texture match are major problems. The contracture and displacement of the reconstructed eyelids and eye socket are also serious matters. To resolve these problems, we have performed a three-step reconstruction using a free rectus abdominis myocutaneous (RAM) flap and an expanded cervicofacial flap with cartilage grafts. In the first step, a free RAM flap was transplanted to the defect after extended total maxillectomy. In the second step, tissue expanders were placed under the skin of the cheek and neck a year after the RAM flap transplantation. After expansion of the cheek and neck skin, the third step was performed. The inferior part of the external skin island of the RAM flap was raised and sutured to the superior margin of the skin island to create a pouch for the eye socket. Costal cartilage was grafted to reconstruct the orbital floor and malar prominence, and auricular cartilage was grafted to reconstruct the tarsal plates. Finally, the expanded cervicofacial flap was rotated to cover this construct. Two weeks after reconstruction, the neo-eyelids were divided to form the lid fissure. We performed the three-step reconstruction on six cases after extended total maxillectomy. In all cases, a deep and stable eye socket was reconstructed. The reconstructed eyelids and cheek were natural in appearance with good colour and texture match without conspicuous scars. To obtain symmetry and natural appearance in the orbitomaxillary reconstruction, there are five points that should be formed; the eye socket, the groundwork of the eye socket, the orbital floor and malar prominence, the tarsal plates and the surface of the eyelids and cheek. We do not reconstruct the palate to set prosthetic

Fibrous cartilage of human menisci is less shock-absorbing and energy-dissipating than hyaline cartilage.

PubMed

Gaugler, Mario; Wirz, Dieter; Ronken, Sarah; Hafner, Mirjam; Göpfert, Beat; Friederich, Niklaus F; Elke, Reinhard

2015-04-01

To test meniscal mechanical properties such as the dynamic modulus of elasticity E* and the loss angle δ at two loading frequencies ω at different locations of the menisci and compare it to E* and δ of hyaline cartilage in indentation mode with spherical indenters. On nine pairs of human menisci, the dynamic E*-modulus and loss angle δ (as a measure of the energy dissipation) were determined. The measurements were performed at two different strain rates (slow sinusoidal and fast single impact) to show the strain rate dependence of the material. The measurements were compared to previous similar measurements with the same equipment on human hyaline cartilage. The resultant E* at fast indentation (median 1.16 MPa) was significantly higher, and the loss angle was significantly lower (median 10.2°) compared to slow-loading mode's E* and δ (median 0.18 MPa and 16.9°, respectively). Further, significant differences for different locations are shown. On the medial meniscus, the anterior horn shows the highest resultant dynamic modulus. In dynamic measurements with a spherical indenter, the menisci are much softer and less energy-dissipating than hyaline cartilage. Further, the menisci are stiffer and less energy-dissipating in the middle, intermediate part compared to the meniscal base. In compression, the energy dissipation of meniscus cartilage plays a minor role compared to hyaline cartilage. At high impacts, energy dissipation is less than on low impacts, similar to cartilage.

Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST study.

PubMed

Crema, M D; Felson, D T; Roemer, F W; Wang, K; Marra, M D; Nevitt, M C; Lynch, J A; Torner, J; Lewis, C E; Guermazi, A

2013-02-01

To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI). The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0 T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders. Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% confidence interval (CI) 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]). Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cartilage quantification using contrast-enhanced MRI in the wrist of rheumatoid arthritis: cartilage loss is associated with bone marrow edema.

PubMed

Fujimori, Motoshi; Nakamura, Satoko; Hasegawa, Kiminori; Ikeno, Kunihiro; Ichikawa, Shota; Sutherland, Kenneth; Kamishima, Tamotsu

2017-08-01

To quantify wrist cartilage using contrast MRI and compare with the extent of adjacent synovitis and bone marrow edema (BME) in patients with rheumatoid arthritis (RA). 18 patients with RA underwent post-contrast fat-suppressed T 1 weighted coronal imaging. Cartilage area at the centre of the scaphoid-capitate and radius-scaphoid joints was measured by in-house developed software. We defined cartilage as the pixels with signal intensity between two thresholds (lower: 0.4, 0.5 and 0.6 times the muscle signal, upper: 0.9, 1.0, 1.1, 1.2 and 1.3 times the muscle signal). We investigated the association of cartilage loss with synovitis and BME score derived from RA MRI scoring system. Cartilage area was correlated with BME score when thresholds were adequately set with lower threshold at 0.6 times the muscle signal and upper threshold at 1.2 times the muscle signal for both SC (r s =-0.469, p < 0.05) and RS (r s =-0.486, p < 0.05) joints, while it showed no significant correlation with synovitis score at any thresholds. Our software can accurately quantify cartilage in the wrist and BME associated with cartilage loss in patients with RA. Advances in knowledge: Our software can quantify cartilage using conventional MR images of the wrist. BME is associated with cartilage loss in RA patients.

Effects of growth factors and glucosamine on porcine mandibular condylar cartilage cells and hyaline cartilage cells for tissue engineering applications.

PubMed

Wang, Limin; Detamore, Michael S

2009-01-01

Temporomandibular joint (TMJ) condylar cartilage is a distinct cartilage that has both fibrocartilaginous and hyaline-like character, with a thin proliferative zone that separates the fibrocartilaginous fibrous zone at the surface from the hyaline-like mature and hypertrophic zones below. In this study, we compared the effects of insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGF-beta1), and glucosamine sulphate on porcine TMJ condylar cartilage and ankle cartilage cells in monolayer culture. In general, TMJ condylar cartilage cells proliferated faster than ankle cartilage cells, while ankle cells produced significantly greater amounts of glycosaminoglycans (GAGs) and collagen than TMJ condylar cartilage cells. IGF-I and bFGF were potent stimulators of TMJ cell proliferation, while no signals statistically outperformed controls for ankle cell proliferation. IGF-I was the most effective signal for GAG production with ankle cells, and the most potent upregulator of collagen synthesis for both cell types. Glucosamine sulphate promoted cell proliferation and biosynthesis at specific concentrations and outperformed growth factors in certain instances. In conclusion, hyaline cartilage cells had lower cell numbers and superior biosynthesis compared to TMJ condylar cartilage cells, and we have found IGF-I at 100 ng/mL and glucosamine sulphate at 100 microg/mL to be the most effective signals for these cells under the prescribed conditions.

Uncoupled poroelastic and intrinsic viscoelastic dissipation in cartilage.

PubMed

Han, Guebum; Hess, Cole; Eriten, Melih; Henak, Corinne R

2018-04-26

This paper studies uncoupled poroelastic (flow-dependent) and intrinsic viscoelastic (flow-independent) energy dissipation mechanisms via their dependence on characteristic lengths to understand the root of cartilage's broadband dissipation behavior. Phase shift and dynamic modulus were measured from dynamic microindentation tests conducted on hydrated cartilage at different contact radii, as well as on dehydrated cartilage. Cartilage weight and thickness were recorded during dehydration. Phase shifts revealed poroelastic- and viscoelastic-dominant dissipation regimes in hydrated cartilage. Specifically, phase shift at a relatively small radius was governed by poroviscoelasticity, while phase shift at a relatively large radius was dominantly governed by intrinsic viscoelasticity. The uncoupled dissipation mechanisms demonstrated that intrinsic viscoelastic dissipation provided sustained broadband dissipation for all length scales, and additional poroelastic dissipation increased total dissipation at small length scales. Dehydration decreased intrinsic viscoelastic dissipation of cartilage. The findings demonstrated a possibility to measure poroelastic and intrinsic viscoelastic properties of cartilage at similar microscale lengths. Also they encouraged development of broadband cartilage like-dampers and provided important design parameters to maximize their performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Triiodothyronine stimulates cartilage growth and maturation by different mechanisms

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

Burch, W.M.; Van Wyk, J.J.

1987-02-01

The mechanisms by which triiodothyronine (T3) stimulates growth and maturation of growth-plate cartilage in vitro were studied by incubating embryonic chick pelvic cartilages in serum-free medium in the presence and absence of T3 for 3 days. To determine whether T3 might stimulate production of somatomedins by the cartilage, medium from cartilage incubated with and without T3 was assayed for somatomedin C( Sm-C) by radioimmunoassay. No difference in Sm-C content was found. However, cartilage incubated with T3 and increasing amounts of human Sm-C (0.5-20 ng/ml) weighed more and had greater amounts of glycosaminoglycan that cartilage incubated in the same concentrations ofmore » Sm-C without T3, suggesting that T3 enhances the growth effect of somatomedin. The authors added a monoclonal antibody to Sm-C (anti-Sm-C) to the organ culture to determine whether T3's stimulatory effect on cartilage growth could be blocked. The anti-Sm-C inhibited growth of cartilage incubated in medium alone and blocked the growth response to T3. They propose two different mechanisms by which T3 affects growth-plate cartilage: (1) T3 promotes cartilage growth primarily through enhancing the effect of somatomedin, and (2) T3 stimulates cartilage maturation possibly by accelerating the normal process of cartilage differentiation from proliferative to hypertrophic chondrocytes.« less

A New Technique for Conchal Cartilage Harvest.

PubMed

Kim, Joon Young; Yang, Ho Jik; Jeong, Ji Won

2017-03-01

The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear.

A New Technique for Conchal Cartilage Harvest

PubMed Central

Kim, Joon Young; Jeong, Ji Won

2017-01-01

The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear. PMID:28352607

Papain-induced changes in rabbit cartilage; alterations in the chemical structure of the cartilage matrix.

PubMed

TSALTAS, T T

1958-10-01

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S(35) content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S(35) in the serum and an increase of S(35) and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery.

Tissue-engineered articular cartilage exhibits tension-compression nonlinearity reminiscent of the native cartilage.

PubMed

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

2013-07-26

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±83kPa for FS and 678±473kPa for DL) and compressive (161±33kPa for FS and 348±203kPa 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Research progress of articular cartilage scaffold for tissue engineering].

PubMed

Liu, Qingyu; Wang, Fuyou; Yang, Liu

2012-10-01

To review the research progress of articular cartilage scaffold materials and look into the future development prospects. Recent literature about articular cartilage scaffold for tissue engineering was reviewed, and the results from experiments and clinical application about natural and synthetic scaffold materials were analyzed. The design of articular cartilage scaffold for tissue engineering is vital to articular cartilage defects repair. The ideal scaffold can promote the progress of the cartilage repair, but the scaffold materials still have their limitations. It is necessary to pay more attention to the research of the articular cartilage scaffold, which is significant to the repair of cartilage defects in the future.

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

PubMed

Pretzel, David; Linss, Stefanie; Ahrem, Hannes; Endres, Michaela; Kaps, Christian; Klemm, Dieter; Kinne, Raimund W

2013-01-01

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. 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. 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. Although TGF-β1 stimulation showed

Cartilage Repair in Football (Soccer) Athletes

PubMed Central

Bekkers, J.E.J.; de Windt, Th.S.; Brittberg, M.

2012-01-01

The prevalence of focal articular cartilage lesions among athletes is higher than in the general population. Treatment goals differ considerably between the professional and recreational athlete. High financial stakes and the short duration of a professional career influence the treatment selection for the professional athlete, while such parameters weigh differently in recreational sports. This article describes our investigation of the relation between sports and a high prevalence of focal cartilage lesions. In addition, we provide a critical review of the best available evidence for cartilage surgery and treatment selection, evaluate specific patient profiles for professional and recreational athletes, and propose a treatment algorithm for the treatment of focal cartilage lesions in football (soccer) players. PMID:26069606

Articular cartilage changes in chondromalacia patellae.

PubMed

Bentley, G

1985-11-01

Full thickness samples of articular cartilage were removed from areas of chondromalacia on the medial and "odd" facets of the patellae of 21 adults and examined by histology, autoradiography and electron microscopy. Surface fibrillation, loss of superficial matrix staining and reduced 35SO4 labelling was seen, with little change in the deep zone. Ten cases showed "fibrous metaplasia" of the superficial cartilage with definite evidence of cell division and apparent smoothing of the surface. Scattered chondrocyte replication appeared to occur in the surrounding intact cartilage. The findings suggest that early lesions in chondromalacia patellae may heal either by cartilage or fibrous metaplasia and that this may account for the resolution of clinical symptoms.

Vascular Canals in Permanent Hyaline Cartilage: Development, Corrosion of Nonmineralized Cartilage Matrix, and Removal of Matrix Degradation Products.

PubMed

Gabner, Simone; Häusler, Gabriele; Böck, Peter

2017-06-01

Core areas in voluminous pieces of permanent cartilage are metabolically supplied via vascular canals (VCs). We studied cartilage corrosion and removal of matrix degradation products during the development of VCs in nose and rib cartilage of piglets. Conventional staining methods were used for glycosaminoglycans, immunohistochemistry was performed to demonstrate collagens types I and II, laminin, Ki-67, von Willebrand factor, VEGF, macrophage marker MAC387, S-100 protein, MMPs -2,-9,-13,-14, and their inhibitors TIMP1 and TIMP2. VCs derived from connective tissue buds that bulged into cartilage matrix ("perichondrial papillae", PPs). Matrix was corroded at the tips of PPs or resulting VCs. Connective tissue stromata in PPs and VCs comprised an axial afferent blood vessel, peripherally located wide capillaries, fibroblasts, newly synthesized matrix, and residues of corroded cartilage matrix (collagen type II, acidic proteoglycans). Multinucleated chondroclasts were absent, and monocytes/macrophages were not seen outside the blood vessels. Vanishing acidity characterized areas of extracellular matrix degradation ("preresorptive layers"), from where the dismantled matrix components diffused out. Leached-out material stained in an identical manner to intact cartilage matrix. It was detected in the stroma and inside capillaries and associated downstream veins. We conclude that the delicate VCs are excavated by endothelial sprouts and fibroblasts, whilst chondroclasts are specialized to remove high volumes of mineralized cartilage. VCs leading into permanent cartilage can be formed by corrosion or inclusion, but most VCs comprise segments that have developed in either of these ways. Anat Rec, 300:1067-1082, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

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

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.

Regulatory Challenges for Cartilage Repair Technologies

PubMed Central

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

Articular cartilage. Part II. The osteoarthritic joint.

PubMed

Muehleman, C; Arsenis, C H

1995-05-01

Articular hyaline cartilage, though a metabolically active tissue, has limited capacity for repair. Though the integrity of the cartilage is dependent upon a certain level of force placed upon it, excessive force leads to damage. It is when the breakdown of the cartilage exceeds the capacity of the cartilage for repair that osteoarthritis results. At present, pharmacologic treatment of osteoarthritis is focused toward the control of pain and stiffness. This treatment, however, masks the symptoms of the disease and effectively allows the patient to do further damage to the joint.

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

Fibrin hydrogels functionalized with cartilage extracellular matrix and incorporating freshly isolated stromal cells as an injectable for cartilage regeneration.

PubMed

Almeida, H V; Eswaramoorthy, R; Cunniffe, G M; Buckley, C T; O'Brien, F J; Kelly, D J

2016-05-01

Freshly isolated stromal cells can potentially be used as an alternative to in vitro expanded cells in regenerative medicine. Their use requires the development of bioactive hydrogels or scaffolds which provide an environment to enhance their proliferation and tissue-specific differentiation in vivo. The goal of the current study was to develop an injectable fibrin hydrogel functionalized with cartilage ECM microparticles and transforming growth factor (TGF)-β3 as a putative therapeutic for articular cartilage regeneration. ECM microparticles were produced by cryomilling and freeze-drying porcine articular cartilage. Up to 2% (w/v) ECM could be incorporated into fibrin without detrimentally affecting its capacity to form stable hydrogels. To access the chondroinductivity of cartilage ECM, we compared chondrogenesis of infrapatellar fat pad-derived stem cells in fibrin hydrogels functionalized with either particulated ECM or control gelatin microspheres. Cartilage ECM particles could be used to control the delivery of TGF-β3 to IFP-derived stem cells within fibrin hydrogels in vitro, and furthermore, led to higher levels of sulphated glycosaminoglycan (sGAG) and collagen accumulation compared to control constructs loaded with gelatin microspheres. In vivo, freshly isolated stromal cells generated a more cartilage-like tissue within fibrin hydrogels functionalized with cartilage ECM particles compared to the control gelatin loaded constructs. These tissues stained strongly for type II collagen and contained higher levels of sGAGs. These results support the use of fibrin hydrogels functionalized with cartilage ECM components in single-stage, cell-based therapies for joint regeneration. An alternative to the use of in vitro expanded cells in regenerative medicine is the use of freshly isolated stromal cells, where a bioactive scaffold or hydrogel is used to provide an environment that enhances their proliferation and tissue-specific differentiation in vivo. The

Raman microspectrometry of laser-reshaped rabbit auricular cartilage: preliminary study on laser-induced cartilage mineralization

NASA Astrophysics Data System (ADS)

Heger, Michal; Mordon, Serge R.; Leroy, Gérard; Fleurisse, Laurence; Creusy, Collette

2006-03-01

Laser-assisted cartilage reshaping (LACR) is a relatively novel technique designed to noninvasively and permanently restructure cartilaginous tissue. It is believed that heat-induced stress relaxation, in which a temperature-mediated disruption of H2O binding is associated with conformational alterations in the proteoglycan and collagen-rich matrix, constitutes the underlying mechanism of LACR. Several reports have suggested that laser-mediated cartilage mineralization may contribute to the permanent shape change of laser-reshaped cartilage. In an effort to validate these results in the context of Er:glass LACR, we performed a preliminary Raman microspectrometric study to characterize the crystal deposits in laser-irradiated chondrocytes and extracellular matrix. For the first time, we identified intracellular calcium sulfate deposits and extracellular calcium phosphate (apatite) crystals in laser-reshaped rabbit auricular cartilage. Calcium carbonate deposits are localized in both irradiated and nonirradiated samples, suggesting that this mineral plays no role in conformational retention. In our discussion, we elaborate on the possible molecular and cellular mechanisms responsible for intra- and extracellular crystallization, and propose a novel hypothesis on the formation of apatite, inasmuch as the biological function of this mineral (providing structure and rigidity in bones and dental enamel) may be extrapolated to the permanent shape change of laser-irradiated cartilage.

The Role of Inorganic Polyphosphates in the Formation of Bioengineered Cartilage Incorporating a Zone of Calcified Cartilage In Vitro

NASA Astrophysics Data System (ADS)

St-Pierre, Jean-Philippe

The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects

Mechanisms of ear trauma and reconstructive techniques in 105 consecutive patients.

PubMed

Kolodzynski, Michail N; Kon, Moshe; Egger, Silvan; Breugem, Corstiaan C

2017-02-01

Acquired auricular deformities may diminish facial esthetics and cause psychological distress. The aim of this article is to provide an overview of the type of injuries and applied reconstructive techniques in a large academic hospital in The Netherlands. A retrospective chart review was conducted for the last 105 patients who underwent auricular reconstruction for an acquired deformity. Data concerning gender, affected side, cause of injury, anatomical region, the previous and further surgeries, type of cartilage, and skin cover used were collected and analyzed. 105 patients were included. Acquired auricular deformities were mainly caused by bite injuries (22 %), traffic accidents (17 %), burns (9.5 %), and post-otoplasty complications (9.5 %). The upper third of the auricle was most often injured (41 %), followed by the entire auricle (19 %). 70 % of cases required reconstruction with costal cartilage. The most common form of cutaneous cover was a postauricular skin flap (40 % of cases). This study gives a complete overview of causes and treatment of acquired auricular deformities. The results are comparable with the results of similar studies found in literature. Bite wounds are the leading cause of acquired auricular injuries. The upper third is most commonly affected. In the largest percentage of reconstructions, costal cartilage and a postauricular flap were used to correct the deformity.

Magnetic resonance imaging of cartilage repair.

PubMed

Potter, Hollis G; Chong, Le Roy; Sneag, Darryl B

2008-12-01

Magnetic resonance imaging is an important noninvasive modality in characterizing cartilage morphology, biochemistry, and function. It serves as a valuable objective outcome measure in diagnosing pathology at the time of initial injury, guiding surgical planning, and evaluating postsurgical repair. This article reviews the current literature addressing the recent advances in qualitative and quantitative magnetic resonance imaging techniques in the preoperative setting, and in patients who have undergone cartilage repair techniques such as microfracture, autologous cartilage transplantation, or osteochondral transplantation.

T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled study.

PubMed

Bittersohl, Bernd; Kircher, Jörn; Miese, Falk R; Dekkers, Christin; Habermeyer, Peter; Fröbel, Julia; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph

2015-10-01

Cartilage biochemical imaging modalities that include the magnetic resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective instruments for early diagnosis and reliable follow-up of cartilage damage. The purpose of this study was to provide T2* mapping and dGEMRIC values in various histologic grades of cartilage degeneration in humeral articular cartilage. A histologically controlled in vitro study was conducted that included human humeral head cartilage specimens with various histologic grades of cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and dGEMRIC were performed that enabled the correlation of MRI and histology data. Cartilage degeneration was graded according to the Mankin score, which evaluates surface morphology, cellularity, toluidine blue staining, and tidemark integrity. SPSS software was used for statistical analyses. Both MRI mapping values decreased significantly (P < .001) with increasing cartilage degeneration. Spearman rank analysis revealed a significant correlation (correlation coefficients ranging from -0.315 to 0.784; P < .001) between the various histologic parameters and the T2* and T1Gd mapping values. This study demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic grades of cartilage damage of humeral articular cartilage. With regard to the advantages of these mapping techniques with high image resolution and the ability to accomplish a 3D biochemically sensitive imaging, we consider that these imaging techniques can make a positive contribution to the currently evolving science and practice of cartilage biochemical imaging. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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.

Human acellular cartilage matrix powders as a biological scaffold for cartilage tissue engineering with synovium-derived mesenchymal stem cells.

PubMed

Chang, Chih-Hung; Chen, Chia-Chun; Liao, Cheng-Hao; Lin, Feng-Huei; Hsu, Yuan-Ming; Fang, Hsu-Wei

2014-07-01

In our previous study, we found that cartilage fragments from osteoarthritic knee promoted chondrogenesis of mesenchymal stem cells. In this study, we further transformed the cartilage tissues into acellular cartilage matrix (ACM) and explored the feasibility of using ACM as a biological scaffold. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery and were successfully fabricated into ACM powders. The ACM powders and human synovium-derived mesenchymal stem cells (SMSCs) were mixed into collagen gel for in vitro culture. Histological results showed a synergistic effect of ACM powders and chondrogenic growth factors in the formation of engineered cartilage. The findings of real-time polymerase chain reaction (PCR) suggested that ACM powders had the potential of promoting type II collagen gene expression in the growth factors-absent environment. Moreover, with growth factors induction, the ACM powders could reduce the hypertrophy in chondrogenesis of SMSCs. In summary, ACM powders could serve as a functional scaffold that benefited the chondrogenesis of SMSCs for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc.

Cell-based cartilage repair strategies in the horse.

PubMed

Ortved, Kyla F; Nixon, Alan J

2016-02-01

Damage to the articular cartilage surface is common in the equine athlete and, due to the poor intrinsic healing capabilities of cartilage, can lead to osteoarthritis (OA). Joint disease and OA are the leading cause of retirement in equine athletes and currently there are no effective treatments to stop the progression of OA. Several different cell-based strategies have been investigated to bolster the weak regenerative response of chondrocytes. Such techniques aim to restore the articular surface and prevent further joint degradation. Cell-based cartilage repair strategies include enhancement of endogenous repair mechanisms by recruitment of stem cells from the bone marrow following perforation of the subchondral bone plate; osteochondral implantation; implantation of chondrocytes that are maintained in defects by either a membrane cover or scaffold, and transplantation of mesenchymal stem cells into cartilage lesions. More recently, bioengineered cartilage and scaffoldless cartilage have been investigated for enhancing repair. This review article focuses on the multitude of cell-based repair techniques for cartilage repair across several species, with special attention paid to the horse. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expansion and redifferentiation of chondrocytes from osteoarthritic cartilage: cells for human cartilage tissue engineering.

PubMed

Hsieh-Bonassera, Nancy D; Wu, Iwen; Lin, Jonathan K; Schumacher, Barbara L; Chen, Albert C; Masuda, Koichi; Bugbee, William D; Sah, Robert L

2009-11-01

To determine if selected culture conditions enhance the expansion and redifferentiation of chondrocytes isolated from human osteoarthritic cartilage with yields appropriate for creation of constructs for treatment of joint-scale cartilage defects, damage, or osteoarthritis. Chondrocytes isolated from osteoarthritic cartilage were analyzed to determine the effects of medium supplement on cell expansion in monolayer and then cell redifferentiation in alginate beads. Expansion was assessed as cell number estimated from DNA, growth rate, and day of maximal growth. Redifferentiation was evaluated quantitatively from proteoglycan and collagen type II content, and qualitatively by histology and immunohistochemistry. Using either serum or a growth factor cocktail (TFP: transforming growth factor beta1, fibroblast growth factor 2, and platelet-derived growth factor type bb), cell growth rate in monolayer was increased to 5.5x that of corresponding conditions without TFP, and cell number increased 100-fold within 17 days. In subsequent alginate bead culture with human serum or transforming growth factor beta1 and insulin-transferrin-selenium-linoleic acid-bovine serum albumin, redifferentiation was enhanced with increased proteoglycan and collagen type II production. Effects of human serum were dose dependent, and 5% or higher induced formation of chondron-like structures with abundant proteoglycan-rich matrix. Chondrocytes from osteoarthritic cartilage can be stimulated to undergo 100-fold expansion and then redifferentiation, suggesting that they may be useful as a cell source for joint-scale cartilage tissue engineering.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note.

PubMed

Benthien, Jan P; Behrens, Peter

2013-11-01

The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access. A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed. As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing. The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.

Surgical correction of cauliflower ear.

PubMed

Yotsuyanagi, T; Yamashita, K; Urushidate, S; Yokoi, K; Sawada, Y; Miyazaki, S

2002-07-01

We have classified the cauliflower ear into different types according to the zone and the degree of deformity. One major group is deformity without change in the outline of the ear, and this is divided into four subgroups according to the zone. All of these subgroups can be treated by shaving the deformed cartilage through suitable incision lines. For deformities accompanied by a skin deficit, a postauricular skin flap should be used. The other major group is deformity accompanied by a change in the outline of the ear, which is divided into two subgroups. If the ear is rigid, a conchal cartilage graft is used. If the structural integrity of the ear is poor, costal cartilage is used to provide rigidity.

In situ hybridization and immunohistochemistry of bone sialoprotein and secreted phosphoprotein 1 (osteopontin) in the developing mouse mandibular condylar cartilage compared with limb bud cartilage

PubMed Central

Shibata, Shunichi; Fukada, Kenji; Suzuki, Shoichi; Ogawa, Takuya; Yamashita, Yasuo

2002-01-01

Mandibular condylar cartilage is often classified as a secondary cartilage, differing from the primary cartilaginous skeleton in its rapid progress from progenitor cells to hypertrophic chondrocytes. In this study we used in situ hybridization and immunohistochemistry to investigate whether the formation of primary (tibial) and secondary (condylar) cartilage also differs with respect to the expression of two major non-collagenous glycoproteins of bone matrix, bone sialoprotein (BSP) and secreted phosphoprotein 1 (Spp1, osteopontin). The mRNAs for both molecules were never expressed until hypertrophic chondrocytes appeared. In the tibial cartilage, hypertrophic chondrocytes first appeared at E14 and the expression of BSP and Spp1 mRNAs was detected in the lower hypertrophic cell zone, but the expression of BSP mRNA was very weak. In the condylar cartilage, hypertrophic chondrocytes appeared at E15 as soon as cartilage tissue appeared. The mRNAs for both molecules were expressed in the newly formed condylar cartilage, although the proteins were not detected by immunostaining; BSP mRNA in the condylar cartilage was more extensively expressed than that in the tibial cartilage at the corresponding stage (first appearance of hypertrophic cell zone). Endochondral bone formation started at E15 in the tibial cartilage and at E16 in the condylar cartilage. At this stage (first appearance of endochondral bone formation), BSP mRNA was also more extensively expressed in the condylar cartilage than in the tibial cartilage. The hypertrophic cell zone in the condylar cartilage rapidly extended during E15–16. These results indicate that the formation process of the mandibular condylar cartilage differs from that of limb bud cartilage with respect to the extensive expression of BSP mRNA and the rapid extension of the hypertrophic cell zone at early stages of cartilage formation. Furthermore, these results support the hypothesis that, in vivo, BSP promotes the initiation of

A simple in vitro culture system for tracheal cartilage development.

PubMed

Park, Jinhyung; Zhang, Jennifer J R; Choi, Ruth; Trinh, Irene; Kim, Peter C W

2010-02-01

Semi-circular tracheal cartilage is a critical determinant of maintaining architectural integrity of the respiratory airway. The current effort to understand the morphogenesis of tracheal cartilage is challenged by the lack of appropriate model systems. Here we report an in vitro tracheal cartilage system using embryonic tracheal–lung explants to recapitulate in vivo tracheal cartilage developmental processes. With modifications of a current lung culture protocol, we report a consistent in vitro technique of culturing tracheal cartilage from primitive mouse embryonic foregut for the first time. This tracheal culture system not only induces the formation of tracheal cartilage from the mouse embryonic foregut but also allows for the proper patterning of the developed tracheal cartilage. Furthermore, we show that this culture technique can be applied to culturing other types of cartilage in vertebrae, limbs, and ribs. We believe that this novel application of our in vitro culture system will facilitate the manipulation of cartilage development under various conditions and thus enabling us to advance our current limited knowledge on cartilage biology and development.

Cell and matrix modulation in prenatal and postnatal equine growth cartilage, zones of Ranvier and articular cartilage

PubMed Central

Löfgren, Maria; Ekman, Stina; Svala, Emilia; Lindahl, Anders; Ley, Cecilia; Skiöldebrand, Eva

2014-01-01

Formation of synovial joints includes phenotypic changes of the chondrocytes and the organisation of their extracellular matrix is regulated by different factors and signalling pathways. Increased knowledge of the normal processes involved in joint development may be used to identify similar regulatory mechanisms during pathological conditions in the joint. Samples of the distal radius were collected from prenatal and postnatal equine growth plates, zones of Ranvier and articular cartilage with the aim of identifying Notch signalling components and cells with stem cell-like characteristics and to follow changes in matrix protein localisation during joint development. The localisation of the Notch signalling components Notch1, Delta4, Hes1, Notch dysregulating protein epidermal growth factor-like domain 7 (EGFL7), the stem cell-indicating factor Stro-1 and the matrix molecules cartilage oligomeric matrix protein (COMP), fibromodulin, matrilin-1 and chondroadherin were studied using immunohistochemistry. Spatial changes in protein localisations during cartilage maturation were observed for Notch signalling components and matrix molecules, with increased pericellular localisation indicating new synthesis and involvement of these proteins in the formation of the joint. However, it was not possible to characterise the phenotype of the chondrocytes based on their surrounding matrix during normal chondrogenesis. The zone of Ranvier was identified in all horses and characterised as an area expressing Stro-1, EGFL7 and chondroadherin with an absence of COMP and Notch signalling. Stro-1 was also present in cells close to the perichondrium, in the articular cartilage and in the fetal resting zone, indicating stem cell-like characteristics of these cells. The presence of stem cells in the articular cartilage will be of importance for the repair of damaged cartilage. Perivascular chondrocytes and hypertrophic cells of the cartilage bone interface displayed positive staining for

Cartilage-targeting drug delivery: can electrostatic interactions help?

PubMed

Bajpayee, Ambika G; Grodzinsky, Alan J

2017-03-01

Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.

Exercise-driven metabolic pathways in healthy cartilage.

PubMed

Blazek, A D; Nam, J; Gupta, R; Pradhan, M; Perera, P; Weisleder, N L; Hewett, T E; Chaudhari, A M; Lee, B S; Leblebicioglu, B; Butterfield, T A; Agarwal, S

2016-07-01

Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise. Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights

Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: its significance in cartilage repair and replacement.

PubMed

Freemont, Anthony J; Hoyland, Judith

2006-01-01

Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.

The development of hyaline-cell cartilage in the head of the black molly, Poecilia sphenops. Evidence for secondary cartilage in a teleost.

PubMed Central

Benjamin, M

1989-01-01

The development of hyaline-cell cartilage attached to membrane (dentary, maxilla, nasal, lacrimal and cleithrum) and cartilage (basioccipital) bones has been studied in the viviparous black molly, Poecilia sphenops. Intramembranous ossification commences before the first appearance of hyaline cells. As hyaline-cell cartilage is densely cellular and as that attached to the dentary, maxilla and cleithrum develops from the periosteum of these membrane bones, it must be regarded as secondary cartilage according to current concepts. It is also argued that the hyaline-cell cartilage attached to the perichondral bone of the basioccipital (a cartilage bone), could also be viewed as secondary. The status of the cartilage on the nasal and lacrimal bones is less clear, for it develops, at least in part, from mucochondroid (mucous connective) tissue. This is the first definitive report of secondary cartilage in any lower vertebrate. The tissue is therefore not restricted to birds and mammals as hitherto believed, and a multipotential periosteum must have arisen early in vertebrate evolution. Images Fig. 1 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:2481666

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

Cartilage can be thicker in advanced osteoarthritic knees: a tridimensional quantitative analysis of cartilage thickness at posterior aspect of femoral condyles.

PubMed

Omoumi, Patrick; Babel, Hugo; Jolles, Brigitte M; Favre, Julien

2018-04-16

To test, through tridimensional analysis, whether (1) cartilage thickness at the posterior aspect of femoral condyles differs in knees with medial femorotibial osteoarthritis (OA) compared to non-OA knees; (2) the location of the thickest cartilage at the posterior aspect of femoral condyles differs between OA and non-OA knees. CT arthrograms of knees without radiographic OA (n = 30) and with severe medial femorotibial OA (n = 30) were selected retrospectively from patients over 50 years of age. The groups did not differ in gender, age and femoral size. CT arthrograms were segmented to measure the mean cartilage thickness, the maximal cartilage thickness and its location in a region of interest at the posterior aspect of condyles. For the medial condyle, mean and maximum cartilage thicknesses were statistically significantly higher in OA knees compared to non-OA knees [1.66 vs 1.46 mm (p = 0.03) and 2.56 vs 2.14 mm (p = 0.003), respectively]. The thickest cartilage was located in the half most medial aspect of the posterior medial condyle for both groups, without significant difference between groups. For the lateral condyle, no statistically significant difference between non-OA and OA knees was found (p ≥ 0.17). Cartilage at the posterior aspect of the medial condyle, but not the lateral condyle, is statistically significantly thicker in advanced medial femorotibial OA knees compared to non-OA knees. The thickest cartilage was located in the half most medial aspect of the posterior medial condyle. These results will serve as the basis for future research to determine the histobiological processes involved in this thicker cartilage. Advances in knowledge: This study, through a quantitative tridimensional approach, shows that cartilage at the posterior aspect of the medial condyles is thicker in severe femorotibial osteoarthritic knees compared to non-OA knees. In the posterior aspect of the medial condyle, the thickest cartilage is located in the vicinity

Transcriptional network systems in cartilage development and disease.

PubMed

Nishimura, Riko; Hata, Kenji; Nakamura, Eriko; Murakami, Tomohiko; Takahata, Yoshifumi

2018-04-01

Transcription factors play important roles in the regulation of cartilage development by controlling the expression of chondrogenic genes. Genetic studies have revealed that Sox9/Sox5/Sox6, Runx2/Runx3 and Osterix in particular are essential for the sequential steps of cartilage development. Importantly, these transcription factors form network systems that are also required for appropriate cartilage development. Molecular cloning approaches have largely contributed to the identification of several transcriptional partners for Sox9 and Runx2 during cartilage development. Although the importance of a negative-feedback loop between Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) in chondrocyte hypertrophy has been well established, recent studies indicate that several transcription factors interact with the Ihh-PTHrP loop and demonstrated that Ihh has multiple functions in the regulation of cartilage development. The most common cartilage disorder, osteoarthritis, has been reported to result from the pathological action of several transcription factors, including Runx2, C/EBPβ and HIF-2α. On the other hand, NFAT family members appear to play roles in the protection of cartilage from osteoarthritis. It is also becoming important to understand the homeostasis and regulation of articular chondrocytes, because they have different cellular and molecular features from chondrocytes of the growth plate. This review summarizes the regulation and roles of transcriptional network systems in cartilage development and their pathological roles in osteoarthritis.

Recent advances in hydrogels for cartilage tissue engineering.

PubMed

Vega, S L; Kwon, M Y; Burdick, J A

2017-01-30

Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

From gristle to chondrocyte transplantation: treatment of cartilage injuries

PubMed Central

Lindahl, Anders

2015-01-01

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. PMID:26416680

From gristle to chondrocyte transplantation: treatment of cartilage injuries.

PubMed

Lindahl, Anders

2015-10-19

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. © 2015 The Author(s).

The Application of Sheet Technology in Cartilage Tissue Engineering.

PubMed

Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

2016-04-01

Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions.

An overview of cartilage tissue engineering.

PubMed

Kim, H W; Han, C D

2000-12-01

Articular cartilage regeneration refers to the formation of new tissue that is indistinguishable from the native articular cartilage with respect to zonal organization, biochemical composition, and mechanical properties. Due to a limited capacity to repair cartilage, scar tissue frequently has a poorly organized structure and lacks the functional characteristics of normal cartilage. The degree of success to date achieved using a purely cell- or biological-based approach has been modest. Potentially the development of a hybrid strategy, whereby, chondrocytes or chondrogenic stem cells are combined with a matrix, making cartilage in vitro, which is then subsequently transplanted, offers a route towards a new successful treatment modality. The success of this approach depends upon the material being biocompatible, processable into a suitable three-dimensional structure and eventually biodegradable without harmful effects. In addition, the material should have a sufficient porosity to facilitate high cell loading and tissue ingrowth, and it should be able to support cell proliferation, differentiation, and function. The cell-polymer-bioreactor system provides a basis for studying the structural and functional properties of the cartilaginous matrix during its development, because tissue concentrations of glycosaminoglycan and collagen can be modulated by altering the conditions of tissue cultivation.

Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs.

PubMed

Marlovits, Stefan; Mamisch, Tallal Charles; Vekszler, György; Resinger, Christoph; Trattnig, Siegfried

2008-04-01

Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

PAPAIN-INDUCED CHANGES IN RABBIT CARTILAGE

PubMed Central

Tsaltas, Theodore T.

1958-01-01

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S35 content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S35 in the serum and an increase of S35 and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery. PMID:13575681

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.

Microscopic and histochemical manifestations of hyaline cartilage dynamics.

PubMed

Malinin, G I; Malinin, T I

1999-01-01

Structure and function of hyaline cartilages has been the focus of many correlative studies for over a hundred years. Much of what is known regarding dynamics and function of cartilage constituents has been derived or inferred from biochemical and electron microscopic investigations. Here we show that in conjunction with ultrastructural, and high-magnification transmission light and polarization microscopy, the well-developed histochemical methods are indispensable for the analysis of cartilage dynamics. Microscopically demonstrable aspects of cartilage dynamics include, but are not limited to, formation of the intracellular liquid crystals, phase transitions of the extracellular matrix and tubular connections between chondrocytes. The role of the interchondrocytic liquid crystals is considered in terms of the tensegrity hypothesis and non-apoptotic cell death. Phase transitions of the extracellular matrix are discussed in terms of self-alignment of chondrons, matrix guidance pathways and cartilage growth in the absence of mitosis. The possible role of nonenzymatic glycation reactions in cartilage dynamics is also reviewed.

Mechanical confinement regulates cartilage matrix formation by chondrocytes

NASA Astrophysics Data System (ADS)

Lee, Hong-Pyo; Gu, Luo; Mooney, David J.; Levenston, Marc E.; Chaudhuri, Ovijit

2017-12-01

Cartilage tissue equivalents formed from hydrogels containing chondrocytes could provide a solution for replacing damaged cartilage. Previous approaches have often utilized elastic hydrogels. However, elastic stresses may restrict cartilage matrix formation and alter the chondrocyte phenotype. Here we investigated the use of viscoelastic hydrogels, in which stresses are relaxed over time and which exhibit creep, for three-dimensional (3D) culture of chondrocytes. We found that faster relaxation promoted a striking increase in the volume of interconnected cartilage matrix formed by chondrocytes. In slower relaxing gels, restriction of cell volume expansion by elastic stresses led to increased secretion of IL-1β, which in turn drove strong up-regulation of genes associated with cartilage degradation and cell death. As no cell-adhesion ligands are presented by the hydrogels, these results reveal cell sensing of cell volume confinement as an adhesion-independent mechanism of mechanotransduction in 3D culture, and highlight stress relaxation as a key design parameter for cartilage tissue engineering.

Co-culture systems-based strategies for articular cartilage tissue engineering.

PubMed

Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

2018-03-01

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

Deformational behaviour of knee cartilage and changes in serum cartilage oligomeric matrix protein (COMP) after running and drop landing.

PubMed

Niehoff, A; Müller, M; Brüggemann, L; Savage, T; Zaucke, F; Eckstein, F; Müller-Lung, U; Brüggemann, G-P

2011-08-01

To investigate (1) the effect of running and drop landing interventions on knee cartilage deformation and serum cartilage oligomeric matrix protein (COMP) concentration and (2) if the changes in cartilage volume correlate with the changes in serum COMP level. Knee joint cartilage volume and thickness were determined using magnetic resonance imaging (MRI) as well as COMP concentration from serum samples before and after in vivo loading of 14 healthy adults (seven male and seven female). Participants performed different loading interventions of 30 min duration on three different days: (1) 100 vertical drop landings from a 73 cm high platform, (2) running at a velocity of 2.2m/s (3.96 km), and (3) resting on a chair. Blood samples were taken immediately before, immediately after and 0.5h, 1h, 2h and 3h post intervention. Pre- and post-loading coronal and axial gradient echo MR images with fat suppression were used to determine the patellar, tibial and femoral cartilage deformation. Serum COMP levels increased immediately after the running (+30.7%, pre: 7.3U/l, 95% confidence interval (CI): 5.6, 8.9, post: 9.1U/l, 95% CI: 7.2, 11.0, P=0.001) and after drop landing intervention (+32.3%, pre: 6.8U/l, 95% CI: 5.3, 8.4; post: 8.9U/l, 95% CI: 6.8, 10.9, P=0.001). Cartilage deformation was more pronounced after running compared to drop landing intervention, with being significant (volume: P=0.002 and thickness: P=0.001) only in the lateral tibia. We found a significant correlation (r(2)=0.599, P=0.001) between changes in serum COMP (%) and in cartilage volume (%) after the drop landing intervention, but not after running. In vivo exercise interventions differentially regulate serum COMP concentrations and knee cartilage deformations. The relation between changes in COMP and in cartilage volume seems to depend on both mechanical and biochemical factors. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Assessing the effect of football play on knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

PubMed

Wei, Wenbo; Lambach, Becky; Jia, Guang; Flanigan, David; Chaudhari, Ajit M W; Wei, Lai; Rogers, Alan; Payne, Jason; Siston, Robert A; Knopp, Michael V

2017-06-01

The prevalence of cartilage lesions is much higher in football athletes than in the general population. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been shown to quantify regional variations of glycosaminoglycan (GAG) concentrations which is an indicator of early cartilage degeneration. The goal of this study is to determine whether dGEMRIC can be used to assess the influence in cartilage GAG concentration due to college level football play. Thirteen collegiate football players with one to four years of collegiate football play experience were recruited and both knee joints were scanned using a dedicated 8-channel phased array knee coil on a 3T MRI system. The contrast concentrations within cartilage were calculated based on the T 1 values from dGEMRIC scans. No substantial differences were found in the contrast concentrations between the pre- and post-season across all the cartilage compartments. One year collegiate football players presented an average contrast concentration at the pre-season of 0.116±0.011mM and post-season of 0.116±0.011mM. In players with multiple years of football play, contrast uptake was elevated to 0.141±0.012mM at the pre-season and 0.139±0.012mM at the post-season. The pre-season 0.023±0.016mM and post-season 0.025±0.016mM increase in contrast concentration within the group with multiple years of experience presented with a >20% increase in contrast uptake. This may indicate the gradual, cumulative damage of football play to the articular cartilage over years, even though the effect may not be noticeable after a season of play. Playing collegiate football for a longer period of time may lead to cartilage microstructural alterations, which may be linked to early knee cartilage degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Injectable hydrogels for cartilage and bone tissue engineering

PubMed Central

Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

2017-01-01

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

Tracheal reconstruction with a composite graft: fascial flap-wrapped allogenic aorta with external cartilage-ring support

PubMed Central

Wurtz, Alain; Hysi, Ilir; Kipnis, Eric; Zawadzki, Christophe; Hubert, Thomas; Jashari, Ramadan; Copin, Marie-Christine; Jude, Brigitte

2013-01-01

OBJECTIVES Animal and clinical studies have demonstrated the feasibility of tracheal replacement by silicone-stented allogenic aortas. In clinical trials, however, this graft did not show mature cartilage regeneration into the grafts as was observed in animal models. To solve this issue, we investigated tracheal replacement with a composite graft based on a fascial flap-wrapped allogenic aorta with external cartilage-ring support in a rabbit model. METHODS Seven male 'Géant des Flandres' and 'New Zealand' rabbits served as donors of aortas and cartilage rings, respectively. Nineteen female 'New Zealand' rabbits were used as recipients. First, in nine animals, neoangiogenesis of the composite graft following a wrap using a pedicled lateral thoracic fascial flap and implantation under the skin of the chest wall was investigated. Animal sacrifice was scheduled at regular intervals up to 38 days. Second, 10 animals underwent tracheal replacement with the composite graft after a 7-to-9 day revascularization period, and were followed-up to death. Macroscopic and microscopic examinations were used to study the morphology, stiffness and viability of the construct. RESULTS There was one operative death after tracheal replacement. The first group of animals was found to have a satisfactory tubular morphology and stiffness of their construct associated with preserved histological structure of cartilages and moderate to severe aortic ischaemic lesions. In the group of rabbits having undergone tracheal replacement, the anatomical results were characterized by a discrepancy between the severity of ischaemic lesions involving both allogenic aorta and cartilage rings and the satisfactory biomechanical characteristics of the graft in 7 of 10 animals, probably due to cartilage calcification deposits associated with inflammatory scar tissue ensuring the stiffness of the construct. CONCLUSIONS Our investigations demonstrate the feasibility of the replacement of circumferential

Bioengineered porous composite curcumin/silk scaffolds for cartilage regeneration.

PubMed

Kim, Do Kyung; In Kim, Jeong; Sim, Bo Ra; Khang, Gilson

2017-09-01

Articular cartilage repair is a challenge due to its limited self-repair capacity. Cartilage tissue engineering supports to overcome following injuries or degenerative diseases. Herein, we fabricated the scaffold composed of curcumin and silk fibroin as an appropriate clinical replacement for defected cartilage. The scaffolds were designed to have adequate pore size and mechanical strength for cartilage repair. Cell proliferation, sulfated glycosaminoglycan (sGAG) content and mRNA expression analysis indicated that chondrocytes remained viable and showed its growth ability in the curcumin/silk scaffolds. Especially, in 1mg/ml curcumin/silk scaffold showed higher cell viability rate and extracellular matrix formation than other experimental groups. Furthermore, curcumin/silk scaffold showed its biocompatibility and favorable environment for cartilage repair after transplantation in vivo, as indicated in histological examination results. Overall, the functional composite curcumin/silk scaffold can be applied in cartilage tissue engineering and promising substrate for cartilage repair. Copyright © 2017. Published by Elsevier B.V.

Association of baseline knee bone size, cartilage volume, and body mass index with knee cartilage loss over time: a longitudinal study in younger or middle-aged adults.

PubMed

Antony, Benny; Ding, Changhai; Stannus, Oliver; Cicuttini, Flavia; Jones, Graeme

2011-09-01

To determine the association of knee bone size, cartilage volume, and body mass index (BMI) at baseline with knee cartilage loss over 2 years in younger or middle-aged adults. A total of 324 subjects (mean age 45 yrs, range 26-61) were measured at baseline and about 2 years later. Knee cartilage volume and bone size were determined using T1-weighted fat-saturated magnetic resonance imaging. In multivariable analysis, baseline knee bone size was negatively associated with annual change in knee cartilage volume at medial and lateral tibial sites (ß = -0.62% to -0.47%/cm(2), all p < 0.001). The associations disappeared at medial tibial site after adjustment for baseline cartilage volume and became of borderline statistical significance at lateral tibial site after adjustment for both baseline cartilage volume and osteophytes (ß = -0.29, p = 0.059). Baseline knee cartilage volume was consistently and negatively associated with annual change in knee cartilage volume at all 3 medial tibial, lateral tibial, and patellar sites (ß = -4.41% to -1.37%/ml, all p < 0.001). Baseline BMI was negatively associated with an annual change in knee cartilage volume, but only in subjects within the upper tertile of baseline cartilage volume, even after adjusting for cartilage defects (ß = -0.16% to -0.34%/kg/m(2), all p < 0.05). Our study suggests that both higher baseline tibial bone area and knee cartilage volume (most likely due to cartilage swelling) are associated with greater knee cartilage loss over 2 years. A higher BMI was associated with greater knee cartilage loss only in subjects with higher baseline cartilage volume.

Resection of costal exostosis using piezosurgery associated with uniportal video-assisted thoracoscopy.

PubMed

Santini, Mario; Fiorelli, Alfonso; Santagata, Mario; Tartaro, Gian Paolo

2015-03-01

We report a case of a 35-year-old woman affected by costal exostosis, originating from the posterior arc of the left fifth rib, who complained of a persistent intractable neuralgia in the left T5 dermatome. Both pain and the risk of visceral injury led us to resect exostosis. The procedure was performed using a uniportal videothoracoscopic approach without additional incisions. For bone resection, we used Piezosurgery, a soft tissue-sparing system based on ultrasound vibrations. Piezosurgery allowed the complete resection of exostosis without injuring the intercostal nerve and vessels. The histologic analysis confirmed the diagnosis of osteochondroma and showed no sign of malignancy. The patient was discharged 2 days after the operation. Considering the lack of symptoms, the low risk of degeneration, and the absence of recurrence at 12-month follow-up, the simple resection of exostosis without performing a more extensive rib resection was judged to be optimal. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

THE REMOVAL OF CARTILAGE MATRIX, IN VIVO, BY PAPAIN

PubMed Central

McCluskey, Robert T.; Thomas, Lewis

1958-01-01

The intravenous injection of crystalline papain into young rabbits results in depletion of cartilage matrix throughout the body, with loss of rigidity and collapse of the ears, provided the enzyme is inactivated by oxidation or sulfhydryl blocking agents prior to administration. Cysteine-activated crystalline papain, when injected intravenously, produces little or no change in cartilage. The changes which occur in cartilage following an injection of inactivated crystalline papain are indistinguishable from those produced by crude papain. Activation of crude papain by cysteine prior to injection results in loss of its capacity to produce in vivo changes in cartilage. The progressive changes which take place in cartilage in vivo also occur in vitro in isolated rabbit ears removed shortly after an injection of crude papain or inactivated crystalline papain. In vitro ear collapse occurs rapidly at 37°C. and does not occur at 4°C. Collapse is enhanced by exposing the cartilage to cysteine and prevented by exposure to iodoacetamide or p-chloromercuribenzoate. The direct action of crystalline papain on plates of normal cartilage, in vitro, results in the same gross and histological changes which were observed in vivo. The direct action is accelerated by cysteine and inhibited by iodoacetamide or p-chloromercuribenzoate. The intravenous injection of iodoacetamide-treated bromelin produces the same in vivo changes in cartilage as papain. Untreated bromelin has no demonstrable effect on cartilage. It is suggested that the reason for the failure of activated papain to enter cartilage, after being injected intravenously, is that it probably reacts with a substrate or substrates in the blood. Oxidized or otherwise inactivated papain, in contrast, is readily taken up by cartilage and there converted to its active form. PMID:13575673

Treatment of Articular Cartilage Defects in the Goat with Frozen Versus Fresh Osteochondral Allografts: Effects on Cartilage Stiffness, Zonal Composition, and Structure at Six Months

PubMed Central

Pallante, Andrea L.; Görtz, Simon; Chen, Albert C.; Healey, Robert M.; Chase, Derek C.; Ball, Scott T.; Amiel, David; Sah, Robert L.; Bugbee, William D.

2012-01-01

Background: Understanding the effectiveness of frozen as compared with fresh osteochondral allografts at six months after surgery and the resultant consequences of traditional freezing may facilitate in vivo maintenance of cartilage integrity. Our hypothesis was that the state of the allograft at implantation affects its performance after six months in vivo. Methods: The effect of frozen as compared with fresh storage on in vivo allograft performance was determined for osteochondral allografts that were transplanted into seven recipient goats and analyzed at six months. Allograft performance was assessed by examining osteochondral structure (cartilage thickness, fill, surface location, surface degeneration, and bone-cartilage interface location), zonal cartilage composition (cellularity, matrix content), and cartilage biomechanical function (stiffness). Relationships between cartilage stiffness or cartilage composition and surface degeneration were assessed with use of linear regression. Results: Fresh allografts maintained cartilage load-bearing function, while also maintaining zonal organization of cartilage cellularity and matrix content, compared with frozen allografts. Overall, allograft performance was similar between fresh allografts and nonoperative controls. However, cartilage stiffness was approximately 80% lower (95% confidence interval [CI], 73% to 87%) in the frozen allografts than in the nonoperative controls or fresh allografts. Concomitantly, in frozen allografts, matrix content and cellularity were approximately 55% (95% CI, 22% to 92%) and approximately 96% (95% CI, 94% to 99%) lower, respectively, than those in the nonoperative controls and fresh allografts. Cartilage stiffness correlated positively with cartilage cellularity and matrix content, and negatively with surface degeneration. Conclusions: Maintenance of cartilage load-bearing function in allografts is associated with zonal maintenance of cartilage cellularity and matrix content. In

Critical temperature transitions in laser-mediated cartilage reshaping

NASA Astrophysics Data System (ADS)

Wong, Brian J.; Milner, Thomas E.; Kim, Hong H.; Telenkov, Sergey A.; Chew, Clifford; Kuo, Timothy C.; Smithies, Derek J.; Sobol, Emil N.; Nelson, J. Stuart

1998-07-01

In this study, we attempted to determine the critical temperature [Tc] at which accelerated stress relaxation occurred during laser mediated cartilage reshaping. During laser irradiation, mechanically deformed cartilage tissue undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. When a critical temperature is attained, cartilage becomes malleable and may be molded into complex new shapes that harden as the tissue cools. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures such as the ear, larynx, trachea, and nose. The principal advantages of using laser radiation for the generation of thermal energy in tissue are precise control of both the space-time temperature distribution and time- dependent thermal denaturation kinetics. Optimization of the reshaping process requires identification of the temperature dependence of this phase transformation and its relationship to observed changes in cartilage optical, mechanical, and thermodynamic properties. Light scattering, infrared radiometry, and modulated differential scanning calorimetry (MDSC) were used to measure temperature dependent changes in the biophysical properties of cartilage tissue during fast (laser mediated) and slow (conventional calorimetric) heating. Our studies using MDSC and laser probe techniques have identified changes in cartilage thermodynamic and optical properties suggestive of a phase transformation occurring near 60 degrees Celsius.

The mechanobiology of articular cartilage development and degeneration.

PubMed

Carter, Dennis R; Beaupré, Gary S; Wong, Marcy; Smith, R Lane; Andriacchi, Tom P; Schurman, David J

2004-10-01

The development, maintenance, and destruction of cartilage are regulated by mechanical factors throughout life. Mechanical cues in the cartilage fetal endoskeleton influence the expression of genes that guide the processes of growth, vascular invasion, and ossification. Intermittent fluid pressure maintains the cartilage phenotype whereas mild tension (or shear) promotes growth and ossification. The articular cartilage thickness is determined by the position at which the subchondral growth front stabilizes. In mature joints, cartilage is thickest and healthiest where the contact pressure and cartilage fluid pressure are greatest. The depth-dependent histomorphology reflects the local fluid pressure, tensile strain, and fluid exudation. Osteoarthritis represents the final demise and loss of cartilage in the skeletal elements. The initiation and progression of osteoarthritis can follow many pathways and can be promoted by mechanical factors including: (1) reduced loading, which activates the subchondral growth front by reducing fluid pressure; (2) blunt impact, causing microdamage and activation of the subchondral growth front by local shear stress; (3) mechanical abnormalities that increase wear at the articulating surface; and (4) other mechanically related factors. Research should be directed at integrating our mechanical understanding of osteoarthritis pathogenesis and progression within the framework of cellular and molecular events throughout ontogeny.

The effect of fixed charge density and cartilage swelling on mechanics of knee joint cartilage during simulated gait.

PubMed

Räsänen, Lasse P; Tanska, Petri; Zbýň, Štefan; van Donkelaar, Corrinus C; Trattnig, Siegfried; Nieminen, Miika T; Korhonen, Rami K

2017-08-16

The effect of swelling of articular cartilage, caused by the fixed charge density (FCD) of proteoglycans, has not been demonstrated on knee joint mechanics during simulated walking before. In this study, the influence of the depth-wise variation of FCD was investigated on the internal collagen fibril strains and the mechanical response of the knee joint cartilage during gait using finite element (FE) analysis. The FCD distribution of tibial cartilage was implemented from sodium ( 23 Na) MRI into a 3-D FE-model of the knee joint ("Healthy model"). For comparison, models with decreased FCD values were created according to the decrease in FCD associated with the progression of osteoarthritis (OA) ("Early OA" and "Advanced OA" models). In addition, a model without FCD was created ("No FCD" model). The effect of FCD was studied with five different collagen fibril network moduli of cartilage. Using the reference fibril network moduli, the decrease in FCD from "Healthy model" to "Early OA" and "Advanced OA" models resulted in increased axial strains (by +2 and +6%) and decreased fibril strains (by -3 and -13%) throughout the stance, respectively, calculated as mean values through cartilage depth in the tibiofemoral contact regions. Correspondingly, compared to the "Healthy model", the removal of the FCD altogether in "NoFCD model" resulted in increased mean axial strains by +16% and decreased mean fibril strains by -24%. This effect was amplified as the fibril network moduli were decreased by 80% from the reference. Then mean axial strains increased by +6, +19 and +49% and mean fibril strains decreased by -9, -20 and -32%, respectively. Our results suggest that the FCD in articular cartilage has influence on cartilage responses in the knee during walking. Furthermore, the FCD is suggested to have larger impact on cartilage function as the collagen network degenerates e.g. in OA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Particulated articular cartilage: CAIS and DeNovo NT.

PubMed

Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

2012-03-01

Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

Injectable tissue-engineered cartilage using commercially available fibrin glue.

PubMed

Cakmak, Ozcan; Babakurban, Seda T; Akkuzu, Hatice G; Bilgi, Selcuk; Ovalı, Ercüment; Kongur, Merve; Altintas, Hande; Yilmaz, Bayram; Bilezikçi, Banu; Celik, Zerrin Y; Yakicier, Mustafa C; Sahin, Feride I

2013-12-01

To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration. Animal research. A total of 28 immunocompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis. The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference. We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

PubMed

Honkanen, Juuso T J; Turunen, Mikael J; Freedman, Jonathan D; Saarakkala, Simo; Grinstaff, Mark W; Ylärinne, Janne H; Jurvelin, Jukka S; Töyräs, Juha

2016-10-01

Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

Correction of cleft lip nose deformity with rib cartilage.

PubMed

Hafezi, Farhad; Naghibzadeh, Bijan; Ashtiani, Abbas Kazemi; Mousavi, S Jaber; Nouhi, Amir Hossein; Naghibzadeh, Ghazal

2013-07-01

Correction of cleft lip nasal deformities (CLND) is often unsatisfactory because of problems resulting from cartilage weakness and strong soft tissue forces. Therefore, strong cartilaginous support, such as rib cartilage, is mandatory. The authors describe placement of rib cartilage grafts to create a more symmetric and aesthetically acceptable repair of CLND with improved nasal air flow. Two groups of patients, including those with unilateral and bilateral CLND, underwent operations with different sources of autologous cartilage. Group 1 received grafts from the septum and ear, whereas group 2 received grafts from the septum and ribs. Results were evaluated by 2 independent physicians who rated improvement between pre- and postoperative photographs. There were significant differences in postoperative improvement between patients who received septal/ear cartilage grafts and those who received septal/rib cartilage grafts in both unilateral and bilateral cases (P = .028 and P = .043, respectively). The authors' results demonstrate that rib cartilage has a positive effect on the aesthetic outcome of CLND operations and provides a strong support structure for correcting this deformity with minimal postoperative complications.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Animal models used for testing hydrogels in cartilage regeneration.

PubMed

Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

2018-05-14

Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tissue engineering strategies to study cartilage development, degeneration and regeneration.

PubMed

Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

2015-04-01

Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm. Copyright © 2014 Elsevier B.V. All rights reserved.

Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation.

PubMed

Tan, C F; Ng, K K; Ng, S H; Cheung, Y C

2003-12-01

The purpose of this study was to investigate the regenerative potential of hyaline cartilage in a neocartilage graft implant with the aid of MR cartilage imaging using a rabbit model. Surgical osteochondral defects were created in the femoral condyles of 30 mature New Zealand rabbits. The findings of neocartilage in autologous cartilage grafts packed into osteochondral defects were compared with control group of no implant to the osteochondral defect. The outcome of the implantations was correlated with histologic and MR cartilage imaging findings over a 3-month interval. Neocartilage grafts packed into osteochondral defects showed regeneration of hyaline cartilage at the outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage developed at the outer layer of the autologous cartilage graft together with an inflammatory reaction within the osteochondral defect. This animal study provides evidence of the regenerative ability of hyaline cartilage in neocartilage transplants to repair articular cartilage.

Automatic knee cartilage delineation using inheritable segmentation

NASA Astrophysics Data System (ADS)

Dries, Sebastian P. M.; Pekar, Vladimir; Bystrov, Daniel; Heese, Harald S.; Blaffert, Thomas; Bos, Clemens; van Muiswinkel, Arianne M. C.

2008-03-01

We present a fully automatic method for segmentation of knee joint cartilage from fat suppressed MRI. The method first applies 3-D model-based segmentation technology, which allows to reliably segment the femur, patella, and tibia by iterative adaptation of the model according to image gradients. Thin plate spline interpolation is used in the next step to position deformable cartilage models for each of the three bones with reference to the segmented bone models. After initialization, the cartilage models are fine adjusted by automatic iterative adaptation to image data based on gray value gradients. The method has been validated on a collection of 8 (3 left, 5 right) fat suppressed datasets and demonstrated the sensitivity of 83+/-6% compared to manual segmentation on a per voxel basis as primary endpoint. Gross cartilage volume measurement yielded an average error of 9+/-7% as secondary endpoint. For cartilage being a thin structure, already small deviations in distance result in large errors on a per voxel basis, rendering the primary endpoint a hard criterion.

Can Glucosamine Supplements Protect My Knee Cartilage from Osteoarthritis?

MedlinePlus

... Can glucosamine supplements protect my knee cartilage from osteoarthritis? Answers from Brent A. Bauer, M.D. Study results on this question have ... build cartilage. The most common type of arthritis, osteoarthritis wears away the slick cartilage that covers the ...

Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage

PubMed Central

Beddoes, Charlotte M.; Whitehouse, Michael R.; Briscoe, Wuge H.; Su, Bo

2016-01-01

Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour. PMID:28773566

Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage.

PubMed

Beddoes, Charlotte M; Whitehouse, Michael R; Briscoe, Wuge H; Su, Bo

2016-06-03

Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

PubMed

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

Chondroptosis in Alkaptonuric Cartilage

PubMed Central

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

2015-01-01

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. J. Cell. Physiol. 230: 1148–1157, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25336110

Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

PubMed

Jeong, Da-Un; Choi, Je-Yong; Kim, Dae-Won

2017-01-01

Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

In-vivo study and histological examination of laser reshaping of cartilage

NASA Astrophysics Data System (ADS)

Sviridov, Alexander P.; Sobol, Emil N.; Bagratashvili, Victor N.; Omelchenko, Alexander I.; Ovchinnikov, Yuriy M.; Shekhter, Anatoliy B.; Svistushkin, Valeriy M.; Shinaev, Andrei A.; Nikiforova, G.; Jones, Nicholas

1999-06-01

The results of recent study of cartilage reshaping in vivo are reported. The ear cartilage of piglets of 8-12 weeks old have been reshaped in vivo using the radiation of a holmium laser. The stability of the shape and possible side effects have been examined during four months. Histological investigation shown that the healing of irradiated are could accompany by the regeneration of ear cartilage. Finally, elastic type cartilage has been transformed into fibrous cartilage or cartilage of hyaline type.

T1ρ Dispersion in Articular Cartilage

PubMed Central

Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

2015-01-01

Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

An energetic orphan in an endocrine tissue: a revised perspective of the function of estrogen receptor-related receptor alpha in bone and cartilage.

PubMed

Bonnelye, Edith; Aubin, Jane E

2013-02-01

Estrogen receptor-related receptor alpha (ERRα) is an orphan nuclear receptor with sequence homology to the estrogen receptors, ERα/β, but it does not bind estrogen. ERRα not only plays a functional role in osteoblasts but also in osteoclasts and chondrocytes. In addition, the ERRs, including ERRα, can be activated by coactivators such as peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC1α and β) and are implicated in adipogenesis, fatty acid oxidation, and oxidative stress defense, suggesting that ERRα-through its activity in bone resorption and adipogenesis--may regulate the insulin and leptin pathways and contribute to aging-related changes in bone and cartilage. In this review, we discuss data on ERRα and its cellular and molecular modes of action, which have broad implications for considering the potential role of this orphan receptor in cartilage and bone endocrine function, on whole-organism physiology, and in the bone aging process. Copyright © 2013 American Society for Bone and Mineral Research.

Changing partners: moving from non-homologous to homologous centromere pairing in meiosis

PubMed Central

Stewart, Mara N.; Dawson, Dean S.

2010-01-01

Reports of centromere pairing in early meiotic cells have appeared sporadically over the past thirty years. Recent experiments demonstrate that early centromere pairing occurs between non-homologous centromeres. As meiosis proceeds, centromeres change partners, becoming arranged in homologous pairs. Investigations of these later centromere pairs indicate that paired homologous centromeres are actively associated rather than positioned passively, side-by-side. Meiotic centromere pairing has been observed in organisms as diverse as mice, wheat and yeast, indicating that non-homologous centromere pairing in early meiosis and active homologous centromere pairing in later meiosis might be themes in meiotic chromosome behavior. Moreover, such pairing could have previously unrecognized roles in mediating chromosome organization or architecture that impact meiotic segregation fidelity. PMID:18804891

Mandibular angle augmentation with the use of distraction and homologous lyophilized cartilage in a case of morphing to Michael Jackson surgery.

PubMed

Mommaerts, M Y; Abeloos, J S; Gropp, H

2001-08-01

Correction of an ill-defined mandibular angle is not an easy task, whether it is requested by the "congenital, orthognathic or cosmetic" patient. Deliberate over-correction has not been reported to our knowledge. This article presents a combination of distraction osteogenesis and lyophilized cartilage used to three-dimensionally over-augment the mandibular angle of a long-face prognathic patient who had the wish to be morphed to Michael Jackson or at least as far as current technique and his endogenic features allowed.

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

PubMed

Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automatic atlas-based three-label cartilage segmentation from MR knee images

PubMed Central

Shan, Liang; Zach, Christopher; Charles, Cecil; Niethammer, Marc

2016-01-01

Osteoarthritis (OA) is the most common form of joint disease and often characterized by cartilage changes. Accurate quantitative methods are needed to rapidly screen large image databases to assess changes in cartilage morphology. We therefore propose a new automatic atlas-based cartilage segmentation method for future automatic OA studies. Atlas-based segmentation methods have been demonstrated to be robust and accurate in brain imaging and therefore also hold high promise to allow for reliable and high-quality segmentations of cartilage. Nevertheless, atlas-based methods have not been well explored for cartilage segmentation. A particular challenge is the thinness of cartilage, its relatively small volume in comparison to surrounding tissue and the difficulty to locate cartilage interfaces – for example the interface between femoral and tibial cartilage. This paper focuses on the segmentation of femoral and tibial cartilage, proposing a multi-atlas segmentation strategy with non-local patch-based label fusion which can robustly identify candidate regions of cartilage. This method is combined with a novel three-label segmentation method which guarantees the spatial separation of femoral and tibial cartilage, and ensures spatial regularity while preserving the thin cartilage shape through anisotropic regularization. Our segmentation energy is convex and therefore guarantees globally optimal solutions. We perform an extensive validation of the proposed method on 706 images of the Pfizer Longitudinal Study. Our validation includes comparisons of different atlas segmentation strategies, different local classifiers, and different types of regularizers. To compare to other cartilage segmentation approaches we validate based on the 50 images of the SKI10 dataset. PMID:25128683

Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

PubMed

Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

2017-10-01

Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

On mechanical mechanism of damage evolution in articular cartilage.

PubMed

Men, Yu-Tao; Jiang, Yan-Long; Chen, Ling; Zhang, Chun-Qiu; Ye, Jin-Duo

2017-09-01

Superficial lesions of cartilage are the direct indication of osteoarthritis. To investigate the mechanical mechanism of cartilage with micro-defect under external loading, a new plain strain numerical model with micro-defect was proposed and damage evolution progression in cartilage over time has been simulated, the parameter were studied including load style, velocity of load and degree of damage. The new model consists of the hierarchical structure of cartilage and depth-dependent arched fibers. The numerical results have shown that not only damage of the cartilage altered the distribution of the stress but also matrix and fiber had distinct roles in affecting cartilage damage, and damage in either matrix or fiber could promote each other. It has been found that the superficial cracks in cartilage spread preferentially along the tangent direction of the fibers. It is the arched distribution form of fibers that affects the crack spread of cartilage, which has been verified by experiment. During the process of damage evolution, its extension direction and velocity varied constantly with the damage degree. The rolling load could cause larger stress and strain than sliding load. Strain values of the matrix initially increased and then decreased gradually with the increase of velocity, and velocity had a greater effect on matrix than fibers. Damage increased steadily before reaching 50%, sharply within 50 to 85%, and smoothly and slowly after 85%. The finding of the paper may help to understand the mechanical mechanism why the cracks in cartilage spread preferentially along the tangent direction of the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

PubMed

Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

2016-07-01

To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P < .05, compared with preoperative evaluation) at short-term follow-up. Furthermore, magnetic resonance imaging showed that 76% cases in all included case series showed at least 75% defect coverage in each lesion, and 3 studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. Level IV, systematic review of Level II and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.

PubMed

Wiener, E; Hodler, J; Pfirrmann, C W A

2009-01-01

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.

Magneto-therapy of human joint cartilage.

PubMed

Wierzcholski, Krzysztof; Miszczak, Andrzej

2017-01-01

The topic of the present paper concerns the human joint cartilage therapy performed by the magnetic induction field. There is proved the thesis that the applied magnetic field for concrete cartilage illness should depend on the proper relative and concrete values of applied magnetic induction, intensity as well the time of treatment duration. Additionally, very important are frequencies and amplitudes of magnetic field as well as magnetic permeability of the synovial fluid. The research methods used in this paper include: magnetic induction field produced by a new Polish and German magneto electronic devices for the therapy of human joint cartilage diseases, stationary and movable magnetic applicators, magnetic bandage, ferrofluid injections, author's experience gained in Germany research institutes and practical results after measurements and information from patients. The results of this paper concern concrete parameters of time dependent electro-magnetic field administration during the joint cartilage therapy duration and additionally concern the corollaries which are implied from reading values gained on the magnetic induction devices. The main conclusions obtained in this paper are as follows: Time dependent magnetic induction field increases the dynamic viscosity of movable synovial fluid and decreases symptoms of cartilage illness for concrete intensity of magnetic field and concrete field line architecture. The ferrofluid therapy and phospholipids bilayer simultaneously with the administrated external electromagnetic field, increases the dynamic viscosity of movable synovial fluid.

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

Ex vivo culture platform for assessment of cartilage repair treatment strategies.

PubMed

Schwab, Andrea; Meeuwsen, Annick; Ehlicke, Franziska; Hansmann, Jan; Mulder, Lars; Smits, Anthal; Walles, Heike; Kock, Linda

2017-01-01

There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we evaluated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, matrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivo testing.

Development of a computational technique to measure cartilage contact area.

PubMed

Willing, Ryan; Lapner, Michael; Lalone, Emily A; King, Graham J W; Johnson, James A

2014-03-21

Computational measurement of joint contact distributions offers the benefit of non-invasive measurements of joint contact without the use of interpositional sensors or casting materials. This paper describes a technique for indirectly measuring joint contact based on overlapping of articular cartilage computer models derived from CT images and positioned using in vitro motion capture data. The accuracy of this technique when using the physiological nonuniform cartilage thickness distribution, or simplified uniform cartilage thickness distributions, is quantified through comparison with direct measurements of contact area made using a casting technique. The efficacy of using indirect contact measurement techniques for measuring the changes in contact area resulting from hemiarthroplasty at the elbow is also quantified. Using the physiological nonuniform cartilage thickness distribution reliably measured contact area (ICC=0.727), but not better than the assumed bone specific uniform cartilage thicknesses (ICC=0.673). When a contact pattern agreement score (s(agree)) was used to assess the accuracy of cartilage contact measurements made using physiological nonuniform or simplified uniform cartilage thickness distributions in terms of size, shape and location, their accuracies were not significantly different (p>0.05). The results of this study demonstrate that cartilage contact can be measured indirectly based on the overlapping of cartilage contact models. However, the results also suggest that in some situations, inter-bone distance measurement and an assumed cartilage thickness may suffice for predicting joint contact patterns. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

PubMed

Franke, O; Durst, K; Maier, V; Göken, M; Birkholz, T; Schneider, H; Hennig, F; Gelse, K

2007-11-01

Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies.

Autofluorescence lifetime metrology for label-free detection of cartilage matrix degradation

NASA Astrophysics Data System (ADS)

Nickdel, Mohammad B.; Lagarto, João. L.; Kelly, Douglas J.; Manning, Hugh B.; Yamamoto, Kazuhiro; Talbot, Clifford B.; Dunsby, Christopher; French, Paul; Itoh, Yoshifumi

2014-03-01

Degradation of articular cartilage extracellular matrix (ECM) by proteolytic enzyme is the hallmark of arthritis that leads to joint destruction. Detection of early biochemical changes in cartilage before irreversible structural damages become apparent is highly desirable. Here we report that the autofluorescence decay profile of cartilage is significantly affected by proteolytic degradation of cartilage ECM and can be characterised by measurements of the autofluorescence lifetime (AFL). A multidimensional fluorometer utilizing ultraviolet excitation at 355 nm or 375 nm coupled to a fibreoptic probe was developed for single point time-resolved AFL measurements of porcine articular cartilage explants treated with different proteinases. Degradation of cartilage matrix components by treating with bacterial collagenase, matrix metalloproteinase 1, or trypsin resulted in significant reduction of AFL of the cartilage in both a dose and time dependent manner. Differences in cartilage AFL were also confirmed by fluorescence lifetime imaging microscopy (FLIM). Our data suggest that AFL of cartilage tissue is a potential non-invasive readout to monitor cartilage matrix integrity that may be utilized for diagnosis of arthritis as well as monitoring the efficacy of anti-arthritic therapeutic agents.

Automatic segmentation of the glenohumeral cartilages from magnetic resonance images.

PubMed

Neubert, A; Yang, Z; Engstrom, C; Xia, Y; Strudwick, M W; Chandra, S S; Fripp, J; Crozier, S

2016-10-01

Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone-cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head and glenoid fossa, respectively

Update on mesenchymal stem cell therapies for cartilage disorders

PubMed Central

Paschos, Nikolaos K; Sennett, Mackenzie L

2017-01-01

Cartilage disorders, including focal cartilage lesions, are among the most common clinical problems in orthopedic practice. Left untreated, large focal lesions may result in progression to osteoarthritis, with tremendous impact on the quality of life of affected individuals. Current management strategies have shown only a modest degree of success, while several upcoming interventions signify better outcomes in the future. Among these, stem cell therapies have been suggested as a promising new era for cartilage disorders. Certain characteristics of the stem cells, such as their potential to differentiate but also to support healing made them a fruitful candidate for lesions in cartilage, a tissue with poor healing capacity. The aim of this editorial is to provide an update on the recent advancements in the field of stem cell therapy for the management of focal cartilage defects. Our goal is to present recent basic science advances and to present the potential of the use of stem cells in novel clinical interventions towards enhancement of the treatment armamentarium for cartilage lesions. Furthermore, we highlight some thoughts for the future of cartilage regeneration and repair and to explore future perspectives for the next steps in the field. PMID:29312843

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.

Prestructural cartilage assessment using MRI.

PubMed

Link, Thomas M; Neumann, Jan; Li, Xiaojuan

2017-04-01

Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware. 5 J. Magn. Reson. Imaging 2017;45:949-965. © 2016 International Society for Magnetic Resonance in Medicine.

Nanoparticles for diagnostics and laser medical treatment of cartilage in orthopaedics

NASA Astrophysics Data System (ADS)

Baum, O. I.; Soshnikova, Yu. M.; Omelchenko, A. I.; Sobol, Emil

2013-02-01

Laser reconstruction of intervertebral disc (LRD) is a new technique which uses local, non-destructive laser irradiation for the controlled activation of regenerative processes in a targeted zone of damaged disc cartilage. Despite pronounced advancements of LRD, existing treatments may be substantially improved if laser radiation is absorbed near diseased and/or damaged regions in cartilage so that required thermomechanical stress and strain at chondrocytes may be generated and non-specific injury reduced or eliminated. The aims of the work are to study possibility to use nanoparticles (NPs) to provide spatial specificity for laser regeneration of cartilage. Two types of porcine joint cartilage have been impregnated with magnetite NPs: 1) fresh cartilage; 2) mechanically damaged cartilage. NPs distribution was studied using transition electron microscopy, dynamic light scattering and analytical ultracentrifugation techniques. Laser radiation and magnetic field have been applied to accelerate NPs impregnation. It was shown that NPs penetrate by diffusion into the mechanically damaged cartilage, but do not infiltrate healthy cartilage. Temperature dynamics in cartilage impregnated with NPs have been theoretically calculated and measurements using an IR thermo vision system have been performed. Laser-induced alterations of cartilage structure and cellular surviving have been studied for cartilage impregnated with NPs using histological and histochemical techniques. Results of our study suggest that magnetite NPs might be used to provide spatial specificity of laser regeneration. When damaged, the regions of cartilage impreganted with NPs have higher absorption of laser radiation than that for healthy areas. Regions containing NPs form target sites that can be used to generate laser-induced thermo mechanical stress leading to regeneration of cartilage of hyaline type.

Importance of Patella, Quadriceps Forces, and Depthwise Cartilage Structure on Knee Joint Motion and Cartilage Response During Gait.

PubMed

Halonen, K S; Mononen, M E; Jurvelin, J S; Töyräs, J; Klodowski, A; Kulmala, J-P; Korhonen, R K

2016-07-01

In finite-element (FE) models of the knee joint, patella is often omitted. We investigated the importance of patella and quadriceps forces on the knee joint motion by creating an FE model of the subject's knee. In addition, depthwise strains and stresses in patellar cartilage with different tissue properties were determined. An FE model was created from subject's magnetic resonance images. Knee rotations, moments, and translational forces during gait were recorded in a motion laboratory and used as an input for the model. Three material models were implemented into the patellar cartilage: (1) homogeneous model, (2) inhomogeneous (arcadelike fibrils), and (3) random fibrils at the superficial zone, mimicking early stages of osteoarthritis (OA). Implementation of patella and quadriceps forces into the model substantially reduced the internal-external femoral rotations (versus without patella). The simulated rotations in the model with the patella matched the measured rotations at its best. In the inhomogeneous model, maximum principal stresses increased substantially in the middle zone of the cartilage. The early OA model showed increased compressive strains in the superficial and middle zones of the cartilage and decreased stresses and fibril strains especially in the middle zone. The results suggest that patella and quadriceps forces should be included in moment- and force-driven FE knee joint models. The results indicate that the middle zone has a major role in resisting shear forces in the patellar cartilage. Also, early degenerative changes in the collagen network substantially affect the cartilage depthwise response in the patella during walking.

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.

Fabrication of a Neotrachea Using Engineered Cartilage

PubMed Central

Weidenbecher, Mark; Tucker, Harvey M.; Awadallah, Amad; Dennis, James E.

2008-01-01

Objectives Surgical management of long-segment tracheal stenosis is an ongoing problem. Many types of tracheal prostheses have been tried but with limited success because of immune rejection, graft ischemia, or restenosis. Tissue engineered cartilage may offer a solution to this problem, although scaffolds, which are currently often used for support, can lead to biocompatibility problems. This study investigated the feasibility of scaffold-free cartilage to tissue engineer a vascularized neotrachea in rabbits. Study Design Animal study. Methods Autologous neotracheal constructs were implanted in the abdomen of six New Zealand white rabbits. Auricular chondrocytes were used to engineer scaffold-free cartilage sheets. A muscle flap raised from the external abdominal oblique muscle and the engineered cartilage were wrapped around a silicone stent to fabricate a vascularized neotrachea in vivo. In two of the six rabbits, a full thickness skin graft was used to create an epithelial lining. The constructs were harvested after either 6 or 10 weeks. Results All neotracheal constructs were healthy with well-vascularized and integrated layers. The implanted engineered cartilage underwent a remodeling process, forming a solid tracheal framework. Constructs harvested after 10 weeks proved to have significantly better mechanical properties than after 6 weeks and were comparable with the rabbit's native trachea. Conclusion Scaffold-free engineered cartilage can successfully fabricate a well-vascularized, autologous neotrachea with excellent mechanical properties. The results suggest that this approach can be used to reconstruct tracheal defects in rabbits. PMID:18197138

Experimental validation of arthroscopic cartilage stiffness measurement using enzymatically degraded cartilage samples

NASA Astrophysics Data System (ADS)

Lyyra, T.; Arokoski, J. P. A.; Oksala, N.; Vihko, A.; Hyttinen, M.; Jurvelin, J. S.; Kiviranta, I.

1999-02-01

In order to evaluate the ability of the arthroscopic indentation instrument, originally developed for the measurement of cartilage stiffness during arthroscopy, to detect cartilage degeneration, we compared changes in the stiffness with the structural and constitutional alterations induced by enzymes on the tissue in vitro. The culturing of osteochondral plugs on Petri dishes was initiated in Minimum Essential Medium with Earle's salts and the baseline stiffness was measured. Then, the experimental specimens were digested using trypsin for 24 h, chondroitinase ABC or purified collagenase (type VII) for 24 h or 48 h ( n = 8-15 per group). The control specimens were incubated in the medium. After the enzyme digestion, the end-point stiffness was measured and the specimens for the microscopic analyses were processed. The proteoglycan (PG) distribution was analysed using quantitative microspectrophotometry and the quantitative evaluation of the collagen network was made using a computer-based polarized light microscopy analysis. Decrease of cartilage stiffness was found after 24 h trypsin (36%) and 48 h chondroitinase ABC (24%) digestion corresponding to a decrease of up to 80% and up to 30% in the PG content respectively. Decrease of the superficial zone collagen content or arrangement (78%, ) after 48 h collagenase digestion also induced a decrease (30%, ) in cartilage stiffness. We conclude that our instrument is capable of

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

PubMed

Vinatier, C; Guicheux, J

2016-06-01

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Impact of synovial fluid flow on temperature regulation in knee cartilage.

PubMed

Moghadam, Mohamadreza Nassajian; Abdel-Sayed, Philippe; Camine, Valérie Malfroy; Pioletti, Dominique P

2015-01-21

Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro physical stimulation of tissue-engineered and native cartilage.

PubMed

Li, Kelvin W; Klein, Travis J; Chawla, Kanika; Nugent, Gayle E; Bae, Won C; Sah, Robert L

2004-01-01

Because of the limited availability of donor cartilage for resurfacing defects in articular surfaces, there is tremendous interest in the in vitro bioengineering of cartilage replacements for clinical applications. However, attaining mechanical properties in engineered cartilaginous constructs that approach those of native cartilage has not been previously achieved when constructs are cultured under free-swelling conditions. One approach toward stimulating the development of constructs that are mechanically more robust is to expose them to physical environments that are similar, in certain ways, to those encountered by native cartilage. This is a strategy motivated by observations in numerous short-term experiments that certain mechanical signals are potent stimulators of cartilage metabolism. On the other hand, excess mechanical loading can have a deleterious effect on cartilage. Culture conditions that include a physical stimulation component are made possible by the use of specialized bioreactors. This chapter addresses some of the issues involved in using bioreactors as integral components of cartilage tissue engineering and in studying the physical regulation of cartilage. We first consider the generation of cartilaginous constructs in vitro. Next we describe the rationale and design of bioreactors that can impart either mechanical deformation or fluid-induced mechanical signals.

Changes in articular cartilage following arthroscopic partial medial meniscectomy.

PubMed

Eichinger, Martin; Schocke, Michael; Hoser, Christian; Fink, Christian; Mayr, Raul; Rosenberger, Ralf E

2016-05-01

To examine degenerative changes in all cartilage surfaces of the knee following arthroscopic partial medial meniscectomy. For this prospective cohort study, 14 patients (five female) with a mean age of 47.9 ± 12.9 years who had undergone isolated arthroscopic partial medial meniscectomy were evaluated. Cartilage-sensitive magnetic resonance imaging (MRI) scans were acquired from the operated knees before the index operations, as well as at 6, 12, and 24 months after surgery. The MRI scans were assessed for the prevalence, severity, and size of cartilage degenerations. The clinical outcome was assessed using the SF-36 physical and mental component score and the International Knee Documentation Committee Knee Evaluation Form and was correlated with radiological findings. There was a significant increase in the severity of cartilage lesions in the medial tibial plateau (P = 0.019), as well as a trend towards an increase in the lateral tibial plateau. The size of the cartilage lesions increased significantly in the medial femoral condyle (P = 0.005) and lateral femoral condyle (P = 0.029), as well as in the patella (P = 0.019). Functional outcome scores improved significantly throughout the follow-up period. There was no correlation between cartilage wear and functional outcome. Arthroscopic partial medial meniscectomy is associated with adverse effects on articular cartilage and may lead to an increase in the severity and size of cartilage lesions. Post-operative cartilage wear predominantly affected the medial compartment and also affected the other compartments of the knee. Strategies to reduce subsequent osteoarthritic changes need to involve all compartments of the knee. IV.

Longitudinal change in patellofemoral cartilage thickness, cartilage T2 relaxation times, and subchondral bone plate area in adolescent vs mature athletes.

PubMed

Culvenor, Adam G; Wirth, Wolfgang; Maschek, Susanne; Boeth, Heide; Diederichs, Gerd; Duda, Georg; Eckstein, Felix

2017-07-01

Patellofemoral cartilage changes have been evaluated in knee trauma and osteoarthritis; however, little is known about changes in patellar and trochlear cartilage thickness, T2 relaxation-time and subchondral bone plate area (tAB) during growth. Our prospective study aimed to explore longitudinal change in patellofemoral cartilage thickness, T2 and tAB in adolescent athletes, and to compare these data with those of mature (i.e., adult) athletes. 20 adolescent (age 16±1years) and 20 mature (46±5years) volleyball players were studied over 2-years (10 men and 10 women each group). 1.5T MRI 3D-VIBE and multi-echo spin-echo sequences were acquired at baseline and 2-year follow-up. Using manual segmentation and 3D reconstruction, longitudinal changes in patellar and trochlear cartilage thickness, patellar cartilage T2 (mono-exponential decay curve with five echoes [9.7-67.9ms]), and patellar and trochlear tAB were determined. The annual increase in both patellar and trochlear cartilage thickness was 0.8% (95% confidence interval [CI] 0.6, 1.0) and 0.6% (0.3, 0.9), for adolescent males and females respectively; the longitudinal gain in patellar and trochlear tAB was 1.3% (1.1, 1.5) and 0.5% (0.2, 0.8), and 1.6% (1.1, 2.2) and 0.8% (0.3, 0.7) for adolescent males and females, respectively (no significant between-sex differences). Mature athletes showed smaller gains in tAB, and loss of <1% of cartilage thickness annually. While no significant sex-differences existed in adolescent patellar T2 changes, mature males gained significantly greater T2 than mature females (p=0.002-0.013). Patellar and trochlear cartilage thickness and tAB were observed to increase in young athletes in late adolescence, without significant differences between sexes. Mature athletes displayed patellar cartilage loss (and T2 increases in mature males), potentially reflecting degenerative changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Homologous and Homologous like Microwave Solar Radio Bursts

NASA Astrophysics Data System (ADS)

Trevisan, R. H.; Sawant, H. S.; Kalman, B.; Gesztelyi, L.

1990-11-01

ABSTRACT. Solar radio observations at 1.6 GHz were carried out in the month of July, 1985 by using 13.7 m diameter Itapetinga antenna with time resolution of 3 ms. Homologous Bursts, with total duration of about couple of seconds and repeated by some seconds were observed associated with Homologous H- flares. These H- flares were having periodicities of about 40 min. Observed long periodicities were attributed to oscillation of prominences, and small periods were attributed to removal of plasma from the field interaction zone. Also observed are "Homologous-Like" bursts. These bursts are double peak bursts with same time profile repeating in time. In addition to this, the ratio of the total duration of the bursts to time difference in the peaks of bursts remain constant. Morphological studies of these bursts have been presented. Keq tuoit : SUN-BURSTS - SUN-FLARE

Cartilage formation in the CELLS 'double bubble' hardware

NASA Technical Reports Server (NTRS)

Duke, P. J.; Arizpe, Jorge; Montufar-Solis, Dina

1991-01-01

The CELLS experiment scheduled to be flown on the first International Microgravity Laboratory is designed to study the effect of microgravity on the cartilage formation, by measuring parameters of growth in a differentiating cartilage cell culture. This paper investigates the conditions for this experiment by studying cartilage differentiation in the 'bubble exchange' hardware with the 'double bubble' design in which the bubbles are joined by a flange which also overlays the gasket. Four types of double bubbles (or double gas permeable membranes) were tested: injection-molded bubbles 0.01- and 0.005-in. thick, and compression molded bubbles 0.015- and 0.01-in. thick. It was found that double bubble membranes of 0.005- and 0.010-in. thickness supported cartilage differentiation, while the 0.015-in. bubbles did not. It was also found that nodule count, used in this study as a parameter, is not the best measure of the amount of cartilage differentiation.

Indian hedgehog contributes to human cartilage endplate degeneration.

PubMed

Wang, Shaowei; Yang, Kun; Chen, Shuai; Wang, Jiying; Du, Guoqing; Fan, Shunwu; Wei, Lei

2015-08-01

To determine the role of Indian hedgehog (Ihh) signaling in human cartilage endplate (CEP) degeneration. CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracture patients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.

High fat diet accelerates cartilage repair in DBA/1 mice.

PubMed

Wei, Wu; Bastiaansen-Jenniskens, Yvonne M; Suijkerbuijk, Mathijs; Kops, Nicole; Bos, Pieter K; Verhaar, Jan A N; Zuurmond, Anne-Marie; Dell'Accio, Francesco; van Osch, Gerjo J V M

2017-06-01

Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering.

PubMed

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

2014-12-07

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.

The Role of Cartilage Stress in Patellofemoral Pain

PubMed Central

Besier, Thor F.; Pal, Saikat; Draper, Christine E.; Fredericson, Michael; Gold, Garry E.; Delp, Scott L.; Beaupré, Gary S.

2015-01-01

Purpose Elevated cartilage stress has been identified as a potential mechanism for retropatellar pain; however, there are limited data in the literature to support this mechanism. Females are more likely to develop patellofemoral pain than males, yet the causes of this dimorphism are unclear. We used experimental data and computational modeling to determine whether patients with patellofemoral pain had elevated cartilage stress compared to pain-free controls and test the hypothesis that females exhibit greater cartilage stress than males. Methods We created finite element models of 24 patients with patellofemoral pain (11 males; 13 females) and 16 pain-free controls (8 males; 8 females) to estimate peak patellar cartilage stress (strain energy density) during a stair climb activity. Simulations took into account cartilage morphology from MRI, joint posture from weight-bearing MRI, and muscle forces from an EMG-driven model. Results We found no difference in peak patellar strain energy density between patellofemoral pain (1.9 ± 1.23 J/m3) and control subjects (1.66 ± 0.75 J/m3, p=0.52). Females exhibited greater cartilage stress compared to males (2.2 vs 1.3 J/m3, respectively, p=0.0075), with large quadriceps muscle forces (3.7BW females vs 3.3BW males) and 23% smaller joint contact area (females: 467 ± 59 mm2 vs males: 608 ± 95mm2). Conclusion Patellofemoral pain patients did not display significantly greater patellar cartilage stress compared to pain-free controls; however, there was a great deal of subject variation. Females exhibited greater peak cartilage stress compared to males, which might explain the greater prevalence of patellofemoral pain in females compared to males but other mechanical and biological factors are clearly involved in this complex pathway to pain. PMID:25899103

The interaction between physical activity and amount of baseline knee cartilage.

PubMed

Teichtahl, Andrew J; Wang, Yuanyuan; Heritier, Stephane; Wluka, Anita E; Strauss, Boyd J; Proietto, Joseph; Dixon, John B; Jones, Graeme; Cicuttini, Flavia M

2016-07-01

Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ⩽ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New cell engineering approaches for cartilage regenerative medicine.

PubMed

Cucchiarini, Magali

2017-01-01

Articular cartilage injuries have an inadequate aptitude to reproduce the original structure and functions of this highly specialized tissue. As most of the currently available options also do not lead to the restoration of the original hyaline cartilage, novel treatments are critically needed to address this global problems in the clinics. Gene therapy combined with tissue engineering approaches offers effective tools capable of enhancing cartilage repair experimentally, especially those based on the controlled delivery of the highly effective, clinically adapted recombinant adeno-associated viral (rAAV) vectors. This work presents an overview of the most recent evidence showing the benefits of using rAAV vectors and biocompatible materials for the elaboration of adapted treatments against cartilage injuries.

Three-dimensional autologous cartilage framework fabrication assisted by new additive manufactured ear-shaped templates for microtia reconstruction.

PubMed

Zhou, Jiayu; Pan, Bo; Yang, Qinghua; Zhao, Yanyong; He, Leren; Lin, Lin; Sun, Hengyun; Song, Yupeng; Yu, Xiaobo; Sun, Zhongyang; Jiang, Haiyue

2016-10-01

During microtia reconstruction, the intraoperative design of the cartilage framework is important for the appearance and symmetry of the bilateral auricles. Templates (traditionally, the X-ray film template) are usually utilized to complete the task, which can provide cues regarding size, cranioauricular angle and positioning to the surgeons. With a combination of three-dimensional (3D) scanning and additive manufacturing (AM) techniques, we utilized two different ear-shaped templates (sheet moulding and 3D templates) during the fabrication of 3D-customized autologous cartilage frameworks for auricle reconstruction. Forty unilateral microtia patients were included in the study. All the patients underwent auricle reconstruction using the tissue-expanding technique assisted by the new AM templates. Images were processed using computer-aided design software and exported to print two different AM ear-shaped templates: sheet moulding and 3D. Both templates were assisted by the 3D framework fabrication. The 3D images of each patient's head were captured preoperatively using a 3D scanner. X-ray film templates were also made for the patients. The lengths and widths of the contralateral auricles, X-ray film and sheet moulding templates were measured in triplicate. The error of the template and the contralateral auricle were used to compare the accuracy between the two templates. Between January and May 2014, 40 unilateral microtia patients aged 6-29 years were included in this study. All patients underwent auricle reconstruction using autogenous costal cartilage. The sterilized AM templates were used to assist in the framework fabrication. The operative time was decreased by an average of 15 min compared with the method assisted by the X-ray film template. Postoperative appearance evaluation (based on five indexes: symmetry, length, width, cranioauricular angle and the substructure of the reconstructed ear) was performed by both the doctors and the patients (or their

[Current status of bone/cartilage tissue engineering towards clinical applications].

PubMed

Ohgushi, Hajime

2014-10-01

Osteo/chondrogenic differentiation capabilities are seen after in vivo implantation of mesenchymal stem cells (MSCs), which are currently used for the patients having bone/cartilage defects. Importantly, the differentiation capabilities are induced by culturing technology, resulting in in vitro bone/cartilage formation. Especially, the in vitro bone tissue is useful for bone tissue regeneration. For cartilage regeneration, culture expanded chondrocytes derived from patient's normal cartilage are also used for the patients having cartilage damages. Recently, the cultured chondrocytes embedded in atelocollagen gel are obtainable as tissue engineered products distributed by Japan Tissue Engineering Co. Ltd. The products are available in the well-regulated hospitals by qualified orthopedic surgeons. The criteria for these hospitals/surgeons have been established. This review paper focuses on current status of bone/cartilage tissue engineering towards clinical applications in Japan.

Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

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

Neubert, A., E-mail: ales.neubert@csiro.au

Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hipmore » joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral

Quasi-static elastography comparison of hyaline cartilage structures

NASA Astrophysics Data System (ADS)

McCredie, A. J.; Stride, E.; Saffari, N.

2009-11-01

Joint cartilage, a load bearing structure in mammals, has only limited ability for regeneration after damage. For tissue engineers to design functional constructs, better understanding of the properties of healthy tissue is required. Joint cartilage is a specialised structure of hyaline cartilage; a poroviscoelastic solid containing fibril matrix reinforcements. Healthy joint cartilage is layered, which is thought to be important for correct tissue function. However, the behaviour of each layer during loading is poorly understood. Ultrasound elastography provides access to depth-dependent information in real-time for a sample during loading. A 15 MHz focussed transducer provided details from scatterers within a small fixed region in each sample. Quasi-static loading was applied to cartilage samples while ultrasonic signals before and during compressions were recorded. Ultrasonic signals were processed to provide time-shift profiles using a sum-squared difference method and cross-correlation. Two structures of hyaline cartilage have been tested ultrasonically and mechanically to determine method suitability for monitoring internal deformation differences under load and the effect of the layers on the global mechanical material behaviour. Results show differences in both the global mechanical properties and the ultrasonically tested strain distributions between the two structures tested. It was concluded that these differences are caused primarily by the fibril orientations.

Cartilage immunoprivilege depends on donor source and lesion location.

PubMed

Arzi, B; DuRaine, G D; Lee, C A; Huey, D J; Borjesson, D L; Murphy, B G; Hu, J C Y; Baumgarth, N; Athanasiou, K A

2015-09-01

The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of "cartilage immunoprivilege". The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium. Through a series of in vivo studies this research demonstrates that articular cartilage is not fully immunoprivileged. In addition, we now show that anatomical location of the defect, even within the same joint compartment, strongly influences the degree of the

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

PubMed Central

Szychlinska, Marta Anna; Trovato, Francesca Maria; Di Rosa, Michelino; Malaguarnera, Lucia; Puzzo, Lidia; Leonardi, Rosy; Castrogiovanni, Paola; Musumeci, Giuseppe

2016-01-01

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease. PMID:26978347

Using Cartilage MRI T2-Mapping to Analyze Early Cartilage Degeneration in the Knee Joint of Young Professional Soccer Players.

PubMed

Waldenmeier, Leonie; Evers, Christoph; Uder, Michael; Janka, Rolf; Hennig, Frank Friedrich; Pachowsky, Milena Liese; Welsch, Götz Hannes

2018-02-01

Objective To evaluate and characterize the appearance of articular cartilage in the tibiofemoral joint of young professional soccer players using T2-relaxation time evaluation on magnetic resonance imaging (MRI). Design In this study, we included 57 male adolescents from the youth academy of a professional soccer team. The MRI scans were acquired of the knee joint of the supporting leg. An "early unloading" (minute 0) and "late unloading" (minute 28) T2-sequence was included in the set of images. Quantitative T2-analysis was performed in the femorotibial joint cartilage in 4 slices with each 10 regions of interest (ROIs). Statistical evaluation, using Wilcoxon signed-rank tests, was primarily performed to compare the T2 values of the "early unloading" and "late unloading." Results When comparing "early unloading" with "late unloading," our findings showed a significant increase of T2-relaxation times in the weightbearing femoral cartilage of the medial ( P < 0.001) and lateral ( P < 0.001) compartment of the knee and in the tibial cartilage of the medial compartment ( P < 0.001). Conclusion In this study, alterations of the cartilage were found with a maximum in the medial condyle where the biomechanical load of the knee joint is highest, as well as where most of the chronic cartilage lesions occur. To avoid chronic damage, special focus should be laid on this region.

Measurements of surface layer of the articular cartilage using microscopic techniques

NASA Astrophysics Data System (ADS)

Ryniewicz, A. M.; Ryniewicz, A.; Ryniewicz, W.; Gaska, A.

2010-07-01

The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid.

PubMed

Englert, Carsten; McGowan, Kevin B; Klein, Travis J; Giurea, Alexander; Schumacher, Barbara L; Sah, Robert L

2005-04-01

To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and (3)H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated (3)H-proline. Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

Airflow accelerates bovine and human articular cartilage drying and chondrocyte death.

PubMed

Paterson, S I; Amin, A K; Hall, A C

2015-02-01

Exposure of articular cartilage to static air results in changes to the extracellular matrix (ECM) and stimulates chondrocyte death, which may cause joint degeneration. However during open orthopaedic surgery, cartilage is often exposed to laminar airflow, which may exacerbate these damaging effects. We compared drying in static and moving air in terms of cartilage appearance, hydration and chondrocyte viability, and tested the ability of saline-saturated gauze to limit the detrimental effects of air exposure. Articular cartilage from bovine metatarsophalangeal joints (N = 50) and human femoral heads (N = 6) was exposed for 90 min to (1) static air (2) airflow (up to 0.34 m/s), or (3) airflow (0.18 m/s), covered with gauze. Following air exposure, cartilage was also rehydrated (0.9% saline; 120 min) to determine the reversibility of drying effects. The influence of airflow was assessed by studying macroscopic appearance, and quantifying superficial zone (SZ) chondrocyte viability and cartilage hydration. Airflow caused advanced changes to cartilage appearance, accelerated chondrocyte death, and increased dehydration compared to static air. These effects were prevented if cartilage was covered by saline-saturated gauze. Cartilage rehydration reversed macroscopic changes associated with drying but the chondrocyte death was not altered. Chondrocytes at the cut edge of cartilage were more sensitive to drying compared to cells distant from the edge. Airflow significantly increased articular cartilage dehydration and chondrocyte death compared to static air. As laminar airflow is routinely utilised in operating theatres, it is essential that articular cartilage is kept wet via irrigation or by covering with saline-saturated gauze to prevent chondrocyte death. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

STUDIES ON CARTILAGE

PubMed Central

Sheldon, Huntington; Robinson, Robert A.

1960-01-01

Electron microscope observations on rabbit ear cartilage following the administration of papain show that both the elastic component of the matrix and the amorphous material disappear leaving a matrix which consists of delicate fibrils which are presumed to be collagen. This unmasking of fibrils coincides with the appearance of an abnormal component in the electrophoretic pattern of the rabbit's serum. The chondrocytes show vacuoles in their cytoplasm which appear at the same time that the cells appear crenated in the light microscope. A ruffly appearance of the cell surface membrane coincides with this vacuolization, and vacuoles often appear open and in continuity with the extracellular space. The resurgence of the rabbit ear is accompanied by a reconstitution of both the amorphous material and the elastic component of the matrix. During this period numerous dilated cisternae of the endoplasmic reticulum which contain a moderately dense material are present in the chondrocyte cytoplasm. We have been unable to demonstrate a direct relationship between the elastic component of the matrix and a particular component of the chondrocyte cytoplasm, but it is clear that changes occur in the cartilage cell cytoplasm during both the depletion and reconstitution of the matrix. Previous studies on the effect of papain on elastic tissue are noted and the possible relationships between changes in the cells and matrix of this elastic cartilage are discussed. PMID:19866569

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.

Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

PubMed Central

Raya, José G.

2014-01-01

Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits.

PubMed

Zhang, Z; Li, L; Yang, W; Cao, Y; Shi, Y; Li, X; Zhang, Q

2017-02-01

To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively. Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

PubMed

Li, Kuei-Chang; Hu, Yu-Chen

2015-05-01

Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cartilage and bone damage in rheumatoid arthritis

PubMed Central

Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Nieciecki, Michał; Sudoł-Szopińska, Iwona

2018-01-01

Rheumatoid arthritis (RA), which is a chronic inflammatory disease with a multifactorial aetiology, leads to partial or permanent disability in the majority of patients. It is characterised by persistent synovitis and formation of pannus, i.e. invasive synovial tissue, which ultimately leads to destruction of the cartilage, subchondral bone, and soft tissues of the affected joint. Moreover, inflammatory infiltrates in the subchondral bone, which can lead to inflammatory cysts and later erosions, play an important role in the pathogenesis of RA. These inflammatory infiltrates can be seen in magnetic resonance imaging (MRI) as bone marrow oedema (BME). BME is observed in 68–75% of patients in early stages of RA and is considered a precursor of rapid disease progression. The clinical significance of synovitis and bone marrow oedema as precursors of erosions is well established in daily practice, and synovitis, BME, cysts, hyaline cartilage defects and bone erosions can be detected by ultrasonography (US) and MRI. A less explored subject is the inflammatory and destructive potential of intra- and extra-articular fat tissue, which can also be evaluated in US and MRI. Finally, according to certain hypotheses, hyaline cartilage damage may trigger synovitis and lead to irreversible joint damage, and MRI may be used for preclinical detection of cartilage biochemical abnormalities. This review discusses the pathomechanisms that lead to articular cartilage and bone damage in RA, including erosion precursors such as synovitis and osteitis and panniculitis, as well as the role of imaging techniques employed to detect early cartilage damage and bone erosions. PMID:29853727

PPARD is an Inhibitor of Cartilage Growth in External Ears.

PubMed

Zhang, Zhen; Duan, Yanyu; Wu, Zhongping; Zhang, Hui; Ren, Jun; Huang, Lusheng

2017-01-01

Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle. At the transcription level, PPARD upregulates a set of genes that are associated with CSPCs apoptosis and chondrogenic differentiation, chondroblast differentiation and extracellular matrix degradation. ChIP-seq identified direct target genes of PPARD, including a well-documented gene for cartilage development: PPARG . We further show that compared to wild-type PPARD, the G32E mutant up-regulates the expression of PPARG and subsequently leads to the downregulation of critical genes that inhibit cartilage growth. These findings allow us to conclude that PPARD is an inhibitor of auricular cartilage growth in pigs. The causative mutation (G32E) in the PPARD gene attenuates the PPARD-mediated retardation of cartilage growth in the auricle, contributing to enlarged ears in pigs. The findings advance our understanding of the mechanisms underlying auricular development in mammals, and shed insight into the studies of innate pinna disorders and cartilage regeneration medicine in humans.

Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

PubMed

Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

2007-02-01

Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

Magnetic resonance imaging of articular cartilage: trauma, degeneration, and repair.

PubMed

Potter, Hollis G; Foo, Li F

2006-04-01

The assessment of articular cartilage using magnetic resonance imaging has seen considerable advances in recent years. Cartilage morphologic characteristics can now be evaluated with a high degree of accuracy and reproducibility using dedicated pulse sequences, which are becoming standard at many institutions. These techniques detect clinically unsuspected traumatic cartilage lesions, allowing the physician to study their natural history with longitudinal evaluation and also to assess disease status in degenerative osteoarthritis. Magnetic resonance imaging also provides a more objective assessment of cartilage repair to augment the information obtained from more subjective clinical outcome instruments. Newly developed methods that provide detail at an ultrastructural level offer an important addition to cartilage evaluation, particularly in the detection of early alterations in the extracellular matrix. These methods have created an undeniably important role for magnetic resonance imaging in the reproducible, noninvasive, and objective evaluation and monitoring of cartilage. An overview of the advances, current techniques, and impact of magnetic resonance imaging in the setting of trauma, degenerative arthritides, and surgical treatment for cartilage injury is presented.

Nanodrugs to target articular cartilage: An emerging platform for osteoarthritis therapy.

PubMed

Bottini, Massimo; Bhattacharya, Kunal; Fadeel, Bengt; Magrini, Andrea; Bottini, Nunzio; Rosato, Nicola

2016-02-01

Cartilage undergoes drastic structural changes during the development of osteoarthritis and cannot heal itself due to a defective chondrocyte response. Thus, much effort has been invested in the development of disease modifying drugs able to block key mediators within the cartilage matrix and biochemical pathways inside chondrocytes. However, the delivery of therapeutic agents into cartilage is ineffective. This has led to the use of cartilage-targeted nanodrugs to accumulate therapeutic agents into specific cartilage sub-compartments. This review will describe the nanodrugs targeted to specific components of cartilage matrix to generate drug reservoirs within the cartilage. The nanodrugs used as chondrocyte-specific gene delivery systems are also described. Although the use of cartilage-targeted nanodrugs in osteoarthritis is still in its infancy, these studies lay the foundation for the development of novel approaches for preventing the progression of cartilage breakdown and improving the quality of life of patients with osteoarthritis. Osteoarthritis is a degeneration of joint cartilage, which affects a large number of aging people. Current therapy for disease modification is often suboptimal. Recent research in nanomedicine has led to the design and use of nanodrugs with the aim to help reverse the disease process. In this comprehensive review, the authors described and discussed various nanodrugs in the hope that newer drugs could be discovered in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Magnetic resonance imaging with gadolinium arthrography to assess acetabular cartilage delamination.

PubMed

Zaragoza, Edward; Lattanzio, Pierre-Jean; Beaule, Paul E

2009-01-01

Recent reports have demonstrated magnetic resonance imaging (MRI) as a promising technique in detecting articular cartilage lesions of the hip joint. The purpose of our study was to evaluate the diagnostic performance of MRI with gadolinium arthrography in detecting acetabular cartilage delamination in patients with pre-arthritic hip pain. 46 patients (48 hips) underwent surgical dislocation of the hip. Mean age was 38.8 (range 17-56). There were 26 males and 20 females. All patients had Magnetic Resonance Imaging with gadolinium arthrography (MRA) before undergoing open hip surgery where the acetabular cartilage was inspected. Acetabular cartilage delamination on MRA was seen on sagittal images as a linear intra-articular filling defect of low signal intensity >1mm in thickness on T1 weighted images and surrounded by contrast. On MRA all hips had a labral tear confirmed at surgery. At surgery 30 hips had evidence of acetabular cartilage delamination, 4 hips had ulceration and 14 had no articular cartilage damage. The majority of labral tears and cartilage damage were located in the antero-superior quadrant. The sensitivity and specificity of MRA detection of cartilage delamination confirmed at surgery were 97% and 84%, respectively. The positive and negative predictive values of the MRA finding were 90% and 94%, respectively. The presence of the acetabular cartilage delamination represents an early stage of articular cartilage degeneration. When evaluating a young adult with hip pain, labral tears in association with cartilage delamination should be considered. MRA represents an effective diagnostic tool.

Single-Stage Ear Reconstruction and Hearing Restoration Using Polyethylene Implant and Implantable Hearing Devices.

PubMed

Hempel, John Martin

2015-12-01

The use of porous polyethylene in reconstructive surgery of the auricle is becoming increasingly accepted. This is a single-stage procedure providing pleasing cosmetic rehabilitation. Further advantages are the possibility of early implantation and the lack of complications caused by harvesting costal cartilage. Additional hearing restoration using middle ear implants allows functional rehabilitation at an early stage. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Clinical experience with orthotic repair of pectus carinatum.

PubMed

Al-Githmi, Iskander S

2016-01-01

Pectus carinatum is a congenital chest wall deformity characterized by protrusion of the sternum and adjacent costal cartilages. Multiple treatment options are available for correction of pectus carinatum. We report our initial experience with first-line treatment using a custom fitted dynamic compression orthosis. Prospective evaluation of all patients seen between November 2013 and December 2014. University hospital. The treatment protocol for patients who had pressure for initial correction.

Content and synthesis of nucleic acids in the cartilage in chondromalacia patellae.

PubMed

Lund, F; Telhag, H

1978-12-01

The content and the synthesis of nucleic acids in chondromalacian, osteoarthritis and normal cartilage was compared. The chondromalacian cartilage differed from osteoarthritis in that the content of nucleic acids was less. Also, the cell density was less in chondromalacian than in normal cartilage as opposed to previous findings in osteoarthritis. The synthesis of DNA was greater in chondromalacian than in normal cartilage but less than in osteoarthritis. With regard to the RNA synthesis, however, the chondromalacian cartilage showed a higher rate than both normal and osteoarthritic cartilage.

Strategic Design and Fabrication of Engineered Scaffolds for Articular Cartilage Repair

PubMed Central

Izadifar, Zohreh; Chen, Xiongbiao; Kulyk, William

2012-01-01

Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted. PMID:24955748

Homology of vanadium oxide

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

Vasyutinskii, N.A.

1987-05-01

The authors examine the homology of vanadium oxide and note that data on the existence of phases and homogeneity limits in the V-O system are very contradictory. A graphical illustration shows the homologous series of vanadium oxides. The predominant part of the discrete formations in the system V-O is characterized by integral stoichiometry and forms six homologous series. It is found that homologous series of vanadium oxides are not only a basis for systematization of such oxides, but also may serve as a means for predicting the composition of new phases, limits of homogeneity, their structure, and properties.

Sagittal-Plane Knee Moment During Gait and Knee Cartilage Thickness.

PubMed

Schmitz, Randy J; Harrison, David; Wang, Hsin-Min; Shultz, Sandra J

2017-06-02

  Understanding the factors associated with thicker cartilage in a healthy population is important when developing strategies aimed at minimizing the cartilage thinning associated with knee osteoarthritis progression. Thicker articular cartilage is commonly thought to be healthier cartilage, but whether the sagittal-plane biomechanics important to gait are related to cartilage thickness is unknown.   To determine the relationship of a weight-bearing region of the medial femoral condyle's cartilage thickness to sagittal gait biomechanics in healthy individuals.   Descriptive laboratory study.   Laboratory.   Twenty-eight healthy participants (15 women: age = 21.1 ± 2.1 years, height = 1.63 ± 0.07 m, weight = 64.6 ± 9.9 kg; 13 men: age = 22.1 ± 2.9 years, height = 1.79 ± 0.05 m, weight = 75.2 ± 9.6 kg).   Tibiofemoral angle (°) was obtained via goniometric assessment, thickness of the medial femoral condyle cartilage (mm) was obtained via ultrasound imaging, and peak internal knee-extensor moment (% body weight · height) was measured during 10 trials of over-ground walking at a self-selected pace. We used linear regression to examine the extent to which peak internal knee-extensor moment predicted cartilage thickness after accounting for tibiofemoral angle and sex.   Sex and tibiofemoral angle (12.3° ± 3.2°) were entered in the initial step as control factors (R 2 = 0.01, P = .872). In the final step, internal knee-extensor moment (1.5% ± 1.3% body weight · height) was entered, which resulted in greater knee-extensor moment being related to greater cartilage thickness (2.0 ± 0.3 mm; R 2 Δ = 0.31, PΔ = .003).   Individuals who walked with a greater peak internal knee-extensor moment during gait had a cartilage structure that is generally considered beneficial in a healthy population. Our study offers promising findings that a potentially modifiable biomechanical factor is associated with cartilage status in a healthy population

Sagittal-Plane Knee Moment During Gait and Knee Cartilage Thickness

PubMed Central

Harrison, David; Wang, Hsin-Min; Shultz, Sandra J.

2017-01-01

Context:  Understanding the factors associated with thicker cartilage in a healthy population is important when developing strategies aimed at minimizing the cartilage thinning associated with knee osteoarthritis progression. Thicker articular cartilage is commonly thought to be healthier cartilage, but whether the sagittal-plane biomechanics important to gait are related to cartilage thickness is unknown. Objective:  To determine the relationship of a weight-bearing region of the medial femoral condyle's cartilage thickness to sagittal gait biomechanics in healthy individuals. Design:  Descriptive laboratory study. Setting:  Laboratory. Patients or Other Participants:  Twenty-eight healthy participants (15 women: age = 21.1 ± 2.1 years, height = 1.63 ± 0.07 m, weight = 64.6 ± 9.9 kg; 13 men: age = 22.1 ± 2.9 years, height = 1.79 ± 0.05 m, weight = 75.2 ± 9.6 kg). Main Outcome Measure(s):  Tibiofemoral angle (°) was obtained via goniometric assessment, thickness of the medial femoral condyle cartilage (mm) was obtained via ultrasound imaging, and peak internal knee-extensor moment (% body weight · height) was measured during 10 trials of over-ground walking at a self-selected pace. We used linear regression to examine the extent to which peak internal knee-extensor moment predicted cartilage thickness after accounting for tibiofemoral angle and sex. Results:  Sex and tibiofemoral angle (12.3° ± 3.2°) were entered in the initial step as control factors (R2 = 0.01, P = .872). In the final step, internal knee-extensor moment (1.5% ± 1.3% body weight · height) was entered, which resulted in greater knee-extensor moment being related to greater cartilage thickness (2.0 ± 0.3 mm; R2Δ = 0.31, PΔ = .003). Conclusion:  Individuals who walked with a greater peak internal knee-extensor moment during gait had a cartilage structure that is generally considered beneficial in a healthy population. Our study offers promising findings that a

Spider fauna in Caspian Costal region of Iran.

PubMed

Ghavami, Sahra

2007-03-01

The current study investigated spider fauna of Caspian Costal region of Iran (Guilan, Mazandaran and Golestan provinces) during 2005-2006. Spiders were collected from on the ground and under the stones and grasses by bottle, aspirator, Pitfall trap and pans and from branches, leaves and trunks of different trees and bushes by Steiner and Baggiolini method and insect net. They transferred to the laboratory and classified in 52 species and 51 genera belonged to 20 families. Thirty species, 13 genera and 2 families are reported for the first time from Iran, as follows: Family Agelenidae: Agelena labyrinthica (Clerck, 1757), Cicurina sp., Family Araneidae: Agalenatea redii (Scopoli, 1763), Araniella inconspicua (Simon, 1874), Araniella alpica (C.L. Koch, 1869), Araneus diadematus Clerck, 1757, Cercidia sp., Cyclosa conica (Pallas, 1772), Hypsosinga sanguinea (C.L. Koch,1845), Family Clubionidae: Clubiona neglecta O.P. Camridge, 1862, Family Amaurobiidae, Family Eresidae: Eresus sp., Dresserus sp., Family Gnaphosidae: Aphantaulax sp., Micaria sp., Family Metidae: Zygiella x-notata (Clerck,1757), Family Miturgidae: Cheiracanthium erraticum (Walckenaer, 1802), Cheiracanthium pennyi O.P. Cambridge, 1873, Family Linyphiidae: Microlinyphia sp., Family Lycosidae: Alopecosa pulverulenta (Clerck, 1757), Pardosa amentata (Clerck, 1757), Pardosa agrestis (Westring, 1861), Pardosa monticola (Clerck, 1757), Family Oxyopidae: Oxyopes salticus (Hentx, 1802), Family Philodromidae: Philodromus cespitum (Walckenaer, 1802),Family Pholcidae: Psilochorus simoni (Berland, 1911), Pholcus phalangioides (Fuesslin, 1775), Family Salticidae: Salticus scenicus (Clerck, 1757), Family Tetragnathidae: Tetragnatha montana, Simon, 1874, Tetragnatha javana (Thorell, 1890), Family Theridiidae: Dipoena prona (Menge, 1868), Steatoda albomaculata (Degeer, 1778), Theridion impressum C. L. Koch, Theridion simile C.L. Koch,1836, Family Thomisidae: Misumena vatia (Clerck, 1757), Thanatus formicinus (Clerck

Calcification of in vitro developed hypertrophic cartilage

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

Tacchetti, C.; Quarto, R.; Campanile, G.

1989-04-01

We have recently reported that dedifferentiated cells derived from stage 28-30 chick embryo tibiae, when transferred in suspension culture in the presence of ascorbic acid, develop in a tissue closely resembling hypertrophic cartilage. Ultrastructural examination of this in vitro formed cartilage showed numerous matrix vesicles associated with the extracellular matrix. In the present article we report that the in vitro developed hypertrophic cartilage undergoes calcification. We indicate a correlation between the levels of alkaline phosphatase activity and calcium deposition at different times of development. Following the transfer of cells into suspension culture and an initial lag phase, the level ofmore » alkaline phosphatase activity rapidly increased. In most experiments the maximum of activity was reached after 5 days of culture. When alkaline phosphatase activity and /sup 45/Ca deposition were measured in the same experiment, we observed that the increase in alkaline phosphatase preceded the deposition of nonwashable calcium deposits in the cartilage.« less

Astaxanthin ameliorates cartilage damage in experimental osteoarthritis.

PubMed

Huang, Li-juan; Chen, Wei-Ping

2015-09-01

Astaxanthin is a red-pigment carotenoid found in certain marine animals and plants. Astaxanthin has been shown to inhibit matrix metalloproteinases (MMPs) expression in vitro. However, the effect of astaxanthin on cartilage is still unclear. The aim of this study was to investigate the effects of astaxanthin on cartilage in experimental osteoarthritis (OA). New Zealand rabbits underwent anterior cruciate ligament transection to induce OA in right knee. Rabbits received intra-articular injection containing 0.3 ml of vehicle (dimethyl sulfoxide) or astaxanthin (50 μM). Injection was started on the day of operation, and the injection were performed once weekly for six consecutive weeks. Then, rabbits were sacrificed and the right knees were harvested for study. Cartilage degradation was reduced by astaxanthin, as assessed by morphological and histological examination. Astaxanthin inhibited the gene expression of MMP-1, MMP-3, and MMP-13 in cartilage as compared with the vehicle group. The results suggest that astaxanthin may be considered as pharmaceutical agent in OA treatment.

Nd:YAG 1.44 laser ablation of human cartilage

NASA Astrophysics Data System (ADS)

Cummings, Robert S.; Prodoehl, John A.; Rhodes, Anthony L.; Black, Johnathan D.; Sherk, Henry H.

1993-07-01

This study determined the effectiveness of a Neodymium:YAG 1.44 micrometers wavelength laser on human cartilage. This wavelength is strongly absorbed by water. Cadaveric meniscal fibrocartilage and articular hyaline cartilage were harvested and placed in normal saline during the study. A 600 micrometers quartz fiber was applied perpendicularly to the tissues with a force of 0.098 N. Quantitative measurements were then made of the ablation rate as a function of fluence. The laser energy was delivered at a constant repetition rate of 5 Hz., 650 microsecond(s) pulsewidth, and energy levels ranging from 0.5 joules to 2.0 joules. Following the ablation of the tissue, the specimens were fixed in formalin for histologic evaluation. The results of the study indicate that the ablation rate is 0.03 mm/mj/mm2 for hyaline cartilage and fibrocartilage. Fibrocartilage was cut at approximately the same rate as hyaline cartilage. There was a threshold fluence projected to be 987 mj/mm2 for hyaline cartilage and fibrocartilage. Our results indicate that the pulsed Nd:YAG laser operating at 1.44 micrometers has a threshold fluence above which it will ablate human cartilage, and that its ablation rate is directly proportional to fluence over the range of parameters tested. Fibrocartilage and hyaline cartilage demonstrated similar threshold fluence and ablation rates which is related to the high water content of these tissues.

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

2013-01-09

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.

Early Articular Cartilage MRI T2 Changes After Anterior Cruciate Ligament Reconstruction Correlate With Later Changes in T2 and Cartilage Thickness

PubMed Central

Williams, Ashley; Winalski, Carl S.; Chu, Constance R.

2018-01-01

Anterior cruciate ligament (ACL) injury is a known risk factor for future development of osteoarthritis (OA). This human clinical study seeks to determine if early changes to cartilage MRI T2 maps between baseline and 6 months following ACL reconstruction (ACLR) are associated with changes to cartilage T2 and cartilage thickness between baseline and 2 years after ACLR. Changes to T2 texture metrics and T2 mean values in medial knee cartilage of 17 human subjects 6 months after ACLR were compared to 2-year changes in T2 and in cartilage thickness of the same areas. T2 texture and mean assessments were also compared to that of 11 uninjured controls. In ACLR subjects, six-month changes in mean T2 correlated to 2-year changes in mean T2 (R = 0.80, p = 0.0001), and 6-month changes to T2 texture metrics, but not T2 mean, correlated with 2-year changes in medial femoral cartilage thickness in 9 of the 20 texture features assessed (R = 0.48–0.72, p ≤ 0.05). Both mean T2 and texture differed (p < 0.05) between ALCR subjects and uninjured controls. Clinical Significance These results show that short-term longitudinal evaluation of T2 map and textural changes may provide early warning of cartilage at risk for progressive degeneration after ACL injury and reconstruction. PMID:27381512

Mesenchymal stem cells for cartilage repair in osteoarthritis

PubMed Central

2012-01-01

Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA. PMID:22776206

Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

DTIC Science & Technology

2011-03-01

defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have observed that... self -renewal to their regenerative capacity after transplantation into the cartilage defects (Technical Objective #1). Next, we will determine the...osteochondral defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have

Simple Correction of Alar Retraction by Conchal Cartilage Extension Grafts.

PubMed

Jang, Yong Jun; Kim, Sung Min; Lew, Dae Hyun; Song, Seung Yong

2016-11-01

Alar retraction is a challenging condition in rhinoplasty marked by exaggerated nostril exposure and awkwardness. Although various methods for correcting alar retraction have been introduced, none is without drawbacks. Herein, we report a simple procedure that is both effective and safe for correcting alar retraction using only conchal cartilage grafting. Between August 2007 and August 2009, 18 patients underwent conchal cartilage extension grafting to correct alar retraction. Conchal cartilage extension grafts were fixed to the caudal margins of the lateral crura and covered with vestibular skin advancement flaps. Preoperative and postoperative photographs were reviewed and analyzed. Patient satisfaction was surveyed and categorized into 4 groups (very satisfied, satisfied, moderate, or unsatisfied). According to the survey, 8 patients were very satisfied, 9 were satisfied, and 1 considered the outcome moderate, resulting in satisfaction for most patients. The average distance from the alar rim to the long axis of the nostril was reduced by 1.4 mm (3.6 to 2.2 mm). There were no complications, except in 2 cases with palpable cartilage step-off that resolved without any aesthetic problems. Conchal cartilage alar extension graft is a simple, effective method of correcting alar retraction that can be combined with aesthetic rhinoplasty conveniently, utilizing conchal cartilage, which is the most similar cartilage to alar cartilage, and requiring a lesser volume of cartilage harvest compared to previously devised methods. However, the current procedure lacks efficacy for severe alar retraction and a longer follow-up period may be required to substantiate the enduring efficacy of the current procedure.

Experimental Influences in the Accurate Measurement of Cartilage Thickness in MRI.

PubMed

Wang, Nian; Badar, Farid; Xia, Yang

2018-01-01

Objective To study the experimental influences to the measurement of cartilage thickness by magnetic resonance imaging (MRI). Design The complete thicknesses of healthy and trypsin-degraded cartilage were measured at high-resolution MRI under different conditions, using two intensity-based imaging sequences (ultra-short echo [UTE] and multislice-multiecho [MSME]) and 3 quantitative relaxation imaging sequences (T 1 , T 2 , and T 1 ρ). Other variables included different orientations in the magnet, 2 soaking solutions (saline and phosphate buffered saline [PBS]), and external loading. Results With cartilage soaked in saline, UTE and T 1 methods yielded complete and consistent measurement of cartilage thickness, while the thickness measurement by T 2 , T 1 ρ, and MSME methods were orientation dependent. The effect of external loading on cartilage thickness is also sequence and orientation dependent. All variations in cartilage thickness in MRI could be eliminated with the use of a 100 mM PBS or imaged by UTE sequence. Conclusions The appearance of articular cartilage and the measurement accuracy of cartilage thickness in MRI can be influenced by a number of experimental factors in ex vivo MRI, from the use of various pulse sequences and soaking solutions to the health of the tissue. T 2 -based imaging sequence, both proton-intensity sequence and quantitative relaxation sequence, similarly produced the largest variations. With adequate resolution, the accurate measurement of whole cartilage tissue in clinical MRI could be utilized to detect differences between healthy and osteoarthritic cartilage after compression.

Assessment of hyaline cartilage matrix composition using near infrared spectroscopy.

PubMed

Palukuru, Uday P; McGoverin, Cushla M; Pleshko, Nancy

2014-09-01

Changes in the composition of the extracellular matrix (ECM) are characteristic of injury or disease in cartilage tissue. Various imaging modalities and biochemical techniques have been used to assess the changes in cartilage tissue but lack adequate sensitivity, or in the case of biochemical techniques, result in destruction of the sample. Fourier transform near infrared (FT-NIR) spectroscopy has shown promise for the study of cartilage composition. In the current study NIR spectroscopy was used to identify the contributions of individual components of cartilage in the NIR spectra by assessment of the major cartilage components, collagen and chondroitin sulfate, in pure component mixtures. The NIR spectra were obtained using homogenous pellets made by dilution with potassium bromide. A partial least squares (PLS) model was calculated to predict composition in bovine cartilage samples. Characteristic absorbance peaks between 4000 and 5000 cm(-1) could be attributed to components of cartilage, i.e. collagen and chondroitin sulfate. Prediction of the amount of collagen and chondroitin sulfate in tissues was possible within 8% (w/dw) of values obtained by gold standard biochemical assessment. These results support the use of NIR spectroscopy for in vitro and in vivo applications to assess matrix composition of cartilage tissues, especially when tissue destruction should be avoided. Copyright © 2014. Published by Elsevier B.V.

Articular Cartilage Repair of the Knee in Children and Adolescents

PubMed Central

Salzmann, Gian M.; Niemeyer, Philipp; Hochrein, Alfred; Stoddart, Martin J.; Angele, Peter

2018-01-01

Articular cartilage predominantly serves a biomechanical function, which begins in utero and further develops during growth and locomotion. With regard to its 2-tissue structure (chondrocytes and matrix), the regenerative potential of hyaline cartilage defects is limited. Children and adolescents are increasingly suffering from articular cartilage and osteochondral deficiencies. Traumatic incidents often result in damage to the joint surfaces, while repetitive microtrauma may cause osteochondritis dissecans. When compared with their adult counterparts, children and adolescents have a greater capacity to regenerate articular cartilage defects. Even so, articular cartilage injuries in this age group may predispose them to premature osteoarthritis. Consequently, surgery is indicated in young patients when conservative measures fail. The operative techniques for articular cartilage injuries traditionally performed in adults may be performed in children, although an individualized approach must be tailored according to patient and defect characteristics. Clear guidelines for defect dimension–associated techniques have not been reported. Knee joint dimensions must be considered and correlated with respect to the cartilage defect size. Particular attention must be given to the subchondral bone, which is frequently affected in children and adolescents. Articular cartilage repair techniques appear to be safe in this cohort of patients, and no differences in complication rates have been reported when compared with adult patients. Particularly, autologous chondrocyte implantation has good biological potential, especially for large-diameter joint surface defects. PMID:29568785

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

Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

PubMed

Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

2002-12-01

Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

Biomimetic structured surfaces increase primary adhesion capacity of cartilage implants.

PubMed

Lahner, Matthias; Kalwa, Lukas; Olbring, Roxana; Mohr, Charlotte; Göpfert, Lena; Seidl, Tobias

2015-01-01

In cartilage repair, scaffold-assisted single-step techniques are used to improve the cartilage regeneration. Nevertheless, the fixation of cartilage implants represents a challenge in orthopaedics, particularly in the moist conditions that pertain during arthroscopic surgery. Within the animal kingdom a broad range of species has developed working solutions to intermittent adhesion under challenging conditions. Using a top-down approach we identified promising mechanisms for biomimetic transfer The tree-frog adhesive system served as a test case to analyze the adhesion capacity of a polyglycolic acid (PGA) scaffold with and without a structural modification in a bovine articular cartilage defect model. To this end, PGA implants were modified with a simplified foot-pad structure and evaluated on femoral articular bovine cartilage lesions. Non-structured PGA scaffolds were used as control. Both implants were pressed on 20 mm × 20 mm full-thickness femoral cartilage defects using a dynamometer. The structured scaffolds showed a higher adhesion capacity on the cartilage defect than the non-structured original scaffolds. The results suggest that the adhesion ability can be increased by means of biomimetic structured surfaces without the need of additional chemical treatment and thus significantly facilitate primary fixation procedures.

Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

PubMed Central

Li, Hongyu; Xu, Xin; Ye, Ling; Zhou, Xuedong

2017-01-01

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering. PMID:29123550

Nanoscale Surface Modifications of Medical Implants for Cartilage Tissue Repair and Regeneration

PubMed Central

Griffin, MF; Szarko, M; Seifailan, A; Butler, PE

2016-01-01

Background: Natural cartilage regeneration is limited after trauma or degenerative processes. Due to the clinical challenge of reconstruction of articular cartilage, research into developing biomaterials to support cartilage regeneration have evolved. The structural architecture of composition of the cartilage extracellular matrix (ECM) is vital in guiding cell adhesion, migration and formation of cartilage. Current technologies have tried to mimic the cell’s nanoscale microenvironment to improve implants to improve cartilage tissue repair. Methods: This review evaluates nanoscale techniques used to modify the implant surface for cartilage regeneration. Results: The surface of biomaterial is a vital parameter to guide cell adhesion and consequently allow for the formation of ECM and allow for tissue repair. By providing nanosized cues on the surface in the form of a nanotopography or nanosized molecules, allows for better control of cell behaviour and regeneration of cartilage. Chemical, physical and lithography techniques have all been explored for modifying the nanoscale surface of implants to promote chondrocyte adhesion and ECM formation. Conclusion: Future studies are needed to further establish the optimal nanoscale modification of implants for cartilage tissue regeneration. PMID:28217208

Mesenchymal stem-cell potential in cartilage repair: an update

PubMed Central

Mazor, M; Lespessailles, E; Coursier, R; Daniellou, R; Best, T M; Toumi, H

2014-01-01

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field. PMID:25353372

New Frontiers for Cartilage Repair and Protection.

PubMed

Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

2012-01-01

Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

Crushed Cartilage: A Rescue Procedure in Rhinoplasty.

PubMed

Boccieri, Armando; Marianetti, Tito M; Pascali, Michele

2018-05-01

While the use of crushed cartilage is now universally recognized as a valid procedure in rhinoplasty to mask irregularities and eliminate slight deficits, there is still no consensus as to the optimal degree of crushing and the rate of graft resorption over time. With a view to casting light on these 2 important aspects and providing some guidelines, the authors present a study of 123 patients subjected to grafts of cartilage with different degrees of crushing in the different areas of the nasal pyramid: upper third (45 patients), middle third (40), and lower third (38). The degree of crushing was medium for 95 patients and high for 28 who presented thinner and less elastic skin. Comparison of the performance over time of the cartilage grafts inserted in the same areas but with different degrees of crushing provides important indications as regard the best way of preparing the material. The results proved satisfactory with improvements for all of the 95 patients subjected to grafts of moderately crushed cartilage. The initial defect was instead still present, albeit with some partial improvement, at a distance of 12 months in 17 of the 28 patients where highly crushed cartilage was used. The study suggests that a moderate degree of crushing offers better results as regard flexibility and stability over time.

Xiphoid Process-Derived Chondrocytes: A Novel Cell Source for Elastic Cartilage Regeneration

PubMed Central

Nam, Seungwoo; Cho, Wheemoon; Cho, Hyunji; Lee, Jungsun

2014-01-01

Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage. PMID:25205841

Upregulation of miR-98 Inhibits Apoptosis in Cartilage Cells in Osteoarthritis.

PubMed

Wang, Gui-Long; Wu, Yu-Bo; Liu, Jia-Tian; Li, Cui-Yun

2016-11-01

We aimed to investigate the effects of microRNA-98 (miR-98) on apoptosis in cartilage cells of osteoarthritis (OA) patients. Knee cartilage tissue samples were collected from 31 OA patients, 21 autopsies, and 26 amputation patients due to trauma. The clinicopathological data were recorded. Quantitative real-time polymerase chain reaction was performed to compare the miR-98 expression levels from cartilage cells obtained from the OA and non-OA patients. Clinicopathological characteristics of the patients were also analyzed. Primary chondrocytes were separated from cartilage tissues and transfected with plasmids or siRNA to overexpress or inhibit miR-98. Annexin V-PI double staining and TUNEL assays were used to examine apoptosis in the primary chondrocytes after transfection. Finally, a rat OA model was used to confirm the effects of miR-98 on apoptosis in cartilage cells in vivo. Compared with the normal cartilage tissues, miR-98 expression was reduced in the OA cartilage tissues (p < 0.01). The miR-98 expression levels were also significantly correlated with the OA stage (p < 0.05). In vitro, transfection with the miR-98 inhibitor increased apoptosis in the cartilage cells (p < 0.05), and transfection with a miR-98 mimic inhibited apoptosis in cartilage cells (p < 0.05). In the OA rat model, exogenous injection of the miR-98 mimic inhibited apoptosis in the rat cartilage cells thus alleviating OA. MiR-98 expression is reduced in the cartilage cells of OA patients and the overexpression of miR-98 inhibits cartilage cell apoptosis, while inhibition of microRNA-98 leads to cartilage cell apoptosis. These findings provide a theoretical basis for the development of novel targeted therapies for OA.

Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

PubMed

Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

2018-01-01

Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:52-63, 2018. © 2017 Orthopaedic Research

CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

PubMed

Porter, Erin G; Winter, Matthew D; Sheppard, Barbara J; Berry, Clifford R; Hernandez, Jorge A

2016-09-01

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other. © 2016 American College of Veterinary Radiology.

Wavelength-dependent penetration depth of near infrared radiation into cartilage.

PubMed

Padalkar, M V; Pleshko, N

2015-04-07

Articular cartilage is a hyaline cartilage that lines the subchondral bone in the diarthrodial joints. Near infrared (NIR) spectroscopy is emerging as a nondestructive modality for the evaluation of cartilage pathology; however, studies regarding the depth of penetration of NIR radiation into cartilage are lacking. The average thickness of human cartilage is about 1-3 mm, and it becomes even thinner as OA progresses. To ensure that spectral data collected is restricted to the tissue of interest, i.e. cartilage in this case, and not from the underlying subchondral bone, it is necessary to determine the depth of penetration of NIR radiation in different wavelength (frequency) regions. In the current study, we establish how the depth of penetration varies throughout the NIR frequency range (4000-10 000 cm(-1)). NIR spectra were collected from cartilage samples of different thicknesses (0.5 mm to 5 mm) with and without polystyrene placed underneath. A separate NIR spectrum of polystyrene was collected as a reference. It was found that the depth of penetration varied from ∼1 mm to 2 mm in the 4000-5100 cm(-1) range, ∼3 mm in the 5100-7000 cm(-1) range, and ∼5 mm in the 7000-9000 cm(-1) frequency range. These findings suggest that the best NIR region to evaluate cartilage with no subchondral bone contribution is in the range of 4000-7000 cm(-1).

Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

PubMed

Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

2017-08-01

Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers

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.

Multimodal nonlinear optical imaging of cartilage development in mouse model

NASA Astrophysics Data System (ADS)

He, Sicong; Xue, Wenqian; Sun, Qiqi; Li, Xuesong; Huang, Jiandong; Qu, Jianan Y.

2017-02-01

Kinesin-1 is a kind of motor protein responsible for intracellular transportation and has been studied in a variety of tissues. However, its roles in cartilage development are not clear. In this study, a kinesin-1 heavy chain (Kif5b) knockout mouse model is used to study the functions of kinesin-1 in the cartilage development. We developed a multimodal nonlinear optical (NLO) microscope system integrating stimulated Raman scattering (SRS), second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) to investigate the morphological and biomedical characteristics of fresh tibial cartilage from normal and mutant mice at different developmental stages. The combined forward and backward SHG imaging resolved the fine structure of collagen fibrils in the extracellular matrix of cartilage. Meanwhile, the chondrocyte morphology in different zones of cartilage was visualized by label-free SRS and TPEF images. The results show that the fibrillar collagen in the superficial zone of cartilage in postnatal day 10 and 15 (P10 and P15) knockout mice was significantly less than that of control mice. Moreover, we observed distorted morphology and disorganization of columnar arrangement of chondrocytes in the growth plate cartilage of mutant mice. This study reveals the significant roles of kinesin-1 in collagen formation and chondrocyte morphogenesis.

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

3.0T MR imaging of the ankle: Axial traction for morphological cartilage evaluation, quantitative T2 mapping and cartilage diffusion imaging-A preliminary study.

PubMed

Jungmann, Pia M; Baum, Thomas; Schaeffeler, Christoph; Sauerschnig, Martin; Brucker, Peter U; Mann, Alexander; Ganter, Carl; Bieri, Oliver; Rummeny, Ernst J; Woertler, Klaus; Bauer, Jan S

2015-08-01

To determine the impact of axial traction during high resolution 3.0T MR imaging of the ankle on morphological assessment of articular cartilage and quantitative cartilage imaging parameters. MR images of n=25 asymptomatic ankles were acquired with and without axial traction (6kg). Coronal and sagittal T1-weighted (w) turbo spin echo (TSE) sequences with a driven equilibrium pulse and sagittal fat-saturated intermediate-w (IMfs) TSE sequences were acquired for morphological evaluation on a four-point scale (1=best, 4=worst). For quantitative assessment of cartilage degradation segmentation was performed on 2D multislice-multiecho (MSME) SE T2, steady-state free-precession (SSFP; n=8) T2 and SSFP diffusion-weighted imaging (DWI; n=8) images. Wilcoxon-tests and paired t-tests were used for statistical analysis. With axial traction, joint space width increased significantly and delineation of cartilage surfaces was rated superior (P<0.05). Cartilage surfaces were best visualized on coronal T1-w images (P<0.05). Differences for cartilage matrix evaluation were smaller. Subchondral bone evaluation, motion artifacts and image quality were not significantly different between the acquisition methods (P>0.05). T2 values were lower at the tibia than at the talus (P<0.001). Reproducibility was better for images with axial traction. Axial traction increased the joint space width, allowed for better visualization of cartilage surfaces and improved compartment discrimination and reproducibility of quantitative cartilage parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Susceptibility weighted imaging of cartilage canals in porcine epiphyseal growth cartilage ex vivo and in vivo.

PubMed

Nissi, Mikko J; Toth, Ferenc; Zhang, Jinjin; Schmitter, Sebastian; Benson, Michael; Carlson, Cathy S; Ellermann, Jutta M

2014-06-01

High-resolution visualization of cartilage canals has been restricted to histological methods and contrast-enhanced imaging. In this study, the feasibility of non-contrast-enhanced susceptibility weighted imaging (SWI) for visualization of the cartilage canals was investigated ex vivo at 9.4 T, further explored at 7 and 3 T and demonstrated in vivo at 7 T, using a porcine animal model. SWI scans of specimens of distal femur and humerus from 1 to 8 week-old piglets were conducted at 9.4 T using 3D-GRE sequence and SWI post-processing. The stifle joints of a 2-week old piglet were scanned ex vivo at 7 and 3 T. Finally, the same sites of a 3-week-old piglet were scanned, in vivo, at 7 T under general anesthesia using the vendor-provided sequences. High-contrast visualization of the cartilage canals was obtained ex vivo, especially at higher field strengths; the results were confirmed histologically. In vivo feasibility was demonstrated at 7 T and comparison of ex vivo scans at 3 and 7 T indicated feasibility of using SWI at 3 T. High-resolution 3D visualization of cartilage canals was demonstrated using SWI. This demonstration of fully noninvasive visualization opens new avenues to explore skeletal maturation and the role of vascular supply for diseases such as osteochondrosis. Copyright © 2013 Wiley Periodicals, Inc.

Object-oriented Persistent Homology

PubMed Central

Wang, Bao; Wei, Guo-Wei

2015-01-01

Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

Expression of Keratinocyte Growth Factor and Its Receptor in Rat Tracheal Cartilage: Possible Involvement in Wound Healing of the Damaged Cartilage

PubMed Central

Abo, Takafumi; Nagayasu, Takeshi; Hishikawa, Yoshitaka; Tagawa, Tsutomu; Nanashima, Atsushi; Yamayoshi, Takatomo; Matsumoto, Keitaro; An, Shucai; Koji, Takehiko

2010-01-01

Keratinocyte growth factor (KGF) is involved in the development and regeneration of a variety of tissues. To clarify the role of KGF in cartilage wound healing, we examined the expression of KGF and its receptor (KGFR) immunohistochemically in the wound healing area of rat tracheal cartilage, and the direct effect of recombinant KGF on the proliferation and differentiation of primary cultures of rat chondrocytes. KGF was found in the cytoplasm of both chondrocytes and perichondrial cells. On the other hand, KGFR was detected only in the plasma membrane of chondrocytes. Although the expression of KGF was similar in the cartilage and perichondrial area before and after injury, KGFR expression was induced after injury and limited to proliferating chondrocytes. The staining pattern of KGF and KGFR was same in the mature and the immature rat tracheal cartilage. Moreover, in vitro experiments using primary cultured chondrocytes revealed that KGF at 200 ng/ml significantly increased the number of chondrocytes (~1.5-fold), and significantly reduced acid mucopolysaccharide production. These results indicate that KGF stimulates chondrocyte proliferation, suggesting that KGF could therapeutically modulate the wound healing process in the tracheal cartilage. PMID:20628626

Expression of keratinocyte growth factor and its receptor in rat tracheal cartilage: possible involvement in wound healing of the damaged cartilage.

PubMed

Abo, Takafumi; Nagayasu, Takeshi; Hishikawa, Yoshitaka; Tagawa, Tsutomu; Nanashima, Atsushi; Yamayoshi, Takatomo; Matsumoto, Keitaro; An, Shucai; Koji, Takehiko

2010-06-28

Keratinocyte growth factor (KGF) is involved in the development and regeneration of a variety of tissues. To clarify the role of KGF in cartilage wound healing, we examined the expression of KGF and its receptor (KGFR) immunohistochemically in the wound healing area of rat tracheal cartilage, and the direct effect of recombinant KGF on the proliferation and differentiation of primary cultures of rat chondrocytes. KGF was found in the cytoplasm of both chondrocytes and perichondrial cells. On the other hand, KGFR was detected only in the plasma membrane of chondrocytes. Although the expression of KGF was similar in the cartilage and perichondrial area before and after injury, KGFR expression was induced after injury and limited to proliferating chondrocytes. The staining pattern of KGF and KGFR was same in the mature and the immature rat tracheal cartilage. Moreover, in vitro experiments using primary cultured chondrocytes revealed that KGF at 200 ng/ml significantly increased the number of chondrocytes (~1.5-fold), and significantly reduced acid mucopolysaccharide production. These results indicate that KGF stimulates chondrocyte proliferation, suggesting that KGF could therapeutically modulate the wound healing process in the tracheal cartilage.

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs

PubMed Central

Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Hatsushika, Daisuke; Horie, Masafumi; Tsuji, Kunikazu; Kawarasaki, Tatsuo; Watanabe, Atsuya; Hishikawa, Shuji; Fujimoto, Yasuhiro; Tanaka, Hozumi; Kobayashi, Eiji

2012-01-01

Background aims Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. Methods The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Results Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Conclusions Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs. PMID:22309371

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

PubMed

Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Hatsushika, Daisuke; Horie, Masafumi; Tsuji, Kunikazu; Kawarasaki, Tatsuo; Watanabe, Atsuya; Hishikawa, Shuji; Fujimoto, Yasuhiro; Tanaka, Hozumi; Kobayashi, Eiji

2012-03-01

Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs.

State of the Art: MR Imaging after Knee Cartilage Repair Surgery.

PubMed

Guermazi, Ali; Roemer, Frank W; Alizai, Hamza; Winalski, Carl S; Welsch, Goetz; Brittberg, Mats; Trattnig, Siegfried

2015-10-01

Cartilage injuries are common, especially in athletes. Because these injuries frequently affect young patients, and they have the potential to progress to osteoarthritis, treatment to alleviate symptoms and delay joint degeneration is warranted. A number of surgical techniques are available to treat focal chondral defects, including marrow stimulation, osteochondral auto- and allografting, and autologous chondrocyte implantation. Although arthroscopy is considered the standard of reference for the evaluation of cartilage before and after repair, it is invasive with associated morbidity and cannot adequately depict the deep cartilage layer and underlying bone. Magnetic resonance (MR) imaging provides unparalleled noninvasive assessment of the repair site and all other joint tissues. MR observation of cartilage repair tissue is a well-established semiquantitative scoring system for repair tissue that has primarily been used in clinical research studies. The cartilage repair osteoarthritis knee score (CROAKS) optimizes comprehensive morphologic assessment of the knee joint after cartilage repair. Furthermore, quantitative, compositional MR imaging measurements (eg, T2, T2*, T1ρ), delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC), and sodium imaging are available for biochemical assessment. These quantitative MR imaging techniques help assess collagen content and orientation, water content, and glycosaminoglycan and/or proteoglycan content both in the repair tissue as it matures and in the "native" cartilage. In this review, the authors discuss the principles of state-of-the-art morphologic and compositional MR imaging techniques for imaging of cartilage repair and their application to longitudinal studies. (©) RSNA, 2015.

Laser-assisted cartilage reshaping: in vitro and in vivo animal studies

NASA Astrophysics Data System (ADS)

Wang, Zhi; Pankratov, Michail M.; Perrault, Donald F., Jr.; Shapshay, Stanley M.

1995-05-01

Correction of cartilaginous defects in the head and neck area remains a challenge for the surgeon. This study investigated a new technique for laser-assisted cartilage reshaping. The pulsed 1.44 micrometers Nd:YAG laser was used in vitro and in vivo experiments to irradiate cartilage to change it's shape without carbonization or vaporization of tissue. Two watts of average power in non contact manner was used to irradiate and reshape the cartilage. The extracted reshaped cartilage specimens underwent testing of elastic force with a computer assisted measurement system that recorded the changes in elastic force in the specimens from 1 hr to 11 days post-irradiation. An animal model of defective tracheal cartilage (collapsed tracheal wall) was created, allowed to heal for 6 weeks and then corrected endoscopically with the laser-assisted technique. The results of the in vitro and in vivo investigations demonstrated that it was possible to alter the cartilage and that cartilage would retain its new shape. The clinical significance of the technique is evident and warrants further animal studies and clinical trials.

Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

PubMed

Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

2015-04-01

The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

Chondrogenesis and cartilage tissue engineering: the longer road to technology development.

PubMed

Mahmoudifar, Nastaran; Doran, Pauline M

2012-03-01

Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis; a case-control study of relationship between collagen, glycosaminoglycan and cartilage swelling.

PubMed

Hosseininia, Shahrzad; Lindberg, Lisbeth R; Dahlberg, Leif E

2013-01-09

It remains to be shown whether OA shares molecular similarities between different joints in humans. This study provides evidence for similarities in cartilage molecular damage in osteoarthritic (OA) joints. Articular cartilage from osteoarthritic hip joints were analysed and compared to non-OA controls regarding collagen, glycosaminoglycan and water content. Femoral heads from 16 osteoarthritic (OA) and 20 reference patients were obtained from hip replacement surgery due to OA and femoral neck fracture, respectively. Cartilage histological changes were assessed by Mankin grading and denatured collagen type II immunostaining and cartilage was extracted by α-chymotrypsin. Hydroxyproline and Alcian blue binding assays were used to measure collagen and glycosaminoglycan (GAG) content, respectively. Mankin and immunohistology scores were significantly higher in hip OA samples than in reference samples. Cartilage water content was 6% higher in OA samples than in references. 2.5 times more collagen was extracted from OA than from reference samples. There was a positive association between water content and percentage of extractable collagen pool (ECP) in both groups. The amounts of collagen per wet and dry weights did not differ statistically between OA and reference cartilage. % Extractable collagen was not related to collagen per dry weight in either group. However when collagen was expressed by wet weight there was a negative correlation between % extractable and collagen in OA cartilage. The amount of GAG per wet weight was similar in both groups but the amount of GAG per dry weight was higher in OA samples compared to reference samples, which suggests a capacity for GAG biosynthesis in hip OA cartilage. Neither of the studied parameters was related to age in either group. Increased collagen extractability and water content in human hip cartilage is associated with OA pathology and can be observed at early stages of the degenerative hip OA process. Our results

Two-Stage Parameter Estimation in Confined Costal Aquifers

NASA Astrophysics Data System (ADS)

Hsu, N.

2003-12-01

Using field observations of tidal level and piezometric head at an observation well, this research develops a two-stage parameter estimation approach for estimating the hydraulic conductivity (T) and storage coefficient (S) of a confined aquifer in a costal area. While the y-axis coincides with the coastline, the x-axis extends from zero to infinity and, therefore, the domain of the aquifer is assumed to be a half plane. Other assumptions include homogeneity, isotropy and constant thickness of the aquifer, and zero initial head distribution. In the first stage, fluctuations of the tidal level and piezometric head at the observation well are collected simultaneously without the influence of pumping. Fourier spectra analysis is used to find the autocorrelation and crosscorrelation of the two sets of observations as well as the phase vs. frequency function. The tidal efficiency and time delay can then be computed. The analytical solution of Ferris (1951) is then used to compute the ratio of T/S. In the second stage, the system is stressed with pumping and observations of the tidal level and piezometric head at the observation well are collected simultaneously. The effect of tide to the observation well without pumping can be computed by the analytical solution of Ferris (1951) based upon the identified ratio of T/S and is deducted from the piezometric head observations to obtain the updated piezometric head. Theis equation coupled with the method of image is then applied to the updated piezometric head to obtain the T and S values. The developed approach is applied to a hypothetical aquifer. The results obtained show convergence of the approach. The robustness of the developed approach is also demonstrated by using noise-corrupted observations.

Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction

PubMed Central

Mastbergen, Simon C; Jones, Elena; Calder, Stuart J; Lafeber, Floris P J G; McGonagle, Dennis

2016-01-01

Objectives Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable ‘spontaneous’ cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions. Methods Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF. SF was digested with hyaluronidase (hyase) and its effect on adhesion was observed using confocal microscopy. MRI and microscopy were used to image autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was investigated using gel electrophoresis and densitometry. Results Osteoarthritic-synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF-MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These differences were linked to the SF mediated HA-coat which was larger in OA-SF than in RA-SF. OA-SF contained >9 MDa HA and this correlated with increases in adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was evident and also dependent on HA MW. Conclusions These findings highlight an unappreciated role of SF-HA on MSC interactions and provide proof of concept that endogenous SF-MSCs are capable of adhering to cartilage in a favourable biochemical and biomechanical environment in OA distracted joints, offering novel one-stage strategies towards joint repair. PMID:25948596

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.

[Study on shape and structure of calcified cartilage zone in normal human knee joint].

PubMed

Wang, Fuyou; Yang, Liu; Duan, Xiaojun; Tan, Hongbo; Dai, Gang

2008-05-01

To explore the shape and structure of calcified cartilage zone and its interface between the non-calcified articular cartilage and subchondral bone plate. The normal human condyles of femur (n=20) were obtained from the tissue bank donated by the residents, 10 males and 10 females, aged 17-45 years. The longitudinal and transverse paraffin sections were prepared by the routine method. The shape and structure of calcified cartilage zone were observed with the Safranin O/fast green and von kossa stain method. The interface conjunction among zones of cartilage was researched by SEM and the 3D structural model was established by serial sections and modeling technique. Articular bone-cartilage safranin O/fast green staining showed that cartilage was stained red and subchondral bone was stained blue. The calcified cartilage zone was located between the tidemark and cement line. Von kossa staining showed that calcified cartilage zone was stained black and sharpness of structure border. Upper interface gomphosised tightly with the non-calcified cartilage by the wave shaped tidemark and lower interface anchored tightly with the subchondral bone by the uneven comb shaped cement line. The non-calcified cartilage zone was interlocked tightly in the manner of "ravine-engomphosis" by the calcified cartilage zone as observed under SEM, and the subchondral bone was anchored tightly in the manner of"comb-anchor" by the in the calcified cartilage zone 3D reconstruction model. The calcified cartilage zone is an important structure in the articular cartilage. The articular cartilage is fixed firmly into subchondral bone plate by the distinctive conjunct interfaces of calcified cartilage zone.

Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

2018-02-01

Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

Preclinical Studies for Cartilage Repair

PubMed Central

Hurtig, Mark B.; Buschmann, Michael D.; Fortier, Lisa A.; Hoemann, Caroline D.; Hunziker, Ernst B.; Jurvelin, Jukka S.; Mainil-Varlet, Pierre; McIlwraith, C. Wayne; Sah, Robert L.; Whiteside, Robert A.

2011-01-01

Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures. PMID:26069576

Anatomic analysis of the conchal bowl cartilage.

PubMed

Brockhoff, Hans C; Morris, Christopher D; Throckmorton, Gaylord S; Finn, Rick

2014-11-01

The conchal bowl is a portion of auricular cartilage commonly used as an autologous graft for various maxillofacial procedures. Few studies have attempted to describe the anatomy of this region in detail, particularly in relation to the curvature of the conchal bowl. The present study has provided detailed information about the anatomy of the auricular cartilage in the conchal bowl region that could assist in the surgical design of graft harvesting. A total of 35 pairs of cadaver ears without gross deformity (15 male, 20 female; aged 39 to 99 years) were dissected to completely expose the cartilage skeleton. Each cartilage was stabilized, and the conchal bowl was mapped. The starting reference point was defined as the intersection of the lateral border of the antihelix and the superiormost aspect of the inferior crux. A prefabricated grid was then used to imprint a 4 × 5 matrix of pinpoint ink spots on the surface of each cartilage, with 6-mm increments between each spot. The grid's y and x axes were then aligned with the landmarks above. Next, a MicroScribe 3-dimensional digitizer (ghost3d.com) was used to capture the 3-dimensional coordinates for each point on the ear's surface and the coordinates were transferred into an Excel spreadsheet. After digitization, a Boley gauge was used to measure the thickness of the cartilage at each premarked spot. The gathered data points and measurements were examined to describe our parameters of interest (ie, depth, thickness, and curvature). The average maximum conchal bowl depth was 10.5 ± 3.0 mm in the female ears and 10.7 ± 2.5 mm in the male ears. In general, the conchal bowl depth at each point did not differ significantly between the males and females. The mean cartilage thickness ranged from 0.77 to 1.79 mm (mean 1.15 ± 0.26) in the females and 0.95 to 1.45 mm (mean 1.25 ± 0.23) in the males. Both genders showed an increase in the conchal bowl depth from inferiorly to superiorly and from posteriorly to anteriorly

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.

Cartilage imaging in children: current indications, magnetic resonance imaging techniques, and imaging findings.

PubMed

Ho-Fung, Victor M; Jaramillo, Diego

2013-07-01

Evaluation of hyaline cartilage in pediatric patients requires in-depth understanding of normal physiologic changes in the developing skeleton. Magnetic resonance (MR) imaging is a powerful tool for morphologic and functional imaging of the cartilage. In this review article, current imaging indications for cartilage evaluation pertinent to the pediatric population are described. In particular, novel surgical techniques for cartilage repair and MR classification of cartilage injuries are summarized. The authors also provide a review of the normal anatomy and a concise description of the advances in quantitative cartilage imaging (ie, T2 mapping, delayed gadolinium-enhanced MR imaging of cartilage, and T1rho). Copyright © 2013 Elsevier Inc. All rights reserved.

Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults

PubMed Central

Van Rossom, Sam; Smith, Colin Robert; Zevenbergen, Lianne; Thelen, Darryl Gerard; Vanwanseele, Benedicte; Van Assche, Dieter; Jonkers, Ilse

2017-01-01

Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence) of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading. PMID:28076431

Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

PubMed

Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

2018-07-01

Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Rare association of spondylo costal dysostosis with split cord malformations type II: A case report and a brief review of literature

PubMed Central

Srinivas, Bhavanam Hanuma; Puligopu, Aneel Kumar; Sukhla, Dinesh; Ranganath, Prajnya

2014-01-01

Spondylo costal dysostosis (SCD) is a genetic skeletal disorder characterized by a variety of costo-vertebral malformations. SCD with type I split cord malformation (SCM) have been reported in the literature. We report an unusual association of SCD with type II SCM. Imaging studies revealed multiple vertebral segmentations, rib malformations, spina bifida and low lying cord with type II SCM at the D12-L3 level. She underwent detethering of the cord. To the best of our knowledge, this is the first report of the association of SCD with type II SCM. PMID:25250070

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

UTE bi-component analysis of T2* relaxation in articular cartilage

PubMed Central

Shao, H.; Chang, E.Y.; Pauli, C.; Zanganeh, S.; Bae, W.; Chung, C.B.; Tang, G.; Du, J.

2015-01-01

SUMMARY Objectives To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. Methods Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy (PLM), confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n = 5). Results The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80 ± 0.05 ms and short T2* fraction of 39.93 ± 3.05% in vitro, and a mean short T2* of 0.93 ± 0.58 ms and short T2* fraction of 35.03 ± 4.09% in vivo. Conclusion UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive. PMID:26382110

Label-free characterization of articular cartilage in osteoarthritis model mice by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-02-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this study, we generated an animal OA model surgically induced by knee joint instability, and the femurs were harvested at two weeks after the surgery. We performed Raman spectroscopic analysis for the articular cartilage of distal femurs in OA side and unaffected side in each mouse. In the result, there is no gross findings in the surface of the articular cartilage in OA. On the other hand, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The major finding of this study is that the relative intensity of phosphate band (960 cm-1) increases in the degenerative cartilage. This may be the result of exposure of subchondral bone due to thinning of the cartilage layer. In conclusion, Raman spectroscopic technique is sufficient to characterize articular cartilage in OA as a pilot study for Raman application in cartilage degeneration and regeneration using animal models and human subjects.

Engineering ear-shaped cartilage using electrospun fibrous membranes of gelatin/polycaprolactone.

PubMed

Xue, Jixin; Feng, Bei; Zheng, Rui; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Yanzhong; Zhang, Wen Jie

2013-04-01

Tissue engineering approach continuously requires for emerging strategies to improve the efficacy in repairing and regeneration of tissue defects. Previously, we developed a sandwich model strategy for cartilage engineering, using the combination of acellular cartilage sheets (ACSs) and chondrocytes. However, the process for the preparation of ACSs is complicated, and it is also difficult to obtain large ACSs. The aim of this study was to engineer cartilage with precise three-dimensional (3-D) structures by applying electrospun fibrous membranes of gelatin/polycaprolactone (GT/PCL). We first prepared the electrospun GT/PCL membranes into rounded shape, and then seeded chondrocytes in the sandwich model. After in vitro and in vivo cultivation, the newly formed cartilage-like tissues were harvested. Macroscopic observations and histological analysis confirmed that the engineering of cartilage using the electrospun GT/PCL membranes was feasible. An ear-shaped cartilage was then constructed in the sandwich model, with the help of an ear-shaped titanium alloy mold. After 2 weeks of culture in vitro and 6 weeks of subcutaneous incubation in vivo, the ear-shaped cartilage largely maintained their original shape, with a shape similarity up to 91.41% of the titanium mold. In addition, the engineered cartilage showed good elasticity and impressive mechanical strength. These results demonstrated that the engineering of 3-D cartilage in a sandwich model using electrospun fibrous membranes was a facile and effective approach, which has the potential to be applied for the engineering of other tissues with complicated 3-D structures. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

PubMed Central

Sabaawy, Hatem E.

2015-01-01

Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints. PMID:26029269

Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-04-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

Histochemistry as a Unique Approach for Investigating Normal and Osteoarthritic Cartilage

PubMed Central

Musumeci, G.; Castrogiovanni, P.; Mazzone, V.; Szychlinska, M. A.; Castorina, S.; Loreto, C.

2014-01-01

In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim. PMID:24998926

Can Signal Abnormalities Detected with MR Imaging in Knee Articular Cartilage Be Used to Predict Development of Morphologic Cartilage Defects? 48-Month Data from the Osteoarthritis Initiative

PubMed Central

Gersing, Alexandra S.; Mbapte Wamba, John; Nevitt, Michael C.; McCulloch, Charles E.; Link, Thomas M.

2016-01-01

Purpose To determine the incidence with which morphologic articular cartilage defects develop over 48 months in cartilage with signal abnormalities at baseline magnetic resonance (MR) imaging in comparison with the incidence in articular cartilage without signal abnormalities at baseline. Materials and Methods The institutional review boards of all participating centers approved this HIPAA-compliant study. Right knees of 90 subjects from the Osteoarthritis Initiative (mean age, 55 years ± 8 [standard deviation]; 51% women) with cartilage signal abnormalities but without morphologic cartilage defects at 3.0-T MR imaging and without radiographic osteoarthritis (Kellgren-Lawrence score, 0–1) were frequency matched for age, sex, Kellgren-Lawrence score, and body mass index with right knees in 90 subjects without any signal abnormalities or morphologic defects in the articular cartilage (mean age, 54 years ± 5; 51% women). Individual signal abnormalities (n = 126) on intermediate-weighted fast spin-echo MR images were categorized into four subgrades: subgrade A, hypointense; subgrade B, inhomogeneous; subgrade C, hyperintense; and subgrade D, hyperintense with swelling. The development of morphologic articular cartilage defects (Whole-Organ MR Imaging Score ≥2) at 48 months was analyzed on a compartment level and was compared between groups by using generalized estimating equation logistic regression models. Results Cartilage signal abnormalities were more frequent in the patellofemoral joint than in the tibiofemoral joint (59.5% vs 39.5%). Subgrade A was seen more frequently than were subgrades C and D (36% vs 22%). Incidence of morphologic cartilage defects at 48 months was 57% in cartilage with baseline signal abnormalities, while only 4% of compartments without baseline signal abnormalities developed morphologic defects at 48 months (all compartments combined and each compartment separately, P < .01). The development of morphologic defects was not

Cricoid cartilage masquerading as a tumour on thyroid ultrasound.

PubMed

Strauss, S

1999-07-01

On ultrasound scanning of the thyroid gland in a sagittal plane, the cricoid cartilage can falsely create the impression of a mass in the gland if the transducer is angled slightly medially. The illusion of a mass is fortified on transverse view if the cricothyroid and inferior pharyngeal constrictor muscles, which lie between the upper pole of the thyroid gland and the cricoid cartilage, are misinterpreted as a solid lesion. The purpose of this study was to describe the ultrasound features of the cricoid cartilage and to determine the frequency in which a pseudolesion is created. In 15 of 26 volunteers the cartilage was seen as a hypoechoic structure surrounded by an anechoic halo and containing foci of calcification, closely resembling a thyroid nodule. In 11 of the subjects, with a mean age of 55 years, the cartilage was heavily calcified, poorly visualized and did not simulate a thyroid lesion. Awareness of the cause and appearance of this pseudolesion should help radiologists avoid a potential pitfall and prevent unnecessary invasive procedures.

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

Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance.

PubMed

Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali

2017-06-01

The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity.

PubMed

Dudek, Michal; Gossan, Nicole; Yang, Nan; Im, Hee-Jeong; Ruckshanthi, Jayalath P D; Yoshitane, Hikari; Li, Xin; Jin, Ding; Wang, Ping; Boudiffa, Maya; Bellantuono, Ilaria; Fukada, Yoshitaka; Boot-Handford, Ray P; Meng, Qing-Jun

2016-01-01

Osteoarthritis (OA) is the most prevalent and debilitating joint disease, and there are currently no effective disease-modifying treatments available. Multiple risk factors for OA, such as aging, result in progressive damage and loss of articular cartilage. Autonomous circadian clocks have been identified in mouse cartilage, and environmental disruption of circadian rhythms in mice predisposes animals to OA-like damage. However, the contribution of the cartilage clock mechanisms to the maintenance of tissue homeostasis is still unclear. Here, we have shown that expression of the core clock transcription factor BMAL1 is disrupted in human OA cartilage and in aged mouse cartilage. Furthermore, targeted Bmal1 ablation in mouse chondrocytes abolished their circadian rhythm and caused progressive degeneration of articular cartilage. We determined that BMAL1 directs the circadian expression of many genes implicated in cartilage homeostasis, including those involved in catabolic, anabolic, and apoptotic pathways. Loss of BMAL1 reduced the levels of phosphorylated SMAD2/3 (p-SMAD2/3) and NFATC2 and decreased expression of the major matrix-related genes Sox9, Acan, and Col2a1, but increased p-SMAD1/5 levels. Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage and suggest that circadian rhythm disruption is a risk factor for joint diseases such as OA.

The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity

PubMed Central

Dudek, Michal; Gossan, Nicole; Yang, Nan; Im, Hee-Jeong; Ruckshanthi, Jayalath P.D.; Yoshitane, Hikari; Li, Xin; Jin, Ding; Wang, Ping; Boudiffa, Maya; Bellantuono, Ilaria; Fukada, Yoshitaka; Boot-Handford, Ray P.; Meng, Qing-Jun

2015-01-01

Osteoarthritis (OA) is the most prevalent and debilitating joint disease, and there are currently no effective disease-modifying treatments available. Multiple risk factors for OA, such as aging, result in progressive damage and loss of articular cartilage. Autonomous circadian clocks have been identified in mouse cartilage, and environmental disruption of circadian rhythms in mice predisposes animals to OA-like damage. However, the contribution of the cartilage clock mechanisms to the maintenance of tissue homeostasis is still unclear. Here, we have shown that expression of the core clock transcription factor BMAL1 is disrupted in human OA cartilage and in aged mouse cartilage. Furthermore, targeted Bmal1 ablation in mouse chondrocytes abolished their circadian rhythm and caused progressive degeneration of articular cartilage. We determined that BMAL1 directs the circadian expression of many genes implicated in cartilage homeostasis, including those involved in catabolic, anabolic, and apoptotic pathways. Loss of BMAL1 reduced the levels of phosphorylated SMAD2/3 (p-SMAD2/3) and NFATC2 and decreased expression of the major matrix-related genes Sox9, Acan, and Col2a1, but increased p-SMAD1/5 levels. Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage and suggest that circadian rhythm disruption is a risk factor for joint diseases such as OA. PMID:26657859

Failure of Synthetic Implants: Strategies and Management.

PubMed

Jang, Yong Ju; Kim, Shin Ae; Alharethy, Sami

2018-06-01

Dorsal augmentation with synthetic implants is the most commonly performed rhinoplasty procedure, especially in the East-Asian region. However, as in all other surgical procedures, complications are inevitable. Complications that need to be managed surgically include displacement, deviation, suboptimal aesthetic outcome, extrusion, inflammation, infection, and changes in skin quality. Most complications can be easily managed with revision surgery. After the removal of the synthetic implant from the nasal dorsum, different dorsal implant materials such as dermofat, alloderm, or fascia-wrapped diced cartilage, conchal cartilage with perichondrial attachment, and costal cartilage are preferred. An irreversible change in the skin/soft tissue envelope poses a challenge that usually requires reconstructive surgery with a local flap. Therefore, early detection and prompt management of the complication are essential for minimizing the severity of the deformity and the complexity of the surgical procedures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction.

PubMed

Baboolal, Thomas G; Mastbergen, Simon C; Jones, Elena; Calder, Stuart J; Lafeber, Floris P J G; McGonagle, Dennis

2016-05-01

Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable 'spontaneous' cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions. Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF. SF was digested with hyaluronidase (hyase) and its effect on adhesion was observed using confocal microscopy. MRI and microscopy were used to image autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was investigated using gel electrophoresis and densitometry. Osteoarthritic-synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF-MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These differences were linked to the SF mediated HA-coat which was larger in OA-SF than in RA-SF. OA-SF contained >9 MDa HA and this correlated with increases in adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was evident and also dependent on HA MW. These findings highlight an unappreciated role of SF-HA on MSC interactions and provide proof of concept that endogenous SF-MSCs are capable of adhering to cartilage in a favourable biochemical and biomechanical environment in OA distracted joints, offering novel one-stage strategies towards joint repair. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Utility of Cartilage Grafts Wrapped With Amniotic Membrane in Dorsal Nasal Augmentation.

PubMed

Atespare, Altay; Kara, Hakan; Ilter, Erdin; Boyaci, Zerrin; Çelik, Öner; Midi, Ahmet

2016-06-01

The success of rhinoplasty may be compromised with postoperative problems like rough and rigid nasal dorsum. Biological grafts or alloplastic materials are required to hurdle and correct nasal dorsal deformities and also irregularities. The purpose of this experimental study was to compare pure cartilage graft, cartilage graft wrapped in amniotic membrane, and diced cartilage grafts wrapped in amniotic membrane for soft tissue augmentation. All grafts were transplanted through a subcutaneous tunnel created in the nasal dorsum of 18 rats, 6 in each group. After 3 months follow-up, the histopathological changes in all groups were evaluated by light microscopy and volumetric measurements. With regard to cartilage viability, cartilage wrapped in amniotic membrane had a higher success rate than pure cartilage graft. Also, a further increased success rate was found in the diced group. In the soft tissue augmentation after rhinoplasty surgery, especially diced cartilage wrapped in amniotic membrane keeps the graft viable and adjoined.

Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels.

PubMed

Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A; Saris, Daniel B; Malda, Jos; Anseth, Kristi S; Gill, Thomas J; Randolph, Mark A

2016-06-03

Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10. Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 × 10(7) cells cells were added to each milliliter of macromer/photoinitiator (I2959) solution. Nonpolymerized gel containing the cells (100 μL) was placed in cylindrical molds (4.5 mm diameter × 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically. Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native

Roles of macrophage migration inhibitory factor in cartilage tissue engineering.

PubMed

Fujihara, Yuko; Hikita, Atsuhiko; Takato, Tsuyoshi; Hoshi, Kazuto

2018-02-01

To obtain stable outcomes in regenerative medicine, understanding and controlling immunological responses in transplanted tissues are of great importance. In our previous study, auricular chondrocytes in tissue-engineered cartilage transplanted in mice were shown to express immunological factors, including macrophage migration inhibitory factor (MIF). Since MIF exerts pleiotropic functions, in this study, we examined the roles of MIF in cartilage regenerative medicine. We made tissue-engineered cartilage consisting of auricular chondrocytes of C57BL/6J mouse, atellocollagen gel and a PLLA scaffold, and transplanted the construct subcutaneously in a syngeneic manner. Localization of MIF was prominent in cartilage areas of tissue-engineered cartilage at 2 weeks after transplantation, though it became less apparent by 8 weeks. Co-culture with RAW264 significantly increased the expression of MIF in chondrocytes, suggesting that the transplanted chondrocytes in tissue-engineered cartilage could enhance the expression of MIF by stimulation of surrounding macrophages. When MIF was added in the culture of chondrocytes, the expression of type II collagen was increased, indicating that MIF could promote the maturation of chondrocytes. Meanwhile, toluidine blue staining of constructs containing wild type (Mif+/+) chondrocytes showed increased metachromasia compared to MIF-knockout (Mif-/-) constructs at 2 weeks. However, this tendency was reversed by 8 weeks, suggesting that the initial increase in cartilage maturation in Mif+/+ constructs deteriorated by 8 weeks. Since the Mif+/+ constructs included more iNOS-positive inflammatory macrophages at 2 weeks, MIF might induce an M1 macrophage-polarized environment, which may eventually worsen the maturation of tissue-engineered cartilage in the long term. © 2017 Wiley Periodicals, Inc.

A zebrafish sox9 gene required for cartilage morphogenesis.

PubMed

Yan, Yi-Lin; Miller, Craig T; Nissen, Robert M; Singer, Amy; Liu, Dong; Kirn, Anette; Draper, Bruce; Willoughby, John; Morcos, Paul A; Amsterdam, Adam; Chung, Bon-Chu; Westerfield, Monte; Haffter, Pascal; Hopkins, Nancy; Kimmel, Charles; Postlethwait, John H; Nissen, Robert

2002-11-01

The molecular genetic mechanisms of cartilage construction are incompletely understood. Zebrafish embryos homozygous for jellyfish (jef) mutations show craniofacial defects and lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia. We show that two alleles of jef contain mutations in sox9a, one of two zebrafish orthologs of the human transcription factor SOX9. A mutation induced by ethyl nitrosourea changed a conserved nucleotide at a splice junction and severely reduced splicing of sox9a transcript. A retrovirus insertion into sox9a disrupted its DNA-binding domain. Inhibiting splicing of the sox9a transcript in wild-type embryos with splice site-directed morpholino antisense oligonucleotides produced a phenotype like jef mutant larvae, and caused sox9a transcript to accumulate in the nucleus; this accumulation can serve as an assay for the efficacy of a morpholino independent of phenotype. RNase-protection assays showed that in morpholino-injected animals, the percent of splicing inhibition decreased from 80% at 28 hours post fertilization to 45% by 4 days. Homozygous mutant embryos had greatly reduced quantities of col2a1 message, the major collagen of cartilage. Analysis of dlx2 expression showed that neural crest specification and migration was normal in jef (sox9a) embryos. Confocal images of living embryos stained with BODIPY-ceramide revealed at single-cell resolution the formation of precartilage condensations in mutant embryos. Besides the lack of overt cartilage differentiation, pharyngeal arch condensations in jef (sox9a) mutants lacked three specific morphogenetic behaviors: the stacking of chondrocytes into orderly arrays, the individuation of pharyngeal cartilage organs and the proper shaping of individual cartilages. Despite the severe reduction of cartilages, analysis of titin expression showed normal muscle patterning in jef (sox9a) mutants. Likewise, calcein labeling

Spatially resolved elemental distributions in articular cartilage

NASA Astrophysics Data System (ADS)

Reinert, T.; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gründer, W.

2001-07-01

In this study, the nuclear microprobe technique is employed to analyse the chemistry of joint cartilage in order to correlate internal structures of the collagen network with the elemental distribution. The samples were taken from pig's knee joint. 30 μm thick coronar cross-sections were prepared by means of cryosectioning and freeze-drying. We performed simultaneously particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and elastic recoil detection analysis (ERDA). Thus we obtained spatially resolved distributions of the elements H, C, N, O, P, S, Cl, K and Ca. The main components of the organic matrix are H, C, N and O. It was shown that their relations vary with the cartilage structures. It could be shown that zones with aligned collagen fibrils contain less sulphur and potassium but more chlorine. The higher chlorine concentration is remarkable because newest biochemical studies found that hypochloric acid is involved in cartilage degradation. Furthermore, the calcium distribution is still of great interest. Its correlation to structural changes inside the cartilage is still being discussed. It could be disproved that zones of higher calcium concentration are related to the aligned structures of the collagen network.

Effects of aluminum trichloride on the cartilage stimulatory growth factors in rats.

PubMed

Zhang, Fan; Sun, Xudong; Yu, Hongyan; Yang, Xu; Song, Miao; Han, Yanfei; Li, Yanfei; Zhu, Yanzhu

2017-02-01

Aluminum (Al) is considered to be a potentially toxic metal and inhibits cartilage formation. Transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) are cartilage stimulatory growth factors, which play important roles in regulating the cartilage formation. To investigate the effects of aluminum trichloride (AlCl 3 ) on the regulation of cartilage formation. Eighty Wistar rats were orally exposed to 0 (control group), 0.4 g/L (low-dose group), 0.8 g/L (mid-dose group) and 1.6 g/L (high-dose group) AlCl 3 for 120 days, respectively. The rats body weight were decreased, the cartilage histological structure were disrupted, the cartilage and serum contents of Al and the serum level of C-telopeptide of type II collagen were all increased, the serum level of type II collagen (Col II) and alkaline phosphatase (ALP), and the mRNA expressions of TGF-β1, BMP-2, ALP and Col II were all decreased in the AlCl 3 -treated groups compared with those in control group. These results indicate that AlCl 3 inhibits the cartilage formation through inhibition of the cartilage stimulatory growth factors expressions.

Computational aspects in mechanical modeling of the articular cartilage tissue.

PubMed

Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

2013-04-01

This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.

Permeability and shear modulus of articular cartilage in growing mice.

PubMed

Berteau, J-Ph; Oyen, M; Shefelbine, S J

2016-02-01

Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Understanding the changes in mechanical tissues properties during growth is a critical step in advancing strategies for orthopedics and for cell- and biomaterial- based therapies dedicated to cartilage repair. We hypothesize that at the microscale, the articular cartilage tissue properties of the mouse (i.e., shear modulus and permeability) change with the growth and are dependent on location within the joint. We tested cartilage on the medial femoral condyle and lateral femoral condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks old) using a micro-indentation test. Results indicated that permeability decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of the growth (9 weeks). Within an age group, shear modulus was higher in the MFC than in the LFC, but permeability did not change. We have developed a method that can measure natural alterations in cartilage material properties in a murine joint, which will be useful in identifying changes in cartilage mechanics with degeneration, pathology, or treatment.

Automated classification of articular cartilage surfaces based on surface texture.

PubMed

Stachowiak, G P; Stachowiak, G W; Podsiadlo, P

2006-11-01

In this study the automated classification system previously developed by the authors was used to classify articular cartilage surfaces with different degrees of wear. This automated system classifies surfaces based on their texture. Plug samples of sheep cartilage (pins) were run on stainless steel discs under various conditions using a pin-on-disc tribometer. Testing conditions were specifically designed to produce different severities of cartilage damage due to wear. Environmental scanning electron microscope (SEM) (ESEM) images of cartilage surfaces, that formed a database for pattern recognition analysis, were acquired. The ESEM images of cartilage were divided into five groups (classes), each class representing different wear conditions or wear severity. Each class was first examined and assessed visually. Next, the automated classification system (pattern recognition) was applied to all classes. The results of the automated surface texture classification were compared to those based on visual assessment of surface morphology. It was shown that the texture-based automated classification system was an efficient and accurate method of distinguishing between various cartilage surfaces generated under different wear conditions. It appears that the texture-based classification method has potential to become a useful tool in medical diagnostics.

Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix.

PubMed

Li, Ang; Wei, Yiyong; Hung, Clark; Vunjak-Novakovic, Gordana

2018-08-01

Cartilage extracellular matrix (ECM) has been used for promoting tissue engineering. However, the exact effects of ECM on chondrogenesis and the acting mechanisms are not well understood. In this study, we investigated the chondrogenic effects of cartilage ECM on human mesenchymal stem cells (MSCs) and identified the contributing molecular components. To this end, a preparation of articular cartilage ECM was supplemented to pellets of chondrogenically differentiating MSCs, pellets of human chondrocytes, and bovine articular cartilage explants to evaluate the effects on cell proliferation and the production of cartilaginous matrix. Selective enzymatic digestion and screening of ECM components were conducted to identify matrix molecules with chondrogenic properties. Cartilage ECM promoted MSC proliferation, production of cartilaginous matrix, and maturity of chondrogenic differentiation, and inhibited the hypertrophic differentiation of MSC-derived chondrocytes. Selective digestion of ECM components revealed a contributory role of collagens in promoting chondrogenesis. The screening of various collagen subtypes revealed strong chondrogenic effect of collagen type XI. Finally, collagen XI was found to promote production and inhibit degradation of cartilage matrix in human articular chondrocyte pellets and bovine articular cartilage explants. Our results indicate that cartilage ECM promotes chondrogenesis and inhibits hypertrophic differentiation in MSCs. Collagen type XI is the ECM component that has the strongest effects on enhancing the production and inhibiting the degradation of cartilage matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quality Evaluation of Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair

PubMed Central

Shiraishi, Katsunori; Takeuchi, Shunsuke; Yanada, Shinobu; Mera, Hisashi; Wakitani, Shigeyuki; Adachi, Nobuo

2017-01-01

Quality evaluation of mesenchymal stem cells (MSCs) based on efficacy would be helpful for their clinical application. In this study, we aimed to find the factors of human bone marrow MSCs relating to cartilage repair. The expression profiles of humoral factors, messenger RNAs (mRNAs), and microRNAs (miRNAs) were analyzed in human bone marrow MSCs from five different donors. We investigated the correlations of these expression profiles with the capacity of the MSCs for proliferation, chondrogenic differentiation, and cartilage repair in vivo. The mRNA expression of MYBL1 was positively correlated with proliferation and cartilage differentiation. By contrast, the mRNA expression of RCAN2 and the protein expression of TIMP-1 and VEGF were negatively correlated with proliferation and cartilage differentiation. However, MSCs from all five donors had the capacity to promote cartilage repair in vivo regardless of their capacity for proliferation and cartilage differentiation. The mRNA expression of HLA-DRB1 was positively correlated with cartilage repair in vivo. Meanwhile, the mRNA expression of TMEM155 and expression of miR-486-3p, miR-148b, miR-93, and miR-320B were negatively correlated with cartilage repair. The expression analysis of these factors might help to predict the ability of bone marrow MSCs to promote cartilage repair. PMID:28835756

PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.

PubMed

Klinger, P; Lukassen, S; Ferrazzi, F; Ekici, A B; Hotfiel, T; Swoboda, B; Aigner, T; Gelse, K

2017-01-01

Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

Mechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus

PubMed Central

Xiao, Yinghua; Friis, Elizabeth A.; Gehrke, Stevin H.

2013-01-01

Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context. PMID:23448091

Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

PubMed

Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

2013-10-01

Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

PubMed Central

Zwolanek, Daniela; Flicker, Magdalena; Kirstätter, Elisabeth; Zaucke, Frank; van Osch, Gerjo J.V.M.; Erben, Reinhold G.

2015-01-01

Abstract Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a β1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely β1 integrin-mediated, whereby both RGD- and collagen-binding integrins are involved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future. PMID:26309781

Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits.

PubMed

Sancho-Tello, María; Forriol, Francisco; Martín de Llano, José J; Antolinos-Turpin, Carmen; Gómez-Tejedor, José A; Gómez Ribelles, José L; Carda, Carmen

2017-07-05

To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. 4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores. At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation. Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.

Optimization of the arthroscopic indentation instrument for the measurement of thin cartilage stiffness

NASA Astrophysics Data System (ADS)

Lyyra-Laitinen, Tiina; Niinimäki, Mia; Töyräs, Juha; Lindgren, Reijo; Kiviranta, Ilkka; Jurvelin, Jukka S.

1999-10-01