Tissue engineering methods for repair of articular cartilage defect under special conditions / 中国组织工程研究

BACKGROUND: Although desired cartilage repair has been realized via tissue engineering technology, these achievements mainly focus on small-size defect under a normal physical condition. However, cartilage defects are always accompanied by the underlying diseases in clinical practice, such as osteoarthritis and rheumatoid arthritis. Meanwhile, the location, scope, and depth of cartilage defects are uncertain, which brings a great challenge in cartilage tissue repair. OBJECTIVE: To summarize the methods of repairing articular cartilage defects at different locations and under inflammatory condition. METHODS: We searched PubMed and CNKI with the search terms “cartilage defect regeneration, osteochondral, growth plate, weight-bearing area, inflammatory” in Chiense and English to retrieve related papers published before March 2019. A total of 209 papers were retrieved and 86 were included in the final analysis according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: For articular cartilage defects under different special conditions, the repair goals and strategies are different. For repair of full-layer cartilage defects and osteochondral structure defects, multi-layered scaffolds are often used to repair the unique stratified cartilage structure and subchondral bone structure, while avoiding the problem of heterotopic ossification in neonatal cartilage. To avoid deformity after long bone maturation, growth factors such as insulin-like growth factor and bone morphogenetic protein 7 should be added to continuously stimulate the repair of the growth plate and promote bone growth. For cartilage repair in the weight-bearing area, the scaffolds should have good mechanical property, which ensure not to undergo severe deformation and structural damage when loaded. In addition, the new cartilage tissue has sufficient mechanical strength to support sustained longitudinal pressure and wear. For cartilage defects in the inflammatory state, both inflammation management and cartilage defect repair should be considered, and introduction of mesenchymal stem cells can regulate immune function and promote tissue regeneration, such that articular cartilage defect can be completely repaired.

Repair of Osteochondral Defects in Rabbit Knee Using Menstrual Blood Stem Cells Encapsulated in Fibrin Glue: A Good Stem Cell Candidate for the Treatment of Osteochondral Defects

BACKGROUND: In recent years, researchers discovered that menstrual blood-derived stem cells (MenSCs) have the potential to differentiate into a wide range of tissues including the chondrogenic lineage. In this study, we aimed to investigate the effect of MenSCs encapsulated in fibrin glue (FG) on healing of osteochondral defect in rabbit model. METHODS: We examined the effectiveness of MenSCs encapsulated in FG in comparison with FG alone in the repair of osteochondral defect (OCD) lesions of rabbit knees after 12 and 24 weeks. RESULTS: Macroscopical evaluation revealed that the effectiveness of MenSCs incorporation with FG is much higher than FG alone in repair of OCD defects. Indeed, histopathological evaluation of FG + MenSCs group at 12 weeks post-transplantation demonstrated that defects were filled with hyaline cartilage-like tissue with proper integration, high content of glycosaminoglycan and the existence of collagen fibers especially collagen type II, as well as by passing time (24 weeks post-transplantation), the most regenerated tissue in FG + MenSCs group was similar to hyaline cartilage with relatively good infill and integration. As the same with the result of 12 weeks post-implantation, the total point of microscopical examination in FG + MenSCs group was higher than other experimental groups, however, no significant difference was detected between groups at 24 weeks (p>0.05). CONCLUSION: In summary, MenSCs as unique stem cell population, is suitable for in vivo repair of OCD defects and promising for the future clinical application.

Estrogen promotes spontaneous repair of osteochondral defect via inhibition of osteoclast activity / 中华创伤杂志

Objective To investigate the role of estrogen in spontaneous repair of osteochondral defect,so as to provide guidance for the application of estrogen in tissue engineering.Methods Seventytwo healthy adult female SD rats (4-month-old) were assigned to negative control group (group A,n =24),ovariectomized group (group B,n =24) and ovariectomized + estrogen treatment group (group C,n =24) according to the random number table.Rats in group C were intraperitoneally injected 0.1 mg/kg estradiol benzoate once per week after operation.An osteochondral defect model (diameter:2 mm,height:1.5 mm) was established in femoral trochlea of rats 4 weeks after operation.At 2,10 and 20 weeks after the modeling,8 rats from each group were sacrificed.Femoral condyles were collected to measure bone volume fraction (BVF),number of bone trabeculae (Tb.N),trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp) in the osteochondral defect area by micro-CT scanning.Morphological changes were observed by HE staining,histomorphological changes and cartilage regeneration by safranine O-fast green staining,osteoclast count by tartrate-resistant acid phosphatase (TRAP) staining,distribution of matrix metalloproteinase-9 (MMP-9) by immunohistochemistry and expressions of osteoprotegerin (OPG),receptor activator of nuclear factor-κB ligand (RANKL) and MMP-9 by real-time-PCR.Results Compared to group B,increased BVF and Tb.N and decreased Tb.Sp were observed in groups A and C at each time point.More bone matrix formations were observed in groups A and C than in group B at 2 weeks,cysts (also known as cystic cavities) in regenerated subchondral bone and cracks in subchondral bone plate were observed in group B at 10 and 20 weeks,and proliferation of osteoclasts was active within lesions in group B at 10 and 20 weeks.Compared to group B,lowered levels of RANKL and MMP-9 (P ＜ 0.05) and significantly increased level of OPG (P ＜ 0.01) were observed in groups A and C at each time point,and osteoclast count in groups A and C was lowered at 10 and 20 weeks (P＜0.05).No regeneration of cartilage layer was observed in all groups.Conclusions Excessive proliferation of osteoclasts results in formation of cystic cavities and cracks.Estrogen improves the speed and quality of bone repair by regulating activities of osteoblasts and osteoclasts,so it can be used to treat osteochondral defect in tissue engineering.

Therapeutic Effects of Mesenchymal Stem Cells and Hyaluronic Acid Injection on Osteochondral Defects in Rabbits' Knees

PURPOSE: To evaluate the treatment results of intraarticular injection according to the frequency of hyaluronic acid with mesenchymal stem cells on the osteochondral defect of rabbits' medial femoral condyles. MATERIALS AND METHODS: A 5 mm diameter and 4 mm depth osteochondral defect was made on the medial femoral condyles of 18 rabbits, divided into six groups. One week after osteochondral defect, group B was injected intraarticularly with hyaluronic acid (HA), group C with mesenchymal stem cells (MSCs), and group D, E and F with both HA and MSCs. Group E and F received second HA injection a week after. Further, group F received third HA injection in the third week. RESULTS: In a macroscopic evaluation, groups B (6; range, 5-8), C (6; range, 6-7), D (7; range, 6-7), E (6.5; range, 6-8) and F (7.5; range, 6-8) showed statistically significant improvements in osteochondral defect healing, compared with that of group A (4; range, 3-5) (p=0.002). In histological evaluation, groups B (11.5; range, 11-13), C (13; range, 12-18), D (16; range, 13-18), E (17.5; range, 13-20), and F (19.5; range, 12-22) showed statistically significant differences in osteochondral defect healing, compared with group A (8; range, 6-9) (p=0.006). CONCLUSIONS: The intraarticular injections of MSCs or HA can play an effective role during the healing osteochondral defects in rabbits.

Osteochondral Autograft Using Head of Proximal Phalanx of Toe for Partial Osteochondral Defect of Proximal Interphalangeal Joint: A Case Report

Osteochondral injury due to the trauma of the hand is relatively common. If the size of the osteochondral fracture fragment is large, open reduction and internal fixation are often feasible in treating these problems. However, arthroplasty using osteochondral graft is more preferred when the particle is small and articular surface is comminuted or fully defected. There are many reports of osteochondral graft using the costal osteochondral graft but the osteochondral graft using the interphalangeal joint of the toe is rarely reported. Thoroughly reviewed with relevant articles, this report presents a case of a 33 year old male who was successfully treated with osteochondral autograft using the proximal interphalangeal joint of the toe due to the traumatic osteochondral defect in the head of the second proximal phalanx.

Mosaicoplastia revestida com periósseo no tratamento de perda osteocondral do joelho / Mosaicplasty with periosteal gratf for resurfacing local full-thickness chondral defects of the knee

Introdução e Objetivos: Existem várias formas de tratamento das perdas extensas de substância osteocondral (OC), entre elas, a mosaicoplastia recoberta com periósseo (mosaicambium). Neste trabalho pretende-se avaliar os resultados clínicos a médio dos doentes com defeito osteocondral tratados por esse método. Métodos: Vinte joelhos com defeito osteocondral superior a 2cm2 foram operados entre 1999 e 2005, com recurso a duas técnicas cirúrgicas (mosaicoplastia/mosaicambium). Todos os doentes foram avaliados em pré-operatório clinicamente (escalas ICRS,VAS), radiograficamente e com RM. No ano de 2008 todos foram revistos e avaliados seguindo os mesmos critérios. Os casos foram distribuídos em dois grupos consoante o tipo de tratamento.A avaliação estatística recorreu ao programa informático EPI2000. Utilizou-se o teste do qui-quadrado para variáveis categoriais e o teste t de Student para variáveis contínuas. Aceitou-se como erro alfa um valor de 0,05. Tipo de estudo: Estudo clínico, retrospectivo, nível de evidência 4. Resultados: Antes, todos os doentes estavam nos grupos ICRS C e D. Em 2008, 18 doentes estavam nos grupos A e B (12 no grupo A). Comparando os resultados entre grupos (mosaicoplastia/mosaicambium), não houve diferenças significativas entre os grupos. Radiograficamente, não existiam alterações em 55% dos casos. Discussão: Sem diferenças clínicas, por que a opção mosaicambium? A morbilidade nas zonas dadoras não é desprezível. A opção mosaicambium recorreu a menos cilindros OC, reduzindo a morbilidade resultante. Conclusão: A técnica mosaicambium é uma boa opção alternativa para perdas de substância OC com mais de 2 cm2.

Introduction and Objectives: Clinical and functional assessment comparing cases of full-thickness chondral defects (OC) treated with mosaicplasty or mosaicplasty covered with periosteum (mosaicambium). Methods: 20 knees with chondral defect, (10 mosaicplasty/10 mosaicambium) were operated between 1999 and 2005. All patients were clinically assessed preoperatively using the ICRS scale, VAS scale, X-ray and MRI. During 2008, we reviewed patients using the sameprotocol. For statistical purposes, the patients were divided into two groups, according to the surgical technique. Statistical analysis was performed with EPI2000 program, using chi-squared test and Student's t test, with a significance level of 0.05. Results: Preoperatively, all patients were in group C /D (ICRS scale). In 2008, 18 cases were in groups A and B according to the ICRS scale (12 in A). Between groups, there were no statistical differences. The X-ray study revealed nochanges in 55% of cases. Discussion: With no differences, why mosaicambium option? Morbidity on graft donor zones is not negligible. Mosaicambium uses less chondral grafts, reducing the potential for morbidity at graft donor zones. Conclusion: The mosaicambium technique is an excellent alternative forchondral defects greater than 2 cm2.

Tratamento dos defeitos osteocondrais do joelho / Treatment of the knee osteochondral defects

Os defeitos osteocondrais do joelho acometem toda a espessura da cartilagem e são geralmente de origem traumática, podendo ocorrer isoladamente ou em conjunto com lesões ligamentares ou meniscais. O diagnóstico definitivo geralmente é feito por ressonância magnética, apesar da história e exame físico darem indícios do diagnóstico. As lesões osteocondrais sintomáticas necessitam de tratamento cirúrgico e a escolha da técnica cirúrgica depende de alguns fatores como tamanho da lesão, local da lesão, atividade e idade do paciente. Técnicas, como abrasão e drilling são pouco usadas atualmente. A microfratura é largamente usada e geralmente é a primeira escolha no tratamento de defeitos osteocondrais de 1 a 2,5 cm2. A mosaicoplastia também pode ser usada para lesões desta magnitude, mas em pacientes mais ativos que necessitam um retorno mais rápido às atividades esportivas. Pode também ser usadas em defeitos maiores, porém o transplante autólogo de condrócitos (TAC) aparece como uma boa opção para lesões maiores. A primeira geração do TAC transplanta condrócitos os quais ficam contidos no defeito devido a uma cobertura de periósteo, já a segunda geração de TAC apresenta os condrócitos embebidos em uma matriz e evita o uso da cobertura com periósteo. O transplante alógeno osteocondral também é uma opção para defeitos maiores que 4 cm2. Novas tecnologias estão sendo desenvolvidas, porém ainda sem aplicabilidade clínica.

Autogenous Osteochondral Grafting for Treating Osteochondral Defect of the Femoral Condyle of the Knee Joint / 대한정형외과학회잡지

PURPOSE: We wanted to evaluate the outcomes of an autologous osteochondral graft (Mosaicplasty) for treating chondral defects of the femoral condyle and We assessed the factors affecting the clinical results. MATERIALS AND METHODS: This study enrolled 18 patients (19 cases) who underwent an autogenous osteochondral graft to treat a osteochondral defect in the femoral condyle from July 2000 to June 2006. The average age was 26.2 years old (age range: 16-48 years old). Among the patients, 17 cases were men. In 14 cases, the osteochondral defects were localized in the medial femoral condyle and only 5 cases showed a defect in the lateral femoral condyle. The average size of the osteochondral defects was 4.2 cm2 (1-13 cm2). The Lysholm knee scoring scale and the Tegner's activity score were applied for clinical evaluation. Further, we carried out simple X-ray for all the cases and we performed MRI in 5 cases for the radiological evaluation. Tthe factors affecting the clinical results were also analyzed and the complications were evaluated. RESULTS: The average follow-up period was 22 months (range: 6-55 months). Eighten out of 19 cases (94.7%) were able to return to ordinary life. The Lysholm knee scoring scale and the Tegner's activity score indicated much better clinical results for small lesions and for young patients. For the radiological results, all the cases displayed a decrease in the size of radiolucent zones on the follow up X-ray. Among the 5 cases for which an MRI was performed, graft unions were observed in 3 cases, but 2 cases displayed continuous peri-graft edema. Any other complications involving the donor and recipient site were not observed. CONCLUSION: We conclude that autogenous osteochondral grafting is useful for specific patients depending on the size of the lesion and the patient's age. It is a valuable treatment option for osteochondral defects in the knee joint.

Experimental study of treating osteochondral defects with osteochondral composites constructed in vivo / 中国矫形外科杂志

[Objective]To evaluate the effect of treating the osteochondral defects with implanted cell-scaffold composites,cultured MSCs as seed cells and PLGA as scaffolds,and to acquire desirable seed cells and scaffold materials.[Method]BMSCs were induced to differenciatiated into chondrocytes,co-cultured with PLGA scaffold respectively in vitro,then implanted into osteochondral defects on canine models by using techniques of mosaicplasty,induced BMSC-PLGA scaffold composites in the top of the defect and BMSC-PLGA scaffold composites in the bottom of the defect,osteochondral composites were constructed in vivo,and repair was observed with naked eyes and histology.[Result]At 16 weeks after transplantation the defects of expeirmental group were covered with semi-transparent smooth white tissue and the margins between the repair tissue and the surrounding cartilage were not recognized.Histologically,most of the repair tissue was consisted with chondrocytes,maintained their thickness to the full depth of the original defects.The subchondral bone was well remodeled.The tidemark was observed.The defects of positive control group were covered with repair tissues,and partial were conformed with original cartilage.The repair tissue was partly filled with chondrocytes.However,the defects of negative control group were repaired with soft fibrous tissues without luster,and an obvious boundary between reparative and original cartilage was seen.[Conclusion]MSCs-PLGA scaffold composites,constructed into osteochondral composites by suppressing closely in vivo,are the ideal materials for repairing cartilage defects.

Repair of Osteochondral Defect Using Chitosan-collagen Sponge intheRabbit's Knee / 대한정형외과학회잡지

PURPOSE: To determine the suitability of using a chatoyant-collagen sponge as a scaffold for transplanting a chondrocyte into a full-thickness articular cartilage defect. MATERIALS AND METHODS: The in vitro characterization of a chatoyant-collagen sponge infiltrated with the chondrocyte was combined with an in vivo assessment of the early articular cartilage repair in a rabbit's knee by H&E and MTT staining. These porous chatoyant-collagen sponges were implanted into the osteochondral defects made in the left patellofemoral grooves of 12 rabbits. The osteochondral defects were untreated in the right side and used as controls. The experimental animals were sacrificed 1, 3, 6 and 12 weeks after implantation and the repaired tissue was evaluated by a gross and histological evaluation using the Wakitani score. RESULTS: More primary cells cultured from the articular cartilage of the rabbit's knee were found to attach to and survive within a porous chatoyant-collagen sponge than with a chatoyant sponge. In gross and histological examination, the experimental group showed indications of repair, which appeared similar in color and texture to the surrounding articular cartilage. The Wakitani scoring in the experimental group at 6 (Ave. 10.7) and 12 (Ave. 7.3) weeks were superior to those in the control group at 6 (Ave. 8.7) and 12 (Ave. 3.7) weeks (6 wk: p=0.03, 12 wk: p=0.02). CONCLUSION: Scaffolds composed of porous a chatoyant-collagen sponge enhance the growth of cartilaginous repair and make a milieu for the survival of chondrogenic cells both in vitro and in vivo.

Treatment of Osteochondral Defects with Perichondrial Cells Embedded in Alginate Beads in Rabbit / 대한정형외과연구학회지

PURPOSE: The objective of this study was to investigate the use of cultured rib perichondrial cells embedded in alginate bead on healing in a rabbit osteochondral defect model. The degree of articular cartilage repair was evaluated histologically, histomorphometrically, and biochemical characteristics of the neocartilage. MATERIALS AND METHODS: A single defect, 3.5 mm wide by 3 mm deep, was created in the weight bearing area of the medial femoral chondyle in thirty New Zealand rabbits. The right defect filled with two alginate beads embedded with rabbit rib perichondrial cells, the left defect was empty as the control. The animals were killed at 1, 3, and 12 months, and the repair tissues were examined histologically, and histomorphometric differences were evaluated by an image analysis system. The defects also were examined biochemically for the glycosaminoglycan (GAG) and type II collagen to compare the results with normal articular cartilage. RESULTS: The attachment of repair tissue with the surrounding host tissue was incomplete, many specimens exhibited degenerative changes in adjacent tissue over a post transplant time period. Histomorphometric results showed that the repair groups (0.24+/-0.11 mm, -26.97 (25.62 mm) was decreased in surface roughness, and depression than controls (0.32+/-0.06 mm, -48.73 (32.59 mm) at 12 months. Repair area, repair area ratio, and repair thickness of the repair groups (6.89+/-2.1 mm2, 39.5+/-19.5%, 0.11 (0.01 mm) were increased than controls (2.65+/-2.35 mm2, 2.85+/-2%, 0.09+/-0.04 mm) at 12 months. After 12 months, the content of GAGs of neocartilage (36.45 microgram/mg) was similar to those of normal artilcular cartilage (36.74 microgram/mg), the percentage of type II collagen of the neocartilage increased up to 95%. CONCLUSION: Transplanted rib perichondrial cells were seen to proliferate to fill the osteochodral defect with neocartilage. Histomorphometric analysis should allow a more quantitative described the degree of articular cartilage repair.

Repair of Osteochondral Defect Using Grafts of Cultured Chondrocytes in Rabbits / 대한정형외과학회잡지

Chondrocytes isolated from the articular cartilage of rabbit knee joint were cultured in vitro within fibrin glue carrier for 2 weeks. Histochemical and electromicroscopical approaches were used to study chondrocytes behavior and phenotypic expression. In vitro study, chondrocyte assumed a rounded morphology, accumulated metachromatic matrix and took on the cytological characteristics of in vivo cartilage cells. Allogenic cultured chondrocyte in fibrin glue was transplanted into osteochondral defect in rabbit joint. The contralateral knee joint served as a control in which the defect was left empty. This in vivo study was performed for the investigation of the chondrogenic potential of cultured chondrocytes embedded in fibrin glue. Grafted defects was filled with cartilage in gross finding, repaired tissue consisted of differentiated chondrocytes and matrix resumed that of hyaline cartilage. At sixteen week after transplantation, subchondral region was partially transformed into bone without loss of overlying articular cartilage, but in control group, defect did not heal successfully. Repaired articular cartilage was thicker than host cartilage and tide mark was not shown up to 24 weeks. Some of repaired tissue was degraded partially. These results suggest that fibrin glue provides suitable environment for differentiation of chondrocyte and allograft of cultured chondrocyte in fibrin glue transplanted into large osteochondral defect improves cartilage repair.

An Experimental Study about the Effects of TGF - 1 and Autogenous Periosteal Graft on Healing of Osteochondral Defect in Rabbit / 대한정형외과학회잡지

Articular cartilage is a highly differentiated tissue, lacking a vascular supply and having only limited regenerative capability. Cut or other mechanical damage restricted to the cartilage does not repair. Experimentally and clinically, cartilage defect that penetrate the subchondral bone undergoes repair through the formation of tissue usually characterized as fibrous, fibrocartilaginous or hyaline-like cartilaginous tissue. There is little definitive informations about local or systemic factors that control the differentiation of mesenchymal cells to osteoblast, chondroblast or fibroblast. Our study was designed to evaluate the effect of transforming growth factor-beta (TGF-pl) and autogenous periosteal graft on the healing of osteochondral defect of distal femur of rabbit and also the possibility of these method to be clinically applicable to human. The experimental model used in the present study for including cartilage in rabbit was based mainly on the model used by Frukawa et al14). in rabbit. A full thickness osteochondral defect of 80 rabbit were made with 2mm diameter of drill-bit and electrically driven drill. Experimental animals were divided into four group: 1) group I, osteochondral defect only, 2) group II, osteochondral defect with infiltration of phosphate buffer solution, 3) group III, osteochondral defect with infiltration of TGF-Bl, 4) group IV, osteochondral defect with autogenous periosteal graft. The healing of the defect was assessed at 1 week, 3 weeks, 5 weeks, 12 weeks after operation by gross and histochemical examination. At 1 week, fibrinoid material in edge to edge arcade arrangement was present in group I,II,III,IV. At 3 weeks, spindle shaped undifferentiated mesenchymal cell present in the periphery of fibrinous network, but there is no appearance of mesenchymal cell in group I,II. At 5 weeks, essentially complete repopulation of the defect with progressive differentiation of cells to chondroblast, chondrocyte, osteoblast and synthesis of cartilage and matrix in their appropriate location in group III and IV were found. At 12weeks, hyaline like cartilage formation was observed in group III and IV. but early trace of degeneration of the cartilage were seen in many defect with the prevalence and intensity of the degeneration increasing at group I and 3 . Our study demonstrated in detail the repair of full-thickness defect in rabbit articular cartilage extending into cancellous bone of the marrow cavity under influence of local growth factor (TGF-pl) and autogenous periosteal graft. Excellent reconstruction of articular cartilage was observed in TGF- Bl infiltration group and autogenous periosteal graft group as early as 5 weeks after the creation of defect. Although the further study should be carried out for their clinical application, we conclude that TGF-Bl regulates the overall mechanism of matrix constituent in connective tissue and autogenous periosteal graft have a chondrogenic potential to repair major osteochondral defect. these suggest that TGF-Bl and autogenous periosteal graft may be a important pathophysiological regulator of chondro- genesis.