Evaluation of Articular Cartilage Repair Using Biodegradable Nanofibrous Scaffolds in a Swine Model: A Pilot Study

The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(e-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds , with no implant as a control to repair iatrogenic , 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC- seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage- like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically- derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs , suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair

Comparison of Articular Cartilage Repair by Autologous Chondrocytes with and without in Vitro Cultivation

Objective: autologous chondrocyte implantation usually requires in vitro cell expansion before implantation. We compared the efficacy of cartilage regeneration by in vitro- expanded chondrocytes at high density and freshly harvested chondrocytes at low density. Design: surgically created osteochondral defects at weight-bearing surface of femoral condyles of domestic pigs were repaired by biphasic cylindrical porous plugs of DL- poly-lactide-co-glycolide and beta-tricalcium phosphate. Plugs were seeded with autologous chondrocytes in its chondral phase, and press-fit to defects. Seeded cells were (1) in vitro-expanded chondrocytes harvested from stifle joint 3 weeks before implantation and (2) freshly harvested chondrocytes from recipient knee. Seeding densities were 70 x 10(6) and 7 x 10 (6) cells/mL, respectively. Cell-free plugs served as control and defects remained untreated as null control. Outcome was examined at 6 months with International Cartilage Repair Society Scale. Results: the two experimental groups were repaired by hyaline cartilage with collagen type II and Safranin-O. Tissue in control group was primarily fibrocartilage. No regeneration was found in null control. Experimental groups had higher mean International Cartilage Repair Society scores than control in surface , matrix, and cell distribution, but were comparable with control in cell viability, subchondral bone, and mineralization. No significant difference existed between two experimental groups in any of the six categories. Uni - axial indentation test revealed similar creeping stress- relaxation property as native cartilage on experimental, but not control, specimen. Conclusions: cartilage could regenerate in both experimental models, in comparable quality. Culture of chondrocytes before implantation is not necessary

Repair of Articular Cartilage Defects: Review and Perspectives

Articular cartilage defects heal poorly and lead to catastrophic degenerative arthritis. Clinical experience has indicated that no existing medication substantially promotes the healing process and the cartilage defect requires surgical replacement, preferably with an autograft. However, there is a shortage of articular cartilage that can be donated for autografting. A review of previous unsuccessful experiences reveals the reason for the current strategy to graft cartilage defects with regenerated cartilage. Autologous cartilage regeneration is a cell-based therapy in which autogenous chondrocytes or other chondrogenic cells are cultured to constitute cartilaginous tissue according to the principles of tissue engineering. Current studies are concentrating on improving such techniques from the three elements of tissue engineering, namely the cells , biomaterial scaffolds, and culture conditions. Some models of articular cartilage regeneration have yielded good repair of cartilage defects, in animal models and clinical settings, but the overall results suggest that there is room for improvement of this technique before its routine clinical application. Autologous cartilage regeneration remains the mainstay for repairing articular cartilage defects but more studies are required to optimize the efficacy of regeneration. A more abundant supply of more stable cells, i.e. capable of maintaining the phenotype of chondrogenesis, has to be identified. Porous scaffolds of biocompatible, biodegradable materials that maintain and support the presentation of the chondrogenic cells need to be fabricated. If the cells are not implanted early to allow their in vivo constitution of cartilage, a suitable in vitro cultivation method has to be devised for a consistent yield of regenerative cartilage

Repair of Porcine Articular Cartilage Defect with Autologous Chondrocyte Transplantation

Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation , the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re- suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post -surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null> native cartilage>control>experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype

The Drug Release from Liposomal Carrier within the Chitosan Matrix

The release and regulation of growth factors are very important in the tissue regeneration. Optimal and suitable drug carrier systems combined with scaffold are needed to be exploited. In this study, we developed an injectable scaffold incorporated with drug release system for tissue regeneration. Hydrophilic or hydrophobic drugs can be encapsulated into liposomes and then dispersed in the temperature-reversible chitosan- glycerophosphate ( GP) hydrogel. Experimental results show that liposomes provide excellent sustained drug release from chitosan matrix when compared with that of free drugs, especially for hydrophilic drugs. The negative charge of the liposome will complex with the positive charge of the chitosan's protonized amine group that results in controlling the drugs release

Discoid Lateral Meniscus: Clinical Manifestations and Arthroscopic Treatment

BACKGROUND AND PURPOSE: Discoid lateral menisci are rare in western races but not uncommon among oriental people. This study correlated the clinical manifestations and imaging characteristics of discoid lateral menisci with arthroscopic findings in Taiwanese subjects. METHODS: Cases of lateral discoid menisci including 58 knees of 56 patients were retrospectively analyzed. Standard arthroscopic surgery had been performed in 42 knees of 40 patients to confirm the diagnosis. In 41 knees, anomalous menisci were considered to be the cause of symptoms and partial meniscectomies were performed by removing the redundant central portion to fashion a common semi-lunar pattern. Arthroscopic findings were investigated and correlated with the clinical manifestations and findings of magnetic resonance images. RESULTS: Pain was most frequently the chief complaint but did not necessarily occur in association with a tear of the meniscus. The pain usually began with a minor trauma on the affected knee. Other symptoms included clicking, snapping, locking, and a "tightness", " catching" or "intra-articular foreign body" sensation during motion of the joint. These symptoms were relieved after surgical reshaping of the meniscus of patients. Magnetic resonance imaging identified the anomaly and the existence of a tear, and was especially diagnostic when the tear was confined to the interior. These intra-substance tears were masked by intact external features and overlooked during arthroscopy. The surgical outcomes were followed up using the Ikeuchi scale, yielding results of excellent in 34, good in three, fair in two, and poor in two knees. CONCLUSIONS: Unlike a normal meniscus, pain may exist with an intact discoid meniscus. The symptoms of a discoid meniscus can be relieved effectively by arthroscopic partial meniscectomy

Dome-Shaped High Tibial Osteotomy: A Long-Term Follow-up Study

BACKGROUND: High tibial osteotomy (HTO) is a well- established treatment for unicompartmental gonarthrosis of the knee, but its durability and complications remain controversial. We previously introduced a novel dome- shaped HTO, and the long-term follow-up results using this technique are analyzed in this study. METHODS: We treated 25 varus knees in 22 patients with medial gonarthrosis, using a specially designed calibrated cutting jig along with rigid external fixation and early joint motion postoperatively. A total of 16 patients (19 knees) completed the study protocol and were followed up for 13-16 years (mean, 15 years). RESULTS: The surgery attempted to obtain 8 degrees valgus; the actual postoperative alignment averaged 12.4 degrees valgus, which decreased significantly to 7.8 degrees valgus after 5 years. The outcome as assessed by the Hospital for Special Surgery knee score was excellent or good in 18 knees at 5 years postoperatively, and in 13 knees at the final follow-up, showing a significant deterioration with time. Loss of correction with time was not correlated with the postoperative alignment achieved: at 5 years, loss greater than 2 degrees was found in 12 knees, but their mean corrected angle (11.8 degrees valgus) was not significantly different from that of the others (13.3 degrees valgus). Nor was the loss of correction correlated with the knee scores. The mean amount of joint motion after surgery did not change significantly with time: 124 degrees preoperatively and 114 degrees at the final follow-up. The patellar position also did not change from preoperative values during postoperative follow-up: mean Insall-Salvati index was 0.88 before and 0.90 5 years after surgery, neither showing patella baja. CONCLUSION: Dome-shaped HTO is a durable time-buying procedure for patients with unicompartmental medial gonarthrosis, and can avoid subsequent development of patella baja that may complicate further prosthetic arthroplasty