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.
Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with b-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. ß
This study employs a unified theoretical model to simulate the filling and postfilling stages of the injection-molding process. Implementation of such a model is based on a hybrid finite-element/finite-difference numerical solution of the generalized Hele-Shaw flow of a compressible viscous fluid under nonisothermal conditions. The shear viscosity of the polymeric material is represented by a Cross model for the shear-rate dependence and a WLF-type functional form for the temperature and pressure dependence, whereas the specific volume is modeled in terms of a double-domain Tait equation. The analysis also handles variable specific heat and thermal conductivity of the polymer as a function of temperature. Complex thin parts of variable thickness can be modeled and discretized by flat, triangular finite elements which may have arbitrary orientation in three-dimensional space, whereas runners and possible round pins or bosses in the part are represented as one-dimensional circular-tube elements. A control-volume scheme is employed that leads to automatic melt-front advanctment during the cavity-filling stage.
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