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For cartilage engineering a variety of biomaterials were applied for 3-dimensional chondrocyte embedding and transplantation. In order to find a suitable carrier for the in vitro culture of chondrocytes and the subsequent preparation of cartilage transplants we investigated the feasibility of a combination of the well-established matrices fibrin and alginate. In this work human articular chondrocytes were embedded and cultured either in alginate, a mixture of alginate and fibrin, or in a fibrin gel after the extraction of the alginate component (porous fibrin gel) over a period of 30 days. Histomorphological analysis, electron microscopy, and immunohistochemistry were performed to evaluate the phenotypic changes of the chondrocytes, as well as the quality of the newly formed cartilaginous matrix. Our experiments showed that a mixture of 0.6% alginate with 4.5% fibrin promoted sufficient chondrocyte proliferation and differentiation, resulting in the formation of a specific cartilage matrix. Alginate served as a temporary supportive matrix component during in vitro culture and can be easily removed prior to transplantation. The presented tissue engineering method on the basis of a mixed alginate-fibrin carrier offers the opportunity to create stable cartilage transplants for reconstructive surgery., (Copyright 2000 John Wiley & Sons, Inc.)

The transplantation of chondrogenic cells in a supportive carrier structure proved to be a promising alternative for the treatment of cartilage defects. In the study presented we focused on the transplantation of allogeneic chondrocytes in a biodegradable polymer scaffold (PGLA/Polydioxanon) in articular cartilage defects in a rabbit defect model. Isolated allogeneic chondrocytes embedded in a PGLA polymer scaffold were transplanted into osteochondrogenic defects of the patellar groove and compared with empty defects and transplants of polymer scaffolds without cells. The histological and histochemical analysis was performed after 4 and 12 weeks. The transplant integration and the architecture of the newly formed cartilage were evaluated with a semiquantitative score. After 4 weeks the development of a hyaline-like cartilage tissue of the cell-polymer-transplants was observed, after 12 weeks the defects were nearly completely filled with hyaline-like cartilage. The biodegradation of the polymer construct did not affect the histological structure of the transplant area. Defects of the groups with empty defect and polymer transplants without cells revealed no or insufficient healing indices. The study demonstrated that biodegradable polymers served as suitable carriers for the chondrocyte transplantation, which is due to the in-vitro establishment of a semi-solid cartilage transplant and the resulting effective transplant fixation into the defect. In-vivo the polymer cell transplants seem to provide a supportive microenvironment for the development of hyaline cartilage. The controlled release of morphogenic factors or bioactive molecules and the use of pluripotent mesenchymal progenitor cells opens new perspectives for the optimization of cartilage repair procedures.

Objective: The objective of this study was to assess the feasibility of transplanting embryonic chondrogenic cells within a collagen-fibrin substrate for the reconstitution of full-thickness cartilage defects in chicken knee joints., Methods: Full-thickness cartilage defects were created mechanically on the weight-bearing surface of the tibial condyle in 45 adult chickens and subsequently filled with chondrocytes embedded in a chondrocyte-collagen-fibrin gel. The transplants were compared to untreated defects and collagen-fibrin transplants without cells. The results were analyzed using histochemical and morphometrical methods after 3, 12 and 24 weeks. A semiquantitative histological grading system was applied to evaluate the transplant integration and the newly formed cartilage architecture., Results: Chondrocyte-gel grafts developed to hyaline-like cartilage without any granulation tissue in the interface after 3 weeks. After 12 weeks the defects in the experimental group were filled completely with hyaline cartilage. The defects in the control groups in all cases healed with fibrous repair tissue., Conclusion: Fibrin-collagen gel allowed stable graft fixation and provided an adequate microenvironment for embryonic chondrocytes to generate hyaline-like neocartilage in a full-thickness cartilage defect.

The advances in biomedicine over the past decade have provided revolutionary insights into molecules that mediate cell proliferation and differentiation. Findings on the complex interplay of cells, growth factors, matrix molecules and cell adhesion molecules in the process of tissue patterning have vitalized the revolutionary approach of bioregenerative medicine and tissue engineering. Here we review the impact of recent work in this interdisciplinary field on the treatment of musculoskeletal disorders. This novel concept combines the transplantation of pluripotent stem cells, and the use of specifically tailored biomaterials, arrays of bioactive molecules and gene transfer technologies to direct the regeneration of pathologically altered musculoskeletal tissues.

Objective: To establish a novel 3-dimensional (3-D) in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA)., Methods: Two distinct culture systems were developed, consisting of RA synovial membrane and articular cartilage explants or interactive RA synovial cell/chondrocyte cultures embedded in 3-D fibrin matrices. The expression of proteolytic enzymes, chondrocyte matrix architecture, and matrix degradation parameters was analyzed by immunohistochemistry., Results: Of 28 RA explant cultures, 16 displayed an invasion of synovial tissue into the cartilage explants, compared with 1 of 8 osteoarthritis explants. The expression of collagenase and vascular cell adhesion molecule 1 could be demonstrated at the cartilage-pannus junction. Of 20 interactive cell cultures, 18 revealed invasive behavior and remained vital for extended periods of time., Conclusion: The models presented allow us to study distinct aspects of destructive joint diseases under in vitro conditions that resemble human pathology. Moreover, our model is able to supplement animal experiments in basic research and drug testing.

Calculating the protein binding of six drug series the value sigma/sigma net charge/Mol turned out to be characteristic if the effects of substitutents were considered. Single- and multiple-substituted compounds were calculated in separate groups. For aliphatic-substituted compounds a classification resulted from the length of the substituted chain and from characteristic atoms. Substitution in 3- or 4-position made no significant differences. As an additional value sigma SAP/Mol may be applied to aromatic-substituted compounds.