(from the application): Cartilaginous defects, both in articulating joints as well as other structural tissues like ears and tracheal C-rings, present challenging reconstructive problems to surgeons trying to restore normal structure and function to patients. Several tissue engineering techniques have been developed for growing chondrocytes on or in synthetic or naturally occurring biodegradable polymers in vitro and in vivo in nude mice. These polymers, in the form of hydrogels or porous, branching networks, can serve as a scaffold upon which chondrocytes can produce extracellular matrix resulting in new tissue. This technology allows the transplantation of cell-polymer constructs as a unit with successful engraftment for new cartilage formation. Although our laboratory has generated cartilage in several preliminary studies using different biodegradable matrices in vitro and in vivo in nude mice, we have encountered unexpected obstacles when attempting to employ similar techniques in an immune-competent animal model (rabbit). The objective of this study is to examine the feasibility of employing the techniques for creating tissue engineered cartilage in a model (swine) that more closely parallels the human condition. Experiments have been designed to address the following specific aims:
Aim 1 : To investigate (A) the rates at which hydrogel spheres of calcium alginate and fibrin-based substrates decay after being implanted subcutaneously in an immune-competent animal model (swine) and (B) to establish the degree to which polymers of calcium alginate and fibrin-based substrates promote cartilage formation in an immune-competent animal model (swine).
Aim 2 : To determine if autologous chondrocytes will provoke an immune response when their cell membranes are exposed to the immune system by stripping them of their encasing matrix.
Aim 3 : To investigate (A) whether the number of cell divisions (replicative age) a chondrocyte has undergone in culture influences its rate of matrix production and (B) to investigate what effect chondrocyte donor age has on the rate of matrix production.
| Peretti, G M; Randolph, M A; Zaporojan, V et al. (2001) A biomechanical analysis of an engineered cell-scaffold implant for cartilage repair. Ann Plast Surg 46:533-7 |
| Panossian, A; Ashiku, S; Kirchhoff, C H et al. (2001) Effects of cell concentration and growth period on articular and ear chondrocyte transplants for tissue engineering. Plast Reconstr Surg 108:392-402 |
| Peretti, G M; Randolph, M A; Villa, M T et al. (2000) Cell-based tissue-engineered allogeneic implant for cartilage repair. Tissue Eng 6:567-76 |
