Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds

Abstract

Cartilage implants which could potentially be used to resurface damaged joints were created using rabbit articular chondrocytes and synthetic, biodegradable polymer scaffolds. Cells were serially passaged and then cultured in vitro on fibrous polyglycolic acid (PGA) scaffolds. Cell-PGA constructs were implanted in vivo as allografts to repair 3-mm diameter, full thickness defects in the knee joints of adult rabbits, and cartilage repair was assessed histologically over 6 months. In vitro, chondrocytes proliferated on PGA and regenerated cartilaginous matrix. Collagen and glycosaminoglycan (GAG) represented 20 to 8% of the implant dry weight (dw), respectively, at the time of in vivo implantation; the remainder was PGA and unspecified components. Implants based on passaged chondrocytes had 1.7-times as much GAG and 2.6-times as much collagen as those based on primary chondrocytes. In vivo, cartilaginous repair tissue was observed after implantation of PGA both with and without cultured chondrocytes. Six month repair was qualitatively better for cell-PGA allografts than for PGA alone, with respect to: 1) surface smoothness, 2) columnar alignment of chondrocytes, 3) spatially uniform GAG distribution, 4) reconstitution of the subchondral plate, and 5) bonding of the repair tissue to the underlying bone. These pilot studies demonstrate that it is feasible to use cell-polymer allografts for joint resurfacing in vivo.

Regeneration of whole meniscus using meniscal cells and polymer scaffolds in a rabbit total meniscectomy model

“…The authors supposed that no or minor immune response of the allogeneic chondrocytes at 6 months might be due to the fact that their surface antigens were sequestered by the time of implantation due to matrix deposition during in vitro cultivation. 40 In a similar study, allogeneic rabbit chondrocytes embedded in fibrin gels within PLGA scaffolds, cultured for 2 weeks, and transplanted into articular defects formed cartilage tissue. Numerous mononuclear cells were observed around the cartilage filling the defect 4 weeks after transplantation, but the inflammatory cells disappeared after 12 weeks.…”

Cartilage tissue engineering for degenerative joint disease☆

“…Polylactic/polyglycolic acids, both individually and in combination have been investigated as scaffold material to repair cartilage defects for more than two decades [3,94,168,171,172].…”

“…Compared to fibrin, collagen, Poly(L-lactic acid) (PLLA), and poly (DL-lactic-co-glycolic acid) (PLGA), PGA was shown to provide a better scaffold for in vitro cartilage regeneration, as demonstrated by cell densities equivalent to those found in natural tissues, and by continuous cellular production of type II collagen [174]. Although such engineered constructs have also been tested for articular cartilage repair in animal models, mainly in rabbits [94,171,[175][176][177]), they have not been applied in human patients. The possible reasons include the graft induction of foreign body giant cell reaction [100] and the hydrolytic activity of the polymer substrate, which yields both toxic and partially cytotoxic degradation products.…”

Regaining chondrocyte phenotype in thermosensitive gel culture

“…These cells were then duplicated in culture and transplanted into articular defects, secured by a piece of periosteum or embedded in a collagen gel (Green, 1977;Grande et al, 1989;Brittberg et al, 1994). A newer approach, based on the concept of tissue engineering, uses chondrocyte seeded composite grafts for cartilage repair (Freed et al, 1994;Chu et al, 1995;Tian et al, 1996).…”