* Corresponding author. Tel.: # 39-40-676-3690; fax: # 39-40-676- 3691. E-mail address: vittur@bbcm.univ.trieste.it (F. Vittur) Biomaterials 21 (2000) 795}801 Articular cartilage repair in rabbits by using suspensions of allogenic chondrocytes in alginate E. Fragonas, M. Valente, M. Pozzi-Mucelli , R. To!anin, R. Rizzo, F. Silvestri, F. Vittur* Dipartimento di Biochimica, Bioxsica e Chimica delle Macromolecole, Universita % di Trieste, Via Giorgieri 1, I-34127 Trieste, Italy Istituto di Clinica Ortopedica, Universita % di Trieste, Strada per Fiume 447, I-34149 Trieste, Italy Laboratorio di Microscopia NMR, Universita % di Trieste, Strada per Fiume 447, I-34149 Trieste, Italy Istituto di Anatomia ed Istologia Patologica, Universita % di Trieste, Pza Ospedate 1, I-34129 Trieste, Italy Received 20 December 1998; accepted 1 November 1999 Abstract The feasibility of allogenic implants of chondrocytes in alginate gels was tested for the reconstruction in vivo of arti"cially full-thickness-damaged articular rabbit cartilage.The suspensions of chondrocytes in alginate were gelled by the addition of calcium chloride solution directly into the defects giving in situ a construct perfectly inserted and adherent to the subchondral bone and to the walls of intact cartilage. The tissue repair was controlled at 1, 2, 4 and 6 months after the implant by NMR microscopy, synchrotron radiation induced X-ray emission to map the sulfur of glycosaminoglycans and by histochemistry. Practically a complete repair of the defect was observed 4}6 months from the implant of the chondrocytes with the recovery of a normal tissue structure. Controls in which Ca-alginate alone was implanted developed only a "brous cartilage. 2000 Elsevier Science Ltd. All rights reserved. Keywords: Allogenic implants; Chondrocytes; Alginate gels; Cartilage repair; NMR microscopy, SRIXE 1. Introduction The ability of articular cartilage to repair after an injury is very limited. The limited healing potential of this tissue can potentially be ascribed to the low metabolic and biosinthetic activities of mature chondrocytes and, at least in part, to the lack of chondrogenic cells available for repair [1]. Numerous, di!erent, strategies have been used to induce cartilage repair with the "nal goal to "ll the defects with a repair tissue indistinguishable from the native cartilage. Periosteal and perichondral tissue graft- ing, subchondral drilling, osteochondral allografting and chondrogenic cell transplantation have been widely used in experimental animals and in man (see [1,2] for review). The technical di$culties encountered with the di!erent techniques have promoted an increasing interest in the trasplantation of chondrogenic cells. Both autologous and allogenic transplantations have been performed and cell suspensions have been used in some cases after an in vitro expansion or after the achievement of biocom- patible constructs with natural and arti"cial matrices (see [1] for review). Fibrin, hyaluronate, collagen gels (see [3}5] for review) or arti"cial polymers as biodegradable polyesters [6] of -hydroxyacids [7] have been shown to support tissue ingrowth and repair. Some years ago al- ginate, a family of Ca-gelling algal polysaccharides which are linear copolymers of 1-4 linked -D-man- nuronic acid and -L-guluronic acid, has been tested and employed for suspension cultures of chondrocytes from growing and articular cartilages [8,9]. Since 1995 Paige and coworkers [10] have been using slowly polymerizing calcium alginate gels to provide a three-dimensional scaf- fold for transplantation and engraftment of chondrocytes in plastic and reconstructive surgery. The same authors have also demonstrated that cartilage formation is de- pendent on the concentration of chondrocytes in the construct but not on that of alginate and calcium chlor- ide used for the gel formation [11]. 0142-9612/00/$ - see front matter 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 1 4 2 - 9 6 1 2 ( 9 9 ) 0 0 2 4 1 - 0