Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects—A study in rabbits
Introduction
The highly limited potential of articular cartilage to regenerate has led to various procedures to restore cartilage defects. Classical techniques, such as Pridy drilling [1] and microfracture [2], use the potential of non-differentiated subchondral pluripotent cells to migrate into the defect and to differentiate locally into cartilage cells [3], [4]. Recently, methods have been developed for the repair of articular cartilage on the basis of autologous cartilage–bone transplants [5], [6], [7] or transplantation of cultured autologous chondrocytes [4], [8], [9], [10]. A major concern of all cartilage repair techniques, however, is that the produced cartilage repair tissue tends to be of the mechanical and biological inferior fibro-cartilaginous type [11], [12], [13], [14], [15], [16]. So far it is not known if the results of the more recent techniques are superior to the classical ones, with respect to clinical outcome and the nature of the repair tissue.
An extra dimension to cartilage repair techniques is the use of porous matrices. These matrices may function as vehicles for the transplantation of chondrocytes and offer temporary support to the cells. Matrices can also be used to guide the infiltration of progenitor cells from the bone marrow and to stimulate these cells to adopt a cartilage phenotype [10], [17], [18]. Cell behavior like migration, proliferation and differentiation may be mediated by the physico-chemical properties of the matrices [10], [11], [12], [13], [14], [15], [16], [17], [18], [19].
Various matrices have been used in orthopedic applications. These include matrices based on polylactic acid [9], [20], [21], polyglycolic acid [22], fibrin glue [23], [24], alginate [25], [26], [27], collagen [28], [29], [30], [31], [32] and hyaluronic acid [25], [28], [29]. Particularly, collagen-based matrices may be promising in this respect due to their biocompatibility, biodegradability and mechanical integrity.
In this study, cross-linked type I and type II collagen matrices, with and without attached chondroitin sulfate (CS), were implanted into full-thickness articular cartilage defects in the trochlea of rabbits. Cartilage and subchondral bone remodeling was evaluated 4 and 12 weeks after implantation using histology, and two semi-quantitative histological grading systems.
Section snippets
Preparation, cross-linking and characterization of collagen matrices
Insoluble type I collagen was isolated and purified from bovine Achilles tendon using neutral salt and dilute acid extractions [33]. Reconstituted type II collagen was isolated and purified from bovine tracheal cartilage using pepsin digestions, specific salt precipitation and dialysis against phosphate buffer [34]. CS was isolated and purified from bovine tracheal cartilage using extensive papain digestion, mild alkaline borohydride treatment and DEAE ion exchange chromatography [35]. Porous
Physicochemical characteristics of matrices
The physico-chemical characteristics of the different collagenous matrices are presented in Table 1. EDC treatment of matrices increases the denaturation temperature, and decreases the amine group content, indicating that cross-linking occurred. The amount of CS attached to type I and type II collagen matrices is 13% (w/w) and 18% (w/w), respectively.
Clinical evaluation and gross morphology
No difference in wound repair was observed between rabbits with and without scaffolds. After wound repair there were no clear changes in walking
Discussion
Partial-thickness defects in which damage is limited to the cartilage, and which do not extend into the subchondral bone, never repair spontaneously. This is due to the absence of an appropriate source of cells for repair, and indicates the value of the subchondral bone marrow as a pool for non-differentiated mesenchymal cells. The implantation of collagenous matrices in full-thickness defects may guide the infiltration, proliferation, and differentiation of these progenitor cells, and improve
Acknowledgments
The study was made possible by financial contributions of the foundations “Stichting De Drie Lichten” and the “Stichting Anna Fonds”. The authors wish to thank Mrs. D. Versleyen for skilful technical support with the histology.
References (41)
- et al.
Hama H, Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption
Arthroscopy
(1993) - et al.
Chondrogenesis in a cell-polymer-bioreactor system
Exp Cell Res
(1998) - et al.
Autologous chondrocyte implantation in a canine modelchange in composition of reparative tissue with time
J Orthop Res
(2001) - et al.
Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilagean experimental study in the goat
Biomaterials
(1999) - et al.
Differential effects of IGF-1 and TGF beta-2 on the assembly of proteoglycans in pericellular and territorial matrix by cultured bovine articular chondrocytes
Osteoarthr Cartilage
(1998) - et al.
Matrix collagen type and pore size influence behaviour of seeded canine chondrocytes
Biomaterials
(1997) - et al.
Preparation and characterization of porous crosslinked collagenous matrices containing bioavailable chondroitin sulfate
Biomaterials
(1999) - et al.
Development of tailor-made collagen-glycosaminoglycan matricesEDC/NHS crosslinking, and ultrastructural aspects
Biomaterials
(2000) - et al.
Meniscus cells seeded in type I and type II collagen-GAG matrices in vitro
Biomaterials
(1999) The Pridie debridement operation for osteoarthritis of the knee
Clin Orthop
(1974)
Improvement of full-thickness chondral defect healing in the human knee after debridement and microfracture using continuous passive motion
Am J Knee Surg
Rabbit articular cartilage defects treated with autologous cultured chondrocytes
Clin Orthop
Cartilage resurfacingfacts, fictions, and facets
Orthopedics
Arthroscopic osteochondral autograft transplantation in anterior cruciate ligament reconstructiona preliminary clinical study
Knee Surg Sports Traumatol Arthrosc
The use of a lateral patellar autologous graft for the repair of a large osteochondral defect in the knee
J Bone Joint Surg
Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation [see comments]
N Engl J Med
Current concepts in the treatment of articular cartilage defects
Orthopedics
Articular cartilage. Instr. Course Lecture Vol. 47
J Bone Joint Surg
Repair of partial-thickness defects in articular cartilagecell recruitment from the synovial membrane
J Bone Joint Surg
Cartilage repair. A critical review
Acta Orthop Scand
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