Cartilage, due to its unique physiology (lack of vasculature), can be potentially repaired using tissue engineered in the laboratory, by combining cells and with a supporting scaffold. This requires a marriage between material science, cell biology, and translational medicine, a concept well established as Tissue Engineering. Over the years the in vivo and in vitro chondrogenic potential of periosteum has been recognised by many researchers and as such periosteum is explored both to repair cartilage defects directly by transplanting periosteum into the cartilage defect or by using periosteum as a cell source for cartilage engineering purposes. The initial example hereof is the first generation of Autologous Chondrocyte Transplantation. Graft hypertrophy and ossification remain the primary drawbacks of cartilage repair strategies using engineered cartilage. These drawbacks may (partially) be due to the endochondral ossification process that can take over when cartilage is repaired. In this process chondrogenesis of progenitor cells is followed by hypertrophy of these cells and subsequent ossification. Periosteal progenitor cells go through this process in order to heal bone fractures. This review provides an overview of the role of periosteum in cartilage repair and cartilage tissue engineering and illustrates how periosteum can be used as a model to study the endochondral process. Such studies may provide clues to further optimize cartilage tissue engineering by identifying important factors which are capable of maintaining cells in their chondrogenic phenotype. Finally, the use of periosteum to engineer cartilage in vivo at an extra-articular site is described.

Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to cause skeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 mutations on bone progenitor cells may differ. The objective of this study was to investigate the effect of specific activating FGFR3 mutations on ectopic in vivo bone formation by periosteal derived cells (PDCs) seeded on calcium phosphate/ collagen scaffolds. PDCs were isolated from hypochondroplasic (N540K mutation) and achondroplasic (G380R mutation) patients, along with age/sex matched controls. These cells were characterised in vitro for proliferation, osteogenic differentiation, FGFR3 signalling and in vivo bone formation. Subsequently, empirical modelling was used to find correlations between in vivo formed bone and in vitro cell behaviour. These data showed that in contrast to the G380R mutation, which produced no bone, the N540K mutation induced significant ectopic bone formation on specific carriers. This allowed correlation between percentage of induced bone formation to elevated in vitro proliferation and differentiation. Correlating osteogenic markers included Collagen type 1, alkaline phosphatase and osteocalcin. Enhanced proliferation was attributed to increased phosphorylation of Erk-1/2.

Objective: This pilot study of cartilage defect treatment was designed to establish the horse as a suitable animal model for MACT (Matrix-Associated Autologous Chrondrocyte Transplantation) transplants and to analyse the morphological aspects of repair tissue development and differentiation. Design: Hyaluronan-based and collagen-based biodegradable scaffolds were seeded with autologous chondrocytes and implanted into large (1.5×2 cm) defects in the trochlear ridge of the distal femur of three horses. A non-treated, empty defect was used as control. Three months after surgery, samples of the defect area were investigated using bright field and polarized light microscopy, immunohistochemistry and electron microscopy. Results: In MACT-treated lesions with good defect filling, the repair tissue integrated well into the defect and showed features of differentiation in transition to native cartilage; the matrix was partially masked by proteoglycans, strongly stained for collagen type II, and the fibres had the typical vertical arrangement of articular cartilage. In areas with less intense staining, collagen type II formed a network around the cells. Calcified cartilage was partially decalcified and osteoclasts as well as osteoblasts reorganised the subchondral bone. The control defect was almost empty. Conclusion: This study showed that the horse is a suitable animal model for MACT. Differentiation starts early after transplantation in the periphery of the defect. Collagen type II precedes proteoglycan deposition and undergoes a kind of vertical self-arrangement which is hypothesized to develop from a fibre network around the chondrocytes.