Articular Cartilage Repair with Autografting Under the Influence of Insulin‐Like Growth Factor‐1 in Rabbits

Abstract

Insulin-like growth factor (IGF)-1 has been successfully demonstrated to stimulate proteoglycan synthesis, slow down its catabolism and promote cartilage formation through well defined in vitro studies. It was therefore, assumed that IGF-1 would eventually serve to augment current cartilage repair techniques in vivo. Study was therefore, designed to determine the influence of IGF-1 in cartilage repair with or without autografting. For this purpose articular cartilage repair model was created in the left knee of 48 New Zealand white rabbits of either sex, 6-7 months old, weighing 1-2 kg. The articular cartilage defect was created in the femoral groove of femoro-patellar joint using hand held trephine under xylazine and ketamine anaesthesia in all the animals. The defect created was 3 mm in diameter and 2 mm in depth. For autografting, osteochondral tissues harvested from the proximal patellar groove of the femur were placed in the distal defect and vice versa. The experimental animals were divided mainly into four groups, i.e. Group A (control), Group B (autografting), Group C (control + IGF-1) and Group D (autografting + IGF-1). Animals of group A and B were provided only with collagen scaffolds at 10 mug/cm(2) whereas animals of treatment group C and D were provided with collagen scaffolds holding 30 ng/30 mul of IGF-1 into the defect. Evaluation of cartilage repair was done on days 15, 30 and 45 after ethically killing the animals. Initially IGF-1 had shown the tendency for either in the maintenance of autografted cartilage or helped in proliferation of chondroblast for the repair process. However, later in the process, cartilage formation apparently declined and appeared to converge to osseous tissue. Collectively, non-responsiveness of osteoarthritic chondrocytes to IGF-1 could be partially attributed to either increased IGF-binding proteins in the joint space, micromovement of the graft, lack of nutrition, dose of IGF-1 or its half life in the current study.

Evaluation of the reasons for failure of integration during cartilage repair. A review

“…Intrinsic repair can be stimulated by drilling or microfracturing the subchondral bone plate, an action that exposes the vascular system and bone marrow to the defect void (Steadman et al, 2001). Fibrin clot formation, vascular invasion and recruitment of mesenchymal stem cells into the defect result in chondrogenesis at the wound site.…”

“…There are an abundance of studies that have described agerelated decline in chondrocyte function, such as reductions in proliferative potential, sulphated glycosaminoglycan production, collagen deposition and responsiveness to growth factors (Barbero et al, 2004;Blaney Davidson et al, 2005;Singh et al, 2007;Tew et al, 2001). It is estimated that in vitro expansion ages chondrocytes approximately 30 years based on measurements of telomere length, implying replicative senescence of chondrocytes can potentially impede integration through accelerated aging (Barbero et al, 2004;Parsch et al, 2002).…”

“…At the very least the repair tissue should replicate the biomechanical function of the surrounding normal cartilage, allow pain-free articulation, integrate with surrounding host tissue, and prevent further cartilage degeneration. Intrinsic repair can be stimulated by drilling or microfracturing the subchondral bone plate, an action that exposes the vascular system and bone marrow to the defect void (Steadman et al, 2001). Fibrin clot formation, vascular invasion and recruitment of mesenchymal stem cells into the defect result in chondrogenesis at the wound site.…”

Ressonância magnética na avaliação de enxerto osteocondral autógeno na cartilagem articular de coelhos

“…Especula-se que algumas pequenas lacunas persistentes podem existir entre o enxerto e a cartilagem original, permitindo a infiltração do fluido sinovial no osso subcondral, o que resulta em estímulo tecidual persistente (Efe et al 2012). De acordo com Singh et al (2007) e Bekkers et al (2013), em alguns casos podem ocorrer cistos necróticos provavelmente devido a alterações isquêmi-cas no enxerto. No presente estudo, histologicamente, não foram identificadas lacunas que pudessem ocasionar o acú-mulo de líquido no tecido enxertado, mesmo nos grupos com enxertos macerados.…”

“…A utilização de IGF-1 como um agente terapêutico nas afecções articulares envolve algumas restrições, incluindo principalmente o tempo curto de permanência intra-articular e a escassez intrínseca de condrócitos para servir como células alvo (Madry et al 2005). A falta de resposta ao IGF-1 dos condrócitos pode ser parcialmente atribuída a uma série de fatores, incluindo o aumento na quantidade de proteínas de ligação do IGF-1 no espaço articular, falta de nutrição do tecido enxertado, micromovimentação do enxerto ou a dose administrada (Singh et al 2007). Além disso, em nenhum estudo com enxertos cartilaginosos foi obtido sucesso pleno na formação de um tecido com as características idênticas da cartilagem hialina normal (Kangarlu & Gahunia 2006, Heir et al 2012, Tiwary et al 2013.…”