A NOVEL WEIGHT-BEARING RABBIT SHOULDER MODEL FOR IN VIVO TESTING OF IMPLANTS FOR THE TREATMENT OF OSTEOCHONDRAL LESIONS

The treatment of osteochondral lesions (OCLs) remains challenging. Current surgical treatments have varying but limited success [1]. Tissue-engineered implants have shown promise, but preclinical in vivo studies are needed before their clinical use. In vivo studies assessing bioengineered implants for OCLs have focused in the knee joint, and typically involve the nonweightbearing area of the joint [3]. This study aims to establish and evaluate the viability of a novel weightbearing rabbit shoulder model for in vivo testing of implants. Twelve mature female New Zealand White rabbits (NZWr) (>four months old) were used. Surgeries were performed by an orthopaedic surgeon following institutional ethics approval. Bioengineered osteochondral implants were first created by seeding bone marrow mesenchymal stem cells (isolated from donor NZWr) on top of 5.0-mm diameter biodegradable, porous calcium polyphosphate disks (serving as a bone substitute) and cultured in chondrogenic media. To serve as comparative controls, 5.0-mm diameter osteochondral allograft plugs were harvested from the humeral head of donor NZWr. A posterolateral approach to the shoulder joint was utilized. The humeral head was dislocated, and a 2.8-mm guidewire was inserted and then over-reamed with a 5.0-mm cannulated drill to create a 5.0-mm (diameter) × 5.0-mm (depth) critically-sized defect [3] (Figure-1A). Biodegradable bone cement was inserted into the base of the newly-created defect. The implant was then gently press-fitted into the humeral head defect (Figure-1B). The NZWr were recovered and immediately allowed to weightbear. At 2 months, the NZWr were euthanized and the humeral head specimens harvested. The region containing the implant was scanned using microCT (Figure-1C) prior to being formalin-fixed and embedded undecalcified in methyl methacrylate. The embedded blocks were then cut in half: (1) One half stained with toluidine blue, examined by light microscopy, and the cartilage assessed using the ICRS histologic grading system [2]; (2) The other half analyzed using backscatter electron microscopy (BSEM). All NZWr tolerated immediate weightbearing on their forelimb after surgery. A mild superficial skin infection in one rabbit was treated successfully with antibiotics. No mortality was observed. MicroCT analysis demonstrated the majority of the reconstructions were anatomic, despite the NZWr allowed to immediately weightbear. A few of the tissue-engineered implant reconstructions were near anatomic, with very mild subsidence of the implant seen. There was good press-fit of the implants. For the tissue-engineered implants, the BSEM images showed bone ingrowth into the implant from the native bone, and the histological analysis showing survival of the cartilage layer with integration to adjacent host cartilage (Figure-2A). In comparison, the control osteochondral allograft implants showed complete bone healing but no integration of the cartilage layer to the adjacent host cartilage (Figure-2B). This study successfully demonstrated in vivo testing of osteochondral implants in a novel weightbearing rabbit shoulder model. To our knowledge, this is the first study utilizing the shoulder joint for in vivo testing of implants for the treatment of OCLs. We propose that this model may allow for more representative testing of implants to match the clinical environment. For any figures or tables, please contact authors directly.