Cell-free regenerative medicine (RM) strategies for cartilage and bone put to the test in the challenging equine in vivo model

Abstract

This thesis focuses on in vivo studies in horses for the long-term evaluation of various regenerative approaches for articular cartilage and bone repair using cell-free techniques. The equine tuber coxae was introduced as a novel site to study bone regeneration using tricalcium phosphate (TCP)-based scaffolds, produced by additive manufacturing techniques. The new site proved very convenient, because of easiness to approach, low risk of contamination and minimal clinical impact. The TCP scaffolds showed good incorporation into the surrounding tissue with clear osteoconductivity and good capacity for new bone formation. Constant porosity appeared to achieve enhanced bone formation better than a gradually changing pore size in a follow-up study. Cartilage regeneration was studied in artificially created defects in the stifle (knee) joint. A study on fixation of the implants showed that press-fit placed osteochondral implants were to be preferred over only chondral implants for achieving optimal retention. A scaffold existing completely of decellularized cartilage-derived matrix (CDM) was compared to a scaffold made of the same CDM for the cartilage phase combined with a three-dimensionally (3D) printed calcium phosphate -based scaffold for the bone phase. The latter functioned well for bone repair but failed in producing functional tissue in the cartilage phase. A novel approach for repair of chondral defects relying on a self-sealing hydrogel that adheres to the surrounding cartilage surrounding by covalent bonds showed after 7 months repair tissue that was histologically superior to that in the nano-fracture treated control defects. Though preliminary, this outcome seems promising, warranting further exploration.