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A challenge to the orthopedic surgeons in veterinary and human fields is the treatment of delayed union, malunion and nonunion. Apart from renovation of arrangement and constant fixation, in many cases, adjunctive measures such as bone-grafting or the use of bone-graft substitutes, are of dominant significance. In general bone-graft materials comprise one or more components: an osteoconductive matrix, which acts as a scaffold to new bone growth; osteoinductive proteins, backing the mitogenesis of indistinguishable cells; and osteogenic cells, which can form bone in the proper environment. Our review focuses on the currently existing bone graft and graft substitutes for the novel therapeutic approaches in the clinical situation of orthopedic surgery. This review is based on an extensive literature search of different composite scaffolds developed as bone regenerative therapies. The settlement and drawbacks of different composite scaffold developed techniques, the properties of generally used ceramics and polymers, and the properties of presently investigated synthetic composite grafts. To follow, an exhaustive review of in vivo models is used to test composite scaffolds in segmental bone defects (SBDs) to serve as a guide to design suitable translational studies and to recognize the challenges that require to be overcome in scaffold design for successful transformation. This includes the formative of the anatomical position within the animals, selecting the accurate study period, and an overview of scaffold presentation evaluation.

The aim of this study is to tissue engineer a 3D scaffold that can be used for load bearing segmental bone defects (SBDs) repair. Three different scaffolds were fabricated using cockle shell-derived CaCO3 aragonite nanoparticles (CCAN), gelatin, dextran and dextrin with coated framework via Freeze-Drying Method (FDM) labeled as 5211, 5211GTA+Alginate, 5211PLA. Scaffolds were assessed using Scanning Electron Microscopy (SEM). The cytocompatibility of the organized scaffolds was assessed using cells multiplication and alkaline phosphatase (ALP) concentration via In Vitro cell culture using human Fetal OsteoBlast cells line (hFOB). The results showed a substantial difference in ALP concentrations between the cultures of different scaffolds leachable medium during the study period. The biological evaluation also showed that three scaffolds did enhanced the osteoblast proliferation rate and improved the osteoblast function as demonstrated by the significant increase in ALP concentration. Engineering analyses showed that scaffolds possessed 3D interconnected homogenous porous structure with a porosity ranging 6%-49%, pore sizes ranging 8-345 µm, mechanical strength ranging 20-65 MPa, young’s modulus ranging 166-296 MPa and enzymatic degradation rate between 16%-38% within 2-10 weeks. The in vitro evaluation revealed that the scaffold 5211, 5211GTA+Alginate and 5211PLA fulfill all the main requirements to be considered as an ideal bone replacement.