Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones

Abstract

Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.

Resorbable GBR Scaffolds in Oral and Maxillofacial Tissue Engineering: Design, Fabrication, and Applications

“…Scaffold-based biomimetic bone replacements aim to replicate bone's structural, mechanical, and biological attributes to replace missing tissue. For bone substitutes employed to treat significant segmental defects, they need to encourage osteoinduction, osteoconduc-tion, and osseointegration [43]. Osteoinduction involves prompting pluripotent precursor cells to differentiate into bone-forming osteoblasts [43,44].…”

“…For bone substitutes employed to treat significant segmental defects, they need to encourage osteoinduction, osteoconduc-tion, and osseointegration [43]. Osteoinduction involves prompting pluripotent precursor cells to differentiate into bone-forming osteoblasts [43,44]. Osteoconduction encompasses aiding growth on the scaffold's surface and within its pores or channels through processes like cell adherence, proliferation, and the creation of a new ECM [45].…”

“…Several scaffold properties, including material composition and spatial organisation, must be thoughtfully balanced and considered to achieve this. When used in regenerative techniques, scaffold materials should demonstrate adequate biocompatibility [43]. In contrast to procedures like joint replacement, regenerative strategies require scaffold biodegradability, as the central goal is to encourage and facilitate the inherent healing of tissue [47].…”

“…Furthermore, the scaffold should provide adequate mechanical reinforcement. To achieve this, material characteristics such as compressive strength, stiffness, and elasticity should align with those characteristics of bone during the specific stage of regeneration [43,52,53]. For instance, during endochondral ossification, the biomechanical context is marked by a relatively low Young's modulus of around 8 kilopascal (kPa), whereas fully developed healthy bone tissue exhibits values in the gigapascal (GPa) range (0.1 to 2 GPa for trabecular bone and between 15 and 20 GPa for cortical bone) [54,55].…”

“…Consequently, optimizing factors such as porosity, pore size, and interconnectivity become vital while still meeting the mechanical prerequisites. A pore size of approximately 100 µm has been identified as beneficial for cell migration, encouraging the initial phases of bone formation involving cell recruitment, proliferation, differentiation, and the formation of the ECM [43]. However, larger pore sizes are necessary for effective bone tissue development to facilitate vascularisation.…”