Controlled Delivery of Natural Medicinal Compounds from Tissue Engineering Scaffolds for Critical-Sized Bone Defect Repair

With an increasing life expectancy and aging population, orthopedic defects and bone graft surgeries are increasing in global prevalence. Research to date has greatly advanced the understanding of bone biology and defect repair mechanism, leading to a marked success in the development of synthetic bone substitutes. Yet, the quest for a functionalized bone grafts prompted the researchers to pursue a viable and safer alternative that regulates cellular activity, and supports bone regeneration and healing process without causing serious side-effects and tissue toxicity. In this context, researchers have found a novel treatment regimen by introducing naturally derived medicinal compounds (NMSs) in bone tissue engineering scaffold that enables them to release at a desirable rate and concentration, maintains a sustained release allowing sufficient time for tissue in-growth, and guides bone regeneration process with minimized risk of tissue toxicity. NMCs are gaining popularity in western countries for the last two decades and is now being used by 80% of the population worldwide, according to an estimation by WHO. In contrast to synthetic drugs, NMCs have a broader range of safety window and thus presented as suitable for prolonged localized delivery for bone tissue regeneration. There is limited literature focusing on the integration of bone grafts and natural medicines that provides detailed scientific evidences on each NMCs, their toxic limits and particular application in bone tissue engineering, which could guide the researchers to develop functionalized implants for various bone disorders. This review will discuss the emerging trend of NMC drug delivery from tissue engineering scaffold, including both 3D printed structures and surface modified implants, highlighting the significance and potential of NMCs for bone health, guiding future paths toward the development of an ideal bone tissue engineering scaffold.