Orthobiologics with phytobioactive cues: A paradigm in bone regeneration

Bone injuries occur due to various traumatic and disease conditions. Healing of bone injury occurs via a multi-stage intricate process. Body has the potential to rectify most of the bone injuries but some severe traumatic cases with critical size defects may require interventions. Autografts are still considered the "gold standard" for fracture healing but due to limitations associated with it, new alternatives are warranted. The field of orthobiologics has provided novel approaches using scaffolds, bioactive molecules, stem cells for the treatment of bone defects. Phyto-bioactives have been widely used in alternative medicine and folklore practices for curing bone ailments. It is believed that different bioactive constituents in plants work synergistically to give the therapeutic efficacy. Bioactives in plants extracts act upon different signal transduction pathways aiding in bone healing. The present review focuses on the use, chemical composition, mode of delivery, mechanism of action, and possible future strategies of three medicinal plants popularly used in traditional medicine for bone healing: Cissus quadrangularis, Withania somnifera and Tinospora cordifolia. Plants extracts seem to be a natural and non-toxic therapeutic alternative in treating bone injuries. Most of the studies on bone healing for these plants have reported oral administration of the extracts and presented them as a safe alternative without any side effects despite giving higher doses. Forthcoming studies could be directed towards the local delivery of extracts at the defect site. Unification of herbal extracts and orthobiologics could be an interesting direction in the field of bone healing in future. The present review intends to provide a bird's eye view of different strategies used in bone healing, mechanisms involved and future direction of advancements using phytobioactives and orthobiologics.