[3S06m] 16. Cell and Tissue Engineering for Biomedical Process Innovation - Part 1

11:20 AM - 11:40 AM JST(2:20 AM - 2:40 AM UTC)

[3CTBP-04] Next-Generation phyto-nanoengineered bone substitutes for augmenting regeneration in Critical Defects

○Sneha Singh¹ (1. Dept of Bioengineering & Biotechnology, Birla Institute of Technology, Mesra (India))

Keywords:

Cissus quadrangularis,Bone regeneration,Resveratrol,nanohydroxyapatite,cryogels

Bone is a dynamic connective tissue capable of self-repair; however, critical-sized defects caused by trauma, tumor resection, metabolic disorders, or infections exceed its natural regenerative capacity. Many currently used synthetic substitutes and metallic implants are bio-inactive, non-resorbable, and lack osteoinductive potential. These challenges underscore the urgent need for next-generation bone substitutes that are osteogenic, bioresorbable, osteopromotive, and cost-effective.This work aims to develop bio-inspired multifunctional bone substitutes using interdisciplinary tissue-engineering strategies integrated with phytobioactives as osteoinductive cues. Plant-derived bioactives, traditionally valued for therapeutic efficacy, accessibility, and low toxicity, provide promising alternatives to synthetic drugs that often exhibit poor solubility, adverse effects, and limited bioavailability. Cissus quadrangularis (CQ), and Resveratrol were selected to enhance osteoinductivity through nanocomposite delivery systems. Nano-cement ceramic bone substitutes enriched with CQ phytobioactives, which further enhanced osteogenesis, increased calcium deposition, promoted cell migration, and improved in vivo bone mineral density and fractional bone volume.To further explore osteogenic potential, Resveratrol (cis- and trans) isomeric forms were stabilized on gold nanoparticles (GNPs). Nanotechnological intervention enabled stabilization of the otherwise unstable cis-resveratrol, leading to the formation of biologically synthesized cis-resveratrol-capped GNPs (cRGNPs) with uniform nanoscale size (~25 nm) and physiological stability. These nanoparticles demonstrated hemocompatibility, strong antioxidant activity, and significant enhancement of pre-osteoblast proliferation and migration. Importantly, cRGNPs increased alkaline phosphatase activity and upregulated key osteogenic markers, establishing cis-resveratrol’s osteoinductive role for the first time.Similarly, trans-resveratrol-capped GNPs (tRGNPs; ~22 nm) exhibited excellent cytocompatibility and hemocompatibility, promoted mineral deposition, and displayed potent anti-inflammatory and antioxidant effects. These nanoparticles mitigated oxidative and hyperglycemic stress, enhanced cell survival, and improved cellular proliferation and migration. Incorporation of tRGNPs into a porous polymer–nano-hydroxyapatite scaffold generated a hybrid nano-scaffold with superior surface roughness, protein adsorption, mechanical strength, and cell–material interactions. In a rat critical-sized tibial defect model, this scaffold significantly improved mineralization and neo-bone formation, confirmed through micro-CT and histological evaluation while preserving pore architecture. Successful healing of critical-sized defects in preclinical rodent models highlights the strong translational potential of these cost-effective, bioactive scaffolds for future orthopedic and bone tissue engineering applications.