CBD-conjugated BMP-inhibiting exosomes on collagen scaffold dual-target Achilles tendon repair: Synergistic regeneration and heterotopic ossification prevention

Abstract Tendon injuries in the aging population are often complicated by heterotopic ossification (HO), hindering functional recovery. Exosomes from tendon stem/progenitor cells (TSPCs) promote regeneration but may also induce osteogenesis, contributing to HO. Preconditioning with the BMP inhibitor LDN193189 and modification with collagen-binding peptides (CBD) can enhance the tenogenic potential of exosomes while mitigating osteogenic effects. We evaluated the efficacy of a 3D-printed scaffold loaded with LDN-preconditioned, CBD-modified exosomes (3D-CBD@LDN/Exos) derived from CD26+ TSPCs in promoting Achilles tendon repair and