Table 2. Key Biologics for Bone and Nerve Repair: Examples and Mechanisms of Action.

ECM: extracellular matrix; 3D: 3-dimensional; TGF-β: transforming growth factor-beta; EGF: epidermal growth factor; VEGF: vascular endothelial growth factor; BMP: bone morphogenetic proteins; rhBMP-2: recombinant human bone morphogenetic protein-2; Trk: tyrosine kinase; GDNF: glial cell line-derived neurotrophic factor; GFRα: GDNF family receptor-alpha; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; MSC: mesenchymal stem cell; PRP: platelet-rich plasma; PDGF: platelet-derived growth factor; IGF-1: insulin-like growth factor-1

Biologic Type	Mechanisms in Bone Repair	Mechanisms in Nerve Repair
Decellularized ECM Scaffolds	Acellular tissue matrices (e.g., decalcified bone or decellularized nerve grafts) provide a natural 3D collagenous scaffold that is osteoconductive, guiding new bone growth into the defect [34]. Importantly, these matrices retain native growth factors (such as bone morphogenetic proteins) and bioactive cues, imparting osteoinductive properties that stimulate progenitor cell differentiation and bone formation [34]. With cellular antigens removed, they elicit minimal immune response while promoting "constructive" remodeling of bone tissue.	Removing cellular antigens from nerve or other tissues yields a scaffold with preserved extracellular architecture (e.g., endoneurial tubes or basement membrane) that guides regenerating axons [35]. The decellularized ECM retains essential laminin, collagen, and glycosaminoglycan components that support Schwann cell migration and adhesion of regenerating neurons [35]. These grafts lack immunogenic cells, but are rich in native ECM signals and pro-angiogenic factors. These grafts provide a permissive 3D substrate for axon extension across nerve gaps and encourage revascularization of the repair site.
Perinatal Tissue Derivatives (e.g., Amniotic Membrane)	Amniotic membrane and related perinatal tissues (placenta, Wharton's jelly) serve as biologically active scaffolds that release a rich cocktail of growth factors and cytokines to stimulate osteogenesis [36]. They are inherently anti-inflammatory and anti-fibrotic, dampening local inflammation and scar formation while their resident mesenchymal stem cells and bioactive matrix promote new bone deposition [37]. Used as graft wraps or membranes, perinatal tissues create a favorable milieu for bone regeneration, enhancing healing of fractures and defects by recruiting osteoprogenitor cells and modulating the immune response.	Perinatal-derived biomaterials provide a neuroprotective, pro-regenerative environment for injured nerves. The human amniotic membrane, for example, exhibits low immunogenicity and secretes numerous growth factors (e.g., TGF-β, EGF, VEGF) and neurotrophic factors that support neural outgrowth [30]. When applied as a nerve wrap or conduit, amniotic tissue reduces fibrosis and inflammation around the injury, acting as an anti-adhesive barrier. It also delivers mesenchymal progenitor cells and trophic factors that foster axonal regeneration and remyelination, effectively creating a permissive microenvironment for nerve repair [30].
Growth Factors (Signal Molecules)	Osteogenic growth factors such as BMPs and TGF-β are potent drivers of bone repair. BMP-2, in particular, binds to mesenchymal stem cell receptors to induce osteoblast differentiation and robust bone matrix production [38]. These factors orchestrate the bone healing cascade by stimulating osteoprogenitor proliferation, enhancing angiogenesis, and upregulating osteocalcin and collagen synthesis for mineralized matrix formation. Clinically, the exogenous delivery of BMPs (e.g., rhBMP-2 in grafts) has been shown to significantly augment fracture healing and spinal fusion by recapitulating embryonic bone formation pathways.	Neurotrophic growth factors (e.g., nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor) are essential for peripheral nerve regeneration. They bind to specific neuronal receptors (Trk receptors or GFRα co-receptors) to activate intracellular pathways that promote neuron survival and axon elongation [30]. After nerve injury, endogenous levels of these factors rise but are often insufficient; thus, sustained exogenous supply can markedly improve regeneration [39]. Incorporating growth factors into nerve conduits or injection sites enhances axonal outgrowth and guidance, as demonstrated by improved nerve fiber extension and functional recovery when NGF, BDNF, or GDNF are delivered to repairing nerves.
Mesenchymal Stem Cells (MSCs)	MSC-based therapies aid bone repair through both direct and paracrine mechanisms. These multipotent stromal cells can engraft into bone lesions and differentiate into osteoblasts that deposit new bone matrices. However, an equally critical role of MSCs is immunomodulation: they secrete anti-inflammatory cytokines and growth factors that orchestrate the fracture healing process [40]. By modulating macrophage and T-cell responses at the injury site, MSCs help resolve inflammation and stimulate vascularization and tissue remodeling [40]. The net effect is an enhanced regenerative microenvironment that accelerates bone union, even when only a small fraction of the cells directly become new bone-forming osteocytes.	Transplanted MSCs promote peripheral nerve regeneration primarily via supportive paracrine effects and glial-like activity. Even without full differentiation, MSCs secrete a broad spectrum of neurotrophic factors, angiogenic factors, and extracellular vesicles that collectively support axonal growth and neuronal survival [41]. They can adopt Schwann cell–like phenotypes under appropriate cues, wrapping and remyelinating regenerating axons. Owing to their low immunogenic profile, even allogeneic MSCs survive well in nerve repair sites and continuously release factors that guide axons and suppress hostile inflammation [41]. In experimental nerve injuries, MSC therapy has yielded faster and more complete functional recovery by filling nerve conduits with a pro-regenerative cellular substrate.
Platelet-Rich Plasma (PRP)	PRP is an autologous concentrate of platelets that, upon activation, releases a plethora of growth factors pivotal for bone healing (PDGF, TGF-β, IGF-1, VEGF, etc.). These signaling molecules synergistically accelerate the repair cascade: they promote angiogenesis, collagen deposition, extracellular matrix formation, and the recruitment and proliferation of osteoblast progenitors [42]. PRP thus jump-starts the normal fracture healing stages - inflammation, soft callus, mineralization - often leading to faster and more robust bone regeneration. Because PRP is derived from the patient's own blood, it poses no risk of immune reaction while providing a rich osteogenic stimulus at the injury site [42].	PRP therapy creates a growth factor-enriched milieu at nerve injury sites that can enhance regeneration. Platelet α-granules in PRP contain factors like PDGF, VEGF, and EGF, which not only nourish injured neurons and glia but also modulate the immune response to injury [43]. In the early post-injury phase, PRP-released factors attenuate pro-inflammatory signals and promote macrophage polarization toward the M2 macrophage healing phenotype [43]. The PRP fibrin clot itself provides a transient scaffold that supports cell migration and axon sprouting. Additionally, high levels of VEGF from PRP improve revascularization of the regenerating nerve, ensuring adequate blood supply for metabolically demanding regrowing axons [43]. Together, these actions translate into improved axonal regeneration and functional recovery in preclinical nerve injury models.