Department of Neurological Surgery, University of California Davis Medical Center, California, United States
Abstract: Vascularization is one of the key components of tissue engineering and must accompany the ingrowth of new tissue to establish an environment conducive to the repair and regeneration of damaged tissue. In reconstructive orthopedic procedures, bone graft substitutes (BGS) are implanted to facilitate the repair of osseous tissue, a process during which osteoprogenitor cell infiltration into the BGS scaffold is mediated by the vascular endothelium and dependent on angiogenesis at the defect site for cytokines, growth factors, and osteoblasts necessary for bone formation. Poor bone regeneration is primarily caused by deficient vascularization of the implanted scaffold, which leads to atrophic non-union, excessive fibrotic scar formation, and osteogenesis impairment. To address these issues, porous polymer-based BGS materials have been considered due to high biodegradability, antifibrotic, and pro-angiogenic properties, yet their ability to promote angiogenesis in the repair of critical-sized bone defects has not been well-studied. The overarching objective of this study was to investigate whether hyper-crosslinked carbohydrate polymer (HCCP) BGS could promote the establishment of new vasculature compared to hydroxyapatite/beta-tricalcium phosphate (HA/βTCP) scaffolds, which are widely used in orthopedic procedures. Sprague Dawley rats (n=12) were implanted subcutaneously with HCCP or HA/βTCP and evaluated histologically for the ingrowth of new vasculature at 3, 14, and 28-days post-implantation. Vascularization was assessed by microvessel density, qualitative histological evaluation, and blood perfusion. HCCP demonstrated 5.06X more blood perfusion at 28 days compared to HA/βTCP (p < 0.05), and substantially higher microvessel density (0.073) than HA/βTCP (0.009) at 28 days (p < 0.05). Additionally, HA/βTCP showed transient inflammation at 14-days post-implantation whereas minimal immune activities were noted in HCCP. These findings suggest that HCCP promotes the establishment of new vasculature without a significant immune response. Further studies are underway to assess osteogenic differentiation, matrix remodeling, scaffold degradation, and stem cell recruitment using techniques such as RNA-seq and convolutional neural network architecture.
Funding Source: This research received no external funding.
