An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

Abstract

Background The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. Results Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. Conclusions Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials. Graphic Abstract

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

“…The reconstruction of periodontal tissues including cementum, periodontal ligament fibers, and bone remains a major challenge in periodontal treatment (111). Osteogenesis, inflammatory response, angiogenesis, and remodeling play a significant role in periodontal bone regeneration (112). Reports from the literature indicate that mammalian exosomes stimulate both osteogenesis and angiogenesis (113).…”

Strontium Functionalized in Biomaterials for Bone Tissue Engineering: A Prominent Role in Osteoimmunomodulation

“…During bone reconstruction, the differentiation of MSCs to osteoblasts is accompanied by invasion of the capillaries network which can serve as a template for bone development. Efficient vascularization not only provides the necessary nutrients and oxygen to the damaged site but also is a prerequisite for the repair of bone defects by MSCs and preosteoblasts ( Kargozar et al, 2020 ; Ding et al, 2021 ). In previous studies, Sr 2+ has been reported to promote angiogenesis by stimulating osteoblasts to secrete angiogenesis-related cytokines ( Zhao et al, 2015 ; Mao et al, 2017 ; Offermanns et al, 2018 ).…”

Biomaterials to promote vascularization in tissue engineering organs and ischemic fibrotic diseases

“…In a rat skull defect model, PNM2 microspheres can significantly increase the volume of regenerating vascularized new bone tissue (Figure 4D). 68 69 (F) The engineered exosomes encapsulate a vascular endothelial growth factor (VEGF) plasmid. Copyright permission from Zha et al 70 Angiogenic cytokines, peptides, and nucleic acids loaded on tissue-engineered scaffolds can promote the reconstruction of vascularized bone tissue.…”

“…Copyright permission from Wan et al 68 (E) The role of basic fibroblast growth factor (bFGF) released from in situ tissue engineering scaffold (iTE‐scaffold) on periodontal bone repair. Copyright permission from Ding et al 69 (F) The engineered exosomes encapsulate a vascular endothelial growth factor (VEGF) plasmid. Copyright permission from Zha et al 70 …”

“…Basic FGF loaded with tissue‐engineered scaffolds can significantly promote the vascular regeneration of the periodontal bone in rats (Figure 4E). 69 The angiogenic peptide (AP; Figure 4C) can bind to the VEGF receptor to initiate the angiogenic signaling pathway. The bone tissue‐engineered scaffold surrounding AP can promote new bone formation in rat skull defects and regenerated tissue 67 …”