A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair

Abstract

Introduction Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization. Methods In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo. Results The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway. Conclusion The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.

Advances in the Application of Black Phosphorus-Based Composite Biomedical Materials in the Field of Tissue Engineering

“…The process of vascular formation is highly coupled with skeletal reconstruction; hence, the designs of hydrogel materials that are both pro-angiogenic and osteoconductive have a promising application in promoting bone injury repair. Xu et al [ 65 ] prepared a hydrogel by crosslinking BPNS, deferoxamine (DFO), and gel solution using UV radiation. BPNS was employed to facilitate the controlled release of PO 4 3− and DFO, activating critical angiogenic genes such as vascular endothelial growth factor (VEGF), thereby promoting angiogenesis and accelerating the process of bone defect repair.…”

Research progress on black phosphorus hybrids hydrogel platforms for biomedical applications

“…In vivo studies from a model of a skull lesion in a rabbit shown that BPNs accelerated bone repair. Xu et al [ 37 ] prepared scaffolds by loading BPNs and deferoxamine (BPN-DFO) into gelatin hydrogels using a similar approach. In ischemic tibial areas of SD (Sprague Dawley) rats with acute femoral artery blockage, the scaffolds displayed excellent swelling, degradation, and release rates, and significantly enhanced osteogenesis and blood vessel development.…”

Polymeric Theragnostic Nanoplatforms for Bone Tissue Engineering

“…In contrast, in situ hydrogels fabricated with calcium-enriched nano-fibrillated cellulose exhibited improved biocompatibility, cell attachment, alkaline phosphatase, and calcium deposition activity [62]. Hydroxyapatite, being one of the most biocompatible agents, combined with cellulose to develop into nanocomposites for bone cell proliferation, were three-dimensionally printed and evaluated for the sustained release of strontium and calcium ions and substantial proliferation, bone marrow stem cell differentiation, and bone tissue revival [63]. In another study, cellulose nanocrystals doped with gelatin and alginate developed into 3D-printed hydrogel scaffolds presented considerable matrix mineralization in the bone tissue [64].…”