Gultian Kirstene A, Gandhi Roshni, DeCesari Kayla, Romiyo Vineeth, Kleinbart Emily P, Martin Kelsey, Gentile Pietro M, Kim Tae Won B, Vega Sebastián L
Department of Biomedical Engineering, Rowan University, Glassboro, NJ, United States.
Department of Orthopaedic Surgery, Cooper University Health Care, Camden, NJ, United States.
Front Biomater Sci. 2022;1. doi: 10.3389/fbiom.2022.948493. Epub 2022 Jul 22.
Osteoporosis is a disease characterized by a decrease in bone mineral density, thereby increasing the risk of sustaining a fragility fracture. Most medical therapies are systemic and do not restore bone in areas of need, leading to undesirable side effects. Injectable hydrogels can locally deliver therapeutics with spatial precision, and this study reports the development of an injectable hydrogel containing a peptide mimic of bone morphogenetic protein-2 (BMP-2). To create injectable hydrogels, hyaluronic acid was modified with norbornene (HANor) or tetrazine (HATet) which upon mixing click into covalently crosslinked Nor-Tet hydrogels. By modifying HANor macromers with methacrylates (Me), thiolated BMP-2 mimetic peptides were immobilized to HANor via a Michael addition reaction, and coupling was confirmed with 1H NMR spectroscopy. BMP-2 peptides presented in soluble and immobilized form increased alkaline phosphatase (ALP) expression in MSCs cultured on 2D and encapsulated in 3D Nor-Tet hydrogels. Injection of bioactive Nor-Tet hydrogels into hollow intramedullary canals of Lewis rat femurs showed a local increase in trabecular bone density as determined by micro-CT imaging. The presented work shows that injectable hydrogels with immobilized BMP-2 peptides are a promising biomaterial for the local regeneration of bone tissue and for the potential local treatment of osteoporosis.
骨质疏松症是一种以骨矿物质密度降低为特征的疾病，从而增加了发生脆性骨折的风险。大多数药物治疗是全身性的，不能在需要的部位修复骨骼，会导致不良副作用。可注射水凝胶可以在空间上精确地局部递送治疗药物，本研究报告了一种含有骨形态发生蛋白-2（BMP-2）模拟肽的可注射水凝胶的研发情况。为了制备可注射水凝胶，用降冰片烯（HANor）或四嗪（HATet）对透明质酸进行修饰，二者混合后通过点击化学形成共价交联的Nor-Tet水凝胶。通过用甲基丙烯酸酯（Me）修饰HANor大分子单体，将硫醇化的BMP-2模拟肽通过迈克尔加成反应固定在HANor上，并通过1H NMR光谱确认了偶联。以可溶性和固定化形式存在的BMP-2肽增加了在二维培养以及封装在三维Nor-Tet水凝胶中的间充质干细胞（MSC）中碱性磷酸酶（ALP）的表达。通过微计算机断层扫描（micro-CT）成像确定，将生物活性Nor-Tet水凝胶注射到Lewis大鼠股骨的中空髓腔内，显示小梁骨密度局部增加。本研究表明，固定有BMP-2肽的可注射水凝胶是一种有前景的生物材料，可用于骨组织的局部再生以及骨质疏松症的潜在局部治疗。
