Department of Periodontics, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Graduate Institute of Dental and Craniofacial Science, Chang Gung University, Taoyuan 33302, Taiwan.
J Mater Chem B. 2023 Aug 24;11(33):8007-8019. doi: 10.1039/d3tb00587a.
Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe(μ-SCHCHCOOH)(NO)] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCHCHCOOH] thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (β-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.
颅面/颌骨畸形仍然是恢复面部/牙齿功能和美观的重大临床挑战。尽管有报道称有多种治疗方法可用于临床骨组织再生，但自体移植物的生物利用度问题和异种移植物/合成骨替代物的有限再生效果，仍促使人们不断努力实现功能共轭和改善生物活性骨移植材料。鉴于一氧化氮（NO）在组织工程中的潜力，本文通过将一氧化氮供体二硝酰基铁配合物（DNIC）与骨传导性骨移植材料进行功能共轭，优化了 NO 递送的时空控制，以激活大鼠颅骨骨缺损中的协同成骨和血管生成。在三种仿生 DNIC 中，[Fe(μ-SCHCHCOOH)(NO)]（DNIC-COOH）具有通过 MC3T3-E1 成骨细胞摄取的稳定动力学，随后细胞内组装蛋白结合的 DNIC 并释放 NO。DNIC-COOH 对细胞内 NO 的稳定动力学解释了其生物相容性及其对 MC3T3-E1 成骨细胞和人脐静脉内皮细胞（HUVEC）的广谱细胞增殖作用。此外，DNIC-COOH 中的桥联 [SCHCHCOOH]硫醇配体促进其化学吸附到脱蛋白牛骨矿物质（DBBM）和物理吸附到 TCP（β-磷酸三钙）上，分别为控制负载 DNIC-COOH 的局部释放动力学提供了一种机制。使用颅骨骨缺损大鼠作为模型，DNIC-DBBM/DNIC-TCP 促进了成骨和血管生成活性，归因于骨传导性骨移植材料和一氧化氮供体 DNIC-COOH 的功能共轭。重要的是，DNIC-DBBM/DNIC-TCP 在治疗 4 周和 12 周后对增强皮质骨形成的治疗效果支持了其在再生医学中的临床应用潜力。
