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可注射混合水凝胶介导的钙敏感受体(CaSR)激活以增强成骨作用和骨重塑

Injectable hybrid hydrogel-mediated calcium-sensing receptor (CaSR) activation for enhanced osteogenesis and bone remodeling.

作者信息

Sekar Jeyakumar Grace Felciya, Velswamy Poornima, Gunasekaran Deebasuganya, Vincent Paulraj Alexandar, Paneerselvam Manimegalai Nivethitha, Tiruchirappalli Sivagnanam Uma

机构信息

Biological Materials Laboratory, CSIR-Central Leather Research Institute, Sardar Patel Road, Adyar, Chennai, India.

Department of Leather Technology, Alagappa College of Technology, Anna University, Chennai, India.

出版信息

Biomater Sci. 2025 Jul 21. doi: 10.1039/d5bm00349k.


DOI:10.1039/d5bm00349k
PMID:40686096
Abstract

Injectable hydrogels have transfigured bone tissue engineering by offering minimally invasive solutions for treating irregularly shaped critical-size bone defects. Unlike traditional fixed-shaped bone grafts that require invasive surgeries and precise defect matching, injectable hydrogels adapt to defect geometries and accelerate healing. The hydrogels mimic the extracellular matrix with their porous, interconnected 3D architecture, promoting cell adhesion, proliferation, differentiation, vascularization, and nutrient flow, which are essential for effective bone regeneration and affirm the osteoconductivity. Chitosan-alginate hydrogels are particularly promising due to their mechanical stability, biodegradability, and ability to deliver bioactive compounds sustainably. To enhance its osteoinductive properties, bioinorganic ions such as strontium (Sr)-based hybrid nanocomposites have been explored. Strontium has garnered attention for its ability to activate the calcium-sensing receptor (CaSR)-mediated signaling pathways by regulating bone resorption and bone formation by various bone matrix proteins, thereby promoting bone homeostasis and regeneration. Strontium's ionic similarity to calcium enables it to act as a robust activator of CaSR, triggering pathways that enhance bone regeneration. Building on this, we developed an innovative hybrid material hydrogel by reinforcing the chitosan-alginate hydrogels with a Sr-Fe-TQ (strontium-iron-thymoquinone) nanocomposite. This bioengineered hydrogel system demonstrated excellent hemocompatibility (in human RBCs), cytocompatibility, biocompatibility, and enhanced efficiency in MG-63 osteoblast-like cells. studies using a rabbit critical-size defect model showed accelerated bone remodeling, achieving better defect closure and superior bone volume restoration (∼99%) compared to the controls. This study underscores the transformative potential of the Sr-Fe-TQ hydrogel as an injectable, osteoconductive, and osteoinductive scaffolds for critical-size defect repair. By combining minimally invasive delivery, sustained bioactive release, and superior regenerative outcomes, this hydrogel system addresses key challenges in bone tissue engineering, paving the way for next-generation biomaterials in regenerative medicine.

摘要

可注射水凝胶通过为治疗不规则形状的临界尺寸骨缺损提供微创解决方案,彻底改变了骨组织工程。与需要进行侵入性手术且要求精确缺损匹配的传统固定形状骨移植不同,可注射水凝胶能适应缺损的几何形状并加速愈合。这些水凝胶通过其多孔、相互连接的三维结构模拟细胞外基质,促进细胞黏附、增殖、分化、血管生成和营养物质流动,这些对于有效的骨再生至关重要,并证实了其骨传导性。壳聚糖 - 海藻酸盐水凝胶因其机械稳定性、生物可降解性以及可持续递送生物活性化合物的能力而特别有前景。为了增强其骨诱导特性,人们探索了诸如基于锶(Sr)的生物无机离子杂化纳米复合材料。锶因其能够通过调节各种骨基质蛋白的骨吸收和骨形成来激活钙敏感受体(CaSR)介导的信号通路,从而促进骨稳态和再生而受到关注。锶与钙的离子相似性使其能够作为CaSR的强大激活剂,触发增强骨再生的途径。在此基础上,我们通过用Sr - Fe - TQ(锶 - 铁 - 百里醌)纳米复合材料增强壳聚糖 - 海藻酸盐水凝胶,开发了一种创新的杂化材料水凝胶。这种生物工程水凝胶系统在人红细胞中表现出优异的血液相容性、细胞相容性、生物相容性,并在MG - 63成骨样细胞中提高了效率。使用兔临界尺寸缺损模型的研究表明,与对照组相比,骨重塑加速,实现了更好的缺损闭合和更高的骨体积恢复率(约99%)。这项研究强调了Sr - Fe - TQ水凝胶作为用于临界尺寸缺损修复的可注射、骨传导和骨诱导支架的变革潜力。通过结合微创递送、持续生物活性释放和卓越的再生效果,这种水凝胶系统解决了骨组织工程中的关键挑战,为再生医学中的下一代生物材料铺平了道路。

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