骨组织工程中纳米羟基磷灰石的仿生合成研究进展

Research Progress in Biomimetic Synthesis of Nano-Hydroxyapatite in Bone Tissue Engineering

纳米羟基磷灰石(nano-hydroxyapatite, nHAp)是人体骨、牙无机组成的主要成分,具有优异的生物相容性、生物活性和生物亲和性,可诱导骨组织再生,已广泛应用于骨缺损修复与替代等骨组织工程领域。由于其组成中含有能通过人体正常的新陈代谢途径进行置换的钙、磷等元素,植入体内后可部分或全部被人体组织吸收和取代,能很好地辅助骨的生长,是一种理想的骨修复材料。然而,传统的nHAp陶瓷材料具有一定的脆性且体内降解性差。此外,由于羟基磷灰石纳米粒子表面能大,易发生团聚,导致材料的稳定性差,植入体内后力学强度衰减快,限制了其临床应用。目前,通过负载相关生长因子、蛋白和多肽等活性分子,可有效提高单纯nHAp的力学性能及生物相容性,从而使其更符合骨修复材料的生物学要求。但传统的物理或化学修饰方法步骤繁琐,修饰过程可导致nHAp生物活性受到干扰。近年来,直接利用生物大分子或者微生物活体自身的分子识别和自组装能力来制备纳米材料的仿生合成方法不仅简单,且合成的纳米材料性质稳定。对于nHAp而言,因其独特的晶体结构及理化性能,已有大量研究表明可利用其与生物分子之间的亲和性,通过仿生合成的方法制得具有一定生物活性的nHAp。仿生合成nHAp有望成为主流骨组织工程支架材料,分析和归纳不同nHAp材料的仿生合成过程及其特性,对进一步开发机械、生物学等性能更优的骨缺损修复材料具有一定的指导作用。本文综述了基于不同生物分子模板,仿生合成nHAp的方法,并进一步讨论其在骨组织工程中的应用研究进展,为新一代骨修复生物材料的研发提供参考。

Nano hydroxyapatite(nHAp),a main component of the inorganic composition of human bones and teeth,is widely used in bone tissue engineering,bone defect repair and replacement,for example,for its biocompatibility,bioactivity,bioaffinity and the ability to induce bone regeneration.Nano hydroxyapatite contains calcium and phosphorus,elements that can be replaced through the normal metabolic channels of the human body.Therefore,after implantation,it can be partially or completely absorbed and replaced by human tissues and can effectively assist bone regeneration,which makes it an ideal material for bone repair.However,traditional nHAp material is brittle and hard to be degraded in human body.In addition,nHAp has poor stability due to its high surface energy and tendency for agglomeration,which causes rapid attenuation of its mechanical strength and limits its clinical application.At present,the mechanical properties and biocompatibility of nHAp can be effectively improved by loading the related growth factors,proteins,peptides and other bioactive molecules,so as to better meet the biological requirements of bone repair materials.However,the traditional physicochemical modification methods are complicated and may interfere with the bioactivity of nHAp.It is simple to biomimetically synthesize nanomaterials by direct utilization of the molecular recognition and selfassemble capabilities of biomolecules or living microorganisms.Furthermore,the properties of the synthesized nanomaterials are stable,and the method has been extensively studied in recent years.Due to the unique crystaline structure and physicochemical properties of nHAp,results of a large number of studies have shown that its affinity with biological molecules can be used to produce bioactive nHAp by biomimetic synthesis methods.Biomimetically synthesized nHAp is expected to become the mainstream bone tissue engineering scaffold material.Analyzing and summarizing the biomimetic synthetic process and the characteristics of different nHAp materials will facilitate further development of bone defect repair materials with better mechanical and biological properties.Herein we reviewed methods of biomimetic synthesis of nHAp based on different biomolecular templates.Furthermore,we also discussed applications of biomimetic synthesized nHAp in bone tissue engineering,which can used as reference information for further research and development of new-generation bone repair biomaterials.