富含仿生肽的非织造支架促进磷酸钙矿化
Biomimetic peptide enriched nonwoven scaffolds promote calcium phosphate mineralisation
摘要:
需要无细胞翻译策略来加速矿化组织的修复,特别是使用微创方法的大骨缺损。再生骨支架应理想地模拟多个长度尺度上的组织ECM的方面,并在体内植入期间实现手术处理和固定。利用生物活性自组装肽(SAP)和SAP富集的电纺纤维获得的知识,我们提出了一种无细胞的方法,通过磷灰石沉积和晶体生长,在体外,SAP富集的非织造支架促进矿化。根据聚合物的纤维形成能力和其水解可降解性以及SAP的众所周知的磷灰石成核能力,通过在肽P11-4(Ac-QQRFEWEFEQQ-Am)或P11-8(Ac-QQRFOWOFEQQ-Am)的存在下静电纺丝聚(ε-己内酯)(PCL)来制备非织造支架。肽的11个残基家族(P11-X)具有在纳米尺度下自组装成β-折叠有序结构和在宏观尺度下产生水凝胶的能力,其中一些能够由于其磷灰石成核能力而促进生物矿化。在这项研究中使用的SAP-富集的非织造布的两种变体被证明是与鼠成纤维细胞生物相容的,并支持体外模拟体液(SBF)中磷灰石矿物的成核和生长。纤维非织造物提供了结构坚固的支架,具有控制SAP释放行为的能力。在pH 7.4的水溶液中孵育7天后,高达75%的P11-4和45%的P11-8保留在纤维中。SAP在具有磷灰石形成以及局部和长期SAP递送能力的非织造系统中的封装作为实现用于临界尺寸缺损的成本有效的骨修复疗法的潜在手段是有吸引力的。
英文摘要:
Cell-free translational strategies are needed to accelerate the repair of mineralised tissues, particularly large bone defects, using minimally invasive approaches. Regenerative bone scaffolds should ideally mimic aspects of the tissue's ECM over multiple length scales and enable surgical handling and fixation during implantation in vivo. Leveraging the knowledge gained with bioactive self-assembling peptides (SAPs) and SAP-enriched electrospun fibres, we presented a cell free approach for promoting mineralisation via apatite deposition and crystal growth, in vitro, of SAP-enriched nonwoven scaffolds. The nonwoven scaffold was made by electrospinning poly(epsilon-caprolactone) (PCL) in the presence of either peptide P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac-QQRFOWOFEQQ-Am), in light of the polymer's fibre forming capability and its hydrolytic degradability as well as the well-known apatite nucleating capability of SAPs. The 11-residue family of peptides (P11-X) has the ability to self-assemble into beta-sheet ordered structures at the nano-scale and to generate hydrogels at the macroscopic scale, some of which are capable of promoting biomineralisation due to their apatite-nucleating capability. Both variants of SAP-enriched nonwoven used in this study were proven to be biocompatible with murine fibroblasts and supported nucleation and growth of apatite minerals in simulated body fluid (SBF) in vitro. The fibrous nonwoven provided a structurally robust scaffold, with the capability to control SAP release behaviour. Up to 75% of P11-4 and 45% of P11-8 were retained in the fibres after 7-day incubation in aqueous solution at pH 7.4. The encapsulation of SAP in a nonwoven system with apatite-forming as well as localised and long-term SAP delivery capabilities is appealing as a potential means of achieving cost-effective bone repair therapy for critical size defects.
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