The development of bone implants through bioinspired immobilization of growth factors remains a key issue in the generation of biological interfaces, especially in enhancing osteodifferentiation ability. In this study, we developed a strategy for surface functionalization of poly(lactide‐glycolide) (PLGA) and hydroxyapatite (HA) composite substrates through site‐specific conjugation of bone morphogenetic protein 2 containing 3,4‐hydroxyphenalyalanine (DOPA‐BMP2) mediated by tyrosinase and sortase A (SrtA). Firstly, the growth factor BMP2‐LPETG containing LPETG motif was successfully expressed in Escherichia coli through recombinant DNA technology. The excellent binding affinity of binding growth factor (DOPA‐BMP2) was achieved by converting the tyrosine residue (Y) of YKYKY‐GGG peptide into DOPA (X) by tyrosinase, which bound to the substrates. Then its GGG motif was specifically bound to the end of BMP2‐LPETG mediated by SrtA. Therefore, the generated bioactive DOPA‐BMP2/PLGA/HA substrates significantly promoted the osteogenic differentiation of MC3T3‐E1 cells. Thanks to this microbial‐assisted engineering approach, our work presents a facile and highly site‐specific strategy to engineer biomimetic materials for orthopedics and dentistry by effectively delivering growth factors, peptides, and other biomacromolecules.

中文翻译：

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通过基因技术和位点特异性生长因子结合的生物界面工程实现有效的骨分化


通过生长因子的仿生固定化来开发骨植入物仍然是生物界面生成中的关键问题，特别是在增强骨分化能力方面。在这项研究中，我们开发了一种通过含有 3,4-羟基苯丙氨酸 (DOPA-BMP2) 介导的骨形态发生蛋白 2 的位点特异性缀合，对聚丙交酯-乙交酯 (PLGA) 和羟基磷灰石 (HA) 复合基材进行表面功能化的策略。由酪氨酸酶和分选酶 A (SrtA) 产生。首先，通过重组DNA技术在大肠杆菌中成功表达了含有LPETG基序的生长因子BMP2-LPETG。结合生长因子（DOPA-BMP2）的优异结合亲和力是通过酪氨酸酶将 YKYKY-GGG 肽的酪氨酸残基（Y）转化为 DOPA（X）并与底物结合而实现的。然后其GGG基序在SrtA介导下特异性结合至BMP2-LPETG末端。因此，产生的生物活性DOPA-BMP2/PLGA/HA底物显着促进MC3T3-E1细胞的成骨分化。得益于这种微生物辅助工程方法，我们的工作提出了一种简便且高度特定于位点的策略，通过有效地传递生长因子、肽和其他生物大分子来设计用于骨科和牙科的仿生材料。