Biointerface engineering through amalgamation of gene technology and site-specific growth factor conjugation for efficient osteodifferentiation.

IF 3.5 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2024-09-19 DOI:10.1002/bit.28852

Zhenxu Wu,Li Mo,Zongliang Wang,Liangsong Song,Eiry Kobatake,Yoshihiro Ito,Yi Wang,Peibiao Zhang

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引用次数: 0

Abstract

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.

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通过基因技术与特定位点生长因子结合的生物界面工程，实现高效骨分化。

通过生物启发固定生长因子来开发骨植入物仍然是生物界面生成过程中的一个关键问题，尤其是在增强骨分化能力方面。在这项研究中，我们开发了一种在酪氨酸酶和分选酶 A（SrtA）的介导下，通过特定位点共轭含有 3,4-羟基苯丙氨酸的骨形态发生蛋白 2（DOPA-BMP2），实现聚（乳糖-乙二醇）（PLGA）和羟基磷灰石（HA）复合基底表面功能化的策略。首先，通过 DNA 重组技术在大肠杆菌中成功表达了含有 LPETG 矩阵的生长因子 BMP2-LPETG。通过酪氨酸酶将 YKYKY-GGG 肽中的酪氨酸残基（Y）转化为 DOPA（X），与底物结合，实现了生长因子（DOPA-BMP2）的优异结合亲和力。然后，在 SrtA 的介导下，其 GGG 基序与 BMP2-LPETG 的末端特异性结合。因此，生成的生物活性 DOPA-BMP2/PLGA/HA 基质能显著促进 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定点的策略，通过有效传递生长因子、肽和其他生物大分子，为整形外科和牙科设计生物仿生材料。

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

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