Fabricating a novel HLC-hBMP2 fusion protein for the treatment of bone defects

Chen, Zhuoyue, Zhang, Zhen, Wang, Zhaoyue, Wu, Jiawei, Wang, Yihang, Si, He, Xie, Xin, Shang, Lijun, Fan, Daidi and Chen, Fulin (2020) Fabricating a novel HLC-hBMP2 fusion protein for the treatment of bone defects. Journal of Controlled Release, 329. pp. 270-285. ISSN 0168-3659

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Official URL: https://doi.org/10.1016/j.jconrel.2020.11.058

Abstract / Description

Treating serious bone trauma with an osteo-inductive agent such as bone morphogenetic proteins (BMPs) has been considered as an optimized option when delivered via a collagen sponge (CS). Previous work has shown that the BMP concentration and release rate from approved CS carriers is difficult to control with precision. Here we presented the fabrication of a recombinant fusion protein from recombinant human-like collagen (HLC) and human BMP-2 (hBMP2). The fusion protein preserved the characteristic of HLC allowing the recombinant protein to be expressed in Yeast (such as Pichia pastoris GS115) and purified rapidly and easily with mass production after methanol induction. It also kept the stable properties of HLC and hBMP2 in the body fluid environment with good biocompatibility and no cytotoxicity. Moreover, the recombinant fusion protein fabricated a vertical through-hole structure with improved mechanical properties, and thus facilitated migration of bone marrow mesenchymal stem cells (MSCs) into the fusion materials. Furthermore, the fusion protein degraded and released hBMP-2 in vivo allowing osteoinductive activity and the enhancement of utilization rate and the precise control of the hBMP2 release. This fusion protein when applied to cranial defects in rats was osteoinductively active and improved bone repairing enhancing the repairing rate 3.5- fold and 4.2- fold when compared to the HLC alone and the control, respectively. There were no visible inflammatory reactions, infections or extrusions around the implantation sites observed. Our data strongly suggests that this novel recombinant fusion protein could be more beneficial in the treatment of bone defects than the simple superposition of the hBMP2/collagen sponge.

Item Type: Article
Uncontrolled Keywords: fusion protein; human-like collagen; human bone morphogenetic proteins-2 (hBMP2); controllable release; osteogenic activity
Subjects: 500 Natural Sciences and Mathematics > 540 Chemistry & allied sciences
500 Natural Sciences and Mathematics > 570 Life sciences; biology
600 Technology > 660 Chemical engineering
Department: School of Human Sciences
Depositing User: Lijun Shang
Date Deposited: 01 Dec 2020 11:23
Last Modified: 08 Jan 2021 11:21
URI: http://repository.londonmet.ac.uk/id/eprint/6199

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