2. Academic Validation
  3. Delivery of bone morphogenetic protein-2 by crosslinking heparin to nile tilapia skin collagen for promotion of rat calvaria bone defect repair

Delivery of bone morphogenetic protein-2 by crosslinking heparin to nile tilapia skin collagen for promotion of rat calvaria bone defect repair

  • Prog Biomater. 2022 Dec 10. doi: 10.1007/s40204-022-00213-7.
Lina Ma # 1 2,  Li Fu # 2 3,  Chengxu Gu # 3,  Haonan Wang 4,  Zhenghai Yu 3,  Xiuwei Gao 5,  Dongmei Zhao 6,  Baosheng Ge 7,  Naili Zhang 8 9
Affiliations

Affiliations

  • 1 Department of Diagnostics, The Second School of Medicine, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China.
  • 2 Rongxiang Xu Regenerative Medicine Research Center, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China.
  • 3 Department of Human Anatomy, School of Basic MedicalScience, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China.
  • 4 State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao, 266580, People's Republic of China.
  • 5 Shandong Junxiu Biotechnology Co. LTD, 32 Zhujiang Road, Economic and Technological Development Zone, Yantai, 264006, Shandong, China.
  • 6 Department of Human Anatomy, School of Basic MedicalScience, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China. zhdm76@126.com.
  • 7 State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao, 266580, People's Republic of China. gebaosheng@upc.edu.cn.
  • 8 Rongxiang Xu Regenerative Medicine Research Center, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China. znl-0@163.com.
  • 9 Department of Human Anatomy, School of Basic MedicalScience, Binzhou Medical University, Laishan, Yantai, 264003, Shandong, China. znl-0@163.com.
  • # Contributed equally.
PMID: 36495399 DOI: 10.1007/s40204-022-00213-7
Abstract

Collagen has been widely used as a biomaterial for tissue regeneration. At the present, aqua-collagen derived from fish is poorly explored for biomedical material applications due to its insufficient thermal stability. To improve the bone repair ability and thermal stability of fish collagen, the tilapia skin collagen was crosslinked by EDC/NHS with heparin to bind specifically to BMP-2. The thermal stability of tilapia skin collagen crosslinked with heparin (HC-COL) was detected by differential scanning calorimetry (DSC). Cytotoxicity of HC-COL was assessed by detecting MC3T3-E1 cell proliferation using CCK-8 assay. The specific binding of BMP-2 to HC-COL was tested and the bioactivity of BMP-2-loaded HC-COL (HC-COL-BMP-2) was evaluated in vitro by inducing MC3T3-E1 cell differentiation. In vivo, the bone repair ability of HC-COL-2 was evaluated using micro-CT and histological observation. After crosslinking by EDC/NHS, the heparin-linked and the thermostability of the collagen of Nile Tilapia were improved simultaneously. HC-COL has no cytotoxicity. In addition, the binding of BMP-2 to HC-COL was significantly increased. Furthermore, the in vitro study revealed the effective bioactivity of BMP-2 binding on HC-COL by inducing MC3T3-E1 cells with higher ALP activity and the formation of mineralized nodules. In vivo studies showed that more mineralized and mature bone formation was achieved in HC-COL-BMP-2 group. The prepared HC-COL was an effective BMP-2 binding carrier with enough thermal stability and could be a useful biomaterial for bone repair.

Keywords

Bone morphogenetic protein-2; Bone repair; Crosslinking; Fish skin collagen; Heparin.

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