Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Chunying Shi; Qi Liu; Feng Sun; Guangyu Zhang; Mingru Deng; Bo Xu; Haicheng Yuan

doi:10.34133/bmr.0020

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Biomater Res. 2024 May 2:28:0020. doi: 10.34133/bmr.0020. eCollection 2024.

Authors

Chunying Shi^{1

2}, Qi Liu^{2

3}, Feng Sun¹, Guangyu Zhang⁴, Mingru Deng⁵, Bo Xu¹, Haicheng Yuan¹

Affiliations

¹ The second department of Neurology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province 266042, China.
² Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province 266071, China.
³ Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266000, China.
⁴ School of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province 261053, China.
⁵ Department of Medicine, Qingdao University, Qingdao, Shandong Province 266071, China.

Abstract

Cerebral ischemia was one of the leading causes of mortality and disability worldwide. Extracellular matrix (ECM) hydrogel held great potential to replace volumetric brain tissue loss following ischemic injury but with limited regenerative effect for functional restoration when implanted alone. In the present study, an engineered basic fibroblast growth factor (EBP-bFGF) was constructed, which fused a specific ECM-binding peptide (EBP peptide) with bFGF. The recombinant EBP-bFGF showed typical binding capacity with ECM without affecting the bioactivity of bFGF both in vitro and in vivo. Furthermore, the EBP-bFGF was used for bioactive modification of ECM hydrogel to repair cerebral ischemia. The combination of EBP-bFGF and ECM hydrogels could realize the sustained release of bFGF in the ischemic brain and improve the regenerative effect of ECM, which protected the survival of neurons, enhanced angiogenesis, and decreased the permeability of blood-brain barrier, ultimately promoted the recovery of motor function. In addition, transcriptome analysis revealed neuregulin-1/AKT pathway involved in this process. Therefore, EBP-bFGF/ECM hydrogel would be a promising therapeutic strategy for cerebral ischemia.