1. Academic Validation
  2. Sustained-release of FGF-2 from a hybrid hydrogel of heparin-poloxamer and decellular matrix promotes the neuroprotective effects of proteins after spinal injury

Sustained-release of FGF-2 from a hybrid hydrogel of heparin-poloxamer and decellular matrix promotes the neuroprotective effects of proteins after spinal injury

  • Int J Nanomedicine. 2018 Feb 1;13:681-694. doi: 10.2147/IJN.S152246.
He-Lin Xu  # 1 Fu-Rong Tian  # 1 Jian Xiao  # 1 Pian-Pian Chen 1 Jie Xu 1 Zi-Liang Fan 1 Jing-Jing Yang 1 Cui-Tao Lu 1 Ying-Zheng Zhao 1 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou.
  • 2 Hainan Medical College, Haikou, China.
  • # Contributed equally.
Abstract

Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI).

Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP), as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM) as an affinity depot of drug. By tuning the concentration of HP in formulation, the cold ternary fibroblast growth factor-2 (FGF2)-dscECM-HP solution could rapidly gelatinize into a hydrogel at body temperature. Due to the strong affinity for FGF2, hybrid FGF2-dscECM-HP hydrogel enabled sustained-release of encapsulated FGF2 over an extended period in vitro.

Results: Compared to free FGF2, it was observed that both neuron functions and tissue morphology after SCI were clearly recovered in rats treated with FGF2-dscECM-HP hydrogel. Moreover, the expression of neurofilament protein and the density of axons were increased after treatment with hybrid FGF2-dscECM-HP. In addition, the neuroprotective effects of FGF2-dscECM-HP were related to inhibition of chronic endoplasmic reticulum stress-induced Apoptosis.

Conclusion: The results revealed that a hybrid hydrogel system may be a potential carrier to deliver macromolecular proteins to the injured site and enhance the therapeutic effects of proteins.

Keywords

adsorption; basic fibroblast growth factor; decellularized extracellular matrix; spinal cord injury; thermosensitive hydrogel.

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