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

• Published in: International journal of nanomedicine Vol. 13; pp. 681 - 694
• Main Authors: Xu, He-Lin, Tian, Fu-Rong, Xiao, Jian, Chen, Pian-Pian, Xu, Jie, Fan, Zi-Liang, Yang, Jing-Jing, Lu, Cui-Tao, Zhao, Ying-Zheng
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Adsorption; Animals; Anticoagulants; Apoptosis; Apoptosis - drug effects; Axons - drug effects; basic fibroblast growth factor; Biomedical materials; decellularized extracellular matrix; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Endoplasmic reticulum; Extracellular matrix; Extracellular Matrix - chemistry; Female; Fibroblast Growth Factor 2 - pharmacokinetics; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factors; Fibroblasts; Growth factors; Heparin - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacokinetics; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Hydrogels; Neurons; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacokinetics; Neuroprotective Agents - pharmacology; Novels; Original Research; PC12 Cells; Phase transitions; Poloxamer - chemistry; Polymers; Proteins; Rats; Rats, Sprague-Dawley; Signal transduction; Spinal Cord - cytology; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; spinal cord injury; Stem cells; Studies; Temperature; thermosensitive hydrogel; United States > US; China; decellularized extracellular matrix; spinal cord injury; adsorption; thermosensitive hydrogel; basic fibroblast growth factor
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S152246

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