Abstract
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin. It is capable of binding a variety of growth factors to deliver basic fibroblast growth factor (bFGF) through polyvalent ionic interactions for nerve repair. In vitro assays demonstrated that the bFGF loading efficiency reached 10 μg and this delivery vehicle could control the release of bFGF. In vivo, the coacervate enhanced bFGF bioavailability, which improved both motor and sensory function. It could also acceleratemyelinated fiber regeneration and remyelination and promote Schwann cells proliferation. Furthermore, the neuroprotective effect of bFGF-coacervate in sciatic nerve injury was associated with the alleviation of endoplasmic reticulum stress signal. This heparin-based delivery platform leads to increased bFGF loading efficiency and better controls its release, which will provide an effective strategy for peripheral nerve injury regeneration therapy.
Highlights
Traffic accidents, trauma, and tumor resection can result in peripheral nerve injury (PNI)
Western blot results indicated that the amount of basic fibroblast growth factor (bFGF) in the coacervate was almost the same as in the loading solution (Figure 2B) and our choice of vehicle had a greater bFGF loading efficiency
The release curve of bFGF–Coacervate indicated that this matrix can efficiently control the release of incorporated bFGF
Summary
Trauma, and tumor resection can result in peripheral nerve injury (PNI). Recent advances inbiological materials have given way to a wealth of research about bFGF facilitating axon growth and nerve regeneration after PNI [5, 6]. Based on insufficient endogenous bFGF and its high affinity for heparin [9], we prepared a protein delivery coacervate to bind bFGF via charge interaction consisting of polycation-Poly(ethylene argininylaspartatediglyceride) (PEAD) and heparin [10]. This coacervate controls bFGF release and maintains the bFGF’s endogenous bioactivity [11].
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