Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss.

Caroline Hu,Bugra Ayan,Thomas A Rando,Ngan F Huang,Alex H P Chan,Gladys Chiang

doi:10.3390/bioengineering9010037

Abstract

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

Highlights

Volumetric muscle loss (VML) is characterized by irreversible damage in skeletal muscle structure and function due to the loss of a significant portion of skeletal muscle.Traumatic injuries leading to VML are associated with impaired endogenous muscle regeneration, long-term disability, and cosmetic deformities [1,2]
By evaluating muscle physiology and tissue histology in a mouse model of VML, we show that basic fibroblast growth factor (bFGF) and voluntary exercise have differential therapeutic benefits for the treatment of VML
Aligned nanofibrillar scaffolds were fabricated by a facile shear-based extrusion technique, in which monomeric collagen was extruded from a syringe needle into a pH neutral saline, leading to rapid fibrillogenesis

Summary

Introduction

Volumetric muscle loss (VML) is characterized by irreversible damage in skeletal muscle structure and function due to the loss of a significant portion of skeletal muscle. Traumatic injuries leading to VML are associated with impaired endogenous muscle regeneration, long-term disability, and cosmetic deformities [1,2]. Current surgical approaches to treat VML by muscle flap grafting or scar tissue debridement are associated with significant donor site morbidity and functional deficiency [1,3,4,5]. Muscle regeneration is a highly dynamic process that involves the organized orchestration of growth factor elaboration. Among the growth factors involved in muscle regeneration, basic fibroblast growth factor (bFGF) is elaborated upon injury to stimulate the activation and proliferation of muscle satellite cells to orchestrate muscle

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