Optimization of intrinsic and extrinsic tendon healing through controllable water-soluble mitomycin-C release from electrospun fibers by mediating adhesion-related gene expression.
To balance intrinsic and extrinsic healing during tendon repair is challenging in tendon surgery. We hypothesized that by mediating apoptotic gene and collagen synthesis of exogenous fibroblasts, the adhesion formation induced by extrinsic healing could be inhibited. With the maintenance of intrinsic healing, the tendon could be healed with proper function with no adhesion. In this study, we loaded hydrophilic mitomycin-C (MMC) into hyaluronan (HA) hydrosols, which were then encapsulated in poly(L-lactic acid) (PLLA) fibers by micro-sol electrospinning. This strategy successfully provided a controlled release of MMC to inhibit adhesion formations with no detrimental effect on intrinsic healing. We found that micro-sol electrospinning was an effective and facile approach to incorporate and control hydrophilic drug release from hydrophobic polyester fibers. MMC exhibited an initially rapid, and gradually steadier release during 40 days, and the release rates could be tuned by its concentration. In vitro studies revealed that low concentrations of MMC could inhibit fibroblast adhesion and proliferation. When lacerate tendons were healed using the MMC-HA loaded PLLA fibers in vivo, they exhibited comparable mechanical strength to the naturally healed tendons but with no significant presence of adhesion formation. We further identified the up-regulation of apoptotic protein Bax expression and down-regulation of proteins Bcl2, collage I, collagen III and α-SMA during the healing process associated with minimum adhesion formations. This approach presented here leverages new advances in drug delivery and nanotechnology and offers a promising strategy to balance intrinsic and extrinsic tendon healing through modulating genes associated with fibroblast apoptosis and collagen synthesis.
['Zhao|Xin|X|', 'Jiang|Shichao|S|', 'Liu|Shen|S|', 'Chen|Shuai|S|', 'Lin|Zhi Yuan William|ZY|', 'Pan|Guoqing|G|', 'He|Fan|F|', 'Li|Fengfeng|F|', 'Fan|Cunyi|C|', 'Cui|Wenguo|W|']
D000818:Animals D015815:Cell Adhesion Molecules D003692:Delayed-Action Preparations D004058:Diffusion D004595:Electroplating D005786:Gene Expression Regulation D008297:Male D051379:Mice D016685:Mitomycin D041681:NIH 3T3 Cells D053769:Nanocapsules D057139:Nanofibers D010316:Particle Size D051381:Rats D017207:Rats, Sprague-Dawley D012995:Solubility D052256:Tendinopathy D000267:Tissue Adhesions D016896:Treatment Outcome D014867:Water D014945:Wound Healing
Tendon healing Electrospun fibers Adhesion formation Micro-sol Water-soluble drug