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Exploiting synergistic effect of externally loaded bFGF and endogenous growth factors for accelerated wound healing using heparin functionalized PCL/gelatin co-spun nanofibrous patches
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2020-08-03 , DOI: 10.1016/j.cej.2020.126518
Akshat Joshi , Zhe Xu , Yasuhiro Ikegami , Kozue Yoshida , Yusuke Sakai , Akshay Joshi , Tejinder Kaur , Yosuke Nakao , Yo-ichi Yamashita , Hideo Baba , Shinichi Aishima , Neetu Singh , Hiroyuki Ijima

Growth factors (GFs) are signaling molecules that are principle mediators in tissue regeneration. Biomaterial scaffolds employed as wound dressings are often hampered by their limitations to deliver GFs exogenously due to their instability and low half-life. The key to overcome this challenge lies in the better organization and use of endogenous pro-regenerative GFs released at regenerative site, with an aim to minimize the sole dependency on exogenous factors. Considering such challenges, this research utilizes the exogenous and endogenous GFs sequestering capability of heparin functionalized PCL/gelatin co-spun nanofabrics to mediate synergistically driven tissue regeneration by utilizing combined therapeutic effect of exogenous and endogenous GFs, and thereby minimizing the sole dependency on exogenous GFs for tissue regeneration. Basic fibroblast growth factor (bFGF) was chosen as GF for exogenous loading whereas vascular endothelial growth factor (VEGF) was chosen as a representative example to demonstrate the endogenous pro-regenerative GF sequestration capability of fabricated nanofabrics. From our results, the fabricated nanofabrics showed loading efficiency of 80% for exogenous bFGF and can sequester 15-fold more amount of endogenous VEGF compared to non-heparin functionalized nanofibrous dressings. When applied as wound dressings, heparin functionalized nanofibers showed better therapeutic capability compared to control groups that were treated using patches without heparin functionalization, indicating endogenously driven tissue regeneration. This was indicated by significant higher number of newly formed skin appendages, lesser scarring and lower inflammatory levels in newly formed granulation. Additionally, further improvements in therapeutic effect was observed when exogenous bFGF was employed indicating effectiveness of synergistically mediated tissue regeneration.



中文翻译:

利用肝素功能化的PCL /明胶共纺纳米纤维贴片利用外部bFGF和内源性生长因子的协同作用促进伤口愈合

生长因子(GFs)是信号分子,是组织再生的主要介质。用作伤口敷料的生物材料支架通常因其不稳定和半衰期短而受到限制,无法外生地输送GF。克服这一挑战的关键在于更好地组织和利用在再生位点释放的内源促再生GFs,目的是最大程度地减少对外源因素的唯一依赖。考虑到此类挑战,本研究利用肝素功能化PCL /明胶共纺纳米纤维的外源性和内源性GFs螯合能力,通过利用外源性和内源性GFs的联合治疗作用来介导协同驱动的组织再生,从而最大程度地减少了对外源性GFs的唯一依赖用于组织再生。选择碱性成纤维细胞生长因子(bFGF)作为外源负荷的GF,而选择血管内皮生长因子(VEGF)作为代表性实例,以证明制造的纳米纤维的内源性促再生GF螯合能力。根据我们的结果,与非肝素功能化的纳米纤维敷料相比,制备的纳米纤维对外源性bFGF的负载效率为80%,可以螯合15倍量的内源性VEGF。当用作伤口敷料时,与使用未经肝素功能化的贴剂处理的对照组相比,肝素功能化的纳米纤维显示出更好的治疗能力,表明内源性驱动的组织再生。这可以通过新形成的皮肤附件数量明显增加来表明,新形成的肉芽中疤痕减少,炎症水平降低。另外,当使用外源性bFGF时,观察到治疗效果的进一步改善,表明协同介导的组织再生的有效性。

更新日期:2020-08-06
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