Microporous dermal-mimetic electrospun scaffolds pre-seeded with fibroblasts promote tissue regeneration in full-thickness skin wounds.
Microporous dermal-mimetic electrospun scaffolds pre-seeded with fibroblasts promote tissue regeneration in full-thickness skin wounds.
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DOI：
10.1371/journal.pone.0122359
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Bellis SL
中科院分区：
文献类型：
--
作者：
Bonvallet PP;Schultz MJ;Mitchell EH;Bain JL;Culpepper BK;Thomas SJ;Bellis SL
电纺丝支架由于其纳米纤维结构和易于调整化学成分而成为一种很有前途的组织修复基质。在这项研究中，我们评估了预先植入真皮成纤维细胞的微孔电纺丝支架的再生潜力。先前我们报道了含有160 μm直径孔隙的70% I型胶原和30%聚（Ɛ-caprolactone）电纺丝支架（70:30 col/PCL）具有良好的力学性能，支持成纤维细胞浸润和随后细胞介导的细胞外基质（ECM）沉积，与缺乏微孔的支架相比，促进了更快、更有效的体内皮肤再生。在目前的研究中，我们验证了这样一个假设，即在皮肤伤口植入之前，通过在支架中植入真皮成纤维细胞，可以进一步增强70:30 col/PCL微孔支架的功效。为了验证这一假设，我们采用了Fischer 344 （F344）大鼠同基因模型。体外实验表明，从F344大鼠皮肤中分离的真皮成纤维细胞能够在70:30 col/PCL微孔支架上粘附和增殖，并且细胞在160 μm孔内填充了天然的ECM蛋白，如胶原I和纤维连接蛋白。此外，植入F344成纤维细胞的支架在21天的时间框架内表现出低收缩率（约14%）。为了评估再生潜力，将含有或不含种子F344真皮成纤维细胞的支架植入在F344宿主中产生的全厚度、临界大小的缺陷中。具体来说，我们比较了：含有成纤维细胞的微孔支架植入4天；含有成纤维细胞的支架只播种了1天；无细胞微孔支架；还有假伤口（没有脚手架）。在所有治疗组中，含有成纤维细胞的支架在加速伤口愈合、皮肤基质结构更正常和毛囊再生方面的反应最好。综上所述，这些结果表明预先植入成纤维细胞的微孔电纺丝支架比无细胞支架促进更大的伤口愈合。
Electrospun scaffolds serve as promising substrates for tissue repair due to their nanofibrous architecture and amenability to tailoring of chemical composition. In this study, the regenerative potential of a microporous electrospun scaffold pre-seeded with dermal fibroblasts was evaluated. Previously we reported that a 70% collagen I and 30% poly(Ɛ-caprolactone) electrospun scaffold (70:30 col/PCL) containing 160 μm diameter pores had favorable mechanical properties, supported fibroblast infiltration and subsequent cell-mediated deposition of extracellular matrix (ECM), and promoted more rapid and effective in vivo skin regeneration when compared to scaffolds lacking micropores. In the current study we tested the hypothesis that the efficacy of the 70:30 col/PCL microporous scaffolds could be further enhanced by seeding scaffolds with dermal fibroblasts prior to implantation into skin wounds. To address this hypothesis, a Fischer 344 (F344) rat syngeneic model was employed. In vitro studies showed that dermal fibroblasts isolated from F344 rat skin were able to adhere and proliferate on 70:30 col/PCL microporous scaffolds, and the cells also filled the 160 μm pores with native ECM proteins such as collagen I and fibronectin. Additionally, scaffolds seeded with F344 fibroblasts exhibited a low rate of contraction (~14%) over a 21 day time frame. To assess regenerative potential, scaffolds with or without seeded F344 dermal fibroblasts were implanted into full thickness, critical size defects created in F344 hosts. Specifically, we compared: microporous scaffolds containing fibroblasts seeded for 4 days; scaffolds containing fibroblasts seeded for only 1 day; acellular microporous scaffolds; and a sham wound (no scaffold). Scaffolds containing fibroblasts seeded for 4 days had the best response of all treatment groups with respect to accelerated wound healing, a more normal-appearing dermal matrix structure, and hair follicle regeneration. Collectively these results suggest that microporous electrospun scaffolds pre-seeded with fibroblasts promote greater wound-healing than acellular scaffolds.
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影响因子：
8
作者：
Duan H;Feng B;Guo X;Wang J;Zhao L;Zhou G;Liu W;Cao Y;Zhang WJ
通讯作者：
Zhang WJ
影响因子：
9.7
作者：
Kim, Taek Gyoung;Chung, Hyun Jung;Park, Tae Gwan
通讯作者：
Park, Tae Gwan
影响因子：
14
作者：
Ng, KW;Khor, HL;Hutmacher, DW
通讯作者：
Hutmacher, DW
影响因子：
2.7
作者：
Chiu, T;Burd, A
通讯作者：
Burd, A
影响因子：
--
作者：
Ham, R G
通讯作者：
Ham, R G