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Spatial arrangement of polycaprolactone/collagen nanofiber scaffolds regulates the wound healing related behaviors of human adipose stromal cells.

ABSTRACT: A sufficient cell source and minimal invasiveness in obtaining human adipose stromal cells (hASCs) hold great promise for their utilization in wound repair. However, little is known about how cell-residing microenvironments regulate the cellular response. In this study we explored the effects of polycaprolactone (PCL)/collagen nanofibers with distinct spatial arrangements (aligned and random) on phenotypic expression of hASCs in vitro. Elongated cell morphology, higher proliferation, and faster migration rate were observed for hASCs cultured on the aligned nanofibers, showing that hASCs could detect the nanofiber spatial arrangement and then distinctively respond. This study on the expression of extracellular matrix (ECM) related genes in hASCs revealed higher synthesis capacity for critical ECM molecules including tropoelastin, collagen I, and matrix metalloproteinase (MMP)-1 on the aligned nanofibers. Integrins ?(5), ?(1), ?(3), ?(6,) and transforming growth factor (TGF)-?(1) were differentially regulated by PCL/collagen nanofiber arrangements. Our results indicate that fiber orientation-induced phenotypic change of hASCs may be regulated by integrins and TGF-? signaling synergistically. These findings demonstrate the potential application of hASCs and aligned PCL/collagen nanofibers for accelerated wound repair.

SUBMITTER: Fu X

PROVIDER: S-EPMC4530407 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Spatial arrangement of polycaprolactone/collagen nanofiber scaffolds regulates the wound healing related behaviors of human adipose stromal cells.

Fu Xiaoling X Wang Hongjun H

Tissue engineering. Part A 20111208 5-6

A sufficient cell source and minimal invasiveness in obtaining human adipose stromal cells (hASCs) hold great promise for their utilization in wound repair. However, little is known about how cell-residing microenvironments regulate the cellular response. In this study we explored the effects of polycaprolactone (PCL)/collagen nanofibers with distinct spatial arrangements (aligned and random) on phenotypic expression of hASCs in vitro. Elongated cell morphology, higher proliferation, and faster ...[more]

PMID: 21988596

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Project description:Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.

Project description:Background:The seeding of scaffolds with the stromal vascular fraction (SVF) of adipose tissue is a common prevascularization strategy in tissue engineering. Alternatively, adipose tissue-derived microvascular fragments (ad-MVF) may serve as vascularization units. In contrast to SVF single cells, they represent a mixture of intact arteriolar, capillary and venular vessel segments. Therefore, we herein hypothesized that the ad-MVF-based prevascularization of scaffolds is superior to the conventional SVF single cells-based approach. Results:SVF single cells and ad-MVF were enzymatically isolated from epididymal fat pads of green fluorescent protein (GFP)+ donor mice to assess their viability and cellular composition using fluorescence microscopy and flow cytometry. Moreover, collagen-glycosaminoglycan matrices (Integra®) were seeded with identical amounts of the isolates and implanted into full-thickness skin defects within dorsal skinfold chambers of GFP- recipient mice for the intravital fluorescent microscopic, histological and immunohistochemical analysis of implant vascularization and incorporation throughout an observation period of 2 weeks. Non-seeded matrices served as controls. While both isolates contained a comparable fraction of endothelial cells, perivascular cells, adipocytes and stem cells, ad-MVF exhibited a significantly higher viability. After in vivo implantation, the vascularization of ad-MVF-seeded scaffolds was improved when compared to SVF-seeded ones, as indicated by a significantly higher functional microvessel density. This was associated with an enhanced cellular infiltration, collagen content and density of CD31+/GFP+ microvessels particularly in the center of the implants, demonstrating a better incorporation into the surrounding host tissue. In contrast, non-seeded matrices exhibited a poor vascularization, incorporation and epithelialization over time. Conclusions:The present study demonstrates that ad-MVF are highly potent vascularization units that markedly accelerate and improve scaffold vascularization when compared to the SVF.

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Spatial arrangement of polycaprolactone/collagen nanofiber scaffolds regulates the wound healing related behaviors of human adipose stromal cells.

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Spatial arrangement of polycaprolactone/collagen nanofiber scaffolds regulates the wound healing related behaviors of human adipose stromal cells.

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