Next-Generation Biomaterials for Wound Healing: Development and Evaluation of Collagen Scaffolds Functionalized with a Heparan Sulfate Mimic and Fibroblast Growth Factor 2.

IF 5.2 3区 医学 Q1 ENGINEERING, BIOMEDICAL Journal of Functional Biomaterials Pub Date : 2025-02-07 DOI:10.3390/jfb16020051
Merel Gansevoort, Sabine Wentholt, Gaia Li Vecchi, Marjolein de Vries, Elly M M Versteeg, Bouke K H L Boekema, Agnes Choppin, Denis Barritault, Franck Chiappini, Toin H van Kuppevelt, Willeke F Daamen
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Abstract

Fibrosis after full-thickness wound healing-especially after severe burn wounds-remains a clinically relevant problem. Biomaterials that mimic the lost dermal extracellular matrix have shown promise but cannot completely prevent scar formation. We present a novel approach where porous type I collagen scaffolds were covalently functionalized with ReGeneRating Agent (RGTA®) OTR4120. RGTA® is a glycanase-resistant heparan sulfate mimetic that promotes regeneration when applied topically to chronic wounds. OTR4120 is able to capture fibroblast growth factor 2 (FGF-2), a heparan/heparin-binding growth factor that inhibits the activity of fibrosis-driving myofibroblasts. Scaffolds with various concentrations and distributions of OTR4120 were produced. When loaded with FGF-2, collagen-OTR4120 scaffolds demonstrated sustained release of FGF-2 compared to collagen-heparin scaffolds. Their anti-fibrotic potential was investigated in vitro by seeding primary human dermal fibroblasts on the scaffolds followed by stimulation with transforming growth factor β1 (TGF-β1) to induce myofibroblast differentiation. Collagen-OTR4120(-FGF-2) scaffolds diminished the gene expression levels of several myofibroblast markers. In absence of FGF-2 the collagen-OTR4120 scaffolds displayed an inherent anti-fibrotic effect, as the expression of two fibrotic markers (TGF-β1 and type I collagen) was diminished. This work highlights the potential of collagen-OTR4120 scaffolds as biomaterials to improve skin wound healing.

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用于伤口愈合的新一代生物材料:用硫酸肝素模拟物和成纤细胞生长因子 2 功能化胶原支架的开发与评估。
全层创面愈合后的纤维化,特别是严重烧伤创面愈合后的纤维化,仍然是一个与临床相关的问题。模拟丢失的真皮细胞外基质的生物材料已经显示出希望,但不能完全防止疤痕的形成。我们提出了一种新的方法,将多孔I型胶原支架与再生剂(RGTA®)OTR4120共价功能化。RGTA®是一种抗聚糖酶硫酸肝素模拟物,当局部应用于慢性伤口时促进再生。OTR4120能够捕获成纤维细胞生长因子2 (FGF-2),这是一种肝素/肝素结合生长因子,可抑制纤维化驱动的肌成纤维细胞的活性。制备了不同浓度和分布的OTR4120支架。当加载FGF-2时,与胶原-肝素支架相比,胶原- otr4120支架显示出FGF-2的持续释放。体外实验通过将原代人真皮成纤维细胞置于支架上,然后用转化生长因子β1 (TGF-β1)刺激诱导成肌细胞分化,研究其抗纤维化潜能。胶原- otr4120 (-FGF-2)支架降低了几种肌成纤维细胞标记物的基因表达水平。在缺乏FGF-2的情况下,胶原- otr4120支架显示出固有的抗纤维化作用,因为两种纤维化标志物(TGF-β1和I型胶原)的表达减少。这项工作强调了胶原- otr4120支架作为生物材料改善皮肤伤口愈合的潜力。
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来源期刊
Journal of Functional Biomaterials
Journal of Functional Biomaterials Engineering-Biomedical Engineering
CiteScore
4.60
自引率
4.20%
发文量
226
审稿时长
11 weeks
期刊介绍: Journal of Functional Biomaterials (JFB, ISSN 2079-4983) is an international and interdisciplinary scientific journal that publishes regular research papers (articles), reviews and short communications about applications of materials for biomedical use. JFB covers subjects from chemistry, pharmacy, biology, physics over to engineering. The journal focuses on the preparation, performance and use of functional biomaterials in biomedical devices and their behaviour in physiological environments. Our aim is to encourage scientists to publish their results in as much detail as possible. Therefore, there is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Several topical special issues will be published. Scope: adhesion, adsorption, biocompatibility, biohybrid materials, bio-inert materials, biomaterials, biomedical devices, biomimetic materials, bone repair, cardiovascular devices, ceramics, composite materials, dental implants, dental materials, drug delivery systems, functional biopolymers, glasses, hyper branched polymers, molecularly imprinted polymers (MIPs), nanomedicine, nanoparticles, nanotechnology, natural materials, self-assembly smart materials, stimuli responsive materials, surface modification, tissue devices, tissue engineering, tissue-derived materials, urological devices.
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