A novel chitosan–collagen-based hydrogel for useas a dermal filler: initial in vitro and in vivo investigations
A novel chitosan–collagen-based hydrogel for useas a dermal filler: initial in vitro and in vivo investigations
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一种用作真皮填充剂的新型壳聚糖-胶原蛋白水凝胶：初步体外和体内研究
DOI：
10.1039/c3tb21842b
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发表时间：
2014
影响因子：
7
通讯作者：
Wenjiao Xue
中科院分区：
文献类型：
--
作者：
Xiaoxuan Ma;Jianjun Deng;Yuzhang Du;Xian Li;Daidi Fan;Chenhui Zhu;Junfeng Hui;Pei Ma;Pei Ma;Wenjiao Xue
将类人胶原（HLC）和壳聚糖（CS）与双醛淀粉（DAS）交联，合成了新型水凝胶（HCD）。通过体外和体内试验测定了HCD水凝胶的生物稳定性和生物相容性。利用傅里叶变换红外光谱（FTIR）对水凝胶的形成机理进行了研究，结果表明水凝胶通过缩醛化反应和席夫碱反应形成共价键。通过I类胶原酶、II类胶原酶、I类和II类胶原酶降解HCD水凝胶，并在动物模型皮下注射HCD后，在体内评价其生物稳定性。通过两种方法研究HCD水凝胶的生物学特性：(i) MTT和细胞形态学，细胞毒性和细胞相容性；（ii）在体内，通过组织形态学，透射电镜（TEM）和免疫组织化学来比较不同类型的手术引入的水凝胶，我们的HCD水凝胶，SunMax胶原植入水凝胶（SUM）和OUTLINE&EVOLUTION可注射合成凝胶（EVL）。在手术后1、9、12和28周进行体内分析。水凝胶生物降解结果表明，HCD水凝胶的归一化残重（WR）随DAS含量的变化而变化。在体外，我们发现HCD水凝胶在被I类和II类胶原酶降解28周后的最小WR为42.19%。MTT实验表明，HCD水凝胶培养7 d后，细胞的最小相对生长率（RGR）为93%，具有良好的细胞相容性。体内组织形态测定结果表明，HCD水凝胶有效填充组织空隙，不会引起红肿、溃烂或颜色变化。此外，一些血管生长到水凝胶中，最终产生了薄的纤维囊。透射电镜和免疫组织化学研究表明，与SUM和EVL水凝胶相比，HCD水凝胶产生的炎症反应较弱。总的来说，HCD水凝胶具有增强的生物稳定性和优异的生物相容性，使其在皮肤贴片支架、皱纹治疗和组织腔填充物方面具有潜在的前景。
Novel hydrogels (termed HCD hydrogels) were synthesized based on human-like collagen (HLC) and chitosan (CS) cross-linked with dialdehyde starch (DAS). The biological stability and biocompatibility of HCD hydrogels were determined through in vitro and in vivo tests. The mechanism of hydrogel formation was studied using Fourier transform infrared spectroscopy (FTIR), which showed that covalent bonds formed via acetalization and Schiff base reactions. Biological stability was evaluated in vitro by degrading HCD hydrogels with class I collagenase, class II collagenase, and both class I and class II collagenases and in vivo after subcutaneously injecting HCD into an animal model. The biological characteristics of HCD hydrogels was studied by two methods: (i) MTT and cytomorphology cytotoxicity and cytocompatibility and (ii) in vivo, whereby histomorphometry, transmission electron microscopy (TEM), and immunohistochemistry were used to compare different types of surgically introduced hydrogels, our HCD hydrogels, SunMax Collagen Implant hydrogels (SUM hydrogels), and OUTLINE&EVOLUTION Injectable Synthetic Gel hydrogels (EVL hydrogels). The in vivo analyses were performed at 1, 9, 12, and 28 weeks after surgery. The hydrogel biodegradation results showed that the normalized residual weight (WR) of HCD hydrogels varied with DAS content. In vitro, we found that the minimum WR of HCD hydrogels was 42.19% after 28 weeks when degraded by both types of class I and class II collagenase. The MTT assay indicated that the minimum relative growth rate (RGR) of cells was 93% after they were incubated with HCD hydrogels for 7 days, suggesting good cytocompatibility. In vivo histomorphometry results indicated that HCD hydrogels effectively filled tissue voids and did not cause redness, edema, festering, or color changes. In addition, a few vessels grew into the hydrogel and a thin fibrous capsule was eventually produced. TEM and immunohistochemistry studies suggested that HCD hydrogels produced less intense inflammatory responses than those produced by SUM hydrogels and EVL hydrogels. Overall, HCD hydrogels afford both enhanced biological stability and excellent biocompatibility, making them potentially promising for skin patch scaffolds, wrinkle treatments, and tissue cavity fillers.