Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain; CIBER's Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Health Institute Carlos III, Monforte de Lemos 3-5, 28029 Madrid, Spain; INM - Leibniz Institute for New Materials, Campus D2 2, 66123 Saarbrücken, Germany.
INM - Leibniz Institute for New Materials, Campus D2 2, 66123 Saarbrücken, Germany.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112515. doi: 10.1016/j.msec.2021.112515. Epub 2021 Oct 29.
Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements.
针对慢性伤口愈合过程中的特定事件进行高效的伤口治疗是再生医学的一个重要目标。在这方面，纳米医学可以为提高现有伤口治疗的效果提供新的机会。本研究的目的是开发含有儿茶酚的聚合物纳米粒子（NPs），并评估其在伤口愈合领域的潜力。因此，研究了 NPs 促进伤口愈合的活性、药物包封和控制释放的潜力，以及进一步将其纳入水凝胶生物墨水配方以制备载细胞的 3D 支架。通过纳米沉淀法获得了儿茶酚含量为 2 和 29 M %的 NPs（分别命名为 NP2 和 NP29），其水动力学直径分别为 100 和 75nm。这些纳米载体以 70%的包封效率值包封了疏水性化合物香豆素-6。在细胞培养研究中，这些纳米粒子对 RAW 264.7 巨噬细胞具有抗氧化应激损伤的保护作用，由活性氧（ROS）引起。它们还对受刺激的巨噬细胞的炎症反应具有调节作用，并促进成纤维细胞和内皮细胞中血管内皮生长因子（VEGF）的上调。特别是，NP29 被用于羧甲基壳聚糖和透明质酸作为聚合物基质的水凝胶生物墨水配方中。使用反应性混合生物打印方法，获得了具有良好结构完整性、形状保真度和均匀 NPs 分散的载 NP 水凝胶支架。打印支架的儿茶酚 NPs 释放曲线表明其具有持续释放的特性。生物打印的支架支持包封的 L929 成纤维细胞在 14 天内的存活和增殖。我们设想，本工作中提出的功能化儿茶酚 NPs 和由此产生的生物活性生物墨水为伤口愈合应用提供了有前景的优势，因为它们：1）支持将生物活性儿茶酚 NPs 递送到伤口部位；2）可以通过共包封药物来纳入额外的治疗功能；3）可以根据患者需求打印成具有定制几何形状的 3D 支架。
