Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, China.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, China.
Mater Horiz. 2024 Jun 3;11(11):2667-2684. doi: 10.1039/d3mh01910a.
Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide--propylene glycol--lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes. This material choice provides several benefits: the GelMA shell provides a swelling interface for tissue interlocking and rapid release of mangiferin at an early wound healing stage for anti-inflammation, whereas the PGLADMA core offers long-term encapsulation and release of exosomes (30% release in 3 weeks), promoting sustained angiogenesis and anti-inflammation. Our results demonstrate that the core-shell microneedle possesses anti-inflammatory properties and can induce angiogenesis both in terms of macrophage polarization and tube formation of human umbilical vein endothelial cells (HUVECs), and in terms of anti-inflammation, re-epithelization, and vessel formation. Importantly, we also observe reduced scar formation . Altogether, the degradation dynamics of our hydrophilic/hydrophobic materials enable the design of a core-shell microneedle for differential and prolonged release, promoting scarless skin regeneration, with potential for other therapies of long-term exosome release.
用于皮肤再生的微针通常受到不可控的多药物释放、有限的药物类型和较差的伤口附着力的限制。在这里，开发了一种新型的核壳型微针贴片用于无痕皮肤修复，其中壳由亲水明胶甲基丙烯酰基（GelMA）组成，负载有芒果苷，这是一种抗炎小分子，核由疏水性聚（乳酸-丙二醇-乳酸）二甲基丙烯酸酯（PGLADMA）组成，负载有生物活性大分子和人间充质基质细胞（hMSC）衍生的外泌体。这种材料选择有几个好处：GelMA 壳提供了一个用于组织互锁的肿胀界面，并在早期伤口愈合阶段快速释放芒果苷以抗炎，而 PGLADMA 核提供了外泌体的长期封装和释放（3 周内释放 30%），促进持续的血管生成和抗炎。我们的结果表明，核壳型微针具有抗炎特性，并且可以通过调节巨噬细胞极化和人脐静脉内皮细胞（HUVEC）的管形成来诱导血管生成，并且可以通过抗炎、再上皮化和血管形成来诱导血管生成。重要的是，我们还观察到疤痕形成减少。总之，我们的亲水/疏水材料的降解动力学使我们能够设计出一种用于差异化和延长释放的核壳型微针，促进无痕皮肤再生，并有潜力用于其他长期外泌体释放的治疗方法。
