Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Kowloon 999077, Hong Kong SAR.
Tung Biomedical Sciences Centre, City University of Hong Kong, Kowloon 999077, Hong Kong SAR.
ACS Appl Mater Interfaces. 2023 Nov 8;15(44):50693-50707. doi: 10.1021/acsami.3c09062. Epub 2023 Oct 9.
The patch-based delivery system has been a promising therapeutic approach for treating various vascular diseases. However, conventional methods face several challenges, including labor-intensive and time-consuming processes associated with patch fabrication or factor incorporation, inadequate physical properties, and uncontrolled release of factors. These limitations restrict the potential applications in clinical settings. To overcome these issues, we propose a novel core-shell-shaped droplet patch system called an angiogenic patch (AP). Our system offers several distinct advantages over conventional patches. It enables a rapid and straightforward fabrication process utilizing only two biodegradable ingredients [alginate and ε-poly(l-lysine)], ensuring minimal toxicity. Moreover, the AP exhibits excellent physical integrity to match and withstand physiological mechanics and allows for customizable patch dimensions tailored to individual patients' pathological conditions. Notably, the AP enables facile loading of angiogenic cytokines during patch fabrication, allowing sustained release at a controlled rate through tunable network cross-linking. Subsequently, the AP, delivering a precisely formulated cocktail of angiogenic cytokines (VEGF, bFGF, EGF, and IGF), demonstrated significant effects on endothelial cell functions (migration and tubule formation) and survival under pathological conditions simulating ischemic injury. Likewise, in experiments using a mouse model of hindlimb ischemia, the AP encapsulating the angiogenic cocktail effectively restored blood flow following an ischemic insult, promoting muscle regeneration and preventing limb loss. With its simplicity and rapid processability, user-friendly applicability, physical tunability, and the ability to efficiently load and control the delivery of angiogenic factors, the AP holds great promise as a therapeutic means for treating patients with ischemic diseases.
基于补丁的递药系统一直是治疗各种血管疾病的一种很有前途的治疗方法。然而，传统方法面临着几个挑战，包括与补丁制造或因子掺入相关的劳动密集型和耗时的过程、不理想的物理性能以及因子的失控释放。这些限制限制了其在临床环境中的潜在应用。为了克服这些问题，我们提出了一种称为血管生成补丁 (AP) 的新型核壳状液滴补丁系统。与传统补丁相比，我们的系统具有几个明显的优势。它利用仅两种可生物降解的成分（藻酸盐和 ε-聚赖氨酸）实现了快速而简单的制造过程，确保了最小的毒性。此外，AP 表现出优异的物理完整性，可与生理力学相匹配并承受，并且允许根据个体患者的病理状况定制补丁尺寸。值得注意的是，AP 能够在制造补丁时轻松加载血管生成细胞因子，通过可调节的网络交联以可控的速率实现持续释放。随后，AP 递送精确配方的血管生成细胞因子（VEGF、bFGF、EGF 和 IGF）鸡尾酒，对内皮细胞功能（迁移和小管形成）以及在模拟缺血损伤的病理条件下的存活产生了显著影响。同样，在使用小鼠后肢缺血模型的实验中，AP 包封的血管生成鸡尾酒在缺血性损伤后有效恢复了血流，促进了肌肉再生并防止了肢体丧失。AP 具有简单性和快速加工性、用户友好的适用性、物理可调性以及高效加载和控制血管生成因子递送的能力，有望成为治疗缺血性疾病患者的治疗手段。
