Stromal-Derived Factor 1α (SDF) is an angiogenic, chemotactic protein with significant potential for applications in a range of clinical areas, including wound healing, myocardial infarction and orthopaedic regenerative approaches. The 26-min in vivo half-life of SDF, however, has limited its clinical translation to date. In this study, we investigate the use of star-shaped or linear poly(glutamic acid) (PGA) polypeptides to produce PGA–SDF nanoparticles, which can be incorporated into a tyramine-modified hyaluronic acid hydrogel (HA–TA) to facilitate sustained localised delivery of SDF. The physicochemical properties and biocompatibility of the PGA–SDF nanoparticle formulations were extensively characterised prior to incorporation into a HA–TA hydrogel. The biological activity of the SDF released from the nano-in-gel system was determined on Matrigel^®, scratch and Transwell^® migration assays. Both star-shaped and linear PGA facilitated SDF nanoparticle formation with particle sizes from 255–305 nm and almost complete SDF complexation. Star-PGA–SDF demonstrated superior biocompatibility and was incorporated into a HA–TA gel, which facilitated sustained SDF release for up to 35 days in vitro. Released SDF significantly improved gap closure on a scratch assay, produced a 2.8-fold increase in HUVEC Transwell^® migration and a 1.5-fold increase in total tubule length on a Matrigel^® assay at 12 h compared to untreated cells. Overall, we present a novel platform system for the sustained delivery of bioactive SDF from a nano-in-gel system which could be adapted for a range of biomedical applications.

中文翻译：

---

开发用于趋化和血管生成因子基质衍生因子 1α 的缓释纳米凝胶递送系统。

基质衍生因子 1α (SDF) 是一种血管生成、趋化蛋白，在伤口愈合、心肌梗死和骨科再生方法等一系列临床领域具有巨大的应用潜力。然而，SDF 26 分钟的体内半衰期迄今为止限制了其临床转化。在这项研究中，我们研究了使用星形或线性聚（谷氨酸）（PGA）多肽来生产 PGA-SDF 纳米颗粒，该纳米颗粒可以掺入酪胺修饰的透明质酸水凝胶（HA-TA）中，以促进持续的自卫队的本地化交付。在掺入 HA-TA 水凝胶之前，对 PGA-SDF 纳米颗粒配方的理化性质和生物相容性进行了广泛的表征。纳米凝胶系统释放的 SDF 的生物活性通过 Matrigel ^®、划痕和 Transwell ^®迁移测定来确定。星形和线性 PGA 均促进了 SDF 纳米颗粒的形成，其粒径为 255-305 nm，并且几乎完全 SDF 络合。Star-PGA-SDF 表现出卓越的生物相容性，并被纳入 HA-TA 凝胶中，有助于 SDF 在体外持续释放长达 35 天。与未处理的细胞相比，释放的 SDF 显着改善了划痕实验中的间隙闭合，使 HUVEC Transwell ^®迁移增加了 2.8 倍，并且在 Matrigel ^®实验中，12 小时后总小管长度增加了 1.5 倍。总的来说，我们提出了一种新颖的平台系统，用于从纳米凝胶系统中持续递送生物活性 SDF，该系统可适用于一系列生物医学应用。