Tissue Engineering Research Group, Dept. of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
Tissue Engineering Research Group, Dept. of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland and Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin, Dublin, Ireland and Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland and Department of Biomedical Engineering, University of Massachusetts, Amherst, USA.
Biomater Sci. 2021 Jun 15;9(12):4278-4288. doi: 10.1039/d0bm01277g.
Natural bioactive cue profiles are generally transient with cues switching on/off to coordinate successful outcomes. Dysregulation of these sequences typically leads to disease. Successful wound healing, for example, should progress sequentially through hemostasis, inflammation, granulation tissue formation, and maturation. Chronic wounds, such as diabetic foot ulcers, suffer from uncoordinated signaling, and arrest and cycle between the inflammation and granulation stages. Traditionally, therapeutic delivery in tissue engineering has focused on sustaining delivery of key signaling factors; however, temporal and sequential delivery have increasingly come into focus. To fully take advantage of these signaling systems, a scaffold or matrix material that can house the delivery system is desirable. In this work, we functionalized a collagen-based scaffold - which has proven regenerative potential in wounds - with on-demand delivery of nanoparticles. Building on our previous work with ultrasound-responsive alginate that shows near-zero baseline release and a rapid release in response to an ultrasound trigger, we developed two novel scaffolds. In the first version, homogeneously-distributed microparticles of alginate were incorporated within the collagen-glycosaminoglycan (GAG) scaffold; ultrasound-triggered release of platelet derived growth factor (PDGF) loaded gold nanoparticles was demonstrated; and their maintained bioactivity confirmed. In the second version, pockets of alginate that can be individually loaded and triggered with ultrasound, were incorporated. The ability to sequentially release multiple therapeutics within these scaffolds using ultrasound was successfully confirmed. These platforms offer a precise and versatile way to deliver therapeutic nanoparticles within a proven regenerative template, and can be used to deliver and probe timed therapeutic delivery in wound healing and other tissue engineering applications.
天然生物活性线索谱通常是短暂的，线索的开启和关闭是为了协调成功的结果。这些序列的失调通常会导致疾病。例如，成功的伤口愈合应该依次经历止血、炎症、肉芽组织形成和成熟。慢性伤口，如糖尿病足溃疡，由于信号传导不协调而遭受阻滞，并在炎症和肉芽组织阶段之间循环。传统上，组织工程中的治疗输送集中在维持关键信号因子的输送上；然而，时间和顺序输送越来越受到关注。为了充分利用这些信号系统，需要一种能够容纳输送系统的支架或基质材料。在这项工作中，我们对基于胶原蛋白的支架进行了功能化 - 该支架已被证明在伤口中有再生潜力 - 并实现了按需输送纳米颗粒。在我们之前使用对超声响应的藻酸盐的工作基础上，该藻酸盐显示出接近零的基线释放和对超声触发的快速释放，我们开发了两种新型支架。在第一个版本中，均匀分布的藻酸盐微球被掺入胶原蛋白糖胺聚糖（GAG）支架中；证明了负载血小板衍生生长因子（PDGF）的金纳米颗粒的超声触发释放；并确认了其保持的生物活性。在第二个版本中，掺入了可以单独加载和用超声触发的藻酸盐口袋。成功证实了可以在这些支架中使用超声顺序释放多种治疗药物的能力。这些平台提供了一种精确和多功能的方法，可以在经过验证的再生模板内输送治疗性纳米颗粒，并可用于在伤口愈合和其他组织工程应用中输送和探测定时治疗输送。
