Abstract
Polymers have been used extensively taking forms as scaffolds, patterned surface and nanoparticle for regenerative medicine applications. Angiogenesis is an essential process for successful tissue regeneration, and endothelial cell–cell interaction plays a pivotal role in regulating their tight junction formation, a hallmark of angiogenesis. Though continuous progress has been made, strategies to promote angiogenesis still rely on small molecule delivery or nuanced scaffold fabrication. As such, the recent paradigm shift from top-down to bottom-up approaches in tissue engineering necessitates development of polymer-based modular engineering tools to control angiogenesis. Here, we developed cationic nanocylinders (NCs) as inducers of cell–cell interaction and investigated their effect on angiogenic activities of human umbilical vein endothelial cells (HUVECs) in vitro. Electrospun poly (l-lactic acid) (PLLA) fibers were aminolyzed to generate positively charged NCs. The aninolyzation time was changed to produce two different aspect ratios of NCs. When HUVECs were treated with NCs, the electrostatic interaction of cationic NCs with negatively charged plasma membranes promoted migration, permeability and tubulogenesis of HUVECs compared to no treatment. This effect was more profound when the higher aspect ratio NC was used. The results indicate these NCs can be used as a new tool for the bottom-up approach to promote angiogenesis.
Highlights
Polymers have been extensively used as one of the major materials for tissue engineering and regeneration over the past several decades due to their tunable properties [1,2]
Scanning electron microscope (SEM) images demonstrate that NCs were successfully produced utilizing two different aminolysis reaction times (60 and 90 min) generating NCs with an aspect ratio of 7 (ARS) and 40 (ARL) (Figure 1b,c)
Quantitative analysis of SEM images confirmed that the distribution of NC length between aspect ratio small (ARS) and aspect ratio large (ARL) did not overlap with each other (Figure 1d)
Summary
Polymers have been extensively used as one of the major materials for tissue engineering and regeneration over the past several decades due to their tunable properties [1,2]. Compared to delivery of pro-angiogenic molecules via nanoparticles or scaffolds, physically improving cell–cell interaction of ECs through a bottom-up approach is more advantageous in promoting angiogenesis since manipulating downstream cellular processes of angiogenesis is comparatively easier than altering upstream molecular mechanisms In this way, spatiotemporal variations of pro-angiogenic activities can be mitigated, and biological side effects on alteration of other cell behaviors can be minimized [11]. HUVECs were treated with NCs, the electrostatic interaction of cationic NCs with negatively charged plasma membranes promoted HUVEC migration, permeability and tubulogenesis compared to no treatment This effect was more profound when the longer NC (higher aspect ratio: 40) was used, compared to the shorter NC (lower aspect ratio: 7). These results indicate the NCs can be used as a new tool for the bottom-up approach to promote angiogenesis and consequent tissue regeneration
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