In Vitro Vascular Cell Adhesion and Proliferation on Alkaline Degraded Poly-lactic/glycolic Acid Polymers
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In Vitro Vascular Cell Adhesion and Proliferation on Alkaline Degraded Poly-lactic/glycolic Acid Polymers Thomas J. Webster, Derick C. Miller, Anil Thapa, and Karen M. Haberstroh Department of Biomedical Engineering, Purdue University West Lafayette, IN 47907-1296
ABSTRACT The objective of the present in vitro study was to determine vascular endothelial and smooth muscle cell responses to poly(lactic-co-glycolic acid) (PLGA) films that were exposed apriori to various degrees of alkaline degradation. To model the alkaline environment of blood in arteries, PLGA films were separately soaked in select concentrations (from 0.1 – 10 N) of NaOH for various periods of time (from 10 minutes to 1 hour). Vascular endothelial and smooth muscle cells were then separately allowed to adhere and/or proliferate on the different PLGA degraded surfaces. Results provided the first evidence that smooth muscle adhesion and proliferation increased with larger amounts of alkaline PLGA degradation. In contrast, endothelial cell adhesion and proliferation decreased with increasing amounts of alkaline PLGA degradation. In this manner, the present in vitro study suggests a possible mechanism for insufficient endothelialization on PLGA vascular implants in vivo.
INTRODUCTION Biodegradable polymers (such as poly(lactic acid), poly(glycolic acid), and poly(lacticco-glycolic acid)) have become attractive candidates in vascular tissue engineering [1-4]. Such polymeric scaffolds can be easily shaped into grafts to serve as three-dimensional substrates capable of promoting vascular tissue ingrowth. Moreover, it is hoped that these biologically resorbable scaffolds will dissolve in situ and leave behind a regenerated neo-vascular conduit. Unfortunately, to date, polymer scaffolds containing poly(lactic acid) have not lived up to their potential [1, 2]. Formation of fibrovascular tissue in the intima of implanted grafts often leads to intimal hyperplasia which has resulted in occlusion of the regenerated vascular tissue [1, 2]. Since an endothelial cell lining often fails to develop on the luminal surface of polymers that contain poly(lactic acid), no regulatory mechanisms exist to minimize fibrovascular tissue ingrowth [1]. Clearly, the inability of poly(lactic acid) containing polymers to promote sufficient endothelialization presents serious limitations for this polymer as a successful vascular prosthetic material [1, 2]. The goal of this research was to determine, for the first time, in vitro vascular endothelial and smooth muscle cell responses (specifically, adhesion and proliferation) to poly(lactic-co-glycolic acid) at various stages of alkaline degradation, similar to the degradation which would be experienced in vivo, in order to better understand cellular events that lead to previously observed [2] insufficient endothelialization.
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