Introduction: We have developed a poly (lactide-co-glycolide) (PLGA) scaffold that can be bioengineered to act as a therapeutic factor delivery agent following injury to the central nervous system. Our PLGA scaffold has been designed to degrade over time while releasing proliferation and differentiation factors for endogenous neural progenitor cell (NPC) recruitment. Before this material can be used in vivo its in vitro effects were profiled. We hypothesized that PLGA would not be toxic to NPCs and would affect the differentiation of NPCs.
Methods: The biocompatibility of PLGA for NPCs proliferation, differentiation and survival was assessed using an in vitro neurosphere and differentiation assay. Cells were incubated with and without the biomaterial for 7, 14 and 21 days in vitro (div). Following the proliferation period neurospheres were transferred to differentiation conditions for an additional 7 days. Thus, our longest exposure time point is 28 div (21 div proliferation + 7 div differentiation). At the end of each time point cells were fixed and stained using standard immunocytochemistry techniques.
Results: At both 14 and 21div NPCs were able to survive, proliferate and differentiate in the presence of PLGA with no significant difference when compared to control conditions. However, after prolonged exposure (28 div) to PLGA a significant decrease in the degree of proliferation of the NPCs was observed (ANOVA, p<0.05). Also, 28 div PLGA exposure led to a substantial increase in the proportion of apoptotic positive cells (ANOVA, p<0.05).
Conclusions: The low toxicity and normal proliferation seen at 14 and 21 div but not at 28 div indicate that it is the by-products from the PLGA degradation and not the biomaterial itself that leads to increased toxicity. Therefore, this study reveals the need to control the degradation rate of biomaterials, in order to prevent harmful effects of the by-products of biomaterial degradation.
Patient Care: Understanding the potential toxic effects of biodegradable biomaterials can help us develop improved biomaterials to help repair central nervous system injury in the future.
Learning Objectives: To understand that by-products of biodegradable biomaterials may be toxic to neural stem/progenitor cells and prevent neural stem/progenitor proliferation.