The long-term goals of the proposed research are to develop tissue-engineering materials (TEM) with enhanced biocompatibility, and flexibility to tailor mechanical properties for a wide range of applications. There are two specific aims for this proposal. 1) To develop a biocompatible tissue-engineering scaffold based on visible light-cured polymer that is filled with bioactive glass. 2) To assess the biocompatibility of unfilled and bioactive glass-filled polymer scaffolds. Enhanced biocompatibility will be attained via three basic mechanisms: polymer design, nature of the photo-activation system, and by incorporating bioactive glass (BAG) in the polymer. We will synthesize biodegradable methacrylated monomers using Polyethylene glycol (PEG) and polylactic acid (PLA). By changing the number of PEG repeat units in the PEG-PLA methacrylated monomer, we will systematically control the length of the chain segment between adjacent lactate groups. Consequently, the amount of acidic by-products released per unit volume of the polymer that degrades, and therefore the biocompatibility of the scaffold, will be controlled. This design will indirectly control hydrophilicity and cross-link density of the polymer, and thus the rate of release of acidic products. By adding BAG in the polymer the acidic degradation products will be neutralized as they are released. We will also use a visible light-photoinitiator system along with a polymerizable coinitiator. The latter will be bound within the polymer network, minimizing leachability. Visible light, that is deeper penetrating, will potentially cause a more uniformly cured TEM than currently used UV activation. This will minimize residual monomer in the TEM, and thus enhance biocompatibility. The amount of residual monomers in the TEM cannot be directly measured but can be indirectly determined by measuring degree of conversion (DC) and Knoop hardness (KHN) of the cured TEM. We will measure and compare DC and KHN of the various TEMs. We will also evaluate the effects of polymer design and BAG on acidity by measuring and comparing the pH of solutions surrounding cured samples of TEMs with or without BAG. A photoinitiating system based on visible light that penetrates deep into biological tissues will provide a means of curing scaffolds across intervening structures, e.g., skin and muscles. This will be key to applying less invasive surgery in tissue and organ repair, minimizing damage to surrounding tissues, and reducing recovery time and its associated expenses. PROJECT NARRATIVE: This project seeks to develop improved tissue engineered composite materials with enhanced biocompatibility, and the flexibility to tailor mechanical properties for a wide range of applications. A photo-initiating system based on visible light that penetrates deep into biological tissues will provide a means of curing bioactive glass-reinforced polymer scaffolds across intervening structures, e.g., skin and muscles. This will be crucial to the use of less invasive surgery in tissue and organ repair, minimizing damage to surrounding tissues, and reducing recovery time and its associated expenses.
