Tissue engineering is a promising field working towards developing alternative solutions for the treatment of diseases, for compound testing, and models for biological studies. This work aimed at designing an elastic polymer formulation to use in constructing scaffolds for cardiac tissue engineering. The scaffold is an essential component of the engineered tissue development process, as it plays a role in cell anchorage, signaling, and phenotype development via the scaffold’s topographical and structural properties[1],[2]. Biomaterials with optimized properties for different tissues are still being discovered. This work encompassed a study of a novel, dually-crosslinkable polymer to use as a model for developing other similar polymers. This particular polymer had mechanical properties that could be manipulated by changes in its synthesis process. The objectives of the study were to develop a model from which a biomaterial could be formulated whose mechanical and elastic properties were tailored to specifically suit the properties of native cardiac tissue.
The approach was systematic starting with a four-factor design of experiments (DOE) on a dually-crosslinkable polymer to study the effects of synthesis parameters on resultant polymer elasticity. The polymer studied was called poly (octamethylene maleate [anhydride] citrate) (POMaC), which was synthesized in a simple polycondensation reaction between 1,8-octanediol, maleic anhydride, and citric acid (see Figure 1)[3]. The four factors considered in the DOE were (1) the monomer feed ratio during polymer synthesis, (2) porosity in the polymer by weight fraction, which is achieved by adding a porogen to the mixture and subsequently leaching it out after the polymer is cured, (3) exposure energy during UV curing, and (4) duration of heat exposure during thermal curing. This four-factor DOE, varied on two levels, made for a test of 16 samples that were pulled in a uniaxial tensile test to collect Young’s Modulus data. Four additional replicates at a midpoint were included to improve model accuracy and improve estimates of error. The design matrix overview is presented in Figure 2.
The results of the DOE were used to construct a statistically significant model for the Young’s modulus based on the four factors in the polymer synthesis procedure (shown in Figure 3). Over the defined parameter design space, the measured Young’s Modulus of POMaC ranged from 52.9 ± 7.5 to 1422.6 ± 650.7 kPa (Figure 2). This model was then used to formulate a new polymer, using a recipe dictated by the model, to create a polymer with a specific, predefined elastic modulus that mimics native cardiac tissue.
The model generated could be used to formulate a number of different biomaterials for tissue engineering applications, for a variety of tissue types, and the approach towards modeling materials could be repeated or extended for other polymer types.
References:
[1] Engler, A.J., et al., Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments. J Cell Biol, 2004. 166(6): p. 877-87.
[2] Heidi Au, H.T., et al., Cell culture chips for simultaneous application of topographical and electrical cues enhance phenotype of cardiomyocytes. Lab Chip, 2009. 9(4): p. 564-75.
[3] Tran, R.T., et al., Synthesis and characterization of a biodegradable elastomer featuring a dual crosslinking mechanism. Soft Matter, 2010. 6(11): p. 2449-2461.