A.E. Green, A.G. Byju, B. Haridas
Texas A&M University,
United States
Keywords: hydrolysis, biodegradable polymers, time-concentration superposition, fetal surgery
Summary:
Our lab has designed a resorbable polymeric device to reduce the risk of premature preterm rupture of chorioamniotic membranes(PPROM) during fetal surgery. This device consists of two poly(lactide-co-glycolide) (PLGA) ChorioAnchors connected by poly-tetra-hydroxybutyrate P4HB suture, which is tensioned to fixate the chorioamniotic membrane to the uterine wall, a method inspired by a technique piloted by collaborating surgeons at Texas Children’s Hospital. Hydrolysis, in addition to being the degradation pathway for our polymers of interest, is the primary degradation pathway for many synthetic biodegradable polymers, including polyesters, polyamides, polycarbonates, and polyanhydrides. The most commonly used and well-investigated among these are polyesters such as polylactide (PLA), polyglycolide(PGA), and PLGA, which are commonly used in biodegradable implants; polycaprolactone (PCL), which is becoming popular for tissue scaffolding; and polyhydroxyalkanoates (PHAs), which can be used in a wide range of applications from wound dressings to bone plates. Some of these polymers have long degradation times, over one year, making them difficult to evaluate in a reasonable time period especially at the early stages of device development. This makes accelerated degradation studies important for estimating/predicting the long-term performance of these polymers, especially during early stages of development. Currently, temperature-accelerated degradation is the only standard method mentioned in the ISO for performing accelerated hydrolytic degradation. This is problematic when evaluating thermally sensitive polymers and polymers with glass transition temperatures above, but close to 37°C, since it is not recommended to use tests performed above the glass transition temperature to predict degradation behavior below the glass transition temperature. Due to this limitation, various NaOH concentrations have been used as media in academic literature to accelerate hydrolysis in biodegradable polymers, but these approaches have not been translated into an internationally standardized test framework that be more broadly used by developers. To facilitate such a translation, it is important to first determine if there exists a reproducible correlation between time and media concentration similar to well established principles of time-temperature-superposition (TTS). This work investigates the existence of a time-concentration correlation via a concentration-based media-accelerated degradation study of polyglycolide and poly(L-lactide-co-glycolide) ChorioAnchor devices. The results will be analyzed within the framework of a time-concentration superposition(TCS) model to evaluate correlations between real-time and accelerated degradation, hopefully laying the foundation for future standards development. Accelerated degradation of the anchor is being conducted in 4 concentrations (pH) of NaOH; 1N (14), 0.3N (13.5), 0.1N (13), and 0.03N (12.5) at 37°C and real-time degradation is being conducted in phosphate buffered saline (PBS) at 37°C. Mass loss, mechanical strength, glass transition temperature, and molecular weight will be evaluated at various time points during degradation in different media to evaluate degradation kinetics and develop the accelerated hydrolytic degradation model. The data obtained from these experiments will be used to develop modified Williams-Landel-Ferry (WLF) or Arrhenius time-concentration superposition models. Additionally, other potential models will also be investigated. The data and model generated will be used to support the development of a new media-based hydrolytic degradation standard.