Statistical degradation modelling of Poly(D,L-lactide-co-glycolide) copolymers for bioscaffold applications

Abstract

[Abstract] This methodology permits to simulate the performance of different Poly(D,L-lactide-co-glycolide) copolymer formulations (PDLGA) in the human body, to identify the more influencing variables on hydrolytic degradation and, thus, to estimate biopolymer degradation level. The PDLGA characteristic degradation trends, caused by hydrolysis processes, have been studied to define their future biomedical applications as dental scaffolds. For this purpose, the mass loss, pH, glass transition temperature (Tg) and absorbed water mass of the different biopolymers have been obtained from samples into a phosphate-buffered saline solution (PBS) with initial pH of 7.4, at 37°C (human body conditions). The mass loss has been defined as the variable that characterize the biopolymer degradation level. Its dependence relationship with respect to time, pH and biopolymer formulation has been modelled using statistical learning tools. Namely, generalized additive models (GAM) and nonlinear mixed-effects regression with logistic and asymptotic functions have been applied. GAM model provides information about the relevant variables and the parametric functions that relate mass loss, pH and time. Mixed effects are introduced to model and estimate the degradation properties, and to compare the PDLGA biopolymer populations. The degradation path for each polymer formulation has been estimated and compared with respect to the others for helping to use the proper polymer for each specific medical application, performing selection criteria. It was found that the mass loss differences in PDLGA copolymers are strongly related with the way the pH decay versus time, due to carboxylic acid groups formation. This may occur in those environments in which the degradation products remain relatively confined with the non degraded mass. This is the case emulated with the present experimental procedure. The results show that PDLGA polymers degradation degree, in terms of half life and degradation rate, is increasing when acid termination is included, when DL-lactide molar ratio is reduced, decreasing the midpoint viscosity, or when glycolide is not included.