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

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.

An artificial-vision- and statistical-learning-based method for studying the biodegradation of type I collagen scaffolds in bone regeneration systems

“…The linear models are the simplest and most typical parametric models, but in chemistry and biology domains, nonlinear models are also important and useful. In this regard, there are many processes characterized by exponential and sigmoid types of relations between critical variables such as material degradation (Robles-Bykbaev et al, 2018; Ríos-Fachal et al, 2014), crystallization (López-Beceiro, Gracia-Fernández & Artiaga, 2013), oxidation (Tarrío-Saavedra et al, 2013), and material dimensional variation due to magnetic changes (Tarrío-Saavedra et al, 2017). In fact, the requirements of biological growth have popularized sigmoid monotonic nonlinear functions, characterized by exponential growth and a point of inflection from which the speed of growth gradually decreases until reaching a saturation zone (Kahm et al, 2010; Román-Román & Torres-Ruiz, 2012; Kingsland, 1985; Tarrío-Saavedra et al, 2014).…”

D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection

“…Hydrolysis of cellulose is possible 3 BioMed Research International as well [78,79]; there are also protocols for production of Dlactate from methane [80]. Polylactic acid can be degraded by various processes, but hydrolysis of the ester bound is the most common reaction from the chemical point of view [81][82][83]; many organisms like bacterium Rhodopseudomonas palustris [84] and fungi Aspergillus niger and Candida cylindracea [85] are examples that have good ability to hydrolyze polylactic acid. Not a single enzyme is involved in polylactic acid hydrolysis.…”

Modelling operative and routine learning curves in manoeuvres in locks and in transit in the expanded Panama Canal

“…This way of operating changed when, in 1953, the American management decided that piloting through the canal would be different from other navigation waterways: the canal port pilots would no longer act as counsellors but would assume total control of movements and navigation of vessels in transit, replacing the captain in these functions. Under these circumstances, Rodriguez (2011) states that traffic in the Panama Canal is managed and controlled in a very particular and different way from the rest of the world's waterways.…”

“…With this, port services added to the complex transit operations of the canal within the port pilots’ responsibilities. This fact, together with the aforementioned unique piloting concept, has meant that, unlike conventional VTS (vessel traffic service) systems (Hughes, 2009; Ulusçu et al., 2009), traffic control services are managed in the Panama Canal through the MTCC (Rodriguez, 2011).…”