Capturing the Real-Time Hydrolytic Degradation of a Library of Biomedical Polymers by Combining Traditional Assessment and Electrochemical Sensors.

Tiziana Fuoco,Marc Parrilla,Anna Finne-Wistrand,Maria Cuartero,Juan José García-Guzmán,Gaston A. Crespo

doi:10.1021/acs.biomac.0c01621

Abstract

We have developed an innovative methodology to overcome the lack of techniques for real-time assessment of degradable biomedical polymers at physiological conditions. The methodology was established by combining polymer characterization techniques with electrochemical sensors. The in vitro hydrolytic degradation of a series of aliphatic polyesters was evaluated by following the molar mass decrease and the mass loss at different incubation times while tracing pH and l-lactate released into the incubation media with customized miniaturized electrochemical sensors. The combination of different analytical approaches provided new insights into the mechanistic and kinetics aspects of the degradation of these biomedical materials. Although molar mass had to reach threshold values for soluble oligomers to be formed and specimens’ resorption to occur, the pH variation and l-lactate concentration were direct evidence of the resorption of the polymers and indicative of the extent of chain scission. Linear models were found for pH and released l-lactate as a function of mass loss for the l-lactide-based copolymers. The methodology should enable the sequential screening of degradable polymers at physiological conditions and has potential to be used for preclinical material’s evaluation aiming at reducing animal tests.

Highlights

The design and synthesis of degradable polymeric materials that find usability as temporary devices in biomedical applications, such as drug delivery carriers and scaffolds for tissue engineering, rely on the ability to program the degradation rate and profile, as well as the resorption profile to the application needs.[1,2] Degradation is the process of chemical cleavage of macromolecules to form lower molar mass products, which, for degradable polymers such as aliphatic polyesters and in abiotic conditions, occurs through hydrolysis of the ester bonds
We have selected eight different polyesters (Table 1), which undergo degradation by hydrolytic cleavage of ester bonds, and monitored their hydrolysis to demonstrate the feasibility of pH and L-lactate electrochemical sensors as effective analytic devices to follow their degradation profile in real time and at physiological conditions
Under the accelerated hydrolytic conditions used in our experiments (T = 60 °C), PLLA is semicrystalline because the experimental T is below both the Tg and melting temperature (Tm), i.e., the polymer is brittle and in the glassy state

Summary

Introduction

The design and synthesis of degradable polymeric materials that find usability as temporary devices in biomedical applications, such as drug delivery carriers and scaffolds for tissue engineering, rely on the ability to program the degradation rate and profile, as well as the resorption profile to the application needs.[1,2] Degradation is the process of chemical cleavage of macromolecules to form lower molar mass products, which, for degradable polymers such as aliphatic polyesters and in abiotic conditions, occurs through hydrolysis of the ester bonds. The resorption of aliphatic polyesters in hydrolytic conditions arises instead from the loss of mass owing to oligomers and low-molecular-weight products leaving the polymeric matrix and dissolving in the surrounding environment.[3] Degradation is a function encoded in the chemical structure of polymers,[4] being largely affected by the bulk properties, shape, thickness, and porosity of the material, together with environmental factors.[5,6] This implies that for the real and absolute understanding of the mechanism of degradation and resorption of a polymer in a specific physiological environment, and to get information about the clinical outcome of a material, the degradation rate and the service lifetime need to be in vivo evaluated. With the analytical tools available to date, this evaluation is commonly predicted by means of a series of in vitro assays that provide information about polymer degradation under simplified conditions compared to the real physiological environment

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