Study shows that polylactic acid films are altered by glucose and ketones
Implants and medical devices destined for use inside the human body have to meet stringent requirements around their biocompatibility. The surface properties of these biomaterials are particularly important because they determine how an implant will interface and interact with the surrounding tissue. For example, the topography and hydrophobicity of a surface can influence the process of cell adhesion or protein adsorption. In the case of a material designed to degrade, advanced knowledge of how its surface properties change over time will provide confidence in that material’s continued ability to perform. However, in vitro tests paint a limited picture of degradation, due to the simple buffer solutions that are used. They often contain only inorganic species, which makes them a poor substitute for real physiological environments. As a result, there have been numerous incidents of biomaterials degrading faster in vivo than in vitro.
But now, Spanish researchers have taken a step towards realistic in vitro analysis of biomaterials; their findings are reported in Polymer Testing [DOI: 10.1016/j.polymertesting.2023.108189]. The paper focuses on polylactic acid (PLA); a biodegradable and bioabsorbable polymer widely used in medical implants. The research group had previously demonstrated that doping PLA can improve its functionality, so they chose to produce pure PLA films as well as those that contained 10% w/w magnesium (PLA10Mg).
For the solution, they started with m-SBF (modified simulated body fluid), which acted as the control. They then supplemented it with a series of physiologically-relevant compounds. Glucose, a sugar known to stimulate PLA degradation (SBF + G); ketone bodies, including hydroxybutyric acid, methyl acetoacetate, and acetone (SBF + K); or a combination of both glucose and ketones (SBF + GK). The concentrations of these additives were chosen to reflect what would be typically found in healthy individuals.
The films underwent a series of characterisation steps before being immersed vertically in the solution at 37 °C for 28 days. Afterwards, the characterisation steps were repeated to determine what impact the buffer solution had on film degradation.
pH measurements of the degradation solutions showed that SBF and SBF + K initially had very similar pH. However, the addition of K or GK led to a slightly lower initial pH. After the 28-day immersion, pH values were seen to deviate; influenced both by the film (PLA or PLA10Mg) and/or the composition of the solution. When PLA films were subjected to degradation in SBF and SBF + G, the solutions retained their original pH. However, when PLA10Mg films were degraded in the same solutions, the pH increased (from 7.57 to 7.79 in the case of PLA10Mg in SBF + G). The authors attribute this to oxidation of the magnesium particles and the subsequent generation of hydroxide ions. The pH of solutions containing ketone bodies, or ketone bodies and glucose increased in all cases after degradation, regardless of whether PLA or PLA10Mg films were used.
Contact angle measurements using two polar liquids (deionized water and formamide), and non-polar diiodomethane, showed that PLA films were impacted by the degradation; θDW, θF and θD all decreased after 28 days. The size of change in the contact angle measured on the PLA10Mg films depended on the degradation solution. The addition of glucose causes an increase in θDW and θF, while the presence of ketone bodies (without or with glucose) caused a significant decrease in both angles. No changes in θD were observed for the PLA10Mg films.
Profilometry showed that non-degraded PLA films were flatter and smoother than non-degraded PLA10Mg films. After immersion, the roughness of the PLA films was seen to increase, regardless of the solution in which the degradation took place. The roughness of the PLA10Mg films stayed fairly constant throughout. SEM imaging confirmed the presence of salts on the surface of the degraded films. In addition, PLA films were thicker after degradation than PLA10Mg films, regardless of the degradation medium.
Mechanical characterisation of the films found marked differences between the PLA and PLA10Mg films before immersion. After degradation, the accumulation of salts was seen to cause a significant hardening of the surface. For the PLA10Mg films, changes in Young’s modulus were found to be on the order of 150%.
The authors conclude, “The presence of glucose and/or ketone bodies in the degradation medium of Mg-supplemented polylactic acid introduces ionic species into the environment that directly influence the composition of the adsorbed salt surface layers as well as the aging of the polymer… the thickness of the salt layers deposited on [all of] the films increases in the case of aging with both glucose + ketone bodies, which may indicate that these components can be decisive in any in vitro degradation model.”
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Verónica Luque-Agudo, Juan Manuel Casares-López, María Luisa González-Martín, Amparo M. Gallardo-Moreno, Margarita Hierro-Oliva. “PLA-Mg film degradation under in vitro environments supplemented with glucose and/or ketone bodies,” Polymer Testing 127 (2023) 108189. DOI: 10.1016/j.polymertesting.2023.108189