Compositional profiling for biodegradable medical devices: a framework for degradation-informed exposure and risk...

Area of Science:

• Biomaterials Science
• Toxicology
• Polymer Chemistry

Background:

• Biodegradable polymers (BPs) pose unique challenges for chemical characterization and toxicological risk assessment (TRA).
• Exhaustive extraction, a common method for medical devices, is impractical for BPs due to their degradability and solvent incompatibility.
• Existing methods often fail to adequately address the complexities of BP degradation and release profiles.

Purpose of the Study:

• To propose and validate a hybrid approach for TRA of BPs, integrating compositional profiling and in vitro-in vivo correlation (IVIVC).
• To establish a practical and conservative framework for assessing the systemic toxicological risk of biodegradable medical devices.
• To demonstrate the application of this approach using a case study of a biodegradable vessel closure system.

Main Methods:

• Compositional profiling to estimate polymer quantities and worst-case hydrolysis into monomers.
• Calculation of estimated exposure doses (EEDmax) for various durations using ISO 10993-17:2023.
• Refinement of exposure estimates using in vitro-in vivo correlation (IVIVC) data when initial margins of safety (MOS) are low.
• Utilizing degradation-based release kinetics for physiologically plausible exposure scenarios.

Main Results:

• The hybrid approach provides a conservative yet physiologically plausible basis for acute and subacute exposure estimates.
• Compositional profiling combined with IVIVC data offers a practical framework for BP toxicological risk assessment.
• The case study demonstrated the applicability of the proposed methods for a GA-CL-TMC copolymer device.

Conclusions:

• A hybrid TRA approach integrating compositional profiling and IVIVC is effective for biodegradable polymers.
• This method provides a practical and conservative assessment of systemic toxicological risk from BP degradation products.
• Further methods are needed to address manufacturing residues alongside BP degradation products.