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Biomaterials

Biomaterials - Poster Session E

Poster N8 - Design and validation of a multiplexed polycondensation apparatus for efficient synthesis of aliphatic polyesters

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Polyester biomaterials have become foundational in the development of medical devices, ranging from resorbable sutures and drug delivery vehicles to complex tissue engineering scaffolds. Their prominence in the biomedical field has rapidly increased in recent years. Despite their potential, the full capacity of polyester materials remains unexplored. A significant barrier to advancement is the extensive time and experimental load to generate novel materials, characterize their properties, and conduct preliminary testing prior to preclinical studies.

The most popular synthesis mechanism for generating polyesters is condensation polymerization, which involves joining an alcohol reactive group with a dicarboxylic acid to form an ester bond. This process enables the creation of versatile materials from diverse monomers using scalable processes. Unfortunately, condensation polymerization is inherently variable, often resulting in imprecise material properties, such as molecular weight (MW), due to minor changes in input parameters between batches (e.g., monomer purity, humidity, temperature consistency). While this variability may be acceptable in some applications, it becomes problematic for those requiring precise material properties, such as predictable degradation rates for resorbable medical devices.

To address these challenges, this work describes the development and implementations of a multiplexed synthesis apparatus (MSA), the SynPlex, which was designed to include a host of sensors for real-time monitoring and control, aimed at improving batch-to-batch (BtB) variability to generate consistent and predictable materials, toward streamlining polyester material development for degradable medical devices.

Materials and

Methods:  We performed a systematic review of polycondensation-based polyester synthesis to identify critical reaction inputs and sources of variability. This review informed the selection of components and sensors for monitoring and recording reaction data. The SynPlex can control up to five simultaneous reactions under identical or varied conditions across reactors. Infrastructure includes a Schlenk line, vacuum rated glassware and reaction vessels, high-precision heating mantles, thermocouples, pressure sensors and a regulator valve, and stirring motors with torque feedback. All controllable hardware is integrated into a custom control box controlled through a custom companion software.

The software platform, developed in Python, supports dynamic and static setpoint control for temperature, pressure, and stirring to enable semi-automated synthesis processes. Designed to provide users with real-time data monitoring and visualization, allowing users to track reaction progression and adjust parameters as needed. The software's data logging capabilities facilitate detailed post-synthesis analysis, to support identification of key trends and insights.

To validate the utility of SynPlex, we synthesized poly(octylene succinate), from 1,8-octanediol and succinic acid using a one-pot synthesis process, both in traditional batch methods and via the SynPlex system. The validation involved varying reaction parameters, including temperature, pressure, and setpoint ramp rates, to assess the system's ability to maintain consistency and reproducibility. The synthesized polymers were characterized using nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC) to evaluate molecular weight distribution and chemical structure, ensuring the SynPlex's performance matched or exceeded traditional methods.

Results, Conclusions, and Discussions: The SynPlex was constructed to minimize BtB variability and experimental load in the development of polyester materials for biomedical applications. Implementation of the SynPlex highlights its ability to enhance the quality of data gathered during polyester synthesis. Through integrating temperature, pressure, and stirring control systems, along with a custom ramp-builder feature, users can create tailored setpoint maps prior to starting the reaction. This ramping feature is crucial for maintaining consistent reaction conditions while also mitigating common human errors, such as rapid changes in temperature or pressure that can promote changes in stoichiometric ratios of reagents. These features directly impact both the reproducibility and quality of the synthesized materials, while also providing a control suite to simplify high-throughput polyester synthesis.

A notable feature of the stirring control system is the ability to measure motor torque values. This feature, in combination with the control software's real-time graphical display, allows users to track reaction progress via the relationship between reactor viscosity and molecular weight. By graphically displaying torque vs. time, it is also possible to use inflection points in the data to identify key points throughout the reaction. For example, a significant increase in torque can indicate that the transesterification phase has completed, signaling the need to switch to vacuum polycondensation.

Another key feature of the SynPlex is the temperature control of the purge gas. Developed through iterative design, this control ensures that the reactor temperature remains consistent throughout the process, enhancing the removal of reaction by-products such as water or methanol. This feature mitigates temperature fluctuations that could negatively impact reaction kinetics, improving the quality of synthesis data.

The SynPlex system automates many key processes to minimize human error and increase material development throughput, while ensuring consistent execution of each reaction phase across different batches of material. The ability to record comprehensive synthesis data, the SynPlex provides an optimal platform to employ statistically robust design of experiment methodologies. Enabling the generation of extensive libraries of polyester materials, to investigate the relationship between synthesis parameters and material properties. Toward the goal of developing consistent and tunable polyester materials for biomedical applications

Acknowledgements (Optional):