Understanding varied cellular and tissue responses in Microporous Annealed Particle (MAP) hydrogels with differing polymer backbone chemistries; Decentralized clinical trials (DCTs): challenges and opportunities of an innovative paradigm shift in go-to-market strategy for biomedical technologies

In the COVID-19 era, clinical research has become a critical public health priority. Stakeholders across biotechnology, regulatory, academic, and healthcare communities have been forced to adapt to a world in which vaccine time-to-market equates to, in a very real sense, lives saved. In addition to several significant shifts in bioproduct manufacturing, such as manufacturing-at-risk and early process scale-up, and in regulatory processes, such as parallelized clinical research and phased approvals, the way clinical trials themselves are coordinated and executed is also undergoing massive change. Everything from tissue implants to drug therapeutics and vaccines to novel diagnostics equipment and lab testing apparatus, require rigorous proof of product safety and efficacy through one of many long and complicated regulatory approval pipelines. As our body of biomedical knowledge further expands and translational research continues to forge ahead, the biotechnology industry is looking for new ways to optimize clinical research modes by improving patient recruitment, engagement, and retention in an effort to accelerate commercialization timelines.

Microporous annealed particle (MAP) gels are novel class of biomaterials built via a building block assembly of individual hydrogel microspheres that form an immobilized tissue scaffold for wound healing. MAP gels offer numerous advantages over existing tissue fillers and bulk hydrogel constructs, such as injectability, physicochemical tunability, and porosity. There is active research employing different material chemistries, various bioactive compounds, and synthesis procedures to develop customized MAP gel implants to serve as interventional treatments in a variety of tissue repair applications. There are many clinical conditions which are potential therapeutic targets for MAP gel injection. Among these are glottic incompetence, articular joint defects, volumetric muscle loss, diabetic foot ulcers, and maxillofacial deformities. We started our capstone project by noting that it has been previously demonstrated that biomaterial porosity in MAP gel is an important factor affecting the local inflammatory reaction after surgery. While has been well-proven, there still exists contention regarding how material composition, specifically how polymer backbone chemistry, may affect the overall tissue response facilitated by the MAP gel platform. In our capstone project, we aimed to profile several MAP gels, formulated using different synthetic and natural polymer backbone constituents, based on their immunogenic and biocompatibility characteristics. As the MAP gel implant technology enters phase I clinical trials classified as a novel biomedical device, researchers need to be acutely aware of the latest improvements in clinical research so to ensure no time is wasted in bringing the product to market.

For my STS research topic, I set out to investigate an emerging framework in clinical research, known as decentralized clinical trials (DCTs). This approach is taking center-stage in the effort to introduce patient-centricity, and added efficiency, to existing clinical development strategies. Enabled by digital health technologies and guided along by several stakeholders such as patient advocacy groups, regulatory agencies, and biotechnology industry leaders, DCTs have begun to take on a few distinct flavors each with unique identities. These so-called sociotechnical ‘imaginaries’ are different competing visions informing how DCTs will end up developing in the future. In this STS research paper, I attempt to integrate several perspectives to achieve a more robust and comprehensive understanding of how DCTs are changing the game for clinical trials.

These capstone and STS thesis projects come together where the rubber meets the road. Pre-clinical testing of biomedical technologies can only take a product so far. At some point human subjects need to be engaged, not as research participants, but as rather as research partners, creators of knowledge, and contributors to public welfare. While much progress has been made to overcome the shortcomings of traditional clinical research approaches, DCTs still have a long way to go to further improve and increase patient-centricity in clinical trials.

I would like to thank my capstone teammate Christian Jenkins, graduate student mentors Nicholas Cornell and Lauren Pruett, as well as my faculty advisors Professor Donald Griffin and Professor Sean Ferguson for their generosity, guidance, and support in building this final thesis portfolio.

School of Engineering and Applied Science
Bachelor of Science in Biomedical Engineering

Technical Advisor: Donald R. Griffin, PhD

STS Advisor: Sean Ferguson, PhD

Technical Team Members: Christian Jenkins