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Biology subjects

Woodworth, K. E.

Publications and source records attributed to Woodworth, K. E..

2 recordsLinked to original sources

Systematic development of degradable polyester biomaterials via ring-opening copolymerization of succinic anhydride and epoxides

Degradable polyester materials are widely utilized in medicine as resorbable sutures, implantable devices, and drug delivery. These applications require precise and tunable degradation control; predictable number-average molecular weight ([M]n), narrow polydispersity (PDI), and diverse material properties define polyester utility, which are not easily achieved through well-established synthesis approaches. Ring-opening copolymerization (ROCOP) provides reproducible[M] n control, narrow PDI, and expands monomer diversity. In this work, poly(cyclohexene succinate) (PCS) and poly(propylene succinate) (PPS) were synthesized through a central composite design of experiments approach, systematically varying anhydride:epoxide ratio, monomer:catalyst ratio, reaction temperature, and reaction time. Reduced synthesis factor-response models explained significant variation for all characterized properties relevant to degradation control. PCS and PPS readily degraded under base-catalyzed hydrolysis conditions with significantly higher mass loss in PPS materials compared to PCS, highlighting the monomer selection influence in degradation behaviour. These findings highlight the potential for ROCOP to generate degradable biomaterials with reproducible material properties in application-specific biomedical use.

bioengineering↗

Development of itaconate polymer microparticles for intracellular regulation of pro-inflammatory macrophage activation

Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. Its use in immunomodulatory therapies has faced limitations due to inherent challenges in achieving controlled delivery and requirements for high extracellular concentrations to achieve internalization of the highly polar small molecule to achieve its intracellular therapeutic activity. Microparticle (MP)-based delivery strategies are a promising approach for intracellular delivery of small molecule metabolites through macrophage phagocytosis and subsequent intracellular polymer degradation-based delivery. Toward the goal of intracellular delivery of IA, degradable polyester polymer-(poly(itaconate-co-dodecanediol)) based IA polymer microparticles (IA-MPs) were generated using an emulsion method, forming micron-scale ([~] 1.5 {micro}m) degradable microspheres. IA-MPs were characterized with respect to their material properties and IA release kinetics to inform particle fabrication. Treatment of murine bone marrow-derived macrophages with an optimized particle concentration of 0.1 mg/million cells enabled phagocytosis-mediated internalization and low levels of cytotoxicity. Flow cytometry demonstrated IA-MP-specific regulation of IA-sensitive inflammatory targets. Metabolic analyses demonstrated that IA-MP internalization inhibited oxidative metabolism and induced glycolytic reliance, consistent with the established mechanism of IA-associated inhibition of succinate dehydrogenase. This development of IA-based polymer microparticles provides a basis for additional innovative metabolite-based microparticle drug delivery systems for the treatment of inflammatory disease.

bioengineering↗