Design of tunable biopolymers to understand the dynamic wound microenvironment - Project Summary Inflammation, the initial response to injury, plays a pivotal role in wound-healing. In addition to a defense mechanism, inflammation is intertwined with tissue repair, orchestrating a delicate balance between necessary defensive actions and the promotion of tissue regeneration [ref]. However, dysregulation of this inflammatory phase can lead to impaired healing, a critical focus for effective wound management strategies. Therefore, understanding and modulating this inflammatory response is crucial to enhancing wound healing, particularly in chronic wounds where chronic inflammation impairs the healing process. Chronic wound is a debilitating condition affecting the quality of life of approximately 8.5 million people, with an annual expenditure of more than $50 billion in the US. Unfortunately, the number of patients and costs will increase further with risk factors such as diabetes, vascular disease, and aging. Although several strategies to manage chronic wounds are available, the need for effective chronic wound treatment persists. The overarching goal of my research is to develop and optimize bioengineered polymers with tunable properties to modulate inflammatory responses in the tissue microenvironment, thereby enhancing tissue repair and regeneration across a spectrum of wound types. The rationale of this research is to systematically investigate how biopolymers' chemical and mechanical properties influence inflammatory response and tissue healing. By understanding these relationships, the project aims to engineer biopolymers with optimized surface charges, elasticity, and porosity, that can either mitigate excessive inflammation in chronic wounds or enhance necessary inflammatory responses in normal wound healing. This project will integrate immunology with polymer surface chemistry and employ 3D fabrication strategies to modify the surface charges of biopolymers and optimize elasticity and porosity, respectively. Hence, we aim to develop biopolymers contributing to controlled and effective healing processes. Over the next five years, we will delve into investigating how the intrinsic properties of biopolymers can be engineered to actively influence, control, and normalize the wound microenvironment by material characterizations, in vitro and in vivo studies using well-established mouse models to recapitulate skin excision wounds and diabetic wounds. In the first project, we aim to uncover the mechanisms by which the surface charges of biopolymers affect local inflammation. In the second project, we aim to investigate the tailoring of physical-mechanical properties to enhance the therapeutic efficacy of biopolymers in wound healing applications. If successful, such understanding is vital for advancing the design and application of biopolymers in a way that is not only biocompatible but also contributes positively to the local tissue environment and overall patient health.
