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The majority of biological processes step through precisely orchestrated phases, with bioactive cues switching on and off to drive these phases. When this co-ordination is disrupted, it typically results in pathology. This phenomenon motivates the central engineering and biological questions in our lab.
Engineering Question: Can we build tools to deliver timed delivery profiles?
Biological Question: Can we restore co-ordination with these tools?
on-demand delivery of therapeutics
This research focuses on the precisely timed delivery of therapeutics in response to external triggers. Given that the majority of our applications focus on regenerative medicine, our hydrogel systems are designed to be locally implanted at the treatment site, thereby locally delivering a bioactive agent. For triggers we typically employ ultrasound, but are also exploring magnetic and light stimulation. For therapeutics, we utilize a range of different particles ranging from small molecule drugs, proteins, and nucleic acid-based therapeutics. Most recently, we are employing nanoparticles as these have demonstrated the most precise on/off switch in our system. The developed devices are employed to explore the effects of bioactive cue delivery timing on repair and co-ordination (e.g., diabetic foot ulcers, vascularization).
extracellular matrix-enriched tissue engineering scaffolds
Porous collagen-based scaffolds have been widely explored in research labs, with several devices translating to the clinic. We are researching ways to enhance the regenerative potential of these devices by incorporating additional matrix models. In wound healing, for example, older individuals and certain diseases show slower healing or may not heal at all. By functionalizing collagen-based scaffolds, with an extracellular matrix milieu that mimics a younger/healthier version of ourselves, we can potentially enhance wound healing. Induced pluripotent stem cells (iPSC) technology reprograms adult cells into an embryonic-like state, rejuvenating cells and erasing some age-related pathologies. These cells can be differentiated back into 'younger, fitter, faster' skin cells and used to produce an ECM that we can incorporate into collagen-based scaffolds.
Integrating on-demand drug delivery technologies into collagen-based scaffolds
For complex regenerative medicine applications, it is necessary to provide both the therapeutic signaling, as well as a regenerative template for successful repair. To this end, we develop and test devices that combine our drug delivery technologies within collagen-based scaffolds. Utilizing a compartmentalization approach, this also enables us to trigger release of individual therapeutics sequentially, which can be used to drive co-ordination of biological processes through the various stages of healing and repair.
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