Research

 

Dynamic Materials to Understand and Mimic Biological Phenomena

 

Dynamic cellular microenvironments

The extracellular matrix (ECM) is the natural material niche of the human body. By coordinating a complex array of biochemical and biophysical cues, the ECM plays an important role in both normal physiological processes and disease. However, nearly all commercially available cell culture platforms or scaffolds are static, which can lead to a mismatch between in vitro experiments and in vivo behavior. To further our understanding of in vivo processes, we are developing new materials that can mimic the dynamic properties of real tissues. Our current focus is to engineer well-defined polymeric hydrogels with precise temporal control over bulk and local mechanics using stimuli-responsive and dynamic chemistries. Broadly, we apply our materials toward understanding disease mechanisms, advanced tissue engineering scaffolds, and cell expansion and delivery vehicles. 

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TM FitzSimons, F Oentoro, TV Shanbhag, EV Anslyn, AM Rosales. "Preferential Control of Forward Reaction Kinetics in Hydrogels Crosslinked with Reversible Conjugate Additions," Macromolecules, (2020).

AJ Graham, CM Dundas, A Hillsley, DS Kasprak, AM Rosales, BK Keitz. "Genetic control of radical crosslinking in a semi-synthetic hydrogel," ACS Biomaterials Science and Engineering, (2020).


sequence-defined materials

Biological polymers such as proteins are responsible for nearly every facet of life and contain exquisite properties ranging from structural (e.g., spider silk) to signal transduction (e.g., insulin). Both monomer sequence and chain shape dictate protein function, but such sequence control is difficult to replicate with conventional synthetic polymers. Our work probes the relationship between sequence and structure using multiple types of bio-adjacent materials, including polypeptoids and protected peptides, and we leverage this molecular control to understand the principles governing the structure of these materials and to develop synthetic materials with tunable bioactivity. Because these materials are non-natural, they provide opportunities to interface with biologics in an orthogonal manner and to generate materials with precise control. 

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FitzSimons, T. M.; Duti, I. J.; Conrad, N.; Agrawal, P.; Niemoeller, A.; Guinn, E.; Wang, J.; Vasiukhina-Martin, A.; Rosales, A. M. Gelation behavior of short protected peptides in organic medium. Soft Matter 2025, 21 (23), 4751-4760, 10.1039/D5SM00275C. DOI: 10.1039/D5SM00275C.

A Pineda-Hernandez, DA Castilla-Casadiego, LD Morton, SA Giordano-Nguyen, KN Halwachs, AM Rosales. “Tunable hydrogel networks by varying secondary structures of hydrophilic peptoids provide viable 3D cell culture platforms for hMSCs.” Biomaterials Science (2025). DOI: 10.1039/D5BM00433K.