Welcoming Remarks
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Process Development Division
Sustainable and Green Product Design
Monday, November 11, 2019 - 3:30pm to 3:33pm
Injectable biopolymer hydrogels have gained increasing attention for clinical translation as engineered biomedical scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-MI). However, the majority of hydrogels tested are not candidates for minimally invasive catheter delivery because of excess material viscosity, rapid gelation times, and concerns regarding hemocompatibility and potential for embolism. As a result, clinical translation of most injectable biomaterials for the heart has been hindered. Solutions are needed for this broad class of promising biomaterial.
Here, we describe novel progelator materials formulated in some cases as sterically constrained cyclic peptides to prevent self-assembly and provide a free flowing solution for low resistance injection. Importantly through our design, we provide the first demonstration of self-assembling peptides (SAPs), and related polymer-peptide conjugate scaffolds, amenable to cardiac catheter injection. Ulitmate linearization by MI-associated enzymes induces rapid self-assembly into rehealable hydrogels. The versatility of our platform is shown through the functionalization of two different SAP sequences, which exhibit disparate self-assembly mechanisms, and yet form progelators with identical responsiveness. Hemocompatibility analyses and in vivo application in a rat ischemia repurfusion model provide evidence that our simple synthetic modifications do not induce toxicity nor alter the capacity to self-assemble within a biological environment. Finally, we demonstrate that labeling of our progelators with a small molecule dye (rhodamine) does not interfere with self-assembly. Thus we envision that a chemically complex hydrogel can be generated in vivo through simple mixture of different progelators, each bearing a small molecule drug, tag, or reactive moiety. The work presented sets the stage for structurally dynamic biomaterials for therapeutic hydrogel delivery to the heart for the prevention of negative LV remodeling.
Here, we describe novel progelator materials formulated in some cases as sterically constrained cyclic peptides to prevent self-assembly and provide a free flowing solution for low resistance injection. Importantly through our design, we provide the first demonstration of self-assembling peptides (SAPs), and related polymer-peptide conjugate scaffolds, amenable to cardiac catheter injection. Ulitmate linearization by MI-associated enzymes induces rapid self-assembly into rehealable hydrogels. The versatility of our platform is shown through the functionalization of two different SAP sequences, which exhibit disparate self-assembly mechanisms, and yet form progelators with identical responsiveness. Hemocompatibility analyses and in vivo application in a rat ischemia repurfusion model provide evidence that our simple synthetic modifications do not induce toxicity nor alter the capacity to self-assemble within a biological environment. Finally, we demonstrate that labeling of our progelators with a small molecule dye (rhodamine) does not interfere with self-assembly. Thus we envision that a chemically complex hydrogel can be generated in vivo through simple mixture of different progelators, each bearing a small molecule drug, tag, or reactive moiety. The work presented sets the stage for structurally dynamic biomaterials for therapeutic hydrogel delivery to the heart for the prevention of negative LV remodeling.