Biomaterial strategies to promote hemidesmosome formation on percutaneous devices

Abstract

Millions of percutaneous devices (catheters, dental, and orthopedic implants) fail from infection each year. Infection preventative and treatment strategies have largely ignored the potential of generating sound and durable soft tissue adhesive barriers to prevent bacterial colonization at the tissue-device interface. The tooth, a long-lasting percutaneous organ, features robust soft tissue attachment through formation of keratinocyte adhesive structures, called hemidesmosomes, in the unique junctional epithelium basement membrane adjacent to the tooth. Inspired by this natural impermeable-to-bacteria interface, and after reviewing the history of biomaterials for upregulating hemidesmosome and general characteristics of hemidesmosomes and junctional epithelium, this dissertation describes two orally-relevant approaches for potentiating hemidesmosome formation around percutaneous devices. The first approach described is “hemidesmosome-inducing light-curable biosealants” (HILBs) that demonstrate hemidesmosome bioinstruction without biologics or complex biomaterials. We establish a structure-function relationship based on a thorough mechanical, physicochemical, and biological characterization of HILBs. A model for how these materials affect pericellular matrix and how cells interpret this matrix is provided. The second approach is the use of cell adhesion peptides coatings to upregulate hemidesmosomes and selectively increase keratinocyte proliferation compared to fibroblasts, among other junctional-epithelium-mimicking functions. We also broadly review the use of biomolecules to biofunctionalize dental biomaterials. We then demonstrate the importance of rational chemical method selection for biofunctionalization of materials surfaces and the ultimate biological outcomes. We next engineer multifunctional - hemidesmosome upregulating and antimicrobial – surfaces for a two tiered approach to prevention of percutaneous device infection. We finally demonstrate the untapped potential of basement membrane motifs to trigger hemidesmosomes formation and myriad of other functions for junctional epithelium-like regeneration. Here, we spotlight control of downstream signaling associated with integrin-mediated hemidesmosome formation. A major impact of this work is generation of non-antimicrobial approaches for potentially preventing the infection of percutaneous devices and extending their lifespans. Our approaches avoid antibiotic usage and associated drawbacks and promote further tissue regeneration.