Bones, bones, bones [electronic resource] : using protein-engineered biomaterials to improve bone regeneration and implant osseointegration

Our bones are complex and beautiful structures that highlight that Nature is a masterful materials scientist. These composite structures of minerals, proteins, and cells are capable of maintaining a remarkable, ever-changing balance based on an individual's biomechanical needs. Growing, running, jumping, sitting, sleeping -- all of our actions and inactions are chronicled and inform the processes of new bone formation and old bone resorption. The hierarchical microstructure, building from calcium phosphate nanocrystals embedded in collagen fibers, underscores the importance of mineral and organic components that synergistically contribute to the toughness of bone needed daily. Unfortunately, due to trauma or disease, at times our bones fail and are unable to heal themselves. It is for these instances that the field of Regenerative Medicine works to develop therapies built on expertise from materials science, engineering, and medical fields. Using protein engineering and bone biology as the starting foundation, my thesis work has focused on the development of two protein-engineered biomaterials for the improvement of regenerative medicine therapies focused on osseointegration of implants and bone regeneration. Engineered protein biomaterials harness the extensive toolkit provided to us by Nature, which includes the machinery to synthesize protein materials and myriad functional pieces to mix and match in our novel designs. With these tools I've helped develop an engineered elastin-like protein to be a photocrosslinkable, cell-adhesive, thin-film coating to improve the osseointegration of implants used to stabilize fractures. The material demonstrates increased speed and extent of cell attachment to coated surfaces, serving as proof of principle for use of this material in stimulating integration of coated implants through improved implant-cell interactions. Focusing my attention on non-healing skeletal defects, I worked with MITCH, our Mixing-Induced, Two-Component Hydrogel, to develop it for stem cell delivery and bone regeneration applications. MITCH employs molecular recognition of a peptide domain binding pair for gentle, on-demand, 3D cell encapsulation at constant physiological conditions. Further using this binding strategy to emulate the intimate interface between organic and mineral phases in native bone by crosslinking mineral nanoparticles into the hydrogel network via specific molecular interactions, I created a material capable of delivering adipose-derived stem cells and stimulating fast bone regeneration in critical-size calvarial defects. Regenerative medicine brings together the renewing power of stem cells and the rational design of biomimetic niches to help the body heal when it is incapable of doing so without assistance. Taken together, this body of work validates the strategy of designing protein-engineered biomaterials by taking cues from Nature to further the development of regenerative medicine therapies, improving their success and widespread adoption.

Keywords: Bioengineering.
Advisor: Heilshorn Sarah primary advisor. Thesis advisor
Goodman Stuart B.
Longaker Michael T.