There is a major need for biomaterials that provide improved regeneration of craniofacial tissue and dental defects, where control of interfaces and osteogenesis can be tailored. Specifically, bone regeneration and titanium-bone interfaces are two key areas where improvements in interfacial bonding and bone remodeling are in need of advancements. In this renewal proposal, we build upon our progress in the current grant where we established the foundation for a new family of highly tailored biomaterials for bone regeneration based on silk-silica nanocomposites. Specifically, control of the organic (silk) and inorganic (silica) domains, based on bioengineering and chemistry approaches, and subsequent success in bone regeneration, lays the groundwork for this renewal. Our hypothesis is that this bioengineering approach to biomaterial design, and in particular organic-inorganic nanocomposite systems, can be exploited towards the design of multifunctional biomaterial systems for bone tissue regeneration. Tight control of chemistry, sequence, assembly and material functions (osteogenesis) can be tailored using this approach. We plan to expand the functional features of this new family of chimeric proteins by adding selective bone binding and titanium binding peptides to optimize interfaces, and also include antimicrobial components. These new systems will be evaluated in vitro related to osteogenic markers from hMSCs and mechanisms, and then in vivo in animal models to explore bone interfaces, bone formation and titanium anchoring in bone, as critical needs in the craniofacial and dental fields. The ability to tailor the chemistry and structure of such highly controlled multifunctional biomaterials to regulate the size and morphology of the silica phase, allows the formation of nano-scale composites required in craniofacial and dental repair scenarios. We plan to expand these systems with new functions to provide a novel path forward for improved interfaces in concert with the silica components, such that a new family of biomaterial scaffold designs will be achieved to match craniofacial and dental repair needs. The unprecedented control of all features of these novel chimeric protein biomaterials, due to the design features embedded in the bioengineering approach, has implications for a wide range of new biomaterials for tissue interfaces and tissue regeneration.
New biomaterials that improve craniofacial and dental repairs are critically needed that optimize interfaces and anchoring between bone and implants. Currently, available materials suffer from major limitations such as lack of remodeling, poor interfaces or poor biocompatibility. We have developed a new family of novel functionalized proteins that can address these needs. In our current grant we have established the viability of this approach in a series of published studies wherein the fundamental features of these systems (silk-silica nanocomposites), control of morphological and structural features, and bone formation were demonstrated. We plan to continue to develop these systems by addition of key interfaces to titanium implants and bone tissues, while also fostering control of infections. These new materials offer substantial benefits in needs of craniofacial reconstruction as well as in dental fields due to the tight control of chemistry, morphology and structure, as well as the abiliy to tailor regeneration and optimize osteogenic outcomes. !
|Pei, Yazhen; Liu, Xi; Liu, Shanshan et al. (2015) A mild process to design silk scaffolds with reduced ?-sheet structure and various topographies at the nanometer scale. Acta Biomater 13:168-76|
|Zhou, Shun; Huang, Wenwen; Belton, David J et al. (2015) Control of silicification by genetically engineered fusion proteins: silk-silica binding peptides. Acta Biomater 15:173-80|
|Zhang, W; Zhu, C; Wu, Y et al. (2014) VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation. Eur Cell Mater 27:1-11; discussion 11-2|
|Rnjak-Kovacina, Jelena; Wray, Lindsay S; Golinski, Julianne M et al. (2014) Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for Engineering Critically-sized Tissue Constructs. Adv Funct Mater 24:2188-2196|
|McNamara, Stephanie L; Rnjak-Kovacina, Jelena; Schmidt, Daniel F et al. (2014) Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite load bearing scaffolds. Biomaterials 35:6941-53|
|Hayden, Rebecca S; Vollrath, Moritz; Kaplan, David L (2014) Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk-hydroxyapatite films. Acta Biomater 10:486-93|
|Tokareva, Olena; Jacobsen, Matthew; Buehler, Markus et al. (2014) Structure-function-property-design interplay in biopolymers: spider silk. Acta Biomater 10:1612-26|
|Gil, Eun Seok; Park, Sang-Hyug; Hu, Xiao et al. (2014) Impact of sterilization on the enzymatic degradation and mechanical properties of silk biomaterials. Macromol Biosci 14:257-69|
|Hayden, Rebecca S; Quinn, Kyle P; Alonzo, Carlo A et al. (2014) Quantitative characterization of mineralized silk film remodeling during long-term osteoblast-osteoclast co-culture. Biomaterials 35:3794-802|
|Gomes, Sílvia; Gallego-Llamas, Jabier; Leonor, Isabel B et al. (2013) In vivo biological responses to silk proteins functionalized with bone sialoprotein. Macromol Biosci 13:444-54|
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