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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
4R01DE017207-09
Application #
9052169
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lopez, Orlando
Project Start
2005-12-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
9
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Tufts University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
Martín-Moldes, Zaira; Ebrahimi, Davoud; Plowright, Robyn et al. (2018) Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk-silica Chimeras. Adv Funct Mater 28:
Belton, David J; Plowright, Robyn; Kaplan, David L et al. (2018) A robust spectroscopic method for the determination of protein conformational composition - Application to the annealing of silk. Acta Biomater 73:355-364
Ding, Z Z; Ma, J; He, W et al. (2017) Simulation of ECM with Silk and Chitosan Nanocomposite Materials. J Mater Chem B 5:4789-4796
Guo, Jin; Li, Chunmei; Ling, Shengjie et al. (2017) Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering. Biomaterials 145:44-55
Dinjaski, Nina; Plowright, Robyn; Zhou, Shun et al. (2017) Osteoinductive recombinant silk fusion proteins for bone regeneration. Acta Biomater 49:127-139
Giesa, Tristan; Perry, Carole C; Buehler, Markus J (2016) Secondary Structure Transition and Critical Stress for a Model of Spider Silk Assembly. Biomacromolecules 17:427-36
Ding, Z Z; Fan, Z H; Huang, X W et al. (2016) Bioactive Natural Protein-Hydroxyapatite Nanocarriers for Optimizing Osteogenic Differentiation of Mesenchymal Stem Cells. J Mater Chem B 4:3555-3561
Han, Hongyan; Ning, Hongyan; Liu, Shanshan et al. (2016) Silk Biomaterials with Vascularization Capacity. Adv Funct Mater 26:421-436
Plowright, Robyn; Dinjaski, Nina; Zhou, Shun et al. (2016) Influence of silk-silica fusion protein design on silica condensation in vitro and cellular calcification. RSC Adv 6:21776-21788
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

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