A biomimetic strategy is proposed to develop a new class of adhesives for orthopedic medicine, particularly joint fractures with multiple bone fragments. The adhesive is modeled after a natural underwater adhesive secreted by a marine tubeworm to glue together broken bits of seashells and sand grains. The natural glue is comprised of several proteins with simple repetitive sequences and significant quantities of divalent metal ions. The key features of the glue proteins will be copied with inexpensive, easy to manufacture synthetic polymers. The objectives are: 1.) To quantitatively correlate adhesive effectiveness (a convolution of bond strength, setting/curing kinetics, deliverability, and degradability) with formulation variables and delivery methods. This will be accomplished by mechanical testing on the micro and macro scales. 2.) To optimize the synthetic bone adhesive by fine tuning the structures and chemical properties of the mimetic copolymers. This will be accomplished by using controlled polymerization techniques to synthesize the mimetic copolymers. 3.) To definitively establish the biocompatibility of the mimetic adhesive and potential breakdown products both in vitro and in a living animal model. This will be accomplished in direct contact cell culture experiments with multiple relevant cell lines and by long term analysis of adhesive repaired bone fractures in the animal. Rates of adhesive degradation and resorption will be evaluated both in vitro and in vivo.

Public Health Relevance

An injectable, low-viscosity bone adhesive would improve the clinical outcome for a broad population of orthopedic trauma patients by facilitating more accurate alignment of small bone fragments. Better alignment during bone healing decreases the risk of post- traumatic arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006463-04
Application #
8094338
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Hunziker, Rosemarie
Project Start
2008-09-15
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$322,231
Indirect Cost
Name
University of Utah
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Stewart, Russell J; Wang, Ching Shuen; Song, In Taek et al. (2017) The role of coacervation and phase transitions in the sandcastle worm adhesive system. Adv Colloid Interface Sci 239:88-96
Kaur, Sarbjit; Weerasekare, G Mahika; Stewart, Russell J (2011) Multiphase adhesive coacervates inspired by the Sandcastle worm. ACS Appl Mater Interfaces 3:941-4
Stewart, Russell J; Ransom, Todd C; Hlady, Vladimir (2011) Natural Underwater Adhesives. J Polym Sci B Polym Phys 49:757-771
Shao, Hui; Weerasekare, G Mahika; Stewart, Russell J (2011) Controlled curing of adhesive complex coacervates with reversible periodate carbohydrate complexes. J Biomed Mater Res A :
Stewart, Russell J; Wang, Ching Shuen; Shao, Hui (2011) Complex coacervates as a foundation for synthetic underwater adhesives. Adv Colloid Interface Sci 167:85-93
Stewart, Russell J (2011) Protein-based underwater adhesives and the prospects for their biotechnological production. Appl Microbiol Biotechnol 89:27-33
Winslow, Brent D; Shao, Hui; Stewart, Russell J et al. (2010) Biocompatibility of adhesive complex coacervates modeled after the sandcastle glue of Phragmatopoma californica for craniofacial reconstruction. Biomaterials 31:9373-81
Shao, Hui; Stewart, Russell J (2010) Biomimetic underwater adhesives with environmentally triggered setting mechanisms. Adv Mater 22:729-33
Shao, Hui; Bachus, Kent N; Stewart, Russell J (2009) A water-borne adhesive modeled after the sandcastle glue of P. californica. Macromol Biosci 9:464-71