Maxillofacial bony defects, occurring as a result of tumor resection, infection, trauma, as well as tooth loss or extraction, are often associated with patient morbidity. Development of suitable biomaterials for reconstruction of oral structures through guided bone regeneration (GBR) has reduced morbidity, improved quality of life after surgery, and has benefitted partially or completely edentulous patients by supporting dental implants used to replace the lost teeth. The GBR techniques primarily use a polymeric barrier membrane to stop infiltration of surrounding undesired soft tissue into the defect site and support new bone formation. Currently available barrier membranes display significant shortfalls. For example, the non- bioresorbable membranes need a second surgery for their removal after tissue healing. The synthetic, bioresorbable membranes eliminate this need for the second surgery and provide sufficient mechanical strength but they lead to local inflammation during degradation. The natural, bioresorbable membranes (primarily collagen) eliminate inflammation, but still suffer from rapid degradation and inadequate mechanical strength. More importantly, none of these membranes offer a tunable release of bioactive agents (osteoinductive proteins, growth factors, antibiotics) to enhance the new bone tissue formation. Therefore, it is desirable to have a biomaterial with suitable biocompatibility, mechanical properties, and bioactive agent release. We propose to prepare novel multi-component composite membranes that incorporate a stimulus- responsive smart polymer (elastin-like polypeptide, ELP), biodegradable ceramic (45S5 Bioglass), and collagen as network former. The major component, ELP, is genetically engineered to provide precise control of its properties and exhibits an inverse phase transition behavior in response to changes in its solution environment. We hypothesize that incorporation of ELP and Bioglass will improve the mechanical properties of the membranes, while the inverse phase transition behavior of ELP will control the release rates of bioactive agents from the membranes. This research is divided into following key Specific Aims: (1) Create and Characterize ELP-Bioglass-Collagen Membranes;(2) Characterize Drug Release Profiles for Composite Membranes;(3) Evaluate Drug-loaded ELP-Bioglass-Collagen Membranes for Osteoblast Culture. Our research will significantly impact major technological and biological problems that currently limit the development of barrier membranes for simultaneous drug delivery and tissue engineering in GBR and help achieve: (1) sustained release of bioactive agents;(2) improved bone tissue growth;and (3) reduced post- surgical bacterial infections and infiltration of surrounding undesired soft tissue. While advancing the fundamental understanding of extra-cellular matrix-based composites, our research will provide new composite materials for GBR and other applications requiring bone replacement. Thus, the new ELP- Bioglass-Collagen materials may directly impact biomedical technology in the near future.

Public Health Relevance

Maxillofacial bony defects, occurring as a result of tumor resection, infection, trauma, as well as tooth loss or extraction, lead to patient morbidity. Reconstruction of oral structures through guided bone regeneration (GBR) reduces morbidity, improves quality of life after surgery, and benefits partially or completely edentulous patients by supporting dental implants used to replace the lost teeth. Currently available GBR materials display significant shortfalls. Therefore, development of improved GBR materials with superior biocompatibility, mechanical properties, and drug release characteristics is paramount.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE024257-01
Application #
8684259
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Lumelsky, Nadya L
Project Start
2014-02-20
Project End
2016-01-31
Budget Start
2014-02-20
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$114,375
Indirect Cost
$39,375
Name
University of Mississippi Medical Center
Department
Dentistry
Type
Schools of Dentistry
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Anderson, Tiffany R; Marquart, Mary E; Janorkar, Amol V (2015) Effective release of a broad spectrum antibiotic from elastin-like polypeptide-collagen composite. J Biomed Mater Res A 103:782-90