Abstract

In recent years emphasis in biomaterial engineering has shifted from biostable materials to biodegradable materials that can degrade to non-toxic products under physiological conditions. Polymers of lactic and glycolic acid and their copolymers poly(lactide-co-glycolide), (PLAGA) are some of the most commonly used biodegradable polymers for medical applications. All these polymers are associated with some limitations, which demand the search for novel biodegradable materials that are biocompatible and bioresponsive. Biodegradable polyphosphazenes, a unique class of inorganic polymer developed recently have the potential to become ideal candidates for various biomedical applications due to their unprecedented synthetic flexibility and versatile properties. PI had previously shown that blending polyphosphazenes with PLAGA can significantly preclude the accumulation of acidic degradation products of PLAGA and associated inflammatory reponses, at the same time can significantly improve their mechanical properties and osteoconductivity. We believe that the synthetic flexibility of polyphosphazenes will allow the design of novel macromolecules, which can for miscible blends with PLAGA and increase the bioactivity. These novel blends due to their well-tuned biodegradability, mechanical and biological properties combined with osteointegrity can serve a variety of needs in orthopaedics. This goal will be achieved via the following specific aims:
Specific Aim 1 : To design, synthesize and characterize novel biodegradable polyphosphazenes, which can form miscible blends with PLAGA as candidate materials for bone tissue engineering.
Specific Aim 2 : To construct novel blends of polyphosphazenes with PLAGA and perform optimization studues with these blends focusing on improvements in physico-chemical properties, mechanical properties, in vitro degradation, in vitro mineralization and osteoconductivity.
Specific Aim 3 : To perform biological evaluation of novel blends of polyphosphazenes with PLAGA using in vivo animal models.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB004051-02
Application #
7103619
Study Section
Special Emphasis Panel (ZRG1-MTE (01))
Program Officer
Kelley, Christine A
Project Start
2005-08-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$282,846
Indirect Cost

  Institution

Name
University of Virginia
Department
Orthopedics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Deng, Meng; James, Roshan; Laurencin, Cato T et al. (2012) Nanostructured polymeric scaffolds for orthopaedic regenerative engineering. IEEE Trans Nanobioscience 11:3-14
Lo, Kevin W-H; Ulery, Bret D; Ashe, Keshia M et al. (2012) Studies of bone morphogenetic protein-based surgical repair. Adv Drug Deliv Rev 64:1277-91
Peach, M Sean; Kumbar, Sangamesh G; James, Roshan et al. (2012) Design and optimization of polyphosphazene functionalized fiber matrices for soft tissue regeneration. J Biomed Nanotechnol 8:107-24
James, Roshan; Toti, Udaya S; Laurencin, Cato T et al. (2011) Electrospun nanofibrous scaffolds for engineering soft connective tissues. Methods Mol Biol 726:243-58
Sethuraman, Swaminathan; Nair, Lakshmi S; El-Amin, Saadiq et al. (2010) Mechanical properties and osteocompatibility of novel biodegradable alanine based polyphosphazenes: Side group effects. Acta Biomater 6:1931-7
Deng, Meng; Nair, Lakshmi S; Nukavarapu, Syam P et al. (2010) In Situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide-based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering. Adv Funct Mater 20:2743-2957
Deng, Meng; Nair, Lakshmi S; Nukavarapu, Syam P et al. (2010) Dipeptide-based polyphosphazene and polyester blends for bone tissue engineering. Biomaterials 31:4898-908
Deng, Meng; Nair, Lakshmi S; Nukavarapu, Syam P et al. (2010) Biomimetic, bioactive etheric polyphosphazene-poly(lactide-co-glycolide) blends for bone tissue engineering. J Biomed Mater Res A 92:114-25
Weikel, Arlin L; Owens, Steven G; Morozowich, Nicole L et al. (2010) Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast activity on resulting blends. Biomaterials 31:8507-15
Krogman, Nicholas R; Weikel, Arlin L; Kristhart, Katherine A et al. (2009) The influence of side group modification in polyphosphazenes on hydrolysis and cell adhesion of blends with PLGA. Biomaterials 30:3035-41

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