Craniomaxillofacial reconstruction continues to be a significant clinical challenge. The estimated cost for repairing craniomaxillofacial defects exceeds several billion dollars. Reconstructive surgery is primarily aimed at restoring the patient to normal function using bone grafts such as autografts, allografts, and synthetic materials. However, currently available treatment methods have significant clinical drawbacks. Therefore, there is an urgent clinical need to create a novel bone graft material that can be used to restore craniomaxillofacial defects successfully and avoids drawbacks of current bone grafts. A unique design criterion is developed to synthesize bone putty to achieve a novel multifunctionality that serves for better repair and/or regeneration of damaged or lost craniomaxillofacial bone tissues. We hypothesize that novel, multifunctional bone putty promotes bone formation at the local defect site. The bone putty will be synthesized using growth factors encapsulated chitosan microparticles, calcium chloride, and methyl cellulose. Each material selected for bone putty provides bone-specific properties to enhance bone growth. The multifunctional properties cannot be achieved with currently available bone graft substitutes. One of the main advantage of this approach compared with traditional block scaffolds, is that this bone putty can be administered by injection, creating the possibility of filling defects of different shapes and size through minimally invasive surgery. Upon implantation, our bone putty is expected to mold easily to the irregular implant site, and the pores should provide a space for both bone tissue and vascular ingrowth, as required for effective healing. Our main goal is to create bone putty that has bone-specific multifunctionality using benign biomaterials and mild processing techniques and that will restore and heal bone defects at local sites. Therefore, this bone putty will possess biocompatibility;biodegradability;injectability;osteoconductivity;osteoinductivity moldability;ability to deliver a precise amount of growth factor over time at the local site;structural (not brittle), and mechanical integrity similar to trabecular bone;ability to release C2+ and over time;immobility at the defect site;less mixing and working time at the operation room;porosity required for cell infiltration, bone formation-remodeling, and vascularization at the defect site. Bone morphogenetic protein, (BMP-2) release kinetics from bone putty will be compared with that of commercially available collagen sponge containing BMP-2 (Medtronic) over time. The bone putty will be assessed for the biocompatibility and rate and extent of osteogenesis toward an osteoblast phenotype and production of mineralized matrix in vitro. The bone putty will be implanted into a rat calvarial critical size defect. The outcomes of the bone regeneration from bone putty will be compared with commercially available calcium phosphate cement or collagen sponge with BMP-2.

Public Health Relevance

of this research to public health exists in the development of novel injectable bone putty that can be applied into craniomaxillofacial defects, orthopaedic bone defects, and spine fusion. The potential outcome from this novel interdisciplinary project will have an enormous impact on many scientific and medical communities, including regenerative medicine, bone biology, and craniomaxillofacial and musculoskeletal diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE023356-01A1
Application #
8595654
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Drummond, James
Project Start
2013-07-01
Project End
2018-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$378,750
Indirect Cost
$128,750
Name
University of Toledo
Department
None
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
Mantripragada, Venkata P; Jayasuriya, Ambalangodage C (2014) Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration. J Biomed Mater Res A 102:4276-89
Mantripragada, Venkata P; Jayasuriya, Ambalangodage C (2014) IGF-1 release kinetics from chitosan microparticles fabricated using environmentally benign conditions. Mater Sci Eng C Mater Biol Appl 42:506-16