Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. The best replacement for these wounds is uninjured autologous living tissue. Current clinical methods are effective for transferring this type of tissue. However, the methods are extremely limited by a lack of appropriate specialized tissue. Tissue engineering has shown promise for the reconstruction of complex physical injuries. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goals of this research are to optimize PEG hydrogel conditions to stimulate extensive and stable vessel formation in vivo and to use these hydrogels to increase the volume of vascularized bone that can be engineered for reconstruction of complex skeletal defects These goals are driven by the hypotheses that 1) the speed of endothelial cell migration and invasion is higher within macroporous hydrogels than hydrogels degraded only by cell proteolysis, 2) vessel stability is increased in materials that degrade and release growth factors after vessel invasion, and 3) increasing vascularization in chambers implanted against the periosteum will increase the volume and depth of osteogenesis. These hypotheses will be addressed by completing the following objectives: Specific Objective 1: Identify optimal PEG conditions that permit rapid cell and blood vessel invasion. Specific Objective 2: Identify the effects of material degradation and growth factor release kinetics on vessel persistence and maturation in implanted hydrogels. Specific Objective 3: Quantify the ability of hydrogels that stimulate rapid, stable neovascularization to promote vascularized bone formation in an animal model of guided tissue fabrication and determine whether addition of an osteogenic factor to the hydrogels further enhances bone formation. Completion of theses studies will lead to improved methods for engineering large volume tissues for the treatment of complex wounds resulting from battlefield trauma, civilian trauma, and tumor resection.

Public Health Relevance

Project Narrative Relevance Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. Tissue engineering has shown promise for the reconstruction of these complex wounds. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goal of this research is to design new biomaterials that stimulate blood vessel formation. These materials have the potential to improve the reconstruction and replacement of physical injuries suffered by veterans returning from current conflicts in Iraq and Afghanistan.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01BX000418-03
Application #
8195594
Study Section
Surgery (SURG)
Project Start
2010-04-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Edward Hines Jr VA Hospital
Department
Type
DUNS #
067445429
City
Hines
State
IL
Country
United States
Zip Code
60141
Somo, Sami I; Langert, Kelly; Yang, Chin-Yu et al. (2018) Synthesis and evaluation of dual crosslinked alginate microbeads. Acta Biomater 65:53-65
Vaicik, Marcella K; Blagajcevic, Alen; Ye, Honggang et al. (2018) The Absence of Laminin ?4 in Male Mice Results in Enhanced Energy Expenditure and Increased Beige Subcutaneous Adipose Tissue. Endocrinology 159:356-367
Zivkovic, Lada; Akar, Banu; Roux, Brianna M et al. (2017) Investigation of DNA damage in cells exposed to poly (lactic-co-glycolic acid) microspheres. J Biomed Mater Res A 105:284-291
Somo, Sami I; Khanna, Omaditya; Brey, Eric M (2017) Alginate Microbeads for Cell and Protein Delivery. Methods Mol Biol 1479:217-224
Hsiao, Hui-Yi; Yang, Shu-Rui; Brey, Eric M et al. (2016) Hydrogel Delivery of Mesenchymal Stem Cell-Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair. Plast Reconstr Surg Glob Open 4:e838
Mishra, Ruchi; Roux, Brianna M; Posukonis, Megan et al. (2016) Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds. Biomaterials 77:255-66
Appel, Alyssa A; Ibarra, Veronica; Somo, Sami I et al. (2016) Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast. Tissue Eng Part C Methods 22:1038-1048
Ibarra, Veronica; Appel, Alyssa A; Anastasio, Mark A et al. (2016) This paper is a winner in the Undergraduate category for the SFB awards: Evaluation of the tissue response to alginate encapsulated islets in an omentum pouch model. J Biomed Mater Res A 104:1581-90
Appel, Alyssa A; Larson, Jeffery C; Jiang, Bin et al. (2016) X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants. Ann Biomed Eng 44:773-81
Somo, Sami I; Akar, Banu; Bayrak, Elif S et al. (2015) Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels. Tissue Eng Part C Methods 21:773-85

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