Large skull defects arise frequently following neurosurgery and craniofacial reconstructive surgery for trauma, cancer resection, and congenital deformity. Concerns over revascularization, aesthetics, and protective strength of the patient's own bone or artificial plating are magnified by the post-surgical need to protect the brain from infection and trauma. Tissue engineered bone replacements have been shown to ossify small skeletal defects with potential utility in fracture repair, but currently, these materials do not effectively address skull defects large enough to require graft or prosthetic augmentation. The primary surgical option, autogenous grafts, extend the patient's deficits to a new site and may resorb or become infected. Non-tissue engineered implanted materials interrupt vasculature between the dura, bone and scalp, and risk infection or extrusion. Limited means of diagnostic assay lead to neurocranial repair problems presenting initially as a failure requiring surgery. Tissue engineering neurocranial prosthetics could overcome these limitations if shown to maintain their shape and protective strength while bone migrates from the host into the implant's center. The investigators propose an animal model that extends current work on poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) photopolymer critical size implants to truly large size neurocranial defects. Specifically, the following three hypotheses will be tested: 1) Control peri-implant morphology, resorption environment, and strength concomitant to upward scaling of implant size to a level clinically useful for neurocranial repair (i.e., longest dimension form 1.5 to 4 cm); 2) Use standard clinical MR and CT to track prosthetic vascular ingrowth and ossification; and 3) Use composite solid/foam PPF/beta-TCP prosthetics, micro-machined with channels that promote vascular ingrowth through the solid core without loss of strength. To address these hypotheses, the investigators propose to determine the optimal design for PPF/beta-TCP composite implants seeded with bone marrow's osteoprogenitor cells and growth factors. They will collect in vitro strength before and during PPF/beta-TCP degradation, in vivo ossification and vascular ingrowth, and explant ex vivo strength and histology data.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013740-05
Application #
6691040
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Drummond, James
Project Start
2000-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2006-01-31
Support Year
5
Fiscal Year
2004
Total Cost
$394,590
Indirect Cost
Name
Case Western Reserve University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Wang, Martha O; Bracaglia, Laura; Thompson, Joshua A et al. (2016) Hydroxyapatite-doped alginate beads as scaffolds for the osteoblastic differentiation of mesenchymal stem cells. J Biomed Mater Res A 104:2325-33
Mishra, Ruchi; Bishop, Tyler; Valerio, Ian L et al. (2016) The potential impact of bone tissue engineering in the clinic. Regen Med 11:571-87
Bonda, David J; Manjila, Sunil; Selman, Warren R et al. (2015) The Recent Revolution in the Design and Manufacture of Cranial Implants: Modern Advancements and Future Directions. Neurosurgery 77:814-24; discussion 824
Breger, Joyce C; Yoon, ChangKyu; Xiao, Rui et al. (2015) Self-folding thermo-magnetically responsive soft microgrippers. ACS Appl Mater Interfaces 7:3398-405
Wang, Martha O; Piard, Charlotte M; Melchiorri, Anthony et al. (2015) Evaluating changes in structure and cytotoxicity during in vitro degradation of three-dimensional printed scaffolds. Tissue Eng Part A 21:1642-53
Wang, Martha O; Vorwald, Charlotte E; Dreher, Maureen L et al. (2015) Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering. Adv Mater 27:138-44
Wallace, Jonathan; Wang, Martha O; Thompson, Paul et al. (2014) Validating continuous digital light processing (cDLP) additive manufacturing accuracy and tissue engineering utility of a dye-initiator package. Biofabrication 6:015003
Song, Min Jae; Dean, David; Knothe Tate, Melissa L (2013) Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds. Biomaterials 34:5766-75
Wang, Martha O; Etheridge, Julie M; Thompson, Joshua A et al. (2013) Evaluation of the in vitro cytotoxicity of cross-linked biomaterials. Biomacromolecules 14:1321-9
Song, Min Jae; Brady-Kalnay, Susann M; McBride, Sara H et al. (2012) Mapping the mechanome of live stem cells using a novel method to measure local strain fields in situ at the fluid-cell interface. PLoS One 7:e43601

Showing the most recent 10 out of 27 publications