This Bioengineering Research Partnership proposal is submitted by a multidisciplinary collaboration of scientists in the University of California (UC) system. The lead institution is Lawrence Berkeley National Laboratory, with component groups at UC Berkeley and UC San Francisco campuses. This BRP brings together expertise in materials sciences, chemistry, biology, and dental/medical science to begin the translational phase of this project. Our goal is to develop biomaterials for tissue engineering that will eliminate surgical risks and allow immediate return of function. We will develop and test new implant materials that can support mesenchymal stem cells and bone regeneration, by combining biomimetics with radically new design philosophies that consider anatomic and functional needs, customizing the scaffold to the skeletal defect. The ultimate goal is to develop a range of osteoinductive implant materials or scaffolds that function harmoniously with the surrounding native tissue. This long-term goal will provide materials for optimal repair of craniofacial and orthopedic skeletal defects that would otherwise require a bone graft from a second surgical site. First, hydrogels with varying mechanical responses and biodegradation rates will be synthesized. Different functional groups will be added to the hydrogel structure to template biomimetic mineralization of apatite and other biominerals-and to promote cell adhesion. Second, these materials, and others already developed for our current grant, will be used in the preparation of scaffolds with various compositions and architectures, including anatomically-inspired designs that considers both cortical and cancellous functional anatomy made by robocasting (3-D printing) and lamellar structures prepared using a novel technology developed in our laboratory based on freeze-casting of suspensions. Third, the addition of diverse functional capabilities to these porous scaffolds will be systematically explored. Materials deemed to display optimal mechanical responses will be tested in cell culture and then in vivo in mice, using standardized bone formation assays that allow assessment of the rate and extent of new bone formation. Based on these results, we will select scaffolds that have the greatest translational potential. These will be tested in combination with autologous multipotent stem cells for the ability to promote bone formation in established medium-sized (rabbit) and large-sized (mini-pig) animal models utilizing a consistent protocol of biomechanical and biological assays that will also serve to asses key biological process that determine scaffold integration. Successful completion of these studies will result in the identification of new materials suitable for testing for the repair of craniofacial and orthopedic skeletal defects in humans. The present standard of care for such defects may be altered to eliminate bone grafts, decrease risks to patients, improve quality of life, and increase the armamentarium of the clinician.

Public Health Relevance

The demand for biomaterials to assist or replace organ functions is rapidly increasing. Every year, more than one million patients in the United States with skeletal defects require bone graft procedures. This application will develop novel biomaterials for optimal repair of craniofacial and orthopedic skeletal defects that would otherwise require a bone graft from a second surgical site. Improvement of implants will result in improved health and quality of life for the millions of people who will need implants in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015633-10
Application #
8510621
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
2003-08-04
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
10
Fiscal Year
2013
Total Cost
$1,174,970
Indirect Cost
$378,484
Name
Lawrence Berkeley National Laboratory
Department
Chemistry
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Zimmermann, Elizabeth A; Gludovatz, Bernd; Schaible, Eric et al. (2014) Fracture resistance of human cortical bone across multiple length-scales at physiological strain rates. Biomaterials 35:5472-81
Amugongo, Sarah K; Yao, Wei; Jia, Junjing et al. (2014) Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats. Bone 67:257-68
Amugongo, S K; Yao, W; Jia, J et al. (2014) Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass. Osteoporos Int 25:1735-50
Snyder, Jessica E; Hunger, Philipp M; Wang, Chengyang et al. (2014) Combined multi-nozzle deposition and freeze casting process to superimpose two porous networks for hierarchical three-dimensional microenvironment. Biofabrication 6:015007
Wang, Jianglin; Yang, Mingying; Zhu, Ye et al. (2014) Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds. Adv Mater 26:4961-6
Hunger, Philipp M; Donius, Amalie E; Wegst, Ulrike G K (2013) Structure-property-processing correlations in freeze-cast composite scaffolds. Acta Biomater 9:6338-48
Huang, Jijun; Ten, Elena; Liu, Gao et al. (2013) Biocomposites of pHEMA with HA/ýý -TCP (60/40) for bone tissue engineering: Swelling, hydrolytic degradation, and in vitro behavior. Polymer (Guildf) 54:1197-1207
Genet, Martin; Houmard, Manuel; Eslava, Salvador et al. (2013) A two-scale Weibull approach to the failure of porous ceramic structures made by robocasting: possibilities and limits. J Eur Ceram Soc 33:679-688
Hunger, Philipp M; Donius, Amalie E; Wegst, Ulrike G K (2013) Platelets self-assemble into porous nacre during freeze casting. J Mech Behav Biomed Mater 19:87-93
Saiz, Eduardo; Zimmermann, Elizabeth A; Lee, Janice S et al. (2013) Perspectives on the role of nanotechnology in bone tissue engineering. Dent Mater 29:103-15

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