Skeletal muscle tissue is often required in reconstructive craniofacial surgery following trauma, resection due to cancer, or correction of genetic defects. The long-term goal of the applicants'research is to regenerate functional craniofacial skeletal muscle. While there has been significant success in the field to date in young animals with cell transplantation strategies, the environment in aged animals severely limits the potential of cells to drive regeneration. Further, the need to isolate and then transplat muscle stem cells greatly limits the clinical practicality of current muscle regeneration strategie. The specific hypothesis guiding this application is that biomaterials may be used to provide an environment conducive to the proliferation of both transplanted and host satellite cell recruited t the biomaterial, even in aged mice, and their participation in muscle regeneration. The hypothesis will be addressed with the following aims: (1) Develop and examine the ability of biomaterial vehicles to create a new microenvironment conducive to the proliferation and participation in regeneration of transplanted satellite cells, in young and aged mice. (2) Develop biomaterial vehicles capable of being externally actuated with magnetic fields, and examine their ability to allow cell release on-demand in order to enhance regeneration with transplanted satellite cells. (3) Develop biomaterials to recruit host satellite cells from the damaged muscle o aged mice, promote their proliferation within the device, and release the daughter cells on-demand to participate in muscle regeneration. The successful completion of these aims will lead to new strategies for the regeneration and return to function of damaged muscle tissue. This work will have significant applications in craniofacial reconstructive surgery involving the regeneration of small craniofacial muscles, and will likely apply to the regeneration of muscle throughout the body. The proposed studies will also lead to the development of new biomaterials that enable passive and active release of cells to drive regeneration, and an improved understanding of how environmental cues regulate muscle stem cell activation, proliferation, and participation in regeneration. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page

Public Health Relevance

Skeletal muscle tissue is often required in reconstructive craniofacial surgery following trauma, resection due to cancer, or correction of genetic defects. This project proposes a new approach to muscle regeneration, and specifically addresses the diminished regeneration ability seen in people with age. Success in these studies will provide an important step in translating tissue regeneration strategies out of the lab and into the clinic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE013349-12
Application #
8371909
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lumelsky, Nadya L
Project Start
2000-03-01
Project End
2017-03-31
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
12
Fiscal Year
2012
Total Cost
$428,932
Indirect Cost
$164,011
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Cezar, Christine A; Roche, Ellen T; Vandenburgh, Herman H et al. (2016) Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci U S A 113:1534-9
Koshy, Sandeep T; Desai, Rajiv M; Joly, Pascal et al. (2016) Click-Crosslinked Injectable Gelatin Hydrogels. Adv Healthc Mater 5:541-7
Kennedy, Stephen; Hu, Jennifer; Kearney, Cathal et al. (2016) Sequential release of nanoparticle payloads from ultrasonically burstable capsules. Biomaterials 75:91-101
Kwee, Brian J; Mooney, David J (2015) Manipulating the intersection of angiogenesis and inflammation. Ann Biomed Eng 43:628-40
Fusco, Stefano; Huang, Hen-Wei; Peyer, Kathrin E et al. (2015) Shape-switching microrobots for medical applications: the influence of shape in drug delivery and locomotion. ACS Appl Mater Interfaces 7:6803-11
Desai, Rajiv M; Koshy, Sandeep T; Hilderbrand, Scott A et al. (2015) Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry. Biomaterials 50:30-7
Cezar, Christine A; Mooney, David J (2015) Biomaterial-based delivery for skeletal muscle repair. Adv Drug Deliv Rev 84:188-97
Schmidt-Bleek, Katharina; Kwee, Brian J; Mooney, David J et al. (2015) Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis. Tissue Eng Part B Rev 21:354-64
Wang, Lin; Cao, Lan; Shansky, Janet et al. (2014) Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold. Mol Ther 22:1441-9
Kennedy, Stephen; Bencherif, Sidi; Norton, Daniel et al. (2014) Rapid and extensive collapse from electrically responsive macroporous hydrogels. Adv Healthc Mater 3:500-7

Showing the most recent 10 out of 42 publications