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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Lumelsky, Nadya L
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Harvard University
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Kennedy, Stephen; Bencherif, Sidi; Norton, Daniel et al. (2014) Rapid and extensive collapse from electrically responsive macroporous hydrogels. Adv Healthc Mater 3:500-7
Cezar, Christine A; Kennedy, Stephen M; Mehta, Manav et al. (2014) Biphasic ferrogels for triggered drug and cell delivery. Adv Healthc Mater 3:1869-76
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
Arany, Praveen R; Cho, Andrew; Hunt, Tristan D et al. (2014) Photoactivation of endogenous latent transforming growth factor-?1 directs dental stem cell differentiation for regeneration. Sci Transl Med 6:238ra69
Shvartsman, Dmitry; Storrie-White, Hannah; Lee, Kangwon et al. (2014) Sustained delivery of VEGF maintains innervation and promotes reperfusion in ischemic skeletal muscles via NGF/GDNF signaling. Mol Ther 22:1243-53
Darnell, Max C; Sun, Jeong-Yun; Mehta, Manav et al. (2013) Performance and biocompatibility of extremely tough alginate/polyacrylamide hydrogels. Biomaterials 34:8042-8
Lee, Kuen Yong; Mooney, David J (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37:106-126
Arany, P R; Mooney, D J (2011) At the edge of translation - materials to program cells for directed differentiation. Oral Dis 17:241-51
Borselli, Cristina; Cezar, Christine A; Shvartsman, Dymitri et al. (2011) The role of multifunctional delivery scaffold in the ability of cultured myoblasts to promote muscle regeneration. Biomaterials 32:8905-14
Borselli, Cristina; Storrie, Hannah; Benesch-Lee, Frank et al. (2010) Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci U S A 107:3287-92

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