The objective of this grant proposal is to develop a noninvasive method to implant polymers using photopolymerization. This allows solid hydrogels to be implanted without surgical intervention. Enough light is able to penetrate tissue, including skin, to trigger the photopolymerization of an injected liquid, polymer solution to a solid hydrogel. Further study of transdermal photopolymerization using alternative photoinitiating systems and wavelengths of light is proposed in order to increase depths at which implants can be photopolymerized. Photopolymerization will be applied to the tissue engineering of cartilage. Cartilage lacks the ability to regenerate and its loss by trauma, congenital abnormalities or tumors gives few options to the physician for replacement. Preliminary data has shown that chondrocytes survive encapsulation, injection and photopolymerization to form neocartilage. Important biological factors, including growth factors and adhesion peptides, will be incorporated into photopolymerizing hydrogels to determine if they can accelerate cartilage development and produce cartilage with biochemical and biomechanical properties similar to native cartilage. The tissue engineering of cartilage will be examined both in vitro and in vivo, in particular in an immune competent animal. The integration of photopolymerized tissue engineered cell/polymer implants with surrounding native cartilage is critical to the clinical application of tissue engineered cartilage and will be addressed. In conclusion, this proposal addresses methods for noninvasive polymer implantation, which applied to cartilage tissue engineering, would provide physicians with a significant alternative to cartilage replacement for craniofacial reconstruction and orthopedic surgery. The specific goals of this proposal include: (1) development of a highly efficient, biocompatible transdermal or transtissue photopolymerization system for noninvasive polymer implantation; (2) development of an injectable tissue engineered cartilage using transdermal photopolymerization; (3) increase cellular biocompatibility of the polymer hydrogel through the incorporation of bioactive peptides and proteins; and (4) integration of tissue engineered and native cartilage for the correction of cartilage defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013023-05
Application #
6516531
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M2))
Program Officer
Kousvelari, Eleni
Project Start
1998-09-15
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$327,000
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Tong, Zhixiang; Martyn, Keir; Yang, Andy et al. (2018) Towards a defined ECM and small molecule based monolayer culture system for the expansion of mouse and human intestinal stem cells. Biomaterials 154:60-73
Mead, Benjamin E; Ordovas-Montanes, Jose; Braun, Alexandra P et al. (2018) Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol 16:62
McLean, Will J; Yin, Xiaolei; Lu, Lin et al. (2017) Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells. Cell Rep 18:1917-1929
Doloff, Joshua C; Veiseh, Omid; Vegas, Arturo J et al. (2017) Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat Mater 16:671-680
Vegas, Arturo J; Veiseh, Omid; Gürtler, Mads et al. (2016) Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 22:306-11
Vegas, Arturo J; Veiseh, Omid; Doloff, Joshua C et al. (2016) Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 34:345-52
Langer, Robert; Vacanti, Joseph (2016) Advances in tissue engineering. J Pediatr Surg 51:8-12
Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia et al. (2016) Engineering Stem Cell Organoids. Cell Stem Cell 18:25-38
Jhunjhunwala, Siddharth; Alvarez, David; Aresta-DaSilva, Stephanie et al. (2016) Frontline Science: Splenic progenitors aid in maintaining high neutrophil numbers at sites of sterile chronic inflammation. J Leukoc Biol 100:253-60
Lim, Dong-Kwon; Wylie, Ryan G; Langer, Robert et al. (2016) Selective binding of C-6 OH sulfated hyaluronic acid to the angiogenic isoform of VEGF(165). Biomaterials 77:130-138

Showing the most recent 10 out of 76 publications