Stem cell-mediated functionalization of titanium implants
Prosthetic implants are used daily to treat edentulous people and to restore mobility in patients affected by skeletal defects. Titanium (Ti) is the material of choice in prosthetics, because it can form a stable bond with the surrounding bone following implantation—a process known as osseointegration. Yet, full integration of prosthetic implants takes time, and fails in clinical situations characterized by limited bone quantity and/or compromised regenerative capacity, and in at-risk patients. Intense research efforts are thus made to develop new implants that are cost-effective, safe, and suited to every patient in each clinical situation. In this study, we tested the possibility to functionalize Ti implants using stem cells. Human induced pluripotent stem cell-derived mesenchymal progenitor (iPSC-MP) cells were cultured on Ti model disks for 2 weeks in osteogenic conditions. Samples were then treated using four different decellularization methods to wash off the cells and expose the matrix. The functionalized disks were finally sterilized and seeded with fresh human iPSC-MP cells to study the effect of stem cell-mediated surface functionalization on cell behavior. The results show that different decellularization methods produce diverse surface modifications, and that these modifications promote proliferation of human iPSC-MP cells, affect the expression of genes involved in development and differentiation, and stimulate the release of alkaline phosphatase. Cell-mediated functionalization represents an attractive strategy to modify the surface of prosthetic implants with cues of biological relevance, and opens unprecedented possibilities for development of new devices with enhanced therapeutic potential.
We thank Dr. Daniel Paull, Dr. Cecile Terrenoire, Dr. Ana Sevilla and Dr. TC Ramaraj for assistance with Nanostring analysis, and Dr. Michael Yaffe for proofreading the manuscript. We also thank the staff at the City University of New York’s Advanced Science Research Center for their help with SEM and EDS analysis. Funding was provided by the New York Stem Cell Foundation Research Institute (GMdP), The Ralph and Ricky Lauren Family Foundation (GMdP) and by the EU FP7 NMP Biodesign program (HE).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 1.Global Orthopedic Biomaterial Market Research Report - Forecast To 2022. Cooked Research Reports. ID: MRFR/HC/0101-CRR, December, 2015:296 pages.Google Scholar
- 4.Elias CN, et al. Biomedical applications of titanium and its alloys. J Metals. 2008;60(3):46–9.Google Scholar
- 5.Albrektsson T, et al. Osteoinduction, osteoconduction and osseointegration. The use of bone substitutes in spine surgery. Eur Spine J. 2001;10(Suppl 2):S96–101.Google Scholar
- 8.Jonge L, et al. Organic–inorganic surface modifications for titanium implant surfaces. Pharm Res Pharm Res. 2008;25(10):2357–69.Google Scholar
- 20.Fischer U, et al. Transforming growth factor beta1 immobilized adsorptively on Ti6Al4V and collagen type I coated Ti6Al4V maintains its biological activity. Biomaterials. 2003;24(2631):2641.Google Scholar
- 25.Gilbert TW, et al. Decellularization of tissues and organs. Biomaterials. 2006;27(19):3675–83.Google Scholar
- 37.Maghsoudlou P, et al. A decellularization methodology for the production of a natural acellular intestinal matrix. J Vis Exp 2013;(80):e50658.Google Scholar