A tunable silk-alginate hydrogel scaffold for stem cell culture and transplantation.

One of the major challenges in regenerative medicine is the ability to recreate the stem cell niche, which is defined by its signaling molecules, the creation of cytokine gradients, and the modulation of matrix stiffness. A wide range of scaffolds has been developed in order to recapitulate the stem cell niche, among them hydrogels. This paper reports the development of a new silk-alginate based hydrogel with a focus on stem cell culture. This biocomposite allows to fine tune its elasticity during cell culture, addressing the importance of mechanotransduction during stem cell differentiation. The silk-alginate scaffold promotes adherence of mouse embryonic stem cells and cell survival upon transplantation. In addition, it has tunable stiffness as function of the silk-alginate ratio and the concentration of crosslinker--a characteristic that is very hard to accomplish in current hydrogels. The hydrogel and the presented results represents key steps on the way of creating artificial stem cell niche, opening up new paths in regenerative medicine.

[1]  Betül Çelebi,et al.  Human elastin-based recombinant biopolymers improve mesenchymal stem cell differentiation. , 2012, Macromolecular bioscience.

[2]  H. Blau,et al.  Self-renewal and expansion of single transplanted muscle stem cells , 2008, Nature.

[3]  Uwe Marx,et al.  Physical and biological properties of barium cross-linked alginate membranes. , 2007, Biomaterials.

[4]  J. Benoit,et al.  5-ASA loaded chitosan-Ca-alginate microparticles: Preparation and physicochemical characterization. , 2007, International journal of pharmaceutics.

[5]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[6]  D. Kaplan,et al.  Insoluble and flexible silk films containing glycerol. , 2010, Biomacromolecules.

[7]  M. Hines,et al.  The hematopoietic stem cell niche: what are we trying to replicate? , 2008 .

[8]  Krishnendu Roy,et al.  Biomaterials for stem cell differentiation. , 2008, Advanced drug delivery reviews.

[9]  S. Thrun,et al.  Substrate Elasticity Regulates Skeletal Muscle Stem Cell Self-Renewal in Culture , 2010, Science.

[10]  Jennifer M. Singelyn,et al.  Injectable Materials for the Treatment of Myocardial Infarction and Heart Failure: The Promise of Decellularized Matrices , 2010, Journal of cardiovascular translational research.

[11]  F. Prósper,et al.  Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling. , 2013, Journal of molecular and cellular cardiology.

[12]  Charlotte Collins,et al.  Direct Isolation of Satellite Cells for Skeletal Muscle Regeneration , 2005, Science.

[13]  Anthony Atala,et al.  Smart biomaterials design for tissue engineering and regenerative medicine. , 2007, Biomaterials.

[14]  T. Pan,et al.  Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model , 2011, PloS one.

[15]  E. Fuchs,et al.  Socializing with the Neighbors Stem Cells and Their Niche , 2004, Cell.

[16]  Barjor Gimi,et al.  Encapsulated cell grafts to treat cellular deficiencies and dysfunction. , 2011, Critical reviews in biomedical engineering.

[17]  Sean J. Morrison,et al.  Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life , 2008, Cell.

[18]  Mary Anne Wheeler,et al.  Stem , 1985 .

[19]  Jung‐Ho Yun,et al.  Effect of calcium ion (cross-linker) concentration on porosity, surface morphology and thermal behavior of calcium alginates prepared from algae (Undaria pinnatifida) , 2010 .

[20]  C. Murry,et al.  Engineered Human Cardiac Tissue , 2011, Pediatric Cardiology.

[21]  Pieter van Dokkum,et al.  The nature of , 2006 .

[22]  Dai Fukumura,et al.  In vivo imaging of tumors. , 2010, Cold Spring Harbor protocols.

[23]  David L Kaplan,et al.  Silk as a Biomaterial. , 2007, Progress in polymer science.

[24]  J. Mano,et al.  Polymer‐based microparticles in tissue engineering and regenerative medicine , 2011, Biotechnology progress.

[25]  David F. Williams.  On the nature of biomaterials. , 2009, Biomaterials.

[26]  Kumaraswamy Nanthakumar,et al.  Engineered heart tissue enables study of residual undifferentiated embryonic stem cell activity in a cardiac environment , 2011, Biotechnology and bioengineering.

[27]  M. Post,et al.  The muscle stem cell niche: regulation of satellite cells during regeneration. , 2008, Tissue engineering. Part B, Reviews.

[28]  Tze Chiun Lim,et al.  Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres , 2013, Nature Communications.

[29]  François Berthiaume,et al.  Tissue Engineering and Regenerative Medicine : History , Progress , and Challenges , 2013 .

[30]  Bonghee Lee,et al.  Induced pluripotent stem cells and personalized medicine: current progress and future perspectives , 2011, Anatomy & cell biology.