Review of collagen I hydrogels for bioengineered tissue microenvironments: characterization of mechanics, structure, and transport.

Type I collagen hydrogels have been used successfully as three-dimensional substrates for cell culture and have shown promise as scaffolds for engineered tissues and tumors. A critical step in the development of collagen hydrogels as viable tissue mimics is quantitative characterization of hydrogel properties and their correlation with fabrication parameters, which enables hydrogels to be tuned to match specific tissues or fulfill engineering requirements. A significant body of work has been devoted to characterization of collagen I hydrogels; however, due to the breadth of materials and techniques used for characterization, published data are often disjoint and hence their utility to the community is reduced. This review aims to determine the parameter space covered by existing data and identify key gaps in the literature so that future characterization and use of collagen I hydrogels for research can be most efficiently conducted. This review is divided into three sections: (1) relevant fabrication parameters are introduced and several of the most popular methods of controlling and regulating them are described, (2) hydrogel properties most relevant for tissue engineering are presented and discussed along with their characterization techniques, (3) the state of collagen I hydrogel characterization is recapitulated and future directions are proposed. Ultimately, this review can serve as a resource for selection of fabrication parameters and material characterization methodologies in order to increase the usefulness of future collagen-hydrogel-based characterization studies and tissue engineering experiments.

[1]  Kazuo Tanishita,et al.  Effects of the mechanical properties of collagen gel on the in vitro formation of microvessel networks by endothelial cells. , 2007, Tissue engineering.

[2]  Paul A. Janmey,et al.  Soft biological materials and their impact on cell function. , 2007, Soft matter.

[3]  Jacco van Rheenen,et al.  Collagen-based cell migration models in vitro and in vivo. , 2009, Seminars in cell & developmental biology.

[4]  D. Torchia,et al.  Preparation of intact monomeric collagen from rat tail tendon and skin and the structure of the nonhelical ends in solution. , 1976, The Journal of biological chemistry.

[5]  Cynthia A. Reinhart-King,et al.  A Balance of Substrate Mechanics and Matrix Chemistry Regulates Endothelial Cell Network Assembly , 2008 .

[6]  P. Friedl,et al.  Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44. , 1997, Cancer research.

[7]  Clair Baldock,et al.  Collagens at a glance , 2007, Journal of Cell Science.

[8]  Roger D. Kamm,et al.  Tumor cell migration in complex microenvironments , 2012, Cellular and Molecular Life Sciences.

[9]  M. Yoder,et al.  Collagen-polymer guidance of vessel network formation and stabilization by endothelial colony forming cells in vitro. , 2013, Macromolecular bioscience.

[10]  E. Stites,et al.  Polymerization and matrix physical properties as important design considerations for soluble collagen formulations. , 2010, Biopolymers.

[11]  Laxminarayanan Krishnan,et al.  Design and application of a test system for viscoelastic characterization of collagen gels. , 2004, Tissue engineering.

[12]  M. Dembo,et al.  Cell movement is guided by the rigidity of the substrate. , 2000, Biophysical journal.

[13]  Z. Werb,et al.  The extracellular matrix: A dynamic niche in cancer progression , 2012, The Journal of cell biology.

[14]  L. Bonassar,et al.  Dense type I collagen matrices that support cellular remodeling and microfabrication for studies of tumor angiogenesis and vasculogenesis in vitro. , 2010, Biomaterials.

[15]  P. Sikorski,et al.  Physical and chemical modifications of collagen gels: Impact on diffusion , 2008, Biopolymers.

[16]  P. Panine,et al.  Fibrillogenesis in dense collagen solutions: a physicochemical study. , 2008, Journal of molecular biology.

[17]  S. Arribas,et al.  A simple dot-blot–Sirius red-based assay for collagen quantification , 2013, Analytical and Bioanalytical Chemistry.

[18]  P. Koumoutsakos,et al.  The Fluid Mechanics of Cancer and Its Therapy , 2013 .

[19]  Shawn P. Carey,et al.  Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture. , 2012, Biomaterials.

[20]  K. Piez,et al.  Collagen fibril formation. Optimal in vitro conditions and preliminary kinetic results. , 1978, The Journal of biological chemistry.

[21]  Enrico Gratton,et al.  Image correlation spectroscopy of multiphoton images correlates with collagen mechanical properties. , 2008, Biophysical journal.

[22]  C. Rueden,et al.  Bmc Medicine Collagen Density Promotes Mammary Tumor Initiation and Progression , 2022 .

[23]  Tobias Schmelzle,et al.  Engineering tumors with 3D scaffolds , 2007, Nature Methods.

[24]  E. De Rosa,et al.  Effects of fibronectin and laminin on structural, mechanical and transport properties of 3D collageneous network , 2007, Journal of materials science. Materials in medicine.

[25]  R. Kamm,et al.  Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function , 2012, Proceedings of the National Academy of Sciences.

[26]  Kyle J. Lampe,et al.  Defining and designing polymers and hydrogels for neural tissue engineering , 2012, Neuroscience Research.

[27]  R. Kamm,et al.  In Vitro Model of Tumor Cell Extravasation , 2013, PloS one.

[28]  J. Taylor,et al.  Epidermal growth factor: high and low molecular weight forms. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M Helen Grant,et al.  The mechanical strength of collagen gels containing glycosaminoglycans and populated with fibroblasts. , 2009, Journal of biomedical materials research. Part A.

[30]  D. Kaplan,et al.  Guide to collagen characterization for biomaterial studies. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[31]  J P Stegemann,et al.  Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales. , 2014, Acta biomaterialia.

[32]  Cynthia A. Reinhart-King,et al.  Tensional homeostasis and the malignant phenotype. , 2005, Cancer cell.

[33]  Frank Baaijens,et al.  Modeling collagen remodeling. , 2010, Journal of biomechanics.

[34]  V. Barocas,et al.  Mechanical and Structural Contribution of Non-Fibrillar Matrix in Uniaxial Tension: A Collagen-Agarose Co-Gel Model , 2011, Annals of Biomedical Engineering.

[35]  Samuel K Sia,et al.  Dynamic Hydrogels: Switching of 3D Microenvironments Using Two‐Component Naturally Derived Extracellular Matrices , 2010, Advanced materials.

[36]  L. Kaufman,et al.  Pore size variable type I collagen gels and their interaction with glioma cells. , 2010, Biomaterials.

[37]  J. P. Robinson,et al.  Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. , 2000, Biopolymers.

[38]  Yujie Ma,et al.  25th Anniversary Article: Designer Hydrogels for Cell Cultures: A Materials Selection Guide , 2014, Advanced materials.

[39]  R. Kamm,et al.  Cell migration into scaffolds under co-culture conditions in a microfluidic platform. , 2009, Lab on a chip.

[40]  Kevin W Eliceiri,et al.  Control of 3-dimensional collagen matrix polymerization for reproducible human mammary fibroblast cell culture in microfluidic devices. , 2009, Biomaterials.

[41]  Jong Hwan Sung,et al.  Microtechnology for Mimicking In Vivo Tissue Environment , 2012, Annals of Biomedical Engineering.

[42]  K. Piez,et al.  Collagen fibril formation in vitro. The role of the nonhelical terminal regions. , 1979, The Journal of biological chemistry.

[43]  R. Wells.  The role of matrix stiffness in regulating cell behavior , 2008, Hepatology.

[44]  Mohamed Al-Rubeai,et al.  Monitoring pH and dissolved oxygen in mammalian cell culture using optical sensors , 2008, Cytotechnology.

[45]  A. Panitch,et al.  Influence of chondroitin sulfate on collagen gel structure and mechanical properties at physiologically relevant levels. , 2008, Biopolymers.

[46]  Joel Wise,et al.  Human fibroblast migration in three-dimensional collagen gel in response to noninvasive electrical stimulus. I. Characterization of induced three-dimensional cell movement. , 2004, Tissue engineering.

[47]  Klod Kokini,et al.  Fibril microstructure affects strain transmission within collagen extracellular matrices. , 2009, Journal of biomechanical engineering.

[48]  Eric A Nauman,et al.  Mechanical characterization of collagen fibers and scaffolds for tissue engineering. , 2003, Biomaterials.

[49]  Amit Jain,et al.  Probing cellular mechanobiology in three-dimensional culture with collagen-agarose matrices. , 2010, Biomaterials.

[50]  M. Ingram,et al.  Tissue engineered tumor models , 2010, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[51]  P. Rajagopalan,et al.  Nano-Indentation Device for Investigating the Mechanics of Compliant Materials , 2013 .

[52]  Joe Tien,et al.  Plasma expanders stabilize human microvessels in microfluidic scaffolds. , 2012, Journal of biomedical materials research. Part A.

[53]  W. Saltzman,et al.  Neutrophil motility in extracellular matrix gels: mesh size and adhesion affect speed of migration. , 1997, Biophysical journal.

[54]  Elliot L Chaikof,et al.  Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges , 2011, Cardiovascular engineering and technology.

[55]  William J. Polacheck,et al.  Interstitial flow influences direction of tumor cell migration through competing mechanisms , 2011, Proceedings of the National Academy of Sciences.

[56]  Lance L. Munn,et al.  Fluid forces control endothelial sprouting , 2011, Proceedings of the National Academy of Sciences.

[57]  L. Petzold,et al.  Rheology of reconstituted type I collagen gel in confined compression , 1997 .

[58]  Ming-Zher Poh,et al.  Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. , 2010, Biophysical journal.

[59]  Achim Goepferich,et al.  Rational design of hydrogels for tissue engineering: impact of physical factors on cell behavior. , 2007, Biomaterials.

[60]  Peter Dubruel,et al.  A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. , 2012, Biomaterials.

[61]  Shulamit Levenberg,et al.  Effect of scaffold stiffness on myoblast differentiation. , 2009, Tissue engineering. Part A.

[62]  Melody A. Swartz,et al.  Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro , 2005, Journal of Cell Science.

[63]  R T Tranquillo,et al.  Effects of pdgf-bb on rat dermal fibroblast behavior in mechanically stressed and unstressed collagen and fibrin gels. , 2001, Experimental cell research.

[64]  Steven C George,et al.  Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy. , 2007, Biophysical journal.

[65]  Victor H Barocas,et al.  Microstructural mechanics of collagen gels in confined compression: poroelasticity, viscoelasticity, and collapse. , 2004, Journal of biomechanical engineering.

[66]  F. Guilak,et al.  Diffusional anisotropy in collagenous tissues: fluorescence imaging of continuous point photobleaching. , 2006, Biophysical journal.

[67]  T. Crouzier,et al.  A material's point of view on recent developments of polymeric biomaterials: control of mechanical and biochemical properties. , 2011, Journal of materials chemistry.

[68]  François Berthod,et al.  Collagen-Based Biomaterials for Tissue Engineering Applications , 2010, Materials.

[69]  Kristi S Anseth,et al.  Mechanical Properties of Cellularly Responsive Hydrogels and Their Experimental Determination , 2010, Advanced materials.

[70]  M. Yoder,et al.  Collagen oligomers modulate physical and biological properties of three-dimensional self-assembled matrices. , 2011, Biopolymers.

[71]  E. Bröcker,et al.  Migration of dendritic cells within 3‐D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines , 2000, Journal of leukocyte biology.

[72]  Z. Werb,et al.  Extracellular matrix degradation and remodeling in development and disease. , 2011, Cold Spring Harbor perspectives in biology.

[73]  W. Saltzman,et al.  Three‐dimensional Cell Cultures Mimic Tissues a , 1992, Annals of the New York Academy of Sciences.

[74]  R K Jain,et al.  Fluorescence photobleaching with spatial Fourier analysis: measurement of diffusion in light-scattering media. , 1993, Biophysical journal.

[75]  S. Seiffert,et al.  Systematic evaluation of FRAP experiments performed in a confocal laser scanning microscope , 2005, Journal of microscopy.

[76]  D. Lauffenburger,et al.  Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[77]  H O Ho,et al.  Characterization of collagen gel solutions and collagen matrices for cell culture. , 2001, Biomaterials.

[78]  M. Marotta,et al.  Sensitive spectrophotometric method for the quantitative estimation of collagen. , 1985, Analytical biochemistry.

[79]  David I Shreiber,et al.  Neurite growth in 3D collagen gels with gradients of mechanical properties , 2009, Biotechnology and bioengineering.

[80]  Saroja Ramanujan,et al.  Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. , 2002, Biophysical journal.

[81]  Jui-Sheng Sun,et al.  Epidermal morphogenesis in an in-vitro model using a fibroblasts-embedded collagen scaffold. , 2005, Journal of biomedical science.

[82]  A. Hoffman.  Hydrogels for Biomedical Applications , 2001, Advanced drug delivery reviews.

[83]  D. Hammer,et al.  Assembly of Human Umbilical Vein Endothelial Cells on Compliant Hydrogels , 2010, Cellular and molecular bioengineering.

[84]  Markus J Buehler,et al.  A review of combined experimental and computational procedures for assessing biopolymer structure-process-property relationships. , 2012, Biomaterials.

[85]  Cornelia Altenbuchner,et al.  Crosslinking and mechanical properties significantly influence cell attachment, proliferation, and migration within collagen glycosaminoglycan scaffolds. , 2011, Tissue engineering. Part A.

[86]  Joe Tien,et al.  Formation of perfused, functional microvascular tubes in vitro. , 2006, Microvascular research.

[87]  Mark W. Tibbitt,et al.  Hydrogels as extracellular matrix mimics for 3D cell culture. , 2009, Biotechnology and bioengineering.

[88]  K J Gooch,et al.  The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro. , 2004, Experimental cell research.

[89]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[90]  Marissa Nichole Rylander,et al.  Microfluidic culture models to study the hydrodynamics of tumor progression and therapeutic response , 2013, Biotechnology and bioengineering.

[91]  M. Swartz,et al.  Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. , 2003, American journal of physiology. Heart and circulatory physiology.

[92]  A Rajaram,et al.  Influence of different crosslinking treatments on the physical properties of collagen membranes. , 2003, Biomaterials.

[93]  L. Germain,et al.  Comparative study of bovine, porcine and avian collagens for the production of a tissue engineered dermis. , 2011, Acta biomaterialia.

[94]  F. Grinnell,et al.  The differential regulation of cell motile activity through matrix stiffness and porosity in three dimensional collagen matrices. , 2010, Biomaterials.

[95]  Peter Friedl,et al.  Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. , 2003, Blood.

[96]  E. J. Miller,et al.  Preparation and characterization of the different types of collagen. , 1982, Methods in enzymology.

[97]  J. Hubbell,et al.  Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. , 2005, Biophysical journal.

[98]  Ulrike Haessler,et al.  Migration dynamics of breast cancer cells in a tunable 3D interstitial flow chamber. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[99]  P. Vlachos,et al.  Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization. , 2014, Tissue engineering. Part C, Methods.

[100]  Diego Mantovani,et al.  Tailoring Mechanical Properties of Collagen-Based Scaffolds for Vascular Tissue Engineering: The Effects of pH, Temperature and Ionic Strength on Gelation , 2010 .