Hydrogel Composite Materials for Tissue Engineering Scaffolds

Hydrogels are appealing for biomaterials applications due to their compositional similarity with highly hydrated natural biological tissues. However, for structurally demanding tissue engineering applications, hydrogel use is limited by poor mechanical properties. Here, composite materials approaches are considered for improving hydrogel properties while attempting to more closely mimic natural biological tissue structures. A variety of composite material microstructures is explored, based on multiple hydrogel constituents, particle reinforcement, electrospun nanometer to micrometer diameter polymer fibers with single and multiple fiber networks, and combinations of these approaches to form fully three-dimensional fiber-reinforced hydrogels. Natural and synthetic polymers are examined for formation of a range of scaffolds and across a range of engineered tissue applications. Following a discussion of the design and fabrication of composite scaffolds, interactions between living biological cells and composite scaffolds are considered across the full life cycle of tissue engineering from scaffold fabrication to in vivo use. We conclude with a summary of progress in this area to date and make recommendations for continuing research and for advanced hydrogel scaffold development.

[1]  Jae-Do Nam,et al.  Electrospun dual-porosity structure and biodegradation morphology of Montmorillonite reinforced PLLA nanocomposite scaffolds. , 2005, Biomaterials.

[2]  T. Kurokawa,et al.  Effect of polymer entanglement on the toughening of double network hydrogels. , 2005, The journal of physical chemistry. B.

[3]  Guoping Chen,et al.  The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness. , 2003, Journal of biomedical materials research. Part A.

[4]  J. Winter,et al.  Cell Attachment to Hydrogel-Electrospun Fiber Mat Composite Materials , 2012, Journal of functional biomaterials.

[5]  S. Sakai,et al.  Reinforcement of porous alginate scaffolds by incorporating electrospun fibres , 2008, Biomedical materials.

[6]  J. Alford,et al.  Cartilage Restoration, Part 2: Techniques, Outcomes, and Future Directions , 2005, The American journal of sports medicine.

[7]  Lesley-Anne Turner,et al.  State of the art composites comprising electrospun fibres coupled with hydrogels: a review. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[8]  E. Zussman,et al.  Hydrogel Reinforced by Short Albumin Fibers: Mechanical Characterization and Assessment of Biocompatibility , 2013 .

[9]  A. Clark,et al.  Structural and mechanical properties of agar/gelatin co-gels. Small-deformation studies , 1983 .

[10]  Jason A Burdick,et al.  Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. , 2002, Biomaterials.

[11]  M. Ashby,et al.  Cellular solids: Structure & properties , 1988 .

[12]  D. Cho,et al.  Improving mechanical properties of alginate hydrogel by reinforcement with ethanol treated polycaprolactone nanofibers , 2013 .

[13]  R Langer,et al.  A biodegradable composite scaffold for cell transplantation , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[14]  Won Ho Park,et al.  Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. , 2004, Biomaterials.

[15]  M. Detamore,et al.  Biomimetic method for combining the nucleus pulposus and annulus fibrosus for intervertebral disc tissue engineering , 2011, Journal of tissue engineering and regenerative medicine.

[16]  Christopher S. Chen,et al.  Engineering biomaterials to control cell function , 2005 .

[17]  Nandan L Nerurkar,et al.  Engineered Disc-Like Angle-Ply Structures for Intervertebral Disc Replacement , 2010, Spine.

[18]  S. Agarwal,et al.  Use of electrospinning technique for biomedical applications , 2008 .

[19]  Joachim Aigner,et al.  Alginate as a chondrocyte-delivery substance in combination with a non-woven scaffold for cartilage tissue engineering. , 2002, Biomaterials.

[20]  D. Lim,et al.  Cell infiltration and growth in a low density, uncompressed three-dimensional electrospun nanofibrous scaffold. , 2011, Biomaterials.

[21]  Farshid Guilak,et al.  Composite scaffolds for cartilage tissue engineering. , 2008, Biorheology.

[22]  Gabriela A Silva,et al.  Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. , 2007, Advanced drug delivery reviews.

[23]  S. Madihally,et al.  A multilayered scaffold of a chitosan and gelatin hydrogel supported by a PCL core for cardiac tissue engineering. , 2013, Acta biomaterialia.

[24]  M. Oyen,et al.  Electrospun Fiber - Hydrogel Composites for Nucleus Pulposus Tissue Engineering , 2012 .

[25]  B. Baroli,et al.  Hydrogels for tissue engineering and delivery of tissue-inducing substances. , 2007, Journal of pharmaceutical sciences.

[26]  J. Andrade Hydrogels for medical and related applications , 1976 .

[27]  Wan-Ju Li,et al.  Chondrocyte phenotype in engineered fibrous matrix is regulated by fiber size. , 2006, Tissue engineering.

[28]  V. B. Konkimalla,et al.  Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Seeram Ramakrishna,et al.  Electrospinning and mechanical characterization of gelatin nanofibers , 2004 .

[30]  Julian H. George,et al.  Exploring and Engineering the Cell Surface Interface , 2005, Science.

[31]  Paolo A. Netti,et al.  Dynamic-mechanical properties of a novel composite intervertebral disc prosthesis , 2007, Journal of materials science. Materials in medicine.

[32]  Esmaiel Jabbari,et al.  Material properties and osteogenic differentiation of marrow stromal cells on fiber-reinforced laminated hydrogel nanocomposites. , 2010, Acta biomaterialia.

[33]  Toyoichi Tanaka,et al.  Friction coefficient of polymer networks of gels , 1991 .

[34]  Z. Suo,et al.  Highly stretchable and tough hydrogels , 2012, Nature.

[35]  Cato T Laurencin,et al.  Electrospun nanofibrous structure: a novel scaffold for tissue engineering. , 2002, Journal of biomedical materials research.

[36]  Horst A von Recum,et al.  Electrospinning: applications in drug delivery and tissue engineering. , 2008, Biomaterials.

[37]  K. Anseth,et al.  Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. , 2008, Nature materials.

[38]  Nicole E. Zander,et al.  Electrospun polycaprolactone scaffolds with tailored porosity using two approaches for enhanced cellular infiltration , 2012, Journal of Materials Science: Materials in Medicine.

[39]  Ross A. Marklein,et al.  The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. , 2008, Biomaterials.

[40]  S. Kurtz,et al.  Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. , 2007, The Journal of bone and joint surgery. American volume.

[41]  G. Julius Vancso,et al.  Mechanical Properties of a Single Electrospun Fiber and its Structures , 2005 .

[42]  Kristi S. Anseth,et al.  Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel , 2000 .

[43]  M. Oyen,et al.  Branching toughens fibrous networks. , 2012, Journal of the mechanical behavior of biomedical materials.

[44]  L. Bonassar,et al.  Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. , 2006, Biomaterials.

[45]  Ld Wright,et al.  PDLA/PLLA and PDLA/PCL nanofibers with a chitosan‐based hydrogel in composite scaffolds for tissue engineered cartilage , 2014, Journal of tissue engineering and regenerative medicine.

[46]  Matthew Gibson,et al.  Biomimetics of the Extracellular Matrix: An Integrated Three-Dimensional Fiber-Hydrogel Composite for Cartilage Tissue Engineering. , 2011, Smart structures and systems.

[47]  Haiyang Huang,et al.  Identification of the haematopoietic stem cell niche and control of the niche size , 2003, Nature.

[48]  U. Stachewicz,et al.  Stress delocalization in crack tolerant electrospun nanofiber networks. , 2011, ACS applied materials & interfaces.

[49]  D. G. T. Strange,et al.  Composite hydrogels for nucleus pulposus tissue engineering. , 2012, Journal of the mechanical behavior of biomedical materials.

[50]  K. Lafferty,et al.  The Origin and Mechanism of the Allograft Reaction , 1977, Immunological reviews.

[51]  R. Reis,et al.  Development of nanofiber-reinforced hydrogel scaffolds for nucleus pulposus regeneration by a combination of electrospinning and spraying technique , 2013 .

[52]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[53]  Dietmar W Hutmacher,et al.  Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs. , 2008, Biomacromolecules.

[54]  J. Winter,et al.  Hydrogel-electrospun fiber composite materials for hydrophilic protein release. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[55]  Kwok Yeung Tsang,et al.  The developmental roles of the extracellular matrix: beyond structure to regulation , 2009, Cell and Tissue Research.

[56]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[57]  J. A. Hubbell,et al.  Cell‐Responsive Synthetic Hydrogels , 2003 .

[58]  Liwei Lin,et al.  Near-field electrospinning. , 2006, Nano letters.

[59]  Takehisa Matsuda,et al.  Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. , 2005, Biomaterials.

[60]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[61]  Suwan N Jayasinghe,et al.  Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. , 2006, Biomacromolecules.

[62]  Farshid Guilak,et al.  A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage. , 2007, Nature materials.

[63]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[64]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[65]  P. R. Chatterji Interpenetrating hydrogel networks. I. The gelatin–polyacrylamide system† , 1990 .

[66]  T. Lim,et al.  An Introduction to Electrospinning and Nanofibers , 2005 .

[67]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[68]  David G Simpson,et al.  Electrospinning of collagen nanofibers. , 2002, Biomacromolecules.

[69]  Brendon M. Baker,et al.  Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration , 2012, Cell and Tissue Research.

[70]  A. Steckl,et al.  Versatile Core-Sheath Biofibers using Coaxial Electrospinning , 2008 .

[71]  K. Healy,et al.  Synthesis and characterization of injectable poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links. , 2003, Biomacromolecules.

[72]  Dietmar W Hutmacher,et al.  The three-dimensional vascularization of growth factor-releasing hybrid scaffold of poly (epsilon-caprolactone)/collagen fibers and hyaluronic acid hydrogel. , 2011, Biomaterials.

[73]  Michael S Sacks,et al.  Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy. , 2006, Biomaterials.

[74]  Miqin Zhang,et al.  Alginate‐Based Nanofibrous Scaffolds: Structural, Mechanical, and Biological Properties , 2006 .

[75]  P. Gatenholm,et al.  Electrospinning of highly porous scaffolds for cartilage regeneration. , 2008, Biomacromolecules.

[76]  Linheng Li,et al.  The stem cell niches in bone. , 2006, The Journal of clinical investigation.

[77]  A. Boccaccini,et al.  Simple fabrication technique for multilayered stratified composite scaffolds suitable for interface tissue engineering , 2012 .

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

[79]  Banwart Jc,et al.  Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. , 1995 .

[80]  T. Kurokawa,et al.  Determination of fracture energy of high strength double network hydrogels. , 2005, The journal of physical chemistry. B.

[81]  Alexander Huber,et al.  Mechanical properties and in vivo behavior of a biodegradable synthetic polymer microfiber-extracellular matrix hydrogel biohybrid scaffold. , 2011, Biomaterials.

[82]  Dietmar W. Hutmacher,et al.  Design, fabrication and characterization of PCL electrospun scaffolds—a review , 2011 .

[83]  J. Feijen,et al.  Mechanical properties of single electrospun collagen type I fibers. , 2008, Biomaterials.

[84]  S. Ramakrishna,et al.  Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts. , 2005, Biomacromolecules.

[85]  K. Lee,et al.  Highly porous three-dimensional poly(lactide-co-glycolide) (PLGA) microfibrous scaffold prepared by electrospinning method: A comparison study with other PLGA type scaffolds on its biological evaluation , 2012, Fibers and Polymers.

[86]  Michael S Sacks,et al.  Microstructural manipulation of electrospun scaffolds for specific bending stiffness for heart valve tissue engineering. , 2012, Acta biomaterialia.

[87]  Mark Ahearne,et al.  Portable nanofiber meshes dictate cell orientation throughout three-dimensional hydrogels. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[88]  J. Ramshaw,et al.  Collagen-based layer-by-layer coating on electrospun polymer scaffolds. , 2012, Biomaterials.

[89]  Charles A Vacanti,et al.  Tissue-Engineered Composites of Anulus Fibrosus and Nucleus Pulposus for Intervertebral Disc Replacement , 2004, Spine.

[90]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[91]  Shicheng Wei,et al.  Nanofibrous scaffold prepared by electrospinning of poly(vinyl alcohol)/gelatin aqueous solutions , 2011 .

[92]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[93]  S. Bryant,et al.  Cell encapsulation in biodegradable hydrogels for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[94]  P. Gennes Scaling Concepts in Polymer Physics , 1979 .

[95]  Wan-Ju Li,et al.  Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. , 2008, Tissue engineering. Part A.

[96]  Young Ha Kim,et al.  Composite system of PLCL scaffold and heparin-based hydrogel for regeneration of partial-thickness cartilage defects. , 2012, Biomacromolecules.

[97]  Eric S. Hald,et al.  Collagen-agarose co-gels as a model for collagen-matrix interaction in soft tissues subjected to indentation. , 2011, Journal of biomedical materials research. Part A.

[98]  A. de Mel,et al.  Orchestrating cell/material interactions for tissue engineering of surgical implants. , 2012, Macromolecular bioscience.

[99]  G. Muschler,et al.  Bone graft materials. An overview of the basic science. , 2000, Clinical orthopaedics and related research.

[100]  Peter X Ma,et al.  Biomimetic materials for tissue engineering. , 2008, Advanced drug delivery reviews.

[101]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[102]  Joseph W Freeman,et al.  Evaluation of a hydrogel-fiber composite for ACL tissue engineering. , 2011, Journal of biomechanics.

[103]  A. D'Amore,et al.  Characterization of the complete fiber network topology of planar fibrous tissues and scaffolds. , 2010, Biomaterials.

[104]  J. Karlsson,et al.  Donor-site morbidity and anterior knee problems after anterior cruciate ligament reconstruction using autografts. , 2001, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[105]  M. Oyen,et al.  Poroviscoelastic characterization of particle-reinforced gelatin gels using indentation and homogenization. , 2011, Journal of the mechanical behavior of biomedical materials.

[106]  R. Jaeger,et al.  Electrospinning of ultra-thin polymer fibers , 1998 .

[107]  J. Leroux,et al.  In situ-forming hydrogels--review of temperature-sensitive systems. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.