Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels.

To engineer complex tissues, it is necessary to create hybrid scaffolds with micropatterned structural and biomechanical properties, which can closely mimic the intricate body tissues. The current report describes the synthesis of a novel photocrosslinkable interpenetrating polymeric network (IPN) of collagen and hyaluronic acid (HA) with precisely controlled structural and biomechanical properties. Both collagen and HA are present in crosslinked form in IPNs, and the two networks are entangled with each other. IPNs were also compared with semi-IPNs (SIPN), in which only collagen was in network form and HA chains were entangled in the collagen network without being photocrosslinked. Scanning electron microscopy images revealed that IPNs are denser than SIPNs, which results in their molecular reinforcement. This was further confirmed by rheological experiments. Because of the presence of the HA crosslinked network, the storage modulus of IPNs was almost two orders of magnitude higher than SIPNs. The degradation of the collagen-HA IPNs was slower than the SIPNs because of the presence of the crosslinked HA network. Increasing concentration of HA further altered the properties among IPNs. Cytocompatibility of IPNs was confirmed by Schwann cell and dermal fibroblasts adhesion and proliferation studies. We also fabricated patterned scaffolds with regions of IPNs and SIPNs within a bulk hydrogel, resulting in zonal distribution of crosslinking densities, viscoelasticities, water content and pore sizes at the micro- and macro-scales. With the ability to fine-tune the scaffold properties by performing structural modifications and to create patterned scaffolds, these hydrogels can be employed as potential candidates for regenerative medicine applications.

[1]  Takehisa Matsuda,et al.  The potential of poly(N-isopropylacrylamide) (PNIPAM)-grafted hyaluronan and PNIPAM-grafted gelatin in the control of post-surgical tissue adhesions. , 2005, Biomaterials.

[2]  M. Hanson,et al.  Chemorheology of phenylboronate-salicylhydroxamate crosslinked hydrogel networks with a sulfonated polymer backbone. , 2008, Macromolecules.

[3]  M. Yanagishita Proteoglycans and hyaluronan in female reproductive organs. , 1994, EXS.

[4]  X. Hou,et al.  Novel interpenetrating polymer network electrolytes , 2001 .

[5]  Yi Hong,et al.  Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration. , 2008, Journal of biomedical materials research. Part A.

[6]  C. V. van Blitterswijk,et al.  Integrating novel technologies to fabricate smart scaffolds , 2008, Journal of biomaterials science. Polymer edition.

[7]  J. Peyron A new approach to the treatment of osteoarthritis: viscosupplementation. , 1993, Osteoarthritis and cartilage.

[8]  Jingxuan Liu,et al.  Assessment of dermal wound repair after collagen implantation with optical coherence tomography. , 2008, Tissue engineering. Part C, Methods.

[9]  Kristi S. Anseth,et al.  The effect of bioactive hydrogels on the secretion of extracellular matrix molecules by valvular interstitial cells. , 2008, Biomaterials.

[10]  Hongyan He,et al.  An oral delivery device based on self-folding hydrogels. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[11]  X. Yu,et al.  Hyaluronic acid hydrogel as Nogo-66 receptor antibody delivery system for the repairing of injured rat brain: in vitro. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[12]  I. Hampson,et al.  Angiogenesis induced by degradation products of hyaluronic acid. , 1985, Science.

[13]  B. Toole,et al.  Hyaluronan in morphogenesis. , 2001, Journal of internal medicine.

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

[15]  D. Wise,et al.  Versatility of biodegradable biopolymers: degradability and an in vivo application. , 2001, Journal of biotechnology.

[16]  P. Noble Hyaluronan and its catabolic products in tissue injury and repair. , 2002, Matrix biology : journal of the International Society for Matrix Biology.

[17]  C. Soranzo,et al.  Hyalomatrix: a temporary epidermal barrier, hyaluronan delivery, and neodermis induction system for keratinocyte stem cell therapy. , 2007, Tissue engineering.

[18]  K. Kivirikko,et al.  Collagens and collagen-related diseases , 2001, Annals of medicine.

[19]  Si-Nae Park,et al.  Biological characterization of EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration. , 2003, Biomaterials.

[20]  W. J. Kao,et al.  Macrophage adhesion on gelatin-based interpenetrating networks grafted with PEGylated RGD. , 2005, Tissue engineering.

[21]  R. Schulz,et al.  Cartilage tissue engineering by collagen matrix associated bone marrow derived mesenchymal stem cells. , 2008, Bio-medical materials and engineering.

[22]  A. Engström‐Làurent,et al.  Hyaluronan in joint disease , 1997, Journal of internal medicine.

[23]  Leslie H. Sperling,et al.  Interpenetrating Polymer Networks and Related Materials , 1981 .

[24]  J. Fraser,et al.  Turnover and metabolism of hyaluronan. , 2007, Ciba Foundation symposium.

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

[26]  Ali Khademhosseini,et al.  Mechanically robust and bioadhesive collagen and photocrosslinkable hyaluronic acid semi-interpenetrating networks. , 2009, Tissue engineering. Part A.

[27]  Ivan Martin,et al.  Design of graded biomimetic osteochondral composite scaffolds. , 2008, Biomaterials.

[28]  R. Cortivo,et al.  In vitro reconstructed dermis implanted in human wounds: degradation studies of the HA-based supporting scaffold. , 2000, Biomaterials.

[29]  T. Wight,et al.  Native fibrillar collagen membranes of micron-scale and submicron thicknesses for cell support and perfusion. , 2005, Biomaterials.

[30]  H. S. Azevedo,et al.  Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends , 2007, Journal of The Royal Society Interface.

[31]  T. Laurent,et al.  The structure and function of hyaluronan: An overview. , 1996, Immunology and cell biology.

[32]  Robert Langer,et al.  Collagen composite hydrogels for vocal fold lamina propria restoration. , 2006, Biomaterials.

[33]  Stefanie Turley,et al.  The Hyaluronan Receptor RHAMM Regulates Extracellular-regulated Kinase* , 1998, The Journal of Biological Chemistry.

[34]  G. Prestwich,et al.  Chemical modification of hyaluronic acid by carbodiimides. , 1991, Bioconjugate chemistry.

[35]  B. Toole,et al.  Hyaluronan: from extracellular glue to pericellular cue , 2004, Nature Reviews Cancer.

[36]  Biman B Mandal,et al.  Silk fibroin/polyacrylamide semi-interpenetrating network hydrogels for controlled drug release. , 2009, Biomaterials.

[37]  Christine E Schmidt,et al.  Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. , 2003, Biotechnology and bioengineering.

[38]  M Raspanti,et al.  Collagen structure and functional implications. , 2001, Micron.

[39]  A. Jayakrishnan,et al.  Cross-linked chitosan microspheres as carriers for prolonged delivery of macromolecular drugs. , 1994, Journal of biomaterials science. Polymer edition.

[40]  D. Hutmacher,et al.  Reduced contraction of skin equivalent engineered using cell sheets cultured in 3D matrices. , 2006, Biomaterials.

[41]  Robert J Fisher,et al.  Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. , 2006, Biomaterials.

[42]  W. Knudson,et al.  Cartilage proteoglycans. , 2001, Seminars in cell & developmental biology.

[43]  A. Ramamurthi,et al.  Effects of gamma-irradiation on physical and biologic properties of crosslinked hyaluronan tissue engineering scaffolds. , 2006, Tissue engineering.

[44]  T. Taguchi,et al.  Swelling behavior of hyaluronic acid and type II collagen hydrogels prepared by using conventional crosslinking and subsequent additional polymer interactions , 2002, Journal of biomaterials science. Polymer edition.

[45]  Stephen B Doty,et al.  In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration. , 2008, Journal of biomedical materials research. Part A.

[46]  J. Fraser,et al.  Hyaluronan: its nature, distribution, functions and turnover , 1997, Journal of internal medicine.

[47]  John T Elliott,et al.  The stiffness of collagen fibrils influences vascular smooth muscle cell phenotype. , 2007, Biophysical journal.

[48]  Yi Yan Yang,et al.  Biodegradable poly(ethylene glycol)-peptide hydrogels with well-defined structure and properties for cell delivery. , 2009, Biomaterials.

[49]  Chunyu Xu,et al.  Refolding hydrogels self-assembled from N-(2-hydroxypropyl)methacrylamide graft copolymers by antiparallel coiled-coil formation. , 2006, Biomacromolecules.

[50]  Andrés J. García Get a grip: integrins in cell-biomaterial interactions. , 2005, Biomaterials.

[51]  Tae Gwan Park,et al.  Hyaluronic acid modified biodegradable scaffolds for cartilage tissue engineering. , 2005, Biomaterials.

[52]  R. Mayne,et al.  Mammalian vitreous humor contains networks of hyaluronan molecules: electron microscopic analysis using the hyaluronan-binding region (G1) of aggrecan and link protein. , 1992, Experimental cell research.

[53]  Jennifer H. Elisseeff,et al.  Engineering Structurally Organized Cartilage and Bone Tissues , 2004, Annals of Biomedical Engineering.

[54]  E. Balazs,et al.  Hyaluronic acid and replacement of vitreous and aqueous humor. , 1972, Modern problems in ophthalmology.