Hydrogels derived from central nervous system extracellular matrix.

Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair.

[1]  Donald O Freytes,et al.  Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix. , 2008, Biomaterials.

[2]  Angela Panoskaltsis-Mortari,et al.  Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. , 2010, Tissue engineering. Part A.

[3]  George P McCabe,et al.  Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels. , 2010, Tissue engineering. Part A.

[4]  Melinda Larsen,et al.  Extracellular matrix dynamics in development and regenerative medicine , 2008, Journal of Cell Science.

[5]  Christopher A. Carruthers,et al.  A hydrogel derived from decellularized dermal extracellular matrix. , 2012, Biomaterials.

[6]  D. Weber,et al.  Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. , 2010, Tissue engineering. Part A.

[7]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

[8]  S. Badylak,et al.  Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model. , 2010, The Journal of surgical research.

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

[10]  Ann E Rundell,et al.  Biaxial strength of multilaminated extracellular matrix scaffolds. , 2004, Biomaterials.

[11]  George P McCabe,et al.  Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. , 2009, Biomaterials.

[12]  N. Nath,et al.  PAK5, a New Brain-Specific Kinase, Promotes Neurite Outgrowth in N1E-115 Cells , 2002, Molecular and Cellular Biology.

[13]  Kate Stuart,et al.  Characterization of gels composed of blends of collagen I, collagen III, and chondroitin sulfate. , 2009, Biomacromolecules.

[14]  Stephen F Badylak,et al.  Use of a particulate extracellular matrix bioscaffold for treatment of acquired urinary incontinence in dogs. , 2005, Journal of the American Veterinary Medical Association.

[15]  Thomas W. Gilbert,et al.  Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold. , 2011, Tissue engineering. Part A.

[16]  Anoop Kumar,et al.  Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate , 2007, Science.

[17]  E Ruoslahti,et al.  Brain extracellular matrix. , 1996, Glycobiology.

[18]  S. Badylak,et al.  A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix. , 2008, The Journal of thoracic and cardiovascular surgery.

[19]  D. Hu,et al.  Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model. , 2012, European cells & materials.

[20]  Stephen F Badylak,et al.  Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. , 2007, Tissue engineering.

[21]  D. Hu,et al.  Design and characterization of an injectable pericardial matrix gel: a potentially autologous scaffold for cardiac tissue engineering. , 2010, Tissue engineering. Part A.

[22]  S. Hayward,et al.  Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. , 1996, The Journal of urology.

[23]  D. Piper,et al.  pH stability and activity curves of pepsin with special reference to their clinical importance. , 1965, Gut.

[24]  S. Badylak,et al.  Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells , 2008, Journal of tissue engineering and regenerative medicine.

[25]  Peter M. Crapo,et al.  Small intestinal submucosa gel as a potential scaffolding material for cardiac tissue engineering. , 2010, Acta biomaterialia.

[26]  Li Zhang,et al.  Degradation products of extracellular matrix affect cell migration and proliferation. , 2009, Tissue engineering. Part A.

[27]  Michel Modo,et al.  Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI. , 2012, Biomaterials.

[28]  C. Medberry,et al.  Biologic scaffolds composed of central nervous system extracellular matrix. , 2012, Biomaterials.

[29]  Stephen F Badylak,et al.  Extracellular Matrix Scaffold for Cardiac Repair , 2005, Circulation.

[30]  A. Forge,et al.  A comparative study of gland cells implicated in the nerve dependence of salamander limb regeneration , 2010, Journal of anatomy.

[31]  B. Brown,et al.  Evidence of innervation following extracellular matrix scaffold‐mediated remodelling of muscular tissues , 2009, Journal of tissue engineering and regenerative medicine.

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

[33]  S. Badylak,et al.  Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. , 2009, Tissue engineering. Part A.

[34]  K. Shakesheff,et al.  The effect of delivery via narrow-bore needles on mesenchymal cells. , 2009, Regenerative medicine.

[35]  Jean A. Niles,et al.  Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. , 2010, Tissue engineering. Part A.

[36]  Thore Zantop,et al.  Extracellular matrix scaffolds are repopulated by bone marrow‐derived cells in a mouse model of achilles tendon reconstruction , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  M. Nirenberg,et al.  Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[38]  E. Richelson,et al.  Ionic excitation of a clone of mouse neuroblastoma , 1975, Brain Research.

[39]  M. Nirenberg,et al.  Neurotransmitter Synthesis by Neuroblastoma Clones , 1972 .

[40]  Adam J. Engler,et al.  Supplemental Data Matrix Elasticity Directs Stem Cell Lineage Specification , 2006 .

[41]  John A. Pedersen,et al.  Mechanobiology in the Third Dimension , 2005, Annals of Biomedical Engineering.

[42]  B. Öbrink.  The Influence of Glycosaminoglycans on the Formation of Fibers from Monomeric Tropocollagen in vitro , 1973 .

[43]  K. Piez,et al.  Collagen fibril formation. Evidence for a multistep process. , 1979, The Journal of biological chemistry.

[44]  F H Silver,et al.  Collagen fibrillogenesis in vitro: comparison of types I, II, and III. , 1984, Archives of biochemistry and biophysics.

[45]  S. Badylak,et al.  Macrophage phenotype as a determinant of biologic scaffold remodeling. , 2008, Tissue engineering. Part A.

[46]  F M Watt,et al.  Regulation of development and differentiation by the extracellular matrix. , 1993, Development.

[47]  V. Agrawal,et al.  Recruitment of progenitor cells by an extracellular matrix cryptic peptide in a mouse model of digit amputation. , 2011, Tissue engineering. Part A.

[48]  Donald O Freytes,et al.  Esophageal reconstruction with ECM and muscle tissue in a dog model. , 2005, The Journal of surgical research.

[49]  J. Iannotti,et al.  Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears. A randomized, controlled trial. , 2006, The Journal of bone and joint surgery. American volume.

[50]  Brian A. Aguado,et al.  Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. , 2012, Tissue engineering. Part A.

[51]  J. Brockes.  The nerve dependence of amphibian limb regeneration. , 1987, The Journal of experimental biology.