Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12 myoblasts and mouse primary calvarial cells
Noura Alom
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorHeather Peto
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorGlen R. Kirkham
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorKevin M. Shakesheff
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorCorresponding Author
Lisa J. White
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Correspondence to: L. White; e-mail: [email protected]Search for more papers by this authorNoura Alom
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorHeather Peto
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorGlen R. Kirkham
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorKevin M. Shakesheff
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Search for more papers by this authorCorresponding Author
Lisa J. White
Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
Correspondence to: L. White; e-mail: [email protected]Search for more papers by this authorAbstract
Hydrogel scaffolds derived from the extracellular matrix (ECM) of mammalian tissues have been successfully used to promote tissue repair in vitro and in vivo. The objective of this study was to evaluate the osteogenic potential of ECM hydrogels prepared from demineralized and decellularized bovine bone in the presence and absence of osteogenic medium. Culture of C2C12 and mouse primary calvarial cells (mPCs) on decellularized bone ECM (bECM) and demineralized bone matrix (DBM) gels resulted in increased expression of osteogenic gene markers, including a 3.6- and 13.4-fold increase in osteopontin and 15.7- and 27.1-fold increase in osteocalcin when mPCs were cultured upon bECM with basal and osteogenic media, respectively. bECM hydrogels stimulated the osteogenic differentiation of C2C12 and mPCs even in the absence of osteogenic medium. These results suggest that bECM hydrogel scaffolds may have great utility in future clinical applications for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 900–908, 2018.
REFERENCES
- 1 Bauer TW, Muschler GF. Bone graft materials: An overview of the basic science. Clin Orthop Relat Res 2000; 371: 10–27.
- 2 Griffin M, Iqbal S, Bayat A. Exploring the application of mesenchymal stem cells in bone repair and regeneration. J Bone Joint Surg Br 2011; 93: 427–434.
- 3 Khan Y, Yaszemski MJ, Mikos AG, Laurencin CT. Tissue engineering of bone: material and matrix considerations. J Bone Joint Surg Am 2008; 90(Suppl 1): 36–42.
- 4 Nandi S, Roy S, Mukherjee P, Kundu B, De D, Basu D. Orthopaedic applications of bone graft & graft substitutes: A review. Indian J Med Res 2010; 132: 15–30.
- 5 Yang G, Rothrauff BB, Lin H, Gottardi R, Alexander PG, Tuan RS. Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix. Biomaterials 2013; 34: 9295–9306.
- 6 Lichtenberg A, Cebotari S, Tudorache I, Hilfiker A, Haverich A. Biological scaffolds for heart valve tissue engineering. Methods Mol Med 2007; 140: 309–317.
- 7 Ingenito EP, Sen E, Tsai LW, Murthy S, Hoffman A. Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung. J Tissue Eng Regen Med 2010; 4: 259–272.
- 8 Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials 2011; 32: 3233–3243.
- 9 Schlie-Wolter S, Ngezahayo A, Chichkov BN. The selective role of ECM components on cell adhesion, morphology, proliferation and communication in vitro. Exp Cell Res 2013; 319: 1553–1561.
- 10 Sawkins M, Bowen W, Dhadda P, Markides H, Sidney L, Taylor A, Rose F, Badylak S, Shakesheff K, White L. Hydrogels derived from demineralized and decellularized bone extracellular matrix. Acta Biomater 2013; 9: 7865–7873.
- 11 Okada M, Payne TR, Oshima H, Momoi N, Tobita K, Huard J. Differential efficacy of gels derived from small intestinal submucosa as an injectable biomaterial for myocardial infarct repair. Biomaterials 2010; 31: 7678–7683.
- 12 Wolf MT, Daly KA, Brennan-Pierce EP, Johnson SA, Carruthers CA, D'Amore A, Nagarkar SP, Velankar SS, Badylak SF. A hydrogel derived from decellularized dermal extracellular matrix. Biomaterials 2012; 33: 7028–7038.
- 13 Freytes DO, Martin J, Velankar SS, Lee AS, Badylak SF. Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix. Biomaterials 2008; 29: 1630–1637.
- 14 Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci 2010; 123: 4195–4200.
- 15 Sellaro TL, Ravindra AK, Stolz DB, Badylak SF. Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. Tissue Eng 2007; 13: 2301–2310.
- 16 Uygun BE, Soto-Gutierrez A, Yagi H, Izamis M-L, Guzzardi MA, Shulman C, Milwid J, Kobayashi N, Tilles A, Berthiaume F. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 2010; 16: 814–820.
- 17 Zhang Y, He Y, Bharadwaj S, Hammam N, Carnagey K, Myers R, Atala A, Van Dyke M. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype. Biomaterials 2009; 30: 4021–4028.
- 18 Moroni F, Mirabella T. Decellularized matrices for cardiovascular tissue engineering. Am J Stem Cells 2014; 3: 1–20.
- 19 Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO. Demineralized bone matrix in bone repair: History and use. Adv Drug Deliv Rev 2012; 64: 1063–1077.
- 20 Acarturk TO, Hollinger JO. Commercially available demineralized bone matrix compositions to regenerate calvarial critical-sized bone defects. Plast Reconstr Surg 2006; 118: 862–873.
- 21 Peterson B, Whang PG, Iglesias R, Wang JC, Lieberman JR. Osteoinductivity of commercially available demineralized bone matrix. J Bone Joint Surg Am 2004; 86: 2243–2250.
- 22 Wang JC, Alanay A, Mark D, Kanim LE, Campbell PA, Dawson EG, Lieberman JR. A comparison of commercially available demineralized bone matrix for spinal fusion. Eur Spine J 2007; 16: 1233–1240.
- 23 Wang JC, Kanim LE, Nagakawa IS, Yamane BH, Vinters HV, Dawson EG. Dose-dependent toxicity of a commercially available demineralized bone matrix material. Spine 2001; 26: 1429–1435.
- 24 Bostrom M, Yang X, Kennan M, Sandhu H, Dicarlo E, Lane J. An unexpected outcome during testing of commercially available demineralized bone graft materials: How safe are the nonallograft components? Spine 2001; 26: 1425–1428.
- 25 Markel DC, Guthrie ST, Wu B, Song Z, Wooley PH. Characterization of the inflammatory response to four commercial bone graft substitutes using a murine biocompatibility model. J Inflamm Res 2012; 5: 13–18.
- 26 Keane TJ, Londono R, Turner NJ, Badylak SF. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials 2012; 33: 1771–1781.
- 27 Smith E, Kanczler J, Gothard D, Roberts C, Wells J, White L, Qutachi O, Sawkins M, Peto H, Rashidi H. Evaluation of skeletal tissue repair, part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model. Acta Biomater 2014; 10: 4186–4196.
- 28 Smith E, Kanczler J, Gothard D, Roberts C, Wells J, White L, Qutachi O, Sawkins M, Peto H, Rashidi H. Evaluation of skeletal tissue repair, part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model. Acta Biomater 2014; 10: 4197–4205.
- 29 Gothard D, Smith EL, Kanczler JM, Black CR, Wells JA, Roberts CA, White LJ, Qutachi O, Peto H, Rashidi H. In vivo assessment of bone regeneration in alginate/bone ecm hydrogels with incorporated skeletal stem cells and single growth factors. PLoS One 2015; 10: e0145080.
- 30 Wong DA, Kumar A, Jatana S, Ghiselli G, Wong K. Neurologic impairment from ectopic bone in the lumbar canal: A potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). Spine J 2008; 8: 1011–1018.
- 31 Kaneko H, Arakawa T, Mano H, Kaneda T, Ogasawara A, Nakagawa M, Toyama Y, Yabe Y, Kumegawa M, Hakeda Y. Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone 2000; 27: 479–486.
- 32 Vaidya R, Carp J, Sethi A, Bartol S, Craig J, Les CM. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J 2007; 16: 1257–1265.
- 33 Pietrzak WS, Ali SN, Chitturi D, Jacob M, Woodell-May JE. BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation. Cell Tissue Bank 2011; 12: 81–88.
- 34 Schenke-Layland K, Vasilevski O, Opitz F, König K, Riemann I, Halbhuber K, Wahlers T, Stock U. Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. J Struct Biol 2003; 143: 201–208.
- 35 Li B, Lin M, Tang Y, Wang B, Wang JH-C. A novel functional assessment of the differentiation of micropatterned muscle cells. J Biomech 2008; 41: 3349–3353.
- 36 Luo Y, Shoichet MS. A photolabile hydrogel for guided three-dimensional cell growth and migration. Nat Mater 2004; 3: 249–253.
- 37 Lee J-H, Tachibana H, Morinaga Y, Fujimura Y, Yamada K. Modulation of proliferation and differentiation of C2C12 skeletal muscle cells by fatty acids. Life Sci 2009; 84: 415–420.
- 38 Yang X, Roach H, Clarke N, Howdle S, Quirk R, Shakesheff K, Oreffo R. Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification. Bone 2001; 29: 523–531.
- 39 Sidney LE, Kirkham GR, Buttery LD. Comparison of osteogenic differentiation of embryonic stem cells and primary osteoblasts revealed by responses to IL-1β, TNF-α, and IFN-γ. Stem Cells Dev 2013; 23: 605–617.
- 40 Price J, Oyajobi B, Russell R. The cell biology of bone growth. Eur J Clin Nutr 1994; 48: S131–S149.
- 41 Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2001; 2: 81–94.
- 42 Granéli C, Thorfve A, Ruetschi U, Brisby H, Thomsen P, Lindahl A, Karlsson C. Novel markers of osteogenic and adipogenic differentiation of human bone marrow stromal cells identified using a quantitative proteomics approach. Stem Cell Res 2014; 12: 153–165.
- 43 Burattini S, Ferri P, Battistelli M, Curci R, Luchetti F, Falcieri E. C2C12 murine myoblasts as a model of skeletal muscle development: Morpho-functional characterization. Eur J Histochem 2004; 48: 223.
- 44 Benders KE, van Weeren PR, Badylak SF, Saris DB, Dhert WJ, Malda J. Extracellular matrix scaffolds for cartilage and bone regeneration. Trends Biotechnol 2013; 31: 169–176.
- 45 Datta N, Holtorf HL, Sikavitsas VI, Jansen JA, Mikos AG. Effect of bone extracellular matrix synthesized in vitro on the osteoblastic differentiation of marrow stromal cells. Biomaterials 2005; 26: 971–977.
- 46 Hong Y, Huber A, Takanari K, Amoroso NJ, Hashizume R, Badylak SF, Wagner WR. Mechanical properties and in vivo behavior of a biodegradable synthetic polymer microfiber–extracellular matrix hydrogel biohybrid scaffold. Biomaterials 2011; 32: 3387–3394.
- 47 Abberton K, Bortolotto S, Woods A, Findlay M, Morrison W, Thompson E, Messina A. Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro. Cells Tissues Organs 2008; 188: 347–358.
- 48 Hollinger JO, Schmitt JM, Buck DC, Shannon R, Joh S-P, Zegzula HD, Wozney J. Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J Biomed Mater Res 1998; 43: 356–364.
- 49 Chen B, Lin H, Wang J, Zhao Y, Wang B, Zhao W, Sun W, Dai J. Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2. Biomaterials 2007; 28: 1027–1035.
- 50 Nakamura M, Nishida T. Synergistic effects of hyaluronan and fibronectin on epithelial migration in rabbit cornea in vitro. Cornea 1999; 18: 686–692.
- 51 Olivero DK, Furcht LT. Type IV collagen, laminin, and fibronectin promote the adhesion and migration of rabbit lens epithelial cells in vitro. Invest Ophthalmol Vis Sci 1993; 34: 2825–2834.
- 52 Tsai W-B, Ting Y-C, Yang J-Y, Lai J-Y, Liu H-L. Fibronectin modulates the morphology of osteoblast-like cells (MG-63) on nano-grooved substrates. J Mater Sci Mater Med 2009; 20: 1367–1378.
- 53 Okubo Y, Bessho K, Fujimura K, Iizuka T, Miyatake S-I. Expression of bone morphogenetic protein-2 via adenoviral vector in C2C12 myoblasts induces differentiation into the osteoblast lineage. Biochem Biophys Res Commun 1999; 262: 739–743.
- 54 Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 1994; 127: 1755–1766.
- 55 Sondag GR, Salihoglu S, Lababidi SL, Crowder DC, Moussa FM, Abdelmagid SM, Safadi FF. Osteoactivin induces transdifferentiation of C2C12 myoblasts into osteoblasts. J Cell Physiol 2014; 229: 955–966.
- 56 Manolagas SC. Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis 1. Endocr Rev 2000; 21: 115–137.
- 57 Ichijima T, Matsuzaka K, Tonogi M, Yamane G-Y, Inoue T. Osteogenic differences in cultured rat periosteal cells under hypoxic and normal conditions. Exp Ther Med 2012; 3: 165–170.
- 58 Shakibaei M, Shayan P, Busch F, Aldinger C, Buhrmann C, Lueders C, Mobasheri A. Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: Potential role of Runx2 deacetylation. PLoS One 2012; 7: e35712.
- 59 Ye G, Li C, Xiang X, Chen C, Zhang R, Yang X, Yu X, Wang J, Wang L, Shi Q. Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways. Int J Med Sci 2014; 11: 1065.