Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-26T17:08:28.011Z Has data issue: false hasContentIssue false

Self-Organizing Tissue-Engineered Constructs in Collagen Hydrogels

Published online by Cambridge University Press:  04 January 2012

Robert G. Gourdie*
Affiliation:
Department of Regenerative Medicine and Cell Biology, Clemson-MUSC Bioengineering Program, MUSC, Charleston, SC 29425, USA
Tereance A. Myers
Affiliation:
Department of Regenerative Medicine and Cell Biology, Clemson-MUSC Bioengineering Program, MUSC, Charleston, SC 29425, USA
Alex McFadden
Affiliation:
Department of Cell Biology and Anatomy, Program in Bioengineering, University of South Carolina, School of Medicine, Columbia, SC 29209, USA
Yin-xiong Li
Affiliation:
South China Institute of Stem Cell & Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Jay D. Potts*
Affiliation:
Department of Cell Biology and Anatomy, Program in Bioengineering, University of South Carolina, School of Medicine, Columbia, SC 29209, USA
*
Corresponding author. E-mail: [email protected]
Corresponding author. E-mail: [email protected]
Get access

Abstract

A novel self-organizing behavior of cellularized gels composed of collagen type 1 that may have utility for tissue engineering is described. Depending on the starting geometry of the tissue culture well, toroidal rings of cells or hollow spheroids were prompted to form autonomously when cells were seeded onto the top of gels and the gels released from attachment to the culture well 12 to 24 h after seeding. Cells within toroids assumed distinct patterns of alignment not seen in control gels in which cells had been mixed in. In control gels, cells formed complex three-dimensional arrangements and assumed relatively higher levels of heterogeneity in expression of the fibronectin splice variant ED-A—a marker of epithelial mesenchymal transformation. The tissue-like constructs resulting from this novel self-organizing behavior may have uses in wound healing and regenerative medicine, as well as building blocks for the iterative assembly of synthetic biological structures.

Type
Feature Article
Copyright
Copyright © Microscopy Society of America 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Agarwal, A., Coleno, M.L., Wallace, V.P., Wu, W.Y., Sun, C.H., Tromberg, B.J. & George, S.C. (2001). Two-photon laser scanning microscopy of epithelial cell-modulated collagen density in engineered human lung tissue. Tissue Eng 7, 191202.CrossRefGoogle ScholarPubMed
Badillo, A.T., Redden, R.A., Zhang, L., Doolin, E.J. & Liechty, K.W. (2007). Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure. Cell Tissue Res 329, 301311.CrossRefGoogle ScholarPubMed
Badylak, S.F., Freytes, D.O. & Gilbert, T.W. (2009). Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater 5, 113.CrossRefGoogle ScholarPubMed
Baum, B., Settleman, J. & Quinlan, M.P. (2008). Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol 19, 294308.CrossRefGoogle ScholarPubMed
Carver, W., Molano, I., Reaves, T.A., Borg, T.K. & Terracio, L. (1995). Role of the alpha 1 beta 1 integrin complex in collagen gel contraction in vitro by fibroblasts. J Cell Physiol 165, 425437.CrossRefGoogle ScholarPubMed
Cen, L., Liu, W., Cui, L., Zhang, W. & Cao, Y. (2008). Collagen tissue engineering: Development of novel biomaterials and applications. Pediatr Res 63, 492496.CrossRefGoogle ScholarPubMed
de Castro Brás, L.E., Proffitt, J.L., Bloor, S. & Sibbons, P.D. (2010). Effect of crosslinking on the performance of a collagen-derived biomaterial as an implant for soft tissue repair: A rodent model. J Biomed Mater Res B 95, 239249.CrossRefGoogle ScholarPubMed
DuRant, R., Champion, R. & Potts, J.D. (2002). Collagen gel contraction by lens epithelial cells: Role of the Jak-STAT pathway and tyrosine kinase activity in secondary cataracts. Res Comm Pharm Toxicol 6, 252262.Google Scholar
Eid, H., Larson, D.M., Springhorn, J.P., Attawia, M.A., Nayak, R.C., Smith, T.W. & Kelly, R.A. (1992). Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture. Circ Res 71, 4050.CrossRefGoogle ScholarPubMed
Falanga, V. & Sabolinski, M. (1999). A bilayered living skin construct (APLIGRAF®) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen 7, 201207.CrossRefGoogle ScholarPubMed
Feng, Z., Matsumoto, T. & Nakamura, T. (2003). Measurements of the mechanical properties of contracted collagen gels populated with rat fibroblasts or cardiomyocytes. J Artif Organs 6, 192196.CrossRefGoogle ScholarPubMed
Ford, C.N. (1986). Histologic studies on the fate of soluble collagen injected into canine vocal folds. Laryngoscope 96, 12481257.CrossRefGoogle ScholarPubMed
Ghatnekar, G.S., O'Quinn, M.P., Jourdan, L.J., Gurjarpadhye, A.A., Draughn, R.L. & Gourdie, R.G. (2009). Connexin43 carboxyl-terminal peptides reduce scar progenitor and promote regenerative healing following skin wounding. Regen Med 4, 205223.CrossRefGoogle ScholarPubMed
Glowacki, J. & Mizuno, S. (2008). Collagen scaffolds for tissue engineering. Biopolymers 89, 338344.CrossRefGoogle ScholarPubMed
Hansen, L.K., Wilhelm, J. & Fassett, J.T. (2006). Regulation of hepatocyte cell cycle progression and differentiation by type I collagen structure. Curr Top Dev Biol 72, 205236.CrossRefGoogle ScholarPubMed
Harris, A.K., Stopak, D. & Warner, P. (1984). Generation of spatially periodic patterns by a mechanical instability: A mechanical alternative to the Turing model. J Embryol Exp Morphol 80, 120.Google Scholar
Hay, E.D. & Zuk, A. (1995). Transformations between epithelium and mesenchyme: Normal, pathological, and experimentally induced. Am J Kidney Dis 26, 678690.CrossRefGoogle ScholarPubMed
Hunt, N.C. & Grover, L.M. (2010). Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol Lett 32, 733742.CrossRefGoogle ScholarPubMed
Hunter, A.W., Barker, R.J., Zhu, C. & Gourdie, R.G. (2005). Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell 16, 56865698.CrossRefGoogle ScholarPubMed
Huynh, T., Abraham, G., Murray, J., Brockbank, K., Hagen, P.O. & Sullivan, S. (1999). Remodeling of an acellular collagen graft into a physiologically responsive neovessel. Nat Biotechnol 17, 10831086.CrossRefGoogle ScholarPubMed
Ikuno, Y. & Kazlauskas, A. (2002). TGFbeta1-dependent contraction of fibroblasts is mediated by the PDGFalpha receptor. Invest Ophthalmol Vis Sci 43, 4146.Google ScholarPubMed
Kimura, M., Nito, T., Imagawa, H., Sakakibara, K., Chan, R.W. & Tayama, N. (2010). Collagen injection for correcting vocal fold asymmetry: high-speed imaging. Ann Otol Rhinol Laryngol 119, 359368.CrossRefGoogle ScholarPubMed
Kwon, D.S., Gao, X., Liu, Y.B., Dulchavsky, D.S., Danyluk, A.L., Bansal, M., Chopp, M., McIntosh, K., Arbab, A.S., Dulchavsky, S.A. & Gautam, S.C. (2008). Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. Int Wound J 5, 453463.CrossRefGoogle ScholarPubMed
Lee, E.H. & Joo, C.K. (1999). Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells. Invest Ophthalmol Vis Sci 40, 20252032.Google ScholarPubMed
Levitz, D., Hinds, M.T., Choudhury, N., Tran, N.T., Hanson, S.R. & Jacques, S.L. (2010). Quantitative characterization of developing collagen gels using optical coherence tomography. J Biomed Opt 15, 026019.CrossRefGoogle ScholarPubMed
Luu, Q., Tsai, V., Mangunta, V., Berke, G.S. & Chhetri, D.K. (2007). Safety of percutaneous injection of bovine dermal crosslinked collagen for glottic insufficiency. Otolaryngol Head Neck Surg Mar 136, 445449.CrossRefGoogle ScholarPubMed
Macleod, T.M., Williams, G., Sanders, R. & Green, C.J. (2005). Histological evaluation of Permacol as a subcutaneous implant over a 20-week period in the rat model. Br J Plast Surg 58, 518532.CrossRefGoogle Scholar
McFarlin, K., Gao, X., Liu, Y.B., Dulchavsky, D.S., Kwon, D., Arbab, A.S., Bansal, M., Li, Y., Chopp, M., Dulchavsky, S.A. & Gautam, S.C. (2006). Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat. Wound Repair Regen 14, 471478.CrossRefGoogle ScholarPubMed
Medici, D. & Nawshad, A. (2010). Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-kappaB and LEF-1. Matrix Biol 29, 161165.CrossRefGoogle ScholarPubMed
Mercado-Pimentel, M.E. & Runyan, R.B. (2007). Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart. Cells Tissues Organs 185, 146156.CrossRefGoogle ScholarPubMed
Mironov, V., Boland, T., Trusk, T., Forgacs, G. & Markwald, R.R. (2003). Organ printing: Computer-aided jet-based 3D tissue engineering. Trends Biotechnol 21, 157161.CrossRefGoogle ScholarPubMed
Ngo, P., Ramalingam, P., Phillips, J.A. & Furuta, G.T. (2006). Collagen gel contraction assay. Methods Mol Biol 341, 103109.Google ScholarPubMed
O'Quinn, M.P., Palatinus, J.A., Harris, B.S., Hewett, K.W. & Gourdie, R.G. (2011). A peptide mimetic of the connexin43 carboxyl terminus reduces gap junction remodeling and induced arrhythmia following ventricular injury. Circ Res 108, 704715.CrossRefGoogle ScholarPubMed
Palatinus, J.A., Rhett, J.M. & Gourdie, R.G. (2010). Translational lessons from scarless healing of cutaneous wounds and regenerative repair of the myocardium. J Mol Cell Cardiol 48, 550557.CrossRefGoogle ScholarPubMed
Palatinus, J.A., Rhett, J.M. & Gourdie, R.G. (2011). Enhanced PKCɛ mediated phosphorylation of connexin43 at serine 368 by a carboxyl-terminal mimetic peptide is dependent on injury. Channels 5, 236240.CrossRefGoogle Scholar
Pang, Y. & Greisler, H.P. (2010). Using a type 1 collagen-based system to understand cell scaffold interactions and to deliver chimeric collagen-binding growth factors for vascular tissue engineering. J Investig Med 58, 845848.CrossRefGoogle ScholarPubMed
Patino, M.G., Neiders, M.E., Andreana, S., Noble, B. & Cohen, R.E. (2002). Collagen as an implantable material in medicine and dentistry. J Oral Implantol 28, 220225.2.3.CO;2>CrossRefGoogle Scholar
Pedraza, C.E., Marelli, B., Chicatun, F., McKee, M.D. & Nazhat, S.N. (2010). An in vitro assessment of a cell-containing collagenous extracellular matrix-like scaffold for bone tissue engineering. Tissue Eng Part A 16, 781793.CrossRefGoogle Scholar
Potts, J.D. & Runyan, R.B. (1989). Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev Biol 134, 392401.CrossRefGoogle ScholarPubMed
Reddan, J.R., Chepelinsky, A.B., Dziedzic, D.C., Piatigorsky, J. & Goldenberg, E.M. (1986). Retention of lens specificity in long-term cultures of diploid rabbit lens epithelial cells. Differentiation 33, 168174.CrossRefGoogle ScholarPubMed
Rhett, J.M., Ghatnekar, G.S., Palatinus, J.A., O'Quinn, M.P., Yost, M.J. & Gourdie, R.G. (2008). Novel therapies for scar reduction and regenerative healing of skin wounds. Trends Biotechnol 26, 173180.CrossRefGoogle ScholarPubMed
Rhett, J.M., Jourdan, L.J. & Gourdie, R.G. (2011). Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1. Mol Biol Cell 22, 15161528.CrossRefGoogle ScholarPubMed
Saika, S., Yamanaka, O., Okada, Y., Tanaka, S., Miyamoto, T., Sumioka, T., Kitano, A., Shirai, K. & Ikeda, K. (2009). TGF beta in fibroproliferative diseases in the eye. Front Biosci (Schol Ed) 1, 376390.CrossRefGoogle ScholarPubMed
Shintani, Y., Maeda, M., Chaika, N., Johnson, K.R. & Wheelock, M.J. (2008). Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-beta signaling. Am J Respir Cell Mol Biol 38, 95104.CrossRefGoogle ScholarPubMed
Soder, B.L., Propst, J.T., Brooks, T.M., Goodwin, R.L., Friedman, H.I., Yost, M.J. & Gourdie, R.G. (2009). The connexin43 carboxyl-terminal peptide ACT1 modulates the biological response to silicone implants. Plast Reconstr Surg 123, 14401451.CrossRefGoogle ScholarPubMed
Stopak, D., Wessells, N.K. & Harris, A.K. (1985). Morphogenetic rearrangement of injected collagen in developing chicken limb buds. Proc Natl Acad Sci USA 82, 28042808.CrossRefGoogle ScholarPubMed
Thevenot, P., Nair, A., Dey, J., Yang, J. & Tang, L.P. (2008). Method to analyze three-dimensional cell distribution and infiltration in degradable scaffolds. Tissue Eng Part C Methods 14, 319331.CrossRefGoogle ScholarPubMed
Tonnesen, M.G., Feng, X. & Clark, R.A. (2000). Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5, 4046.CrossRefGoogle ScholarPubMed
Wada, A.M., Smith, T.K., Osler, M.E., Reese, D.E. & Bader, D.M. (2003). Epicardial/mesothelial cell line retains vasculogenic potential of embryonic epicardium. Circ Res 92, 525531.CrossRefGoogle ScholarPubMed
Watanabe, M., Oike, M., Ohta, Y., Nawata, H. & Ito, Y. (2006). Sustained contraction and loss of NO production in TGFbeta1-treated endothelial cells. Br J Pharmacol 149, 355364.CrossRefGoogle ScholarPubMed
Wilson, C.G., Sisco, P.N., Gadala-Maria, F.A., Murphy, C.J. & Goldsmith, E.C. (2009). Polyelectrolyte-coated gold nanorods and their interactions with type I collagen. Biomaterials 30, 56395648.CrossRefGoogle ScholarPubMed
Zerris, V.A., James, K.S., Roberts, J.B., Bell, E. & Heilman, C.B. (2007). Repair of the dura mater with processed collagen devices. J Biomed Mater Res B 83B, 580588.CrossRefGoogle Scholar
Supplementary material: PDF

Gourdie Supplementary Figure

Supplementary Figure 1. Examples in which LECs were seeded on top collagen gels and formed toroids

Download Gourdie Supplementary Figure(PDF)
PDF 198.4 KB