Biotechnology and Bioprocess Engineering

, Volume 22, Issue 6, pp 659–670 | Cite as

Multiple growth factor delivery for skin tissue engineering applications

Review Paper
  • 44 Downloads

Abstract

Administration of exogenous growth factors (GFs) to a damaged site has been investigated for skin tissue regeneration. Among the many types of GFs and cytokines, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and hepatocyte growth factor could be specifically used for stimulating molecules in wound healing as well as for recovery of damaged skin tissues. It is speculated that delivered GFs could stimulate various cellular functions, including proliferation, migration, deposition of extracellular matrix molecules, and remodeling of collagen synthesis. Although the physiological wound healing process is complex, engineering strategies for proper delivery of multiple therapeutic GFs could enhance the quality and quantity of regenerated skin tissues. As compared to single delivery of a GF, recent studies have proven that any combination of multiple GFs and/or therapeutic chemical factors synergistically facilitates the regeneration of damaged skin tissues. In order to maximize the stability, bioactivity, intrinsic therapeutic functionality, and efficiency of internal delivery of cargo GFs, it is essential to utilize tissueengineered biomaterials and related composites as implantable platforms. Successful fabrication and development of skin tissue engineering applications as well as subsequent surgical implantation of these platforms might provide clinical treatment for superior skin regeneration. Therefore, the present review summarizes the biological functions, related signaling mechanisms, and recent developments of tissue engineering applications for multiple GF delivery.

Keywords

skin tissue engineering growth factor delivery biomaterials wound healing skin regeneration 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fife, C. E., M. J. Cartel, D. Walker, and B. Thomson (2012) Wound care outcomes and associated cost among patients treated in us outpatient wound centers: Data from the US wound registry. Wounds 24: 10–17.Google Scholar
  2. 2.
    Singer, A. J. and R. A. Clark (1999) Cutaneous wound healing. New Eng. J. Med. 341: 738–746.CrossRefGoogle Scholar
  3. 3.
    Chen, F. M., M. Zhang, and Z. F. Wu (2010) Toward delivery of multiple growth factors in tissue engineering. Biomat. 31: 6279–6308.CrossRefGoogle Scholar
  4. 4.
    Tziotzios, C., C. Profyris, and J. Sterling (2012) Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part II. Strategies to reduce scar formation after dermatologic procedures. J. Am. Acad. Dermatol. 66: 13–24.CrossRefGoogle Scholar
  5. 5.
    Zielins, E. R., E. A. Brett, A. Luan, M. S. Hu, G. G. Walmsley, K. Paik, K. Senarath-Yapa, D. A. Atashroo, T. Wearda, H. P. Lorenz, D. C. Wan, and M. T. Longaker (2015) Emerging drugs for the treatment of wound healing. Exp. Opin. Emerg. Drugs 20: 235–246.CrossRefGoogle Scholar
  6. 6.
    Caussa, J. E. and E. H. Vila (2015) Epidermal growth factor, innovation and safety. Med. Clin-Barcelona 145: 305–312.CrossRefGoogle Scholar
  7. 7.
    Mendoza, M. C., E. E. Er, and J. Blenis (2011) The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation. Trends Biochem. Sci. 36: 320–328.CrossRefGoogle Scholar
  8. 8.
    Bodnar, R. J. (2013) Epidermal growth factor and epidermal growth factor receptor: The yin and yang in the treatment of cutaneous wounds and cancer. Adv. Wound Care 2: 24–29.CrossRefGoogle Scholar
  9. 9.
    Barrientos, S., O. Stojadinovic, M. S. Golinko, H. Brem, and M. Tomic-Canic (2008) Growth factors and cytokines in wound healing. Wound Rep. Regen. 16: 585–601.CrossRefGoogle Scholar
  10. 10.
    Hardwicke, J., D. Schmaljohann, D. Boyce, and D. Thomas (2008) Epidermal growth factor therapy and wound healing—past, present and future perspectives. Surgeon 6: 172–177.CrossRefGoogle Scholar
  11. 11.
    Xie, Y., Z. Upton, S. Richards, S. C. Rizzi, and D. I. Leavesley (2011) Hyaluronic acid: evaluation as a potential delivery vehicle for vitronectin: Growth factor complexes in wound healing applications. J. Control. Rel.: Offic. J. Control. Rel. Soc. 153: 225–232.CrossRefGoogle Scholar
  12. 12.
    Morell, C. M., L. Fabris, and M. Strazzabosco (2013) Vascular biology of the biliary epithelium. J. Gastroenterol. Hepatol. 28 Suppl 1: 26–32.CrossRefGoogle Scholar
  13. 13.
    Patel-Hett, S. and P. A. D’Amore (2011) Signal transduction in vasculogenesis and developmental angiogenesis. Internat. J. Develop. Biol. 55: 353–363.CrossRefGoogle Scholar
  14. 14.
    Impellitteri, N. A., M. W. Toepke, S. K. Lan Levengood, and W. L. Murphy (2012) Specific VEGF sequestering and release using peptide-functionalized hydrogel microspheres. Biomat. 33: 3475–3484.CrossRefGoogle Scholar
  15. 15.
    Losi, P., E. Briganti, A. Magera, D. Spiller, C. Ristori, B. Battolla, M. Balderi, S. Kull, A. Balbarini, R. Di Stefano, and G. Soldani (2010) Tissue response to poly(ether)urethane-polydimethylsiloxanefibrin composite scaffolds for controlled delivery of proangiogenic growth factors. Biomat. 31: 5336–5344.CrossRefGoogle Scholar
  16. 16.
    Kazlauskas, A. (2017) PDGFs and their receptors. Gene 614: 1–7.CrossRefGoogle Scholar
  17. 17.
    Ishii, Y., T. Hamashima, S. Yamamoto, and M. Sasahara (2017) Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor. Pathol. Internat. 67: 235–246.CrossRefGoogle Scholar
  18. 18.
    Demoulin, J. B. and A. Essaghir (2014) PDGF receptor signaling networks in normal and cancer cells. Cytokine & Growth Factor Rev. 25: 273–283.CrossRefGoogle Scholar
  19. 19.
    Ostendorf, T., F. Eitner, and J. Floege (2012) The PDGF family in renal fibrosis. Pediat. Nephrol. 27: 1041–1050.CrossRefGoogle Scholar
  20. 20.
    Farooqi, A. A., S. Waseem, A. M. Riaz, B. A. Dilawar, S. Mukhtar, S. Minhaj, M. S. Waseem, S. Daniel, B. A. Malik, A. Nawaz, and S. Bhatti (2011) PDGF: The nuts and bolts of signalling toolbox. Tumour Biol.: The J. Internat. Soc. Oncodevelop. Biol.Med. 32: 1057–1070.CrossRefGoogle Scholar
  21. 21.
    Berlanga-Acosta, J., J. G. -Cowley, D. G. del Barco-Herrera, J. Martín-Machado, and G. Guillen-Nieto (2011) Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) as tissue healing agents: Clarifying concerns about their possible role in malignant transformation and tumor progression. J. Carcinogen. Mutagen. 2: 1000115.CrossRefGoogle Scholar
  22. 22.
    Judith, R., M. Nithya, C. Rose, and A. B. Mandal (2010) Application of a PDGF-containing novel gel for cutaneous wound healing. Life Sci. 87: 1–8.CrossRefGoogle Scholar
  23. 23.
    Lee, J., J. J. Yoo, A. Atala, and S. J. Lee (2012) The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration. Biomat. 33: 6709–6720.CrossRefGoogle Scholar
  24. 24.
    Kaltalioglu, K., S. Coskun-Cevher, F. Tugcu-Demiroz, and N. Celebi (2013) PDGF supplementation alters oxidative events in wound healing process: A time course study. Arch. Dermatol. Res. 305: 415–422.CrossRefGoogle Scholar
  25. 25.
    Heynen, G. J., A. Fonfara, and R. Bernards (2014) Resistance to targeted cancer drugs through hepatocyte growth factor signaling. Cell Cycle 13: 3808–3817.CrossRefGoogle Scholar
  26. 26.
    Nakamura, T., K. Sakai, T. Nakamura, and K. Matsumoto (2011) Hepatocyte growth factor twenty years on: Much more than a growth factor. J. Gastroenterol. Hepatol. 26 Suppl 1: 188–202.CrossRefGoogle Scholar
  27. 27.
    Molnarfi, N., M. Benkhoucha, H. Funakoshi, T. Nakamura, and P. H. Lalive (2015) Hepatocyte growth factor: A regulator of inflammation and autoimmunity. Autoimmun. Rev. 14: 293–303.CrossRefGoogle Scholar
  28. 28.
    Li, J. F., H. F. Duan, C. T. Wu, D. J. Zhang, Y. Deng, H. L. Yin, B. Han, H. C. Gong, H. W. Wang, and Y. L. Wang (2013) HGF accelerates wound healing by promoting the dedifferentiation of epidermal cells through beta1-integrin/ILK pathway. BioMed Res. Internat. 2013: 470418.Google Scholar
  29. 29.
    Baek, J. H., C. Birchmeier, M. Zenke, and T. Hieronymus (2012) The HGF receptor/Met tyrosine kinase is a key regulator of dendritic cell migration in skin immunity. J. Immunol. 189: 1699–1707.CrossRefGoogle Scholar
  30. 30.
    Hubel, J. and T. Hieronymus (2015) HGF/Met-signaling contributes to immune regulation by modulating tolerogenic and motogenic properties of dendritic cells. Biomed. 3: 138–148.Google Scholar
  31. 31.
    Rah, D. K., I. S. Yun, C. O. Yun, S. B. Lee, and W. J. Lee (2014) Gene therapy using hepatocyte growth factor expressing adenovirus improves skin flap survival in a rat model. J. Kor. Med. Sci. 29 Suppl 3: S228–236.CrossRefGoogle Scholar
  32. 32.
    Yun, Y. R., J. E. Won, E. Jeon, S. Lee, W. Kang, H. Jo, J. H. Jang, U. S. Shin, and H. W. Kim (2010) Fibroblast growth factors: Biology, function, and application for tissue regeneration. J. Tissue Eng. 2010: 218142.CrossRefGoogle Scholar
  33. 33.
    Ornitz, D. M. and N. Itoh (2015) The fibroblast growth factor signaling pathway. Wiley Interdiscipl. Rev. Develop. Biol. 4: 215–266.CrossRefGoogle Scholar
  34. 34.
    Singla, D. K., R. D. Singla, L. S. Abdelli, and C. Glass (2015) Fibroblast growth factor-9 enhances M2 macrophage differentiation and attenuates adverse cardiac remodeling in the infarcted diabetic heart. PloS one 10: e0120739.CrossRefGoogle Scholar
  35. 35.
    Zhang, H. Y., X. Zhang, Z. G. Wang, H. X. Shi, F. Z. Wu, B. B. Lin, X. L. Xu, X. J. Wang, X. B. Fu, Z. Y. Li, C. J. Shen, X. K. Li, and J. Xiao (2013) Exogenous basic fibroblast growth factor inhibits ER stress-induced apoptosis and improves recovery from spinal cord injury. CNS Neurosci. Therap. 19: 20–29.CrossRefGoogle Scholar
  36. 36.
    Hankenson, K. D., K. Gagne, and M. Shaughnessy (2015) Extracellular signaling molecules to promote fracture healing and bone regeneration. Adv. Drug Del. Rev. 94: 3–12.CrossRefGoogle Scholar
  37. 37.
    De Smet, F., B. Tembuyser, A. Lenard, F. Claes, J. Zhang, C. Michielsen, A. Van Schepdael, J. M. Herbert, F. Bono, M. Affolter, M. Dewerchin, and P. Carmeliet (2014) Fibroblast growth factor signaling affects vascular outgrowth and is required for the maintenance of blood vessel integrity. Chem. Biol. 21: 1310–1317.CrossRefGoogle Scholar
  38. 38.
    Falcon, B. L., M. Swearingen, W. H. Gough, L. Lee, R. Foreman, M. Uhlik, J. C. Hanson, J. A. Lee, D. B. McClure, and S. Chintharlapalli (2014) An in vitro cord formation assay identifies unique vascular phenotypes associated with angiogenic growth factors. PloS one 9: e106901.CrossRefGoogle Scholar
  39. 39.
    Takikawa, M., S. Nakamura, M. Ishihara, Y. Takabayashi, M. Fujita, H. Hattori, T. Kushibiki, and M. Ishihara (2015) Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2-containing low-molecular-weight heparin (Fragmin)/ protamine nanoparticles. J. Surg. Res. 196: 247–257.CrossRefGoogle Scholar
  40. 40.
    Xie, L., M. Zhang, B. Dong, M. Guan, M. Lu, Z. Huang, H. Gao, and X. Li (2011) Improved refractory wound healing with administration of acidic fibroblast growth factor in diabetic rats. Diabetes Res. Clin. Pract. 93: 396–403.CrossRefGoogle Scholar
  41. 41.
    Matsumoto, S., R. Tanaka, K. Okada, K. Arita, H. Hyakusoku, M. Miyamoto, Y. Tabata, and H. Mizuno (2013) The Effect of Control-released basic fibroblast growth factor in wound healing: Histological analyses and clinical application. Plast. Reconstr. Surg. Global Open 1: e44.CrossRefGoogle Scholar
  42. 42.
    Nakamizo, S., G. Egawa, H. Doi, Y. Natsuaki, Y. Miyachi, and K. Kabashima (2013) Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion. Skin Pharmacol. Physiol. 26: 22–29.CrossRefGoogle Scholar
  43. 43.
    Fuhr, M. J., M. Meyer, E. Fehr, G. Ponzio, S. Werner, and H. J. Herrmann (2015) A modeling approach to study the effect of cell polarization on keratinocyte migration. PloS one 10: e0117676.CrossRefGoogle Scholar
  44. 44.
    Peplow, P. V. and M. P. Chatterjee (2013) A review of the influence of growth factors and cytokines in in vitro human keratinocyte migration. Cytokine 62: 1–21.CrossRefGoogle Scholar
  45. 45.
    Akita, S., K. Akino, and A. Hirano (2013) Basic fibroblast growth factor in scarless wound healing. Adv. Wound Care 2: 44–49.CrossRefGoogle Scholar
  46. 46.
    Shi, H. X., C. Lin, B. B. Lin, Z. G. Wang, H. Y. Zhang, F. Z. Wu, Y. Cheng, L. J. Xiang, D. J. Guo, X. Luo, G. Y. Zhang, X. B. Fu, S. Bellusci, X. K. Li, and J. Xiao (2013) The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PloS one 8: e59966.CrossRefGoogle Scholar
  47. 47.
    Abe, M., Y. Yokoyama, and O. Ishikawa (2012) A possible mechanism of basic fibroblast growth factor-promoted scarless wound healing: The induction of myofibroblast apoptosis. Europ. J. Dermatol. 22: 46–53.Google Scholar
  48. 48.
    Mirdailami, O., M. Soleimani, R. Dinarvand, M. R. Khoshayand, M. Norouzi, A. Hajarizadeh, M. Dodel, and F. Atyabi (2015) Controlled release of rhEGF and rhbFGF from electrospun scaffolds for skin regeneration. J. Biomed. Mat. Res. Part A. 103: 3374–3385.CrossRefGoogle Scholar
  49. 49.
    Choi, J. S., S. H. Choi, and H. S. Yoo (2011) Coaxial electrospun nanofibers for treatment of diabetic ulcers with binary release of multiple growth factors. J. Mater. Chem. 21: 5258–5267.CrossRefGoogle Scholar
  50. 50.
    Lai, H. J., C. H. Kuan, H. C. Wu, J. C. Tsai, T. M. Chen, D. J. Hsieh, and T. W. Wang (2014) Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing. Acta Biomat. 10: 4156–4166.CrossRefGoogle Scholar
  51. 51.
    Ribeiro, M. P., P. I. Morgado, S. P. Miguel, P. Coutinho, and I. J. Correia (2013) Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing. Mat. Sci. Eng. C-Mater. 33: 2958–2966.CrossRefGoogle Scholar
  52. 52.
    Yang, D. H., D. I. Seo, D. W. Lee, S. H. Bhang, K. Park, G. Jang, C. H. Kim, and H. J. Chun (2017) Preparation and evaluation of visible-light cured glycol chitosan hydrogel dressing containing dual growth factors for accelerated wound healing. J. Ind. Eng. Chem. 53: 360–370.CrossRefGoogle Scholar
  53. 53.
    Goel, A., A. B. Kunnumakkara, and B. B. Aggarwal (2008) Curcumin as “Curecumin”: From kitchen to clinic. Biochem. Pharmacol. 75: 787–809.CrossRefGoogle Scholar
  54. 54.
    Cheppudira, B., M. Fowler, L. McGhee, A. Greer, A. Mares, L. Petz, D. Devore, D. R. Loyd, and J. L. Clifford (2013) Curcumin: A novel therapeutic for burn pain and wound healing. Expert Opin. Investigat. Drugs 22: 1295–1303.CrossRefGoogle Scholar
  55. 55.
    Li, X., X. Ye, J. Qi, R. Fan, X. Gao, Y. Wu, L. Zhou, A. Tong, and G. Guo (2016) EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent. Internat. J. Nanomed. 11: 3993–4009.CrossRefGoogle Scholar
  56. 56.
    Xie, Z., C. B. Paras, H. Weng, P. Punnakitikashem, L. C. Su, K. Vu, L. Tang, J. Yang, and K. T. Nguyen (2013) Dual growth factor releasing multi-functional nanofibers for wound healing. Acta Biomat. 9: 9351–9359.CrossRefGoogle Scholar
  57. 57.
    Losi, P., E. Briganti, C. Errico, A. Lisella, E. Sanguinetti, F. Chiellini, and G. Soldani (2013) Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice. Acta Biomat. 9: 7814–7821.CrossRefGoogle Scholar
  58. 58.
    Hollier, B., D. G. Harkin, D. Leavesley, and Z. Upton (2005) Responses of keratinocytes to substrate-bound vitronectin: Growth factor complexes. Experim. Cell Res. 305: 221–232.CrossRefGoogle Scholar
  59. 59.
    Ogino, S., N. Morimoto, M. Sakamoto, C. Jinno, Y. Sakamoto, T. Taira, and S. Suzuki (2018) Efficacy of the dual controlled release of HGF and bFGF impregnated with a collagen/gelatin scaffold. J. Surg. Res. 221: 173–182.CrossRefGoogle Scholar
  60. 60.
    Kiso, M., T. S. Hamazaki, M. Itoh, S. Kikuchi, H. Nakagawa, and H. Okochi (2015) Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro. J. Dermatol. Sci. 79: 110–118.CrossRefGoogle Scholar
  61. 61.
    Shi, J., J. Li, H. Guan, W. Cai, X. Bai, X. Fang, X. Hu, Y. Wang, H. Wang, Z. Zheng, L. Su, D. Hu, and X. Zhu (2014) Antifibrotic actions of interleukin-10 against hypertrophic scarring by activation of PI3K/AKT and STAT3 signaling pathways in scarforming fibroblasts. PloS one 9: e98228.CrossRefGoogle Scholar
  62. 62.
    So, K., D. A. McGrouther, J. A. Bush, P. Durani, L. Taylor, G. Skotny, T. Mason, A. Metcalfe, S. O'Kane, and M. W. Ferguson (2011) Avotermin for scar improvement following scar revision surgery: A randomized, double-blind, within-patient, placebocontrolled, phase II clinical trial. Plast. Reconstr. Surg. 128: 163–172.CrossRefGoogle Scholar
  63. 63.
    Kieran, I., A. Knock, J. Bush, K. So, A. Metcalfe, R. Hobson, T. Mason, S. O’Kane, and M. Ferguson (2013) Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: Results of two preclinical and phase II randomized control studies. Wound Rep.Regen. 21: 428–436.CrossRefGoogle Scholar
  64. 64.
    Shi, J. H., H. Guan, S. Shi, W. X. Cai, X. Z. Bai, X. L. Hu, X. B. Fang, J. Q. Liu, K. Tao, X. X. Zhu, C. W. Tang, and D. H. Hu (2013) Protection against TGF-beta 1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarring. Arch. Dermatol. Res. 305: 341–352.CrossRefGoogle Scholar
  65. 65.
    Lee, M. S., T. Ahmad, J. Lee, H. K. Awada, Y. Wang, K. Kim, H. Shin, and H. S. Yang (2017) Dual delivery of growth factors with coacervate-coated poly(lactic-co-glycolic acid) nanofiber improves neovascularization in a mouse skin flap model. Biomat. 124: 65–77.CrossRefGoogle Scholar
  66. 66.
    Finnson, K. W., S. McLean, G. M. Di Guglielmo, and A. Philip (2013) Dynamics of transforming growth factor beta signaling in wound healing and scarring. Adv. Wound Care 2: 195–214.CrossRefGoogle Scholar
  67. 67.
    Arno, A. I., G. G. Gauglitz, J. P. Barret, and M. G. Jeschke (2014) New molecular medicine-based scar management strategies. Burns 40: 539–551.CrossRefGoogle Scholar
  68. 68.
    Chen, W. C., B. G. Lee, D. W. Park, K. Kim, H. Chu, K. Kim, J. Huard, and Y. Wang (2015) Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair. Biomater. 72: 138–151.CrossRefGoogle Scholar
  69. 69.
    Kim, K., W. C. W. Chen, Y. Heo, and Y. D. Wang (2016) Polycations and their biomedical applications. Prog. Polym. Sci. 60: 18–50.CrossRefGoogle Scholar
  70. 70.
    Shin, S., J. U. Shin, Y. Lee, W. Y. Chung, K. H. Nam, T. G. Kwon, and J. H. Lee (2017) The effects of multi-growth factorscontaining cream on post-thyroidectomy Scars: A preliminary study. Ann. Dermatol. 29: 314–320.CrossRefGoogle Scholar
  71. 71.
    Satish, L. (2015) Chemokines as therapeutic targets to improve healing efficiency of chronic wounds. Adv. Wound Care 4: 651–659.CrossRefGoogle Scholar
  72. 72.
    Laiva, A. L., F. J. O'Brien, and M. B. Keogh (2017) Innovations in gene and growth factor delivery systems for diabetic wound healing. J. Tissue Eng. Regen. Med. doi: 10.1002/term.2443.Google Scholar
  73. 73.
    Pereira, R. F., C. C. Barrias, P. L. Granja, and P. J. Bartolo (2013) Advanced biofabrication strategies for skin regeneration and repair. Nanomed. 8: 603–621.CrossRefGoogle Scholar
  74. 74.
    Zamani, M., M. P. Prabhakaran, and S. Ramakrishna (2013) Advances in drug delivery via electrospun and electrosprayed nanomaterials. Internat. J. Nanomed. 8: 2997–3017.Google Scholar
  75. 75.
    Liu, W., X. Wu, and Z. Gao (2011) New potential antiscarring approaches. Wound Rep. Regen. 19 Suppl 1: s22–31.CrossRefGoogle Scholar
  76. 76.
    Gauglitz, G. G., H. C. Korting, T. Pavicic, T. Ruzicka, and M. G. Jeschke (2011) Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies. Mol. Med. 17: 113–125.CrossRefGoogle Scholar
  77. 77.
    Ibrahim, M. M., J. Bond, A. Bergeron, K. J. Miller, T. Ehanire, C. Quiles, E. R. Lorden, M. A. Medina, M. Fisher, B. Klitzman, M. A. Selim, K. W. Leong, and H. Levinson (2014) A novel immune competent murine hypertrophic scar contracture model: A tool to elucidate disease mechanism and develop new therapies. Wound Rep. Regen. 22: 755–764.CrossRefGoogle Scholar
  78. 78.
    Van Den Broek, L. J., F. B. Niessen, R. J. Scheper, and S. Gibbs (2012) Development, validation and testing of a human tissue engineered hypertrophic scar model. ALTEX 29: 389–402.CrossRefGoogle Scholar
  79. 79.
    Hartwell, R., M. S. Poormasjedi-Meibod, C. Chavez-Munoz, R. B. Jalili, A. Hossenini-Tabatabaei, and A. Ghahary (2015) An insitu forming skin substitute improves healing outcome in a hypertrophic scar model. Tissue Eng. Part A. 21: 1085–1094.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Bioengineering, College of Life Sciences and BioengineeringIncheon National UniversityIncheonKorea

Personalised recommendations