Skip to main content
SpringerLink
Log in

Polypeptide Thermogels as Three-Dimensional Scaffolds for Cells

  • Review Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Thermogel is an aqueous solution that exhibits a sol-to-gel transition as the temperature increases. Stem cells, growth factors, and differentiating factors can be incorporated in situ in the matrix during the sol-to-gel transition, leading to the formation of a three-dimensional (3D) cell-culture scaffold.

Methods:

The uses of thermogelling polypeptides, such as collagen, Matrigel™, elastin-like polypeptides, and synthetic polypeptides, as 3D scaffolds of cells, are summarized in this paper.

Results:

The timely supply of growth factors to the cells, cell survival, and metabolite removal is to be insured in the cell culture matrix. Various growth factors were incorporated in the matrix during the sol-to-gel transition of the thermogelling polypeptide aqueous solutions, and preferential differentiation of the incorporated stem cells into specific target cells were investigated. In addition, modulus of the matrix was controlled by post-crosslinking reactions of thermogels or employing composite systems. Chemical functional groups as well as biological factors were selected appropriately for targeted differentiation of the incorporated stem cells.

Conclusion:

In addition to all the advantages of thermogels including mild conditions for cell-incorporation and controlled supplies of the growth factors, polypeptide thermogels provide neutral pH environments to the cells during the degradation of the gel. Polypeptide thermogels as an injectable scaffold can be a promising system for their eventual in vivo applications in stem cell therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Atala A. Regenerative medicine strategies. J Pediatr Surg. 2012;47:17–28.

    Article  PubMed  Google Scholar 

  2. Via AG, Frizziero A, Oliva F. Biological properties of mesenchymal stem cells from different sources. Muscles Ligaments Tendons J. 2012;2:154–62.

    PubMed  Google Scholar 

  3. Griffith LG, Naughton G. Tissue engineering-current challenges and expanding opportunities. Science. 2002;295:1009–14.

    Article  CAS  PubMed  Google Scholar 

  4. Baker BM, Chen CS. Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci. 2012;125:3015–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bonnier F, Keating ME, Wróbel TP, Majzner K, Baranska M, Garcia-Munoz A, et al. Cell viability assessment using the alamar blue assay: a comparison of 2D and 3D cell culture models. Toxicol In Vitro. 2015;29:124–31.

    Article  CAS  PubMed  Google Scholar 

  6. Gauvin R, Chen YC, Lee JW, Soman P, Zorlutuna P, Nichol JW, et al. Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography. Biomaterials. 2012;33:3824–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Choi BG, Park MH, Cho SH, Joo MK, Oh HJ, Kim EH, et al. In situ thermal gelling polypeptide for chondrocytes 3D culture. Biomaterials. 2010;31:9266–72.

    Article  CAS  PubMed  Google Scholar 

  8. Jin GZ, Kim HW. Porous microcarrier-enabled three-dimensional culture of chondrocytes for cartilage engineering: a feasibility study. Tissue Eng Regen Med. 2016;13:235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Petersen OW, Rønnov-Jessen L, Howlett AR, Bissell MJ. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A. 1992;89:9064–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng. 2009;103:655–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lanza R, Langer R, Vacanti J. Principles of tissue engineering. 4th ed. Atlanta: Elsevier Acad; 2013.

    Google Scholar 

  12. Ko DY, Shinde UP, Yeon B, Jeong B. Recent progress of in situ formed gels for biomedical applications. Prog Polym Sci. 2013;38:672–701.

    Article  CAS  Google Scholar 

  13. Loh XJ, Li J. Biodegradable thermosensitive copolymer hydrogels for drug delivery. Expert Opin Ther Pat. 2007;17:965–77.

    Article  CAS  Google Scholar 

  14. Moon HJ, Ko du Y, Park MH, Joo MK, Jeong B. Temperature-responsive compounds as in situ gelling biomedical materials. Chem Soc Rev. 2012;41:4860–83.

    Article  CAS  PubMed  Google Scholar 

  15. Agashi K, Chau DY, Shakesheff KM. The effect of delivery via narrow-bore needles on mesenchymal cells. Regen Med. 2009;4:49–64.

    Article  CAS  PubMed  Google Scholar 

  16. Walker PA, Jimenez F, Gerber MH, Aroom KR, Shah SK, Harting MT, et al. Effect of needle diameter and flow rate on rat and human mesenchymal stromal cell characterization and viability. Tissue Eng Part C Methods. 2010;16:989–97.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Aguado BA, Mulyasasmita W, Su J, Lampe KJ, Heilshorn SC. Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. Tissue Eng Part A. 2012;18:806–15.

    Article  CAS  PubMed  Google Scholar 

  18. Cai L, Dewi RE, Heilshorn SC. Injectable hydrogels with in situ double network formation enhance retention of transplanted stem cells. Adv Funct Mater. 2015;25:1344–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chem Soc Rev. 2008;37:1473–81.

    Article  CAS  PubMed  Google Scholar 

  20. Wang C, Stewart RJ, Kopecek J. Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature. 1999;397:417–20.

    Article  CAS  PubMed  Google Scholar 

  21. Yokoi H, Kinoshita T, Zhang S. Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proc Natl Acad Sci U S A. 2005;102:8414–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Petka WA, Harden JL, McGrath KP, Wirtz D, Tirrell DA. Reversible hydrogels from self-assembling artificial proteins. Science. 1998;281:389–92.

    Article  CAS  PubMed  Google Scholar 

  23. Nowak AP, Breedveld V, Pakstis L, Ozbas B, Pine DJ, Pochan D, et al. Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles. Nature. 2002;417:424–8.

    Article  CAS  PubMed  Google Scholar 

  24. Jones R. Why nanotechnology needs better polymer chemistry. Nat Nanotechnol. 2008;3:699–700.

    Article  CAS  PubMed  Google Scholar 

  25. Deming TJ. Synthetic polypeptides for biomedical applications. Prog Polym Sci. 2007;32:858–75.

    Article  CAS  Google Scholar 

  26. Caliari SR, Burdick JA. A practical guide to hydrogels for cell culture. Nat Methods. 2016;13:405–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Higuchi A, Ling QD, Hsu ST, Umezawa A. Biomimetic cell culture proteins as extracellular matrices for stem cell differentiation. Chem Rev. 2012;112:4507–40.

    Article  CAS  PubMed  Google Scholar 

  28. Zhu J, Kaufman LJ. Collagen I self-assembly: revealing the developing structures that generate turbidity. Biophys J. 2014;106:1822–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hasan A, Khattab A, Islam MA, Hweij KA, Zeitouny J, Waters R, et al. Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv Sci (Weinh). 2015;2:1500122.

    Article  CAS  Google Scholar 

  30. Lanfer B, Seib FP, Freudenberg U, Stamov D, Bley T, Bornhäuser M, et al. The growth and differentiation of mesenchymal stem and progenitor cells cultured on aligned collagen matrices. Biomaterials. 2009;30:5950–8.

    Article  CAS  PubMed  Google Scholar 

  31. Chen XD, Dusevich V, Feng JQ, Manolagas SC, Jilka RL. Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res. 2007;22:1943–56.

    Article  CAS  PubMed  Google Scholar 

  32. Ward DF Jr, Salasznyk RM, Klees RF, Backiel J, Agius P, Bennett K, et al. Mechanical strain enhances extracellular matrix-induced gene focusing and promotes osteogenic differentiation of human mesenchymal stem cells through an extracellular-related kinase-dependent pathway. Stem Cells Dev. 2007;16:467–80.

    Article  CAS  PubMed  Google Scholar 

  33. Park IS, Han M, Rhie JW, Kim SH, Jung Y, Kim IH, et al. The correlation between human adipose-derived stem cells differentiation and cell adhesion mechanism. Biomaterials. 2009;30:6835–43.

    Article  CAS  PubMed  Google Scholar 

  34. Uemura M, Refaat MM, Shinoyama M, Hayashi H, Hashimoto N, Takahashi JJ. Matrigel supports survival and neuronal differentiation of grafted embryonic stem cell-derived neural precursor cells. J Neurosci Res. 2010;88:542–51.

    CAS  PubMed  Google Scholar 

  35. Suzuki A, Iwama A, Miyashita H, Nakauchi H, Taniguchi H. Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development. 2003;130:2513–24.

    Article  CAS  PubMed  Google Scholar 

  36. Donzelli E, Salvadè A, Mimo P, Viganò M, Morrone M, Papagna R, et al. Mesenchymal stem cells cultured on a collagen scaffold: in vitro osteogenic differentiation. Arch Oral Biol. 2007;52:64–73.

    Article  CAS  PubMed  Google Scholar 

  37. Salasznyk RM, Williams WA, Boskey A, Batorsky A, Plopper GE. Adhesion to vitronectin and collagen I promotes osteogenic differentiation of human mesenchymal stem cells. J Biomed Biotechnol. 2004;2004:24–34.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wang J, Yang Q, Mao C, Zhang S. Osteogenic differentiation of bone marrow mesenchymal stem cells on the collagen/silk fibroin bi-template-induced biomimetic bone substitutes. J Biomed Mater Res A. 2012;100:2929–38.

    Article  PubMed  CAS  Google Scholar 

  39. Somaiah C, Kumar A, Mawrie D, Sharma A, Patil SD, Bhattacharyya J, et al. Collagen promotes higher adhesion, survival and proliferation of mesenchymal stem cells. PLoS One. 2015;10:e0145068.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Naito H, Yoshimura M, Mizuno T, Takasawa S, Tojo T, Taniguchi S. The advantages of three-dimensional culture in a collagen hydrogel for stem cell differentiation. J Biomed Mater Res A. 2013;101:2838–45.

    Article  CAS  Google Scholar 

  41. Naito H, Dohi Y, Zimmermann WH, Tojo T, Takasawa S, Eschenhagen T, et al. The effect of mesenchymal stem cell osteoblastic differentiation on the mechanical properties of engineered bone-like tissue. Tissue Eng Part A. 2011;17:2321–9.

    Article  CAS  PubMed  Google Scholar 

  42. George J, Kuboki Y, Miyata T. Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds. Biotechnol Bioeng. 2006;95:404–11.

    Article  CAS  PubMed  Google Scholar 

  43. Di Felice V, Ardizzone NM, De Luca A, Marcianò V, Marino Gammazza A, Macaluso F, et al. OPLA scaffold, collagen I, and horse serum induce a higher degree of myogenic differentiation of adult rat cardiac stem cells. J Cell Physiol. 2009;221:729–39.

    Article  PubMed  CAS  Google Scholar 

  44. Shi C, Li Q, Zhao Y, Chen W, Chen B, Xiao Z, et al. Stem-cell-capturing collagen scaffold promotes cardiac tissue regeneration. Biomaterials. 2011;32:2508–15.

    Article  CAS  PubMed  Google Scholar 

  45. Prabhakaran MP, Venugopal JR, Ramakrishna S. Mesenchymal stem cell differentiation to neuronal cells on electrospun nanofibrous substrates for nerve tissue engineering. Biomaterials. 2009;30:4996–5003.

    Article  CAS  PubMed  Google Scholar 

  46. Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, LaPlaca MC. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med. 2009;3:208–17.

    Article  CAS  PubMed  Google Scholar 

  47. Zheng L, Fan HS, Sun J, Chen XN, Wang G, Zhang L, et al. Chondrogenic differentiation of mesenchymal stem cells induced by collagen-based hydrogel: an in vivo study. J Biomed Mater Res A. 2010;93:783–92.

    CAS  PubMed  Google Scholar 

  48. Lu Z, Doulabi BZ, Huang C, Bank RA, Helder MN. Collagen type II enhances chondrogenesis in adipose tissue-derived stem cells by affecting cell shape. Tissue Eng Part A. 2010;16:81–90.

    Article  CAS  Google Scholar 

  49. Chang CH, Lin HY, Fang HW, Loo ST, Hung SC, Ho YC, et al. Chondrogenesis from immortalized human mesenchymal stem cells: comparison between collagen gel and pellet culture methods. Artif Organs. 2008;32:561–6.

    Article  PubMed  Google Scholar 

  50. Ogawa R, Orgill DP, Murphy GF, Mizuno S. Hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels. Tissue Eng Part A. 2015;21:257–66.

    Article  PubMed  CAS  Google Scholar 

  51. Xie J, Bao M, Bruekers SMC, Huck WTS. Collagen gels with different fibrillar microarchitectures elicit different cellular responses. ACS Appl Mater Interfaces. 2017;9:19630–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T. Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnol Bioeng. 2006;93:1152–63.

    Article  CAS  PubMed  Google Scholar 

  53. Schneider RK, Puellen A, Kramann R, Raupach K, Bornemann J, Knuechel R, et al. The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodeling in three-dimensional collagen scaffolds. Biomaterials. 2010;31:467–80.

    Article  CAS  PubMed  Google Scholar 

  54. Yuan L, Li B, Yang J, Ni Y, Teng Y, Guo L, et al. Effects of composition and mechanical property of injectable collagen I/II composite hydrogels on chondrocyte behaviors. Tissue Eng Part A. 2016;22:899–906.

    Article  CAS  PubMed  Google Scholar 

  55. Mahapatra C, Jin GZ, Kim HW. Alginate-hyaluronic acid-collagen composite hydrogel favorable for the culture of chondrocytes and their phenotype maintenance. Tissue Eng Regen Med. 2016;13:538–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Funayama A, Niki Y, Matsumoto H, Maeno S, Yatabe T, Morioka H, et al. Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model. J Orthop Sci. 2008;13:225–32.

    Article  CAS  PubMed  Google Scholar 

  57. Kontturi LS, Järvinen E, Muhonen V, Collin EC, Pandit AS, Kiviranta I, et al. An injectable in situ forming type II collagen/hyaluronic acid hydrogel vehicle for chondrocyte delivery in cartilage tissue engineering. Drug Deliv Transl Res. 2014;4:149–58.

    Article  CAS  PubMed  Google Scholar 

  58. Jin GZ, Kim HW. Effects of type I collagen concentration in hydrogel on the growth and phenotypic expression of rat chondrocytes. Tissue Eng Regen Med. 2017;14:383–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fu S, Ni P, Wang B, Chu B, Zheng L, Luo F, et al. Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration. Biomaterials. 2012;33:4801–9.

    Article  CAS  PubMed  Google Scholar 

  60. Cunniffe GM, Dickson GR, Partap S, Stanton KT, O’Brien FJ. Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J Mater Sci Mater Med. 2010;21:2293–8.

    Article  CAS  PubMed  Google Scholar 

  61. Curtin CM, Cunniffe GM, Lyons FG, Bessho K, Dickson GR, Duffy GP, et al. Innovative collagen nano-hydroxyapatite scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone formation. Adv Mater. 2012;24:749–54.

    Article  CAS  PubMed  Google Scholar 

  62. Liao S, Nguyen LT, Ngiam M, Wang C, Cheng Z, Chan CK, et al. Biomimetic nanocomposites to control osteogenic differentiation of human mesenchymal stem cells. Adv Healthc Mater. 2014;3:737–51.

    Article  CAS  PubMed  Google Scholar 

  63. Kim SK, Cho TH, Han JJ, Kim IS, Park Y, Hwang SJ. Comparative study of BMP-2 alone and combined with VEGF carried by hydrogel for maxillary alveolar bone regeneration. Tissue Eng Regen Med. 2016;13:171–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Suyama T, Hatta M, Hata S, Ishikawa H, Yamazaki J. Differentiation of rat dermal mesenchymal cells and calcification in three-dimensional cultures. Tissue Eng Regen Med. 2016;13:527–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005;15:378–86.

    Article  CAS  PubMed  Google Scholar 

  66. Norrby K. In vivo models of angiogenesis. J Cell Mol Med. 2006;10:588–612.

    Article  CAS  PubMed  Google Scholar 

  67. Uriel S, Labay E, Francis-Sedlak M, Moya ML, Weichselbaum RR, Ervin N, et al. Extraction and assembly of tissue-derived gels for cell culture and tissue engineering. Tissue Eng Part C Methods. 2009;15:309–21.

    Article  CAS  PubMed  Google Scholar 

  68. Koutsopoulos S, Zhang S. Long-term three-dimensional neural tissue cultures in functionalized self-assembling peptide hydrogels, Matrigel and collagen I. Acta Biomater. 2013;9:5162–9.

    Article  CAS  PubMed  Google Scholar 

  69. Cao F, Sadrzadeh Rafie AH, Abilez OJ, Wang H, Blundo JT, Pruitt B, et al. In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival. J Tissue Eng Regen Med. 2007;1:465–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jin K, Mao X, Xie L, Galvan V, Lai B, Wang Y, et al. Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J Cereb Blood Flow Metab. 2010;30:534–44.

    Article  Google Scholar 

  71. Kothapalli CR, Kamm RD. 3D matrix microenvironment for targeted differentiation of embryonic stem cells into neural and glial lineages. Biomaterials. 2013;34:5995–6007.

    Article  CAS  PubMed  Google Scholar 

  72. Jang JM, Tran SH, Na SC, Jeon NL. Engineering controllable architecture in matrigel for 3D cell alignment. ACS Appl Mater Interfaces. 2015;7:2183–8.

    Article  CAS  PubMed  Google Scholar 

  73. Park YS, Kim HS, Jin YM, Yu Y, Kim HY, Park HS, et al. Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy. Biomaterials. 2015;65:140–52.

    Article  CAS  PubMed  Google Scholar 

  74. Kowalczyk T, Hnatuszko-Konka K, Gerszberg A, Kononowicz AK. Elastin-like polypeptides as a promising family of genetically-engineered protein based polymers. World J Microbiol Biotechnol. 2014;30:2141–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Rodriguez-Cabello JC, Prieto S, Reguera J, Arias FJ, Ribeiro A. Biofunctional design of elastin-like polymers for advanced applications in nanobiotechnology. J Biomater Sci Polymer Ed. 2007;18:269–86.

    Article  CAS  Google Scholar 

  76. Serrano V, Liu W, Franzen S. An infrared spectroscopic study of the conformational transition of elastin-like polypeptides. Biophys J. 2007;93:2429–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Betre H, Liu W, Zalutsky MR, Chilkoti A, Kraus VB, Setton LA. A thermally responsive biopolymer for intra-articular drug delivery. J Control Release. 2006;115:175–82.

    Article  CAS  PubMed  Google Scholar 

  78. Xia XX, Wang M, Lin Y, Xu Q, Kaplan DL. Hydrophobic drug-triggered self-assembly of nanoparticles from silk-elastin-like protein polymers for drug delivery. Biomacromolecules. 2014;15:908–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Betre H, Ong SR, Guilak F, Chilkoti A, Fermor B, Setton LA. Chondrocytic differentiation of human adipose-derived adult stem cells in elastin-like polypeptide. Biomaterials. 2006;27:91–9.

    Article  CAS  PubMed  Google Scholar 

  80. Nettles DL, Chilkoti A, Setton LA. Applications of elastin-like polypeptides in tissue engineering. Adv Drug Deliv Rev. 2010;62:1479–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ravi S, Krishnamurthy VR, Caves JM, Haller CA, Chaikof EL. Maleimide–thiol coupling of a bioactive peptide to an elastin-like protein polymer. Acta Biomater. 2012;8:627–35.

    Article  CAS  PubMed  Google Scholar 

  82. Jin E, Lee PT, Jeon WB, Li WJ. Effects of elastin-like peptide on regulation of human mesenchymal stem cell behavior. Regen Eng Transl Med. 2016;2:85–97.

    Article  Google Scholar 

  83. Wang H, Cai L, Paul A, Enejder A, Heilshorn SC. Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density. Biomacromolecules. 2014;15:3421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lampe KJ, Antaris AL, Heilshorn SC. Design of three-dimensional engineered protein hydrogels for tailored control of neurite growth. Acta Biomater. 2013;9:5590–9.

    Article  CAS  PubMed  Google Scholar 

  85. Gurumurthy B, Bierdeman PC, Janorkar AV. Composition of elastin like polypeptide–collagen composite scaffold influences in vitro osteogenic activity of human adipose derived stem cells. Dent Mater. 2016;32:1270–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhang YN, Avery RK, Vallmajo-Martin Q, Assmann A, Vegh A, Memic A, et al. A highly elastic and rapidly crosslinkable elastin-like polypeptide-based hydrogel for biomedical applications. Adv Funct Mater. 2015;25:4814–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Madl CM, Katz LM, Heilshorn SC. Bio-orthogonally cross-linked, engineered protein hydrogels with tunable mechanics and biochemistry for cell encapsulation. Adv Funct Mater. 2016;26:3612–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. McHale MK, Setton LA, Chilkoti A. Synthesis and in vitro evaluation of enzymatically cross-linked elastin-like polypeptide gels for cartilaginous tissue repair. Tissue Eng. 2005;11:1768–79.

    Article  CAS  PubMed  Google Scholar 

  89. Wang H, Zhu D, Paul A, Cai L, Enejder A, Yang F, et al. Covalently adaptable elastin-like protein–hyaluronic acid (ELP-HA) hybrid hydrogels with secondary thermoresponsive crosslinking for injectable stem cell delivery. Adv Funct Mater. 2017;27:1605609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Patterson J, Martino MM, Hubbell JA. Biomimetic materials in tissue engineering. Mater Today (Kidlington). 2010;13:14–22.

    Article  CAS  Google Scholar 

  91. Jonker AM, Löwik DWPM, van Hest JCM. Peptide- and protein-based hydrogels. Chem Mater. 2012;24:759–73.

    Article  CAS  Google Scholar 

  92. Jeong Y, Joo MK, Bahk KH, Choi YY, Kim HT, Kim WK, et al. Enzymatically degradable temperature-sensitive polypeptide as a new in situ gelling biomaterial. J Control Release. 2009;137:25–30.

    Article  CAS  PubMed  Google Scholar 

  93. Choi YY, Joo MK, Sohn YS, Jeong B. Significance of secondary structure in nanostructure formation and thermosensitivity of polypeptide block copolymer. Soft Matter. 2008;4:2383–7.

    Article  CAS  Google Scholar 

  94. Moon HJ, Choi BG, Park MH, Joo MK, Jeong B. Enzymatically degradable thermogelling poly(alanine-co-leucine)-poloxamer-poly(alanine-co-leucine). Biomacromolecules. 2011;12:1234–42.

    Article  CAS  Google Scholar 

  95. Kim JY, Park MH, Joo MK, Lee SY, Jeong B. End groups adjust molecular nano-assembly pattern and thermal gelation of polypeptide block copolymer aqueous solution. Macromolecules. 2009;42:3147–51.

    Article  CAS  Google Scholar 

  96. Lee H, Choi BG, Moon HJ, Choi J, Park K, Jeong B, et al. Chondrocyte 3D-culture in RGD-modified crosslinked hydrogel with temperature-controllable modulus. Macromol Res. 2012;20:106–11.

    Article  CAS  Google Scholar 

  97. Choi BG, Park MH, Cho SH, Joo MK, Oh HJ, Kim EH, et al. Thermal gelling polyalanine-poloxamine-polyalanine aqueous solution for chondrocytes 3D culture: initial concentration effect. Soft Matter. 2011;7:456–62.

    Article  CAS  Google Scholar 

  98. Park MH, Moon HJ, Park JH, Shinde UP, Ko du Y, Jeong B. PEG-Poly(l-alanine) thermogel as a 3D scaffold of bone-marrow-derived mesenchymal stem cells. Macromol Biosci. 2015;15:464–72.

    Article  CAS  PubMed  Google Scholar 

  99. Park MH, Yu Y, Moon HJ, Ko du Y, Kim HS, Lee H, et al. 3D culture of tonsil- derived mesenchymal stem cells in poly (ethylene glycol)-poly(l-alanine-co-l-phenyl alanine) thermogel. Adv Healthc Mater. 2014;3:1782–91.

    Article  CAS  PubMed  Google Scholar 

  100. Yeon B, Park MH, Moon HJ, Kim SJ, Cheon YW, Jeong B. 3D culture of adipose-tissue-derived stem cells mainly leads to chondrogenesis in poly (ethylene glycol)-poly (l-alanine) diblock copolymer thermogel. Biomacromolecules. 2013;14:3256–66.

    Article  CAS  Google Scholar 

  101. Kim SJ, Park MH, Moon HJ, Park JH, Ko du Y, Jeong B. Polypeptide thermogels as a three dimensional culture scaffold for hepatogenic differentiation of human tonsil-derived mesenchymal stem cells. ACS Appl Mater Interfaces. 2014;6:17034–43.

    Article  CAS  Google Scholar 

  102. Hong JH, Lee HJ, Jeong B. Injectable polypeptide thermogel as a tissue engineering system for hepatogenic differentiation of tonsil-derived mesenchymal stem cells. ACS Appl Mater Interfaces. 2017;9:11568–76.

    Article  CAS  PubMed  Google Scholar 

  103. Kye EJ, Kim SJ, Park MH, Moon HJ, Ryu KH, Jeong B. Differentiation of tonsil-tissue-derived mesenchymal stem cells controlled by surface-functionalized microspheres in PEG polypeptide thermogels. Biomacromolecules. 2014;15:2180–7.

    Article  CAS  PubMed  Google Scholar 

  104. Lee SS, Choi GE, Lee HJ, Kim Y, Choy JH, Jeong B. Layered double hydroxide and polypeptide thermogel nanocomposite system for chondrogenic differentiation of stem cells. ACS Appl Mater Interfaces. 2017;9:42668–75.

    Article  CAS  PubMed  Google Scholar 

  105. Park J, Kim IY, Patel M, Moon HJ, Hwang SJ, Jeong B. 2D and 3D hybrid systems for enhancement of chondrogenic differentiation of tonsil-derived mesenchymal stem cells. Adv Funct Mater. 2015;25:2573–82.

    Article  CAS  Google Scholar 

  106. Patel M, Moon HJ, Ko du Y, Jeong B. Composite system of graphene oxide and polypeptide thermogel as an injectable 3D scaffold for adipogenic differentiation of tonsil- derived mesenchymal stem cells. ACS Appl Mater Interfaces. 2016;8:5160–9.

    Article  CAS  PubMed  Google Scholar 

  107. Moon HJ, Patel M, Chung H, Jeong B. Nanocomposite versus mesocomposite for osteogenic differentiation of tonsil-derived mesenchymal stem cells. Adv Healthc Mater. 2016;5:353–63.

    Article  CAS  PubMed  Google Scholar 

  108. Patel M, Moon HJ, Jung BK, Jeong B. Microsphere-incorporated hybrid thermogel for neuronal differentiation of tonsil derived mesenchymal stem cells. Adv Healthc Mater. 2015;4:1565–74.

    Article  CAS  PubMed  Google Scholar 

  109. Moon HJ, Lee HJ, Patel M, Park S, Chang SH, Jeong B. Hepatogenic supported differentiation of mesenchymal stem cells in a lactobionic acid-conjugated thermogel. ACS Macro Lett. 2017;6:1305–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (2017R1A2B2007356, 2017R1A5A1015365, and 2014M3A9B6034223). MP and HJL equally contributed to this paper.

Author information

Authors and Affiliations

  1. Department of Chemistry and Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Korea

    Madhumita Patel, Sohee Park, Hyun Jung Lee & Byeongmoon Jeong

Authors
  1. Madhumita Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sohee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun Jung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byeongmoon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Byeongmoon Jeong.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

Ethical statement

There are no animal experiments carried out for this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, M., Park, S., Lee, H.J. et al. Polypeptide Thermogels as Three-Dimensional Scaffolds for Cells. Tissue Eng Regen Med 15, 521–530 (2018). https://doi.org/10.1007/s13770-018-0148-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-018-0148-4

Keywords

Search

Navigation