Abstract
Scaffolds with cartilage-like environment and suitable physical properties are critical for tissue-engineered cartilage repair. In this study, decellularized porcine cartilage-derived extracellular matrix (ECM) was utilized to fabricate ECM scaffolds. Mechanically reinforced ECM scaffolds were developed by combining salt-leaching and crosslinking for cartilage repair. The developed scaffolds were investigated with respect to their physicochemical properties and their cartilage tissue formation ability. The mechanically reinforced ECM scaffold showed similar mechanical strength to that of synthetic PLGA scaffold and expressed higher levels of cartilage-specific markers compared to those expressed by the ECM scaffold prepared by simple freeze-drying. These results demonstrated that the physical properties of ECM-derived scaffolds could be influenced by fabrication method, which provides suitable environments for the growth of chondrocytes. By extension, this study suggests a promising approach of natural biomaterials in cartilage tissue engineering.
Similar content being viewed by others
References
Patra D, Sandell LJ. Antiangiogenic and anticancer molecules in cartilage. Expert Rev Mol Med. 2012;14:e10.
Huh SW, Shetty AA, Kim JM, Cho ML, Kim SA, Yang S, et al. Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee. Tissue Eng Regen Med. 2016;13:200–9.
Chung C, Burdick JA. Engineering cartilage tissue. Adv Drug Deliv Rev. 2008;60:243–62.
Lee J, Im GI. Effects of trichostatin A on the chondrogenesis from human mesenchymal stem cells. Tissue Eng Regen Med. 2017;14:403–10.
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.
Chua ILS, Kim HW, Lee JH. Signaling of extracellular matrices for tissue regeneration and therapeutics. Tissue Eng Regen Med. 2016;13:1–12.
Jia S, Liu L, Pan W, Meng G, Duan C, Zhang L, et al. Oriented cartilage extracellular matrix-derived scaffold for cartilage tissue engineering. J Biosci Bioeng. 2012;113:647–53.
Zhang Y, Yang F, Liu K, Shen H, Zhu Y, Zhang W, et al. The impact of PLGA scaffold orientation on in vitro cartilage regeneration. Biomaterials. 2012;33:2926–35.
Choi KH, Song BR, Choi BH, Lee M, Park SR, Min BH. Cartilage tissue engineering using chondrocyte-derived extracellular matrix scaffold suppressed vessel invasion during chondrogenesis of mesenchymal stem cells in vivo. Tissue Eng Regen Med. 2012;9:43–50.
Bryant SJ, Anseth KS. Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. J Biomed Mater Res. 2002;59:63–72.
Shin YS, Lee JS, Choi JW, Min BH, Chang JW, Lim JY, et al. Transplantation of autologous chondrocytes seeded on a fibrin/hyaluronic acid composite gel into vocal fold in rabbits: preliminary results. Tissue Eng Regen Med. 2012;9:203–8.
Kim HJ, Kim KK, Park IK, Choi BS, Kim JH, Kim MS. Hybrid scaffolds composed of hyaluronic acid and collagen for cartilage regeneration. Tissue Eng Regen Med. 2012;9:57–62.
Mahmod SA, Snigh S, Djordjevic I, Yee YM, Yusof R, Ramasamy TS, et al. Phytoestrogen (daidzein) promotes chondrogenic phenotype of human chondrocytes in 2D and 3D culture systems. Tissue Eng Regen Med. 2017;14:103–12.
Luo X, Kulig KM, Finkelstein EB, Nicholson MF, Liu XH, Goldman SM, et al. In vitro evaluation of decellularized ECM-derived surgical scaffold biomaterials. J Biomed Mater Res B Appl Biomater. 2017;105:585–93.
Guan Y, Liu S, Liu Y, Sun C, Cheng G, Luan Y, et al. Porcine kidneys as a source of ECM scaffold for kidney regeneration. Mater Sci Eng C Mater Biol Appl. 2015;56:451–6.
Sreejit P, Verma RS. Natural ECM as biomaterial for scaffold based cardiac regeneration using adult bone marrow derived stem cells. Stem Cell Rev. 2013;9:158–71.
Cheng NC, Estes BT, Awad HA, Guilak F. Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Eng Part A. 2009;15:231–41.
Yang Q, Peng J, Guo Q, Huang J, Zhang L, Yao J, et al. A cartilage ECM-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells. Biomaterials. 2008;29:2378–87.
Choi BH, Choi KH, Lee HS, Song BR, Park SR, Yang JW, et al. Inhibition of blood vessel formation by a chondrocyte-derived extracellular matrix. Biomaterials. 2014;35:5711–20.
Chiang H, Jiang CC. Repair of articular cartilage defects: review and perspectives. J Formos Med Assoc. 2009;108:87–101.
Lu L, Zhu X, Valenzuela RG, Currier BL, Yaszemski MJ. Biodegradable polymer scaffolds for cartilage tissue engineering. Clin Orthop Relat Res. 2001;391:S251–70.
Bacáková L, Filová E, Rypácek F, Svorcík V, Starý V. Cell adhesion on artificial materials for tissue engineering. Physiol Res. 2004;53:S35–45.
Moroni L, de Wijn JR, van Blitterswijk CA. 3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties. Biomaterials. 2006;27:974–85.
Nettles DL, Elder SH, Gilbert JA. Potential use of chitosan as a cell scaffold material for cartilage tissue engineering. Tissue Eng. 2002;8:1009–16.
Yang Z, Shi Y, Wei X, He J, Yang S, Dickson G, et al. Fabrication and repair of cartilage defects with a novel acellular cartilage matrix scaffold. Tissue Eng Part C Methods. 2010;16:865–76.
Liang Q, Wang L, Sun W, Wang Z, Xu J, Ma H. Isolation and characterization of collagen from the cartilage of Amur sturgeon (Acipenser schrenckii). Process Biochem. 2014;49:318–23.
Rieppo L, Saarakkala S, Närhi T, Helminen HJ, Jurvelin JS, Rieppo J. Application of second derivative spectroscopy for increasing molecular specificity of Fourier transform infrared spectroscopic imaging of articular cartilage. Osteoarthritis Cartilage. 2012;20:451–9.
Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials. 2006;27:3675–83.
Elder BD, Eleswarapu SV, Athanasiou KA. Extraction techniques for the decellularization of tissue engineered articular cartilage constructs. Biomaterials. 2009;30:3749–56.
Ozeki M, Narita Y, Kagami H, Ohmiya N, Itoh A, Hirooka Y, et al. Evaluation of decellularized esophagus as a scaffold for cultured esophageal epithelial cells. J Biomed Mater Res A. 2006;79:771–8.
Liao CJ, Chen CF, Chen JH, Chiang SF, Lin YJ, Chang KY. Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method. J Biomed Mater Res. 2002;59:676–81.
Mikos AG, Sarakinos G, Leite SM, Vacanti JP, Langer R. Laminated three-dimensional biodegradable foams for use in tissue engineering. Biomaterials. 1993;14:323–30.
Haugh MG, Murphy CM, O’Brien FJ. Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes. Tissue Eng Part C Methods. 2010;16:887–94.
Griffon DJ, Sedighi MR, Schaeffer DV, Eurell JA, Johnson AL. Chitosan scaffolds: interconnective pore size and cartilage engineering. Acta Biomater. 2006;2:313–20.
Tan JY, Chua CK, Leong KF. Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique. Biomed Microdevices. 2013;15:83–96.
Fiorani A, Gualandi C, Panseri S, Montesi M, Marcacci M, Focarete ML, et al. Comparative performance of collagen nanofibers electrospun from different solvents and stabilized by different crosslinkers. J Mater Sci Mater Med. 2014;25:2313–21.
Hu Y, Liu L, Dan W, Dan N, Gu Z, Yu X. Synergistic effect of carbodiimide and dehydrothermal crosslinking on acellular dermal matrix. Int J Biol Macromol. 2013;55:221–30.
Grover CN, Cameron RE, Best SM. Investigating the morphological, mechanical and degradation properties of scaffolds comprising collagen, gelatin and elastin for use in soft tissue engineering. J Mech Behav Biomed Mater. 2012;10:62–74.
Young JJ, Cheng KM, Tsou TL, Liu HW, Wang HJ. Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide. J Biomater Sci Polym Ed. 2004;15:767–80.
Staros JV, Wright RW, Swingle DM. Enhancement by N-hydroxysulfosuccinimide of water-soluble carbodiimide-mediated coupling reactions. Anal Biochem. 1986;156:220–2.
Cohen NP, Foster RJ, Mow VC. Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state. J Orthop Sports Phys Ther. 1998;28:203–15.
Wenzel RN. Resistance of solid surfaces to wetting by water. Ind Eng Chem. 1936;28:988–94.
Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310:1139–43.
Kong HJ, Polte TR, Alsberg E, Mooney DJ. FRET measurements of cell-traction forces and nano-scale clustering of adhesion ligands varied by substrate stiffness. Proc Natl Acad Sci U S A. 2005;102:4300–5.
Athanasiou KA, Agarwal A, Dzida FJ. Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage. J Orthop Res. 1994;12:340–9.
Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC. Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res. 1991;9:330–40.
Acknowledgements
This research was supported by the National Research Foundation Grant (NRF-2017R1C1B2008327) and funded by the Korea Health Industry Development Institute in Ministry of Health & Welfare, Republic of Korea (HI14C0744).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical statement
All experimental protocols were approved by the Institutional Review Board at Ajou University (Approval No. AJIRB-MED-SMP-10-266).
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary figure 1
Mechanical strengths comparison of native cartilage, PLGA-br, PCP-br and PCP-sp. (TIFF 59459 kb)
Rights and permissions
About this article
Cite this article
Oh, H.J., Kim, S.H., Cho, JH. et al. Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering. Tissue Eng Regen Med 15, 287–299 (2018). https://doi.org/10.1007/s13770-018-0114-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13770-018-0114-1