Abstract
Conventional methods have failed to show the ability of articular cartilage to completely restore. Decellularized extracellular matrix has achieved interest as a potential biomaterial for cartilage tissue engineering approaches. The decellularized cartilage-derived matrix (CDM) scaffolds retain the native composition of cartilage tissue, providing a conducive microenvironment for cellular growth and differentiation, while exhibit limited mechanical support. Our investigation involved the fabrication of a new hybrid CDM- polyvinyl alcohol (PVA) hydrogel scaffold with four different concentrations (5%, 10%, 15%, and 20%), followed by a comprehensive characterization of the construct’s physicochemical, mechanical, and biological properties to elucidate their potential in cartilage regeneration applications. Our results demonstrated that hybridization of the CDM with PVA enhanced the mechanical properties besides ensuring biocompatibility. FTIR and DSC results also confirmed the mechanical improvements in hybrid scaffolds. The hybrid CDM/PVA (15%/5%, 15%/10%, 15%/15%, and 15%/20%) scaffolds showed significantly different compressive strengths (p < 0.0001, p < 0.0004, p < 0.0001, p < 0.012 respectively). Moreover, resazurin test showed cell attachment and growth on all four types of hybrid scaffolds during seven days of three dimensional culture. The cross-linked CDM15%/PVA5% group, demonstrated acceptable mechanical strength, pore size, physicochemical properties, swelling behavior, and cell growth and attachment. Our data indicate that our hybrid CDM/PVA scaffold possess bioactive properties suitable for a promising candidate for cartilage tissue engineering studies.
Similar content being viewed by others
Data Availability
No datasets were generated or analysed during the current study.
References
Diseases GBD, Injuries C (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of Disease Study 2019. Lancet 10258:1204Doi. https://doi.org/10.1016/S0140-6736(20)30925-9
Dai W, Liu Q (2023) Functional injectable hydrogel with spatiotemporal sequential release for recruitment of endogenous stem cells and in situ cartilage regeneration. J Mater Chem B 18:4050Doi. https://doi.org/10.1039/d3tb00105a
Niu X, Li N (2023) Integrated gradient tissue-engineered osteochondral scaffolds: challenges, current efforts and future perspectives. Bioact Mater 574;Doi. https://doi.org/10.1016/j.bioactmat.2022.06.011
Mithoefer K, McAdams T (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 10(2053). https://doi.org/10.1177/0363546508328414
Bannuru RR, Osani MC (2019) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 11(1578). https://doi.org/10.1016/j.joca.2019.06.011
Vinod E, Parasuraman G (2023) Human fetal cartilage-derived chondrocytes and chondroprogenitors display a greater commitment to chondrogenesis than adult cartilage resident cells. PLoS ONE 4:e0285106. https://doi.org/10.1371/journal.pone.0285106
Yari D, MH Ebrahimzadeh (2022) Biochemical aspects of scaffolds for cartilage tissue Engineering; from Basic Science to Regenerative Medicine. Arch Bone Jt Surg 3(229). https://doi.org/10.22038/ABJS.2022.55549.2766
Jess R, Ling T (2023) Mechanical environment for in vitro cartilage tissue engineering assisted by in silico models. Biomater Transl 1:18Doi. https://doi.org/10.12336/biomatertransl.2023.01.004
Yang Z, Shi Y (2010) Fabrication and repair of cartilage defects with a novel acellular cartilage matrix scaffold. Tissue Eng Part C Methods 5(865). https://doi.org/10.1089/ten.TEC.2009.0444
Ramzan F, Ekram S (2022) Decellularized human umbilical tissue-derived hydrogels promote proliferation and chondrogenic differentiation of mesenchymal stem cells. Bioeng (Basel) 6. https://doi.org/10.3390/bioengineering9060239
Rana D, Zreiqat H (2017) Development of decellularized scaffolds for stem cell-driven tissue engineering. J Tissue Eng Regen Med 4(942). https://doi.org/10.1002/term.2061
Yu TH, Yeh TT (2022) Preparation and characterization of Extracellular Matrix Hydrogels Derived from Acellular cartilage tissue. J Funct Biomater 4Doi. https://doi.org/10.3390/jfb13040279
Ma L, Zheng X (2022) Knee osteoarthritis therapy: recent advances in Intra-articular Drug Delivery systems. Drug Des Devel Ther 1311. https://doi.org/10.2147/DDDT.S357386
Sun W, Yang Y (2022) Utilization of an Acellular cartilage matrix-based Photocrosslinking Hydrogel for Tracheal Cartilage Regeneration and Circumferential Tracheal Repair. 31:2201257;Doi:https://doi.org/10.1002/adfm.202201257
Intini C, Lemoine M (2022) A highly porous type II collagen containing scaffold for the treatment of cartilage defects enhances MSC chondrogenesis and early cartilaginous matrix deposition. Biomater Sci 4:970Doi. https://doi.org/10.1039/d1bm01417j
Intini C, Hodgkinson T (2022) Highly Porous Type II Collagen-Containing Scaffolds for Enhanced Cartilage Repair with Reduced Hypertrophic Cartilage Formation. Bioengineering (Basel) 6;https://doi.org/10.3390/bioengineering9060232
Yari D, Ehsanbakhsh Z (2020) Association of TIMP-1 and COL4A4 gene polymorphisms with Keratoconus in an Iranian Population. J Ophthalmic Vis Res 3(299). https://doi.org/10.18502/jovr.v15i3.7448
Rowland CR, Little D (2012) Factors influencing the long-term behavior of extracellular matrix-derived scaffolds for musculoskeletal soft tissue repair. J Long Term Eff Med Implants 3(181). https://doi.org/10.1615/jlongtermeffmedimplants.2013006120
Sevastianov VI, Basok YB (2023) Decellularization of cartilage microparticles: effects of temperature, supercritical carbon dioxide and ultrasound on biochemical, mechanical, and biological properties. J Biomed Mater Res A 4:543Doi. https://doi.org/10.1002/jbm.a.37474
saberi A, Khodaverdi E (2023) Fabrication and characterization of Biomimetic Electrospun Cartilage Decellularized Matrix (CDM)/Chitosan Nanofiber Hybrid for Tissue Engineering Applications: Box-Behnken design for optimization. J Polym Environ. https://doi.org/10.1007/s10924-023-03065-9
Cheng NC, Estes BT (2009) Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Eng Part A 2:231Doi. https://doi.org/10.1089/ten.tea.2008.0253
Cheng NC, Estes BT (2011) Engineered cartilage using primary chondrocytes cultured in a porous cartilage-derived matrix. Regen Med 1(81). https://doi.org/10.2217/rme.10.87
Diekman BO, Rowland CR (2010) Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A 2:523Doi. https://doi.org/10.1089/ten.TEA.2009.0398
Moradi A, Ataollahi F (2016) Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells. J Biomed Mater Res A 1:245Doi. https://doi.org/10.1002/jbm.a.35561
Lee JK, Huwe LW (2017) Tension stimulation drives tissue formation in scaffold-free systems. Nat Mater 8:864Doi. https://doi.org/10.1038/nmat4917
Stampoultzis T, Guo Y (2023) Low-oxygen tension augments chondrocyte sensitivity to biomimetic thermomechanical cues in cartilage-engineered constructs. iScience 8:107491Doi. https://doi.org/10.1016/j.isci.2023.107491
Terzopoulou Z, Zamboulis A (2022) Biocompatible synthetic polymers for tissue Engineering purposes. Biomacromolecules 5:1841Doi. https://doi.org/10.1021/acs.biomac.2c00047
Sardinha VM, Lima LL (2013) Tribological characterization of polyvinyl alcohol hydrogel as substitute of articular cartilage. Wear. https://doi.org/10.1016/j.wear.2012.11.054. 1:218;Doi
Farsi M, Asefnejad A (2022) A hyaluronic acid/PVA electrospun coating on 3D printed PLA scaffold for orthopedic application. Prog Biomater 1:67Doi. https://doi.org/10.1007/s40204-022-00180-z
Irawan V, TC Sung (2018) Collagen scaffolds in cartilage tissue Engineering and relevant approaches for Future Development. Tissue Eng Regen Med 6:673Doi. https://doi.org/10.1007/s13770-018-0135-9
Sanchez-Tellez DA, Tellez-Jurado L (2017) Hydrogels for cartilage regeneration, from Polysaccharides to hybrids. Polym (Basel) 12. https://doi.org/10.3390/polym9120671
Ghassemi T, Saghatolslami N (2017) CNT-decellularized cartilage hybrids for tissue engineering applications. Biomed Mater 6:065008. https://doi.org/10.1088/1748-605X/aa8435
Shen Y, Xu Y (2021) Engineering a highly biomimetic Chitosan-Based Cartilage Scaffold by using short fibers and a cartilage-decellularized Matrix. Biomacromolecules 5(2284). https://doi.org/10.1021/acs.biomac.1c00366
Lin IC, Wang TJ (2020) Chitosan-cartilage extracellular matrix hybrid scaffold induces chondrogenic differentiation to adipose-derived stem cells. Regen Ther 238. https://doi.org/10.1016/j.reth.2020.03.014
Han Y, Lian M (2022) Study on bioactive PEGDA/ECM hybrid bi-layered hydrogel scaffolds fabricated by electro-writing for cartilage regeneration. Appl Mater Today. https://doi.org/10.1016/j.apmt.2022.101547. 101547;Doi
Rynkowska E, Fatyeyeva K (2019) Chemically and thermally crosslinked PVA-Based membranes: Effect on Swelling and Transport Behavior. Polym (Basel) 11. https://doi.org/10.3390/polym11111799
Pinheiro A, Cooley A (2016) Comparison of natural crosslinking agents for the stabilization of xenogenic articular cartilage. J Orthop Res 6:1037. https://doi.org/10.1002/jor.23121
Yang G, Xiao Z (2018) Assessment of the characteristics and biocompatibility of gelatin sponge scaffolds prepared by various crosslinking methods. Sci Rep 1(1616). https://doi.org/10.1038/s41598-018-20006-y
Moradi A, Pramanik S (2014) A comparison study of different physical treatments on cartilage matrix derived porous scaffolds for tissue engineering applications. Sci Technol Adv Mater 6(065001). https://doi.org/10.1088/1468-6996/15/6/065001
Ghassemi T, Saghatoleslami N (2019) A comparison study of different decellularization treatments on bovine articular cartilage. J Tissue Eng Regen Med 10:1861Doi. https://doi.org/10.1002/term.2936
Rahman MA, Sultana N (2022) Alcoholic fixation over formalin fixation: a new, safer option for morphologic and molecular analysis of tissues. Saudi J Biol Sci 1. https://doi.org/10.1016/j.sjbs.2021.08.075. :175;Doi
Davis S, Roldo M (2021) Influence of the mechanical environment on the regeneration of Osteochondral defects. Front Bioeng Biotechnol 603408Doi. https://doi.org/10.3389/fbioe.2021.603408
Wang W, Jin X (2016) Effect of vapor-phase glutaraldehyde crosslinking on electrospun starch fibers. Carbohydr Polym 356;Doi. https://doi.org/10.1016/j.carbpol.2015.12.061
Lan W, Xu M (2021) Physicochemical properties and biocompatibility of the bi-layer polyvinyl alcohol-based hydrogel for osteochondral tissue engineering. Mater Design. https://doi.org/10.1016/j.matdes.2021.109652. 109652;Doi
Kim YS, Majid M (2019) Applications of decellularized extracellular matrix in bone and cartilage tissue engineering. Bioeng Transl Med 1(83). https://doi.org/10.1002/btm2.10110
BH, León-Mancilla MA, Araiza-Téllez (2016) Physico-chemical characterization of collagen scaffolds for tissue engineering. J Appl Res Technol. https://doi.org/10.1016/j.jart.2016.01.001. 1:77;Doi:
Chen Q, Liu S (2022) Construction and Tribological properties of Biomimetic cartilage-lubricating hydrogels. Gels 7Doi. https://doi.org/10.3390/gels8070415
Parisi C, Salvatore L (2020) Biomimetic gradient scaffold of collagen-hydroxyapatite for osteochondral regeneration. J Tissue Eng 2041731419896068Doi. https://doi.org/10.1177/2041731419896068
Bartos M, Suchy T (2018) Note on the use of different approaches to determine the pore sizes of tissue engineering scaffolds: what do we measure? Biomed Eng Online 1(110). https://doi.org/10.1186/s12938-018-0543-z
Lin HY, Tsai WC (2017) Collagen-PVA aligned nanofiber on collagen sponge as bi-layered scaffold for surface cartilage repair. J Biomater Sci Polym Ed 7(664). https://doi.org/10.1080/09205063.2017.1295507
Park Y, You M (2019) Thermal conductivity enhancement in electrospun poly(vinyl alcohol) and poly(vinyl alcohol)/cellulose nanocrystal composite nanofibers. Sci Rep 1(3026). https://doi.org/10.1038/s41598-019-39825-8
Furuike T, Chaochai T (2016) Fabrication of nonwoven fabrics consisting of gelatin nanofibers cross-linked by glutaraldehyde or N-acetyl-d-glucosamine by aqueous method. Int J Biol Macromol Pt B. https://doi.org/10.1016/j.ijbiomac.2016.03.053. :1530;Doi
Hendrawan H, Khoerunnisa F (2019) Poly (vinyl alcohol)/glutaraldehyde/Premna oblongifolia merr extract hydrogel for controlled-release and water absorption application. IOP Conference Series: Materials Science and Engineering 1:012048;https://doi.org/10.1088/1757-899X/509/1/012048
Chitosan/PVA Nanofibers as Potential Material for the Development of Soft Actuators (2023)
Kwon H, WE Brown (2019) Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol 9(550). https://doi.org/10.1038/s41584-019-0255-1
Rogan H, Ilagan F (2019) Comparing single cell Versus Pellet Encapsulation of Mesenchymal Stem cells in three-dimensional hydrogels for cartilage regeneration. Tissue Eng Part A. 19–20:1404;Doi https://doi.org/10.1089/ten.TEA.2018.0289
Zhang W, Du A (2021) Research progress in decellularized extracellular matrix-derived hydrogels. Regen Ther 88. https://doi.org/10.1016/j.reth.2021.04.002
Tan J, Zhang QY (2021) Decellularized scaffold and its elicited immune response towards the host: the underlying mechanism and means of immunomodulatory modification. Biomater Sci 14:4803Doi. https://doi.org/10.1039/d1bm00470k
Fox AJS, Bedi A (2009) The basic science of articular cartilage: structure, composition, and function. Sports Health 6(461). https://doi.org/10.1177/1941738109350438
Setton LA, Elliott DM (1999) Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage 1(2). https://doi.org/10.1053/joca.1998.0170
Vikingsson L, Gallego Ferrer G (2014) An in vitro experimental model to predict the mechanical behavior of macroporous scaffolds implanted in articular cartilage. J Mech Behav Biomed Mater 125Doi. https://doi.org/10.1016/j.jmbbm.2013.12.024
Cai S, Wu C (2020) Recent advance in surface modification for regulating cell adhesion and behaviors. 1:971;Doi:https://doi.org/10.1515/ntrev-2020-0076
Poursamar SA, Lehner AN (2016) The effects of crosslinkers on physical, mechanical, and cytotoxic properties of gelatin sponge prepared via in-situ gas foaming method as a tissue engineering scaffold. Mater Sci Eng C Mater Biol Appl 1;Doi. https://doi.org/10.1016/j.msec.2016.02.034
Thankam FG, Muthu J (2014) Influence of physical and mechanical properties of amphiphilic biosynthetic hydrogels on long-term cell viability. J Mech Behav Biomed Mater 111Doi. https://doi.org/10.1016/j.jmbbm.2014.03.010
Jelodari S, Ebrahimi Sadrabadi A (2022) New insights into cartilage tissue Engineering: improvement of tissue-Scaffold integration to enhance cartilage regeneration. Biomed Res Int 7638245Doi. https://doi.org/10.1155/2022/7638245
Ng KW, Wanivenhaus F (2012) A novel macroporous polyvinyl alcohol scaffold promotes chondrocyte migration and interface formation in an in vitro cartilage defect model. Tissue Eng Part A 1273;11–12. https://doi.org/10.1089/ten.TEA.2011.0276
Funding
This research was financially supported by Babol University of Medical Sciences. (Thesis no: 9807730 and ethical code: IR. MUBABO.REC.1398.019).
Author information
Authors and Affiliations
Contributions
DY: Investigation, Data curation, Project administration, Methodology, Writing- Original draft, Visualization; JM: Supervision, Validation; ME: Resources, Investigation; AS: Investigation, Visualization; DQ; Validation, Supervision, Reviewing, Funding acquisition; AM: Conceptualization, Methodology, Supervision, Reviewing and Editing.
Corresponding authors
Ethics declarations
Competing Interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yari, D., Movaffagh, J., Ebrahimzadeh, M.H. et al. Biomimetic ECM-Based Hybrid Scaffold for Cartilage Tissue Engineering Applications. J Polym Environ (2024). https://doi.org/10.1007/s10924-024-03230-8
Accepted:
Published:
DOI: https://doi.org/10.1007/s10924-024-03230-8