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RESEARCH ARTICLE

3D-printed variable stiffness tissue scaffolds for potential meniscus repair

Caroline A. Murphy1 ,  Aleksandra Serafin1,2 ,  Ibrahim Fatih Cengiz3,4 ,  Rui L. Reis3,4 ,  Joaquim Miguel Oliveira3,4 ,  Maurice N. Collins1,2,5*
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1 Stokes Laboratories, Bernal Institute, School of Engineering, University of Limerick, Limerick, Ireland
2 Health Research Institute, University of Limerick, Limerick, V94 T9PX, Ireland
3 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
4 ICVS/3B’s–PT Government Associate Laboratory, Guimarães, Portugal
5 SFI Centre for Advanced Materials and BioEngineering Research, D02 PN40 Dublin, Ireland
IJB 2024, 10(4), 3784 https://doi.org/10.36922/ijb.3784
Submitted: 29 May 2024 | Accepted: 9 July 2024 | Published: 12 August 2024
(This article belongs to the Special Issue Biomimetic and Bioinspired Printed Structures)
© 2024 by the Author(s).. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The treatment of meniscus injuries has recently shifted toward the field of tissue engineering (TE). In this work, bovine menisci were characterized, and the regionally-dependent mechanical properties were analyzed. Three-dimensional (3D) printing technology was employed to produce a scaffold that mimicked the mechanical properties of the meniscus. A polycaprolactone (PCL) meniscus scaffold was 3D printed, allowing for the deposition of fibers mimicking the internal architecture of the native meniscus, while achieving regional and variable mechanical stiffness, varying from 2.74 to 0.88 MPa. The PCL scaffold was infiltrated with extracellular matrix (ECM)-like hydrogels composed of gelatin methacrylate (GelMA) and glycosaminoglycans (GAGs), such as hyaluronic acid (HA) and chondroitin sulfate (CS), and subsequently freeze-dried. Human mesenchymal stem cells were seeded onto the scaffolds, and the infiltrated cells were observed to produce ECM components of the native meniscus. Collagen and GAGs production was successfully established. The synthesis of a new matrix reportedly enhances the mechanical properties of the hydrogel over time. Additionally, the circumferential PCL fibers within the scaffold guided the newly synthesized matrix, facilitating replication of the native tissue structure. These results indicate that the ECM-infiltrated 3D-printed PCL scaffold is a promising solution for meniscus repair.

Keywords
3D printing
Biomaterials
Biomechanics
Hydrogels
Meniscus
Repair
Scaffolds
Funding
The authors would like to thank the funding provided by the Irish Research Council (Project ID: EPSPG/2015/93) in partnership with Johnson & Johnson and the Government of Ireland (Postdoctoral Fellowship Project ID: GOIPD/2023/1431). I.F.C. thanks the Portuguese Foundation for Science and Technology (FCT) and acknowledges the FCT distinction attributed to I.F.C. under the Estímulo ao Emprego Científico program (2021.01969. CEECIND) (https://doi.org/10.54499/2021.01969. CEECIND/CP1664/CT0017). This study received financial support from the European Commission-funded Oncoscreen project (Grant agreement ID: 101097036). The authors also thank the FEDER program for funds provided under the JUSTHera project (NORTE-01-0145- FEDER-000055) and the 0624_2IQBIONEURO_6_E project (inter-regional cooperation program VA Spain- Portugal POCTEP 2014–2020). The authors thank the financial support provided under the project “HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases” (NORTE-01- 0145-FEDER-000039), funded by the NORTE2020 Program, Norte Portugal Regional Coordination and Development Commission (CCDR-N). The authors also thank FCT for funding LA ICVS/3B: (i) “Base” funding (https://doi.org/10.54499/UIDB/50026/2020); (ii) “Programático” funding: (https://doi.org/10.54499/ UIDP/50026/2020); and iii) “Complementar - LA” funding: (https://doi.org/10.54499/LA/P/0050/2020).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Zhang K, Li L, Yang L, et al. The biomechanical changes of load distribution with longitudinal tears of meniscal horns on knee joint: a finite element analysis. J Orthop Surg Res. 2019;14(1): 237. doi: 10.1186/s13018-019-1255-1
  2. Scotti C, Hirschmann MT, Antinolfi P, Martin I, Peretti GM. Meniscus repair and regeneration: review on current methods and research potential. Eur Cell Mater. 2013;26:150-170. doi: 10.22203/ecm.v026a11
  3. Murphy CA, Costa JB, Silva-Correia J, Oliveira JM, Reis RL, Collins MN. Biopolymers and polymers in the search of alternative treatments for meniscal regeneration: state of the art and future trends. Appl Mater Today. 2018;12:51-71. doi: 10.1016/j.apmt.2018.04.002
  4. Szojka A, Lalh K, Andrews SHJ, Jomha NM, Osswald M, Adesida AB. Biomimetic 3D printed scaffolds for meniscus tissue engineering. Bioprinting. 2017;8:1-7. doi: 10.1016/j.bprint.2017.08.001
  5. Leslie BW, Gardner DL, McGeough JA, Moran RS, Anisotropic response of the human knee joint meniscus to unconfined compression. J Eng Med. 2000;214(6):631-635. doi: 10.1243/0954411001535651
  6. Zhang ZZ, Wang SJ, Zhang JY, et al. 3D-printed poly(ε- caprolactone) scaffold augmented with mesenchymal stem cells for total meniscal substitution: a 12- and 24- week animal study in a rabbit model. Am J Sports Med. 2017;45(7):1497-1511. doi: 10.1177/0363546517691513
  7. Cengiz IF, Pitikakis M, Cesario L, et al. Building the basis for patient-specific meniscal scaffolds: from human knee MRI to fabrication of 3D printed scaffolds. Bioprinting. 2016;1(June):1-10. doi: 10.1016/j.bprint.2016.05.001
  8. Fisher MB, Henning EA, Söegaard N, Esterhai JL, Mauck RL. Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus. Acta Biomater. 2013;9(1):4496-4504. doi: 10.1016/j.actbio.2012.10.018
  9. Tienen TG, Heijkants RG, de Groot JH, et al. Replacement of the knee meniscus by a porous polymer implant: a study in dogs. Am J Sports Med. 2006;34(1):64-71. doi: 10.1177/0363546505280905
  10. Vrancken ACT, Eggermont F, Hannink G, Van Tienen TG. Functional biomechanical performance of a novel anatomically shaped polycarbonate urethane total meniscus replacement. Knee Surg Sports Traumatol Arthrosc. 2016;24(5):1485-1494. doi: 10.1007/s00167-015-3632-6
  11. Cook JL, Fox DB. A novel bioabsorbable conduit augments healing of avascular meniscal tears in a dog model. Am J Sports Med. 2007;35(11):1877-1887. doi: 10.1177/0363546507304330
  12. Baker BM, Nathan AS, Gee AO, Mauck RL. The influence of an aligned nanofibrous topography on human mesenchymal stem cell fibrochondrogenesis. Biomaterials. 2010;31(24):6190-6200. doi: 10.1016/j.biomaterials.2010.04.036
  13. Ahn J-H, Kim J, Han G, et al. 3D-printed biodegradable composite scaffolds with significantly enhanced mechanical properties via the combination of binder jetting and capillary rise infiltration process. Addit Manuf. 2021;41:101988. doi: 10.1016/j.addma.2021.101988
  14. Liu D, Nie W, Li D, et al. 3D printed PCL/SrHA scaffold for enhanced bone regeneration. Chem Eng J. 2019;362: 269-279. doi: 10.1016/j.cej.2019.01.015
  15. Collins MN, Zamboni F, Serafin A, Ren G, Thanusha AV, Culebras M. The role of hyaluronic acid in tissue engineering. In: Oliveira JM, Radhouani H, Reis RL, eds. Polysaccharides of Microbial Origin: Biomedical Applications. Cham: Springer International Publishing; 2022: 1063-1116. doi: 10.1007/978-3-030-42215-8_56
  16. Serafin A, Culebras M, Collins MN. Synthesis and evaluation of alginate, gelatin, and hyaluronic acid hybrid hydrogels for tissue engineering applications. Int J Biol Macromol. 2023;233:123438. doi: 10.1016/j.ijbiomac.2023.123438
  17. Sarem M, Moztarzadeh F, Mozafari M. Optimization strategies on the structural modeling of gelatin/chitosan scaffolds to mimic human meniscus tissue. Mater Sci Eng C Mater Biol Appl. 2013;33(8):4777-4785. doi: 10.1016/j.msec.2013.07.036
  18. Groll J, Burdick JA, Cho DW, et al. A definition of bioinks and their distinction from biomaterial inks. Biofabrication. 2018;11(1):013001. doi: 10.1088/1758-5090/aaec52
  19. Rey-rico A, Klich A, Cucchiarini M, Madry H. Biomedical-grade, high mannuronic acid content (BioMVM) alginate enhances the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D microenvironment. Sci Rep. 2016;6:28170. doi: 10.1038/srep28170
  20. Puetzer JL, Bonassar LJ. High density type i collagen gels for tissue engineering of whole menisci. Acta Biomater. 2013;9(8):7787-7795. doi: 10.1016/j.actbio.2013.05.002
  21. Sarem M, Moztarzadeh F, Mozafari M. How can genipin assist gelatin/carbohydrate chitosan scaffolds to act as replacements of load-bearing soft tissues? Carbohydr Polym. 2013;93(2):635-643. doi: 10.1016/j.carbpol.2012.11.099
  22. Grogan SP, Chung PH, Soman P, et al. Digital micromirror device projection printing system for meniscus tissue engineering. Acta Biomater. 2013;9(7):7218-7226. doi: 10.1016/j.actbio.2013.03.020
  23. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials. 2010;31(21):5536-5544. doi: 10.1016/j.biomaterials.2010.03.064
  24. Benton JA, DeForest CA, Vivekanandan V, Anseth KS. Photocrosslinking of gelatin macromers to synthesize porous hydrogels that promote valvular interstitial cell function. Tissue Eng Part A. 2009;15(11): 3221-3230. doi: 10.1089/ten.TEA.2008.0545
  25. Bahcecioglu G, Hasirci N, Bilgen B, Hasirci V. Hydrogels of agarose, and methacrylated gelatin and hyaluronic acid are more supportive for in vitro meniscus regeneration than three dimensional printed polycaprolactone scaffolds. Int J Biol Macromol. 2019;122:1152-1162. doi: 10.1016/j.ijbiomac.2018.09.06
  26. Habuchi H, Yamagata T, Iwata H, Suzuki S. The occurrence of a wide variety of dermatan sulfate chondroitin sulfate copolymers in fibrous cartilage. J Biol Chem. 1973;248(17):6019-6028. doi: 10.1016/S0021-9258(19)43502-3
  27. Levett PA, Melchels FPW, Schrobback K, Hutmacher DW, Malda J, Klein TJ. A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate. Acta Biomater. 2014;10(1):214-223. doi: 10.1016/j.actbio.2013.10.005
  28. Murphy CA, Cunniffe GM, Garg AK, Collins MN. Regional dependency of bovine meniscus biomechanics on the internal structure and glycosaminoglycan content. J Mech Behav Biomed Mater. 2019;94:186-192. doi: 10.1016/j.jmbbm.2019.02.020
  29. Murphy CM, Haugh MG, O’Brien FJ. The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials. 2010;31(3):461-466. doi: 10.1016/j.biomaterials.2009.09.063
  30. Beck EC, Barragan M, Libeer TB, et al. Chondroinduction from naturally derived cartilage matrix: a comparison between devitalized and decellularized cartilage encapsulated in hydrogel pastes. Tissue Eng Part A. 2016;22(7-8): 665-679. doi: 10.1089/ten.TEA.2015.0546
  31. Costa B, Oliveira JM, Lu R. Biomaterials in meniscus tissue engineering. In: Oliveira JM, Reis RL, eds. Regenerative Strategies for the Treatment of Knee Joint Disabilities. Cham: Springer International Publishing; 2017: 249-270. doi: 10.1007/978-3-319-44785-8_13
  32. Kweon H, Yoo MK, Park IK, et al. A novel degradable polycaprolactone networks for tissue engineering. Biomaterials. 2003;24(5):801-808. doi: 10.1016/s0142-9612(02)00370-8
  33. Baker BM, Mauck RL. The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials. 2007;28(11):1967-1977. doi: 10.1016/j.biomaterials.2007.01.004
  34. Visser J, Melchels FPW, Jeon JE, et al. Reinforcement of hydrogels using three-dimensionally printed microfibres. Nat Commun. 2015;6:6933-6933. doi: 10.1038/ncomms7933
  35. Murphy CM, Haugh MG, O’Brien FJ. The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials. 2010;31(3):461-466. doi: 10.1016/j.biomaterials.2009.09.063
  36. Pan Z, Duan P, Liu X, et al. Effect of porosities of bilayered porous scaffolds on spontaneous osteochondral repair in cartilage tissue engineering. Regen Biomater. 2015;2(1):9-20. doi: 10.1093/rb/rbv001
  37. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26(27): 5474-5491. doi: 10.1016/j.biomaterials.2005.02.002
  38. Murphy CA, Garg AK, Silva-Correia J, Reis RL, Oliveira JM, Collins MN. The meniscus in normal and osteoarthritic tissues: facing the structure property challenges and current treatment trends. Ann Rev Biomed Eng. 2019;21:495-521. doi: 10.1146/annurev-bioeng-060418-052547
  39. Zein I, Hutmacher DW, Tan KC, Teoh SH. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials. 2002;23(4): 1169-1185. doi: 10.1016/s0142-9612(01)00232-0
  40. Shor L, Güçeri S, Chang R, et al. Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication. 2009;1(1):015003. doi: 10.1088/1758-5082/1/1/015003
  41. Kim JY, Yoon JJ, Park EK, Kim DS, Kim SY, Cho DW. Cell adhesion and proliferation evaluation of SFF-based biodegradable scaffolds fabricated using a multi-head deposition system. Biofabrication. 2009;1(1):015002. doi: 10.1088/1758-5082/1/1/015002
  42. Cahill S, Lohfeld S, McHugh PE. Finite element predictions compared to experimental results for the effective modulus of bone tissue engineering scaffolds fabricated by selective laser sintering. J Mater Sci Mater Med. 2009;20(6): 1255-1262. doi: 10.1007/s10856-009-3693-5
  43. McDermott ID, Sharifi F, Bull AMJ, Gupte CM, Thomas RW, Amis AA. An anatomical study of meniscal allograft sizing. Knee Surg Sports Traumatol Arthrosc. 2004;12(2):130-135. doi: 10.1007/s00167-003-0366-7
  44. O’Brien FJ, Harley BA, Waller MA, Yannas VI, Gibson LJ, Prendergast PJ. The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering. Technol Health Care. 2007;15(1):3-17. doi: 10.3233/THC-2007-15102
  45. Zhang Q, Lu H, Kawazoe N, Chen G. Pore size effect of collagen scaffolds on cartilage regeneration. Acta Biomater. 2014;10(5):2005-2013. doi: 10.1016/j.actbio.2013.12.042
  46. O’Brien FJ, Harley BA, Yannas VI, Gibson LJ. The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials. 2005;26(4):433-441. doi: 10.1016/j.biomaterials.2004.02.052
  47. Silva MMCG, Cyster LA, Barry JJA, et al. The effect of anisotropic architecture on cell and tissue infiltration into tissue engineering scaffolds. Biomaterials. 2006;27(35):5909-5917. doi: 10.1016/j.biomaterials.2006.08.010
  48. Lien SM, Ko LY, Huang TJ, Effect of pore size on ECM secretion and cell growth in gelatin scaffold for articular cartilage tissue engineering. Acta Biomater. 2009;5(2):670-679. doi: 10.1016/j.actbio.2008.09.020
  49. 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(5):887-894. doi: 10.1089/ten.TEC.2009.0422
  50. Stenhamre H, Nannmark U, Lindahl A, Gatenholm P, Brittberg M. Influence of pore size on the redifferentiation potential of human articular chondrocytes in poly (urethane urea) scaffolds. J Tissue Eng Regen Med. 2011;5(7):578-588. doi: 10.1002/term.350
  51. Nava MM, Draghi L, Giordano C, Pietrabissa R. The effect of scaffold pore size in cartilage tissue engineering. J Appl Biomater Funct Mater. 2016;14(3):e223-e229. doi: 10.5301/jabfm.5000302
  52. Sheehy EJ, Buckley CT, Kelly DJ. Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells. Biochem Biophys Res Commun. 2012;417(1):305-310. doi: 10.1016/j.bbrc.2011.11.105
  53. Baker BM, Nathan AS,Huffman GR, Mauck RL. Tissue engineering with meniscus cells derived from surgical debris. Osteoarthritis Cartilage. 2009;17(3):336-345. doi: 10.1016/j.joca.2008.08.001
  54. Yoshikawa K, Kitamura N, Kurokawa T, Gong JP, Nohara Y, Yasuda K. Hyaluronic acid affects the in vitro induction effects of synthetic PAMPS and PDMAAm hydrogels on chondrogenic differentiation of ATDC5 cells, depending on the level of concentration. BMC Musculoskelet Disord. 2013;14:56. doi: 10.1186/1471-2474-14-56
  55. Frean SP, Abraham LA, Lees P, In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen. Res Vet Sci. 1999;67(2):183-190. doi: 10.1053/rvsc.1999.0328
  56. Bian L, Hou C, Tous E, Rai R, Mauck RL, Burdick JA. The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. Biomaterials. 2013;34(2):413-421. doi: 10.1016/j.biomaterials.2012.09.052
  57. Re’em T, Kaminer-Israeli Y, Ruvinov E, Cohen S. Chondrogenesis of hMSC in affinity-bound TGF-beta scaffolds. Biomaterials. 2012;33:751. doi: 10.1016/j.biomaterials.2011.10.007
  58. Roberts JJ, Nicodemus GD, Giunta S, Bryant SJ. Incorporation of biomimetic matrix molecules in PEG hydrogels enhances matrix deposition and reduces load-induced loss of chondrocyte-secreted matrix. J Biomed Mater Res A. 2011;97 A(3):281-291. doi: 10.1002/jbm.a.33057
  59. Levett PA, Hutmacher DW, Malda J, Klein TJ. Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs. PLoS ONE. 2014;9(12):e113216. doi: 10.1371/journal.pone.0113216
  60. Eyre DR, Koob TJ, Chun LE. Biochemistry of the meniscus: unique profile of collagen types and site-dependent variations in composition. Orthop Transact. 1983;8:56.
  61. Wu JJ, Eyre DR, Slayter HS. Type VI collagen of the intervertebral disc. Biochemical and electron-microscopic characterization of the native protein. Biochem J. 1987;248(2):373-381. doi: 10.1042/bj248037
  62. Makris EA, Hadidi P, Athanasiou KA. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials. 2011;32(30):7411-7431. doi: 10.1016/j.biomaterials.2011.06.037
  63. Erickson IE, Kestle SR, Zellars KH, et al. High mesenchymal stem cell seeding densities in hyaluronic acid hydrogels produce engineered cartilage with native tissue properties. Acta Biomater. 2012;8(8):3027-3034. doi: 10.1016/j.actbio.2012.04.033
  64. Klein TJ, Rizzi SC, Schrobback K, et al. Long-term effects of hydrogel properties on human chondrocyte behavior. Soft Matter. 2010;6(20):5175-5183. doi: 10.1039/C0SM00229A

 

 

 

 

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