AccScience Publishing / IJB / Volume 10 / Issue 1 / DOI: 10.36922/ijb.1437
RESEARCH ARTICLE

In situ bioprinting for cartilage repair using a parallel manipulator

Hao-Yang Lei1,2† You-Rong Chen1,3,4† Zi-Bin Liu2 Yi-Nong Li2 Bing-Bing Xu1,3,4* Chang-Hui Song2* Jia-Kuo Yu1,3,4*
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1 Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, China
2 School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou, China
3 Beijing Key Laboratory of Sports Injuries, Beijing, China
4 Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, China
IJB 2024, 10(1), 1437 https://doi.org/10.36922/ijb.1437
Submitted: 2 August 2023 | Accepted: 6 October 2023 | Published: 8 January 2024
(This article belongs to the Special Issue Light-based bioprinted scaffolds for tissue engineering)
© 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/ )
Abstract

Regeneration of large-sized cartilage injury is a challenging endeavor. In vitro bioprinting for cartilage repair has several drawbacks, such as the tedious process of material preparation, potential contamination, and the mismatch between implant and defect. This study aimed to investigate the application of in situ bioprinting in cartilage repair using a parallel manipulator. In particular, the material extrusion rate and printing speed were adjusted to obtain the suitable forming parameters in a custom-made parallel manipulator. Cell experiments were conducted to determine the biocompatibility. Finally, a rabbit cartilage defect model was used to evaluate the feasibility of in situ bioprinting combined with machine vision. The results showed that to achieve optimum printing using the custom-made three-dimensional printer, 400–560 mm/min should be set as the standard printing speed, with an extrusion multiplier of 0.09–0.10. Cartilage defects can be precisely and easily segmented using a bimodal method with a 2% deviation error. In vitro experiments revealed that the utilized materials are highly biocompatible. Furthermore, according to the results from in vivo experiments, in situ bioprinting lends itself useful in the repair of cartilage defects. The overall results confirmed the feasibility of applying a parallel manipulator in in situ bioprinting for cartilage repair. Additional optimizations of the proposed approach are warranted prior to translation into clinical applications in the future.

Keywords
In situ bioprinting
Cartilage repair
Tissue engineering
Funding
The authors acknowledge the financial support from the Key-Area Research and Development Program of Dongguan (20221200300182), the Key Clinical Projects of Peking University Third Hospital (BYSY2022046), the Shenzhen Science and Technology Planning Project (JSGG20210802153809029), the National Natural Science Foundation of China (82102565, 82002298, 51920105006), and the Beijing Natural Science Foundation (L192066).
References
  1. Li M, Yin H, Yan Z, et al. The immune microenvironment in cartilage injury and repair. Acta Biomater. 2022;140:23-42. doi: 10.1016/j.actbio.2021.12.006
  2. Guo X, Ma Y, Min Y, et al. Progress and prospect of technical and regulatory challenges on tissue-engineered cartilage as therapeutic combination product. Bioact Mater. 2023;20:501-518. doi: 10.1016/j.bioactmat.2022.06.015
  3. Wei W, Dai H. Articular cartilage and osteochondral tissue engineering techniques: Recent advances and challenges. Bioact Mater. 2021;6(12):4830-4855. doi: 10.1016/j.bioactmat.2021.05.011
  4. Chen YR, Yan X, Yuan FZ, et al. Kartogenin-conjugated double-network hydrogel combined with stem cell transplantation and tracing for cartilage repair. Adv Sci (Weinh). 2022;9(35):e2105571. doi: 10.1002/advs.202105571
  5. Zhang Y, Liu X, Zeng L, et al. Polymer fiber scaffolds for bone and cartilage tissue engineering. Adv Funct Mater. 2019;29(36):1903279. doi: 10.1002/adfm.201903279
  6. Browe D, Burdis R, Diaz-Payno PJ, et al. Promoting endogenous articular cartilage regeneration using extracellular matrix scaffolds. Mater Today Bio. 2022;16:100343. doi: 10.1016/j.mtbio.2022.100343
  7. Li X, Zheng F, Wang X, et al. Biomaterial inks for extrusion-based 3D bioprinting: Property, classification, modification, and selection. Int J Bioprint. 2022;9(2). doi: 10.18063/ijb.v9i2.649
  8. Sadeghianmaryan A, Naghieh S, Yazdanpanah Z, et al. Fabrication of chitosan/alginate/hydroxyapatite hybrid scaffolds using 3D printing and impregnating techniques for potential cartilage regeneration. Int J Biol Macromol. 2022;204:62-75. doi: 10.1016/j.ijbiomac.2022.01.201
  9. Sang S, Mao X, Cao Y, et al. 3D Bioprinting using synovium-derived MSC-laden photo-cross-linked ECM bioink for cartilage regeneration. ACS Appl Mater Interfaces. 2023;15(7):8895-8913. doi: 10.1021/acsami.2c19058
  10. Costa J, Silva-Correia J, Pina S, et al. Indirect printing of hierarchical patient-specific scaffolds for meniscus tissue engineering. Bio-Des Manuf. 2019;2(4):225-241. doi: 10.1007/s42242-019-00050-x
  11. Zou Q, Grottkau BE, He Z, et al. Biofabrication of valentine-shaped heart with a composite hydrogel and sacrificial material. Mater Sci Eng C Mater Biol Appl. 2020;108:110205. doi: 10.1016/j.msec.2019.110205
  12. MacAdam A, Chaudry E, McTiernan CD, Cortes D, Suuronen EJ, Alarcon EI. Development of in situ bioprinting: A mini review. Front Bioeng Biotechnol. 2022;10:940896. doi: 10.3389/fbioe.2022.940896
  13. Mahmoudi Z, Sedighi M, Jafari A, et al. In situ 3D bioprinting: A promising technique in advanced biofabrication strategies. Bioprinting. 2023;e00260. doi: 10.1016/j.bprint.2023.e00260
  14. Zhao W, Hu C, Xu T. In vivo bioprinting: Broadening the therapeutic horizon for tissue injuries. Bioact Mater. 2023;25:201-222. doi: 10.1016/j.bioactmat.2023.01.018
  15. Li L, Yu F, Shi J, et al. In situ repair of bone and cartilage defects using 3D scanning and 3D printing. Sci Rep. 2017;7(1):9416. doi: 10.1038/s41598-017-10060-3
  16. O’Connell CD, Di Bella C, Thompson F, et al. Development of the Biopen: A handheld device for surgical printing of adipose stem cells at a chondral wound site. Biofabrication. 2016;8(1):015019. doi: 10.1088/1758-5090/8/1/015019
  17. Hakimi N, Cheng R, Leng L, et al. Handheld skin printer: In situ formation of planar biomaterials and tissues. Lab Chip. 2018;18(10):1440-1451. doi: 10.1039/c7lc01236e
  18. Chen H, Ma X, Gao T, Zhao W, Xu T, Liu Z. Robot-assisted in situ bioprinting of gelatin methacrylate hydrogels with stem cells induces hair follicle-inclusive skin regeneration. Biomed Pharmacother. 2023;158:114140. doi: 10.1016/j.biopha.2022.114140
  19. Moncal K, Gudapati H, Godzik P, et al. Intra-operative bioprinting of hard, soft, and hard/soft composite tissues for craniomaxillofacial reconstruction. Adv Funct. Mater. 2021;31(29). doi: 10.1002/adfm.202010858
  20. Ozbolat IT, Chen H, Yu Y. Development of ‘multi-arm bioprinter’ for hybrid biofabrication of tissue engineering constructs. Rob Comput Integr Manuf. 2014;30(3):295-304. doi: 10.1016/j.rcim.2013.10.005
  21. Moncal KK, Yeo M, Celik N, et al. Comparison of in-situ versus ex-situ delivery of polyethylenimine-BMP-2 polyplexes for rat calvarial defect repair via intraoperative bioprinting. Biofabrication. 2022;15(1). doi: 10.1088/1758-5090/ac9f70
  22. Di Bella C, Duchi S, O’Connell CD, et al. In situ handheld three-dimensional bioprinting for cartilage regeneration. J Tissue Eng Regen Med. 2018;12(3):611-621. doi: 10.1002/term.2476
  23. Ma K, Zhao T, Yang L, et al. Application of robotic-assisted in situ 3D printing in cartilage regeneration with HAMA hydrogel: An in vivo study. J Adv Res. 2020;23: 123-132. doi: 10.1016/j.jare.2020.01.010
  24. Wang Y, Pereira RF, Peach C, Huang B, Vyas C, Bartolo P. Robotic in situ bioprinting for cartilage tissue engineering. Int J Extreme Manuf. 2023;5(3). doi: 10.1016/j.jare.2020.01.010
  25. Li L, Shi J, Ma K, et al. Robotic in situ 3D bio-printing technology for repairing large segmental bone defects. J Adv Res. 2021;30:75-84. doi: 10.1016/j.jare.2020.11.011
  26. Gholami P, Ahmadi-Pajouh MA, Abolftahi N, et al. Segmentation and measurement of chronic wounds for bioprinting. IEEE J Biomed Health Inform. 2018;22(4): 1269-1277. doi: 10.1109/jbhi.2017.2743526
  27. Lankton S, Tannenbaum A. Localizing region-based active contours. IEEE Trans Image Process. 2008;17(11):2029-2039. doi: 10.1109/TIP.2008.2004611
  28. Yu Y, Wang C, Fu Q, et al. Techniques and challenges of image segmentation: A review. Electronics. 2023;12(5). doi: 10.3390/electronics12051199
  29. Dexter A, Race AM, Steven RT, et al. Two-phase and graph-based clustering methods for accurate and efficient segmentation of large mass spectrometry images. Anal Chem. 2017;89(21):11293-11300. doi: 10.1021/acs.analchem.7b01758
  30. Shi H, Lee W. Image segmentation using K-means clustering, Gabor filter and moving mesh method. Imaging Sci J. 2023; 69(5-8):407-416. doi: 10.1080/13682199.2022.2161159
  31. Zhang F, Sun Z, Song M, Lang X. Progressive 3D shape segmentation using online learning. Comput Aided Design. 2015;58:2-12. doi: 10.1016/j.cad.2014.08.008
  32. Niri R, Gutierrez E, Douzi H, et al. Multi-view data augmentation to improve wound segmentation on 3D surface model by deep learning. IEEE Access. 2021;9: 157628-157638. doi: 10.1109/ACCESS.2021.3130784
  33. Lei H, Song C, Liu Z, et al. Rational design and additive manufacturing of alumina-based lattice structures for bone implant. Mater Design. 2022;221. doi: 10.1016/j.matdes.2022.111003
  34. Mathworks, Computer Vision Toolbox, https://ww2. mathworks.cn/help/vision/index
  35. Murdock M, Badylak S. Biomaterials-based in situ tissue engineering. Curr Opin Biomed Eng. 2017;1:4-7. doi: 10.1016%2Fj.cobme.2017.01.001
  36. Singh S, Choudhury D, Yu F, Mironov V, Naing MW. In situ bioprinting - Bioprinting from benchside to bedside? Acta Biomater. 2020;101:14-25. doi: 10.1016/j.actbio.2019.08.045
  37. Richter F, Lu J, Orosco RK, Yip MC. Robotic tool tracking under partially visible kinematic chain: A unified approach. IEEE Trans Rob. 2022;38(3):1653-1670. doi: 10.48550/arXiv.2102.06235
  38. Feng L, Zhang W, Gong Z, Lin G, Liang D. Developments of delta-like parallel manipulators - A review. Robot (China). 2014; 36(3):375-384. doi: 10.5772/61744
  39. Dong H, Hu B, Zhang W, et al. Robotic-assisted automated in situ bioprinting. Int J Bioprint. 2023;9(1):629. doi: 10.18063%2Fijb.v9i1.629
  40. Gao Q, Niu X, Shao L, et al. 3D printing of complex GelMA-based scaffolds with nanoclay. Biofabrication. 2019;11(3):035006. doi: 10.1088/1758-5090/ab0cf6
  41. Fritz R, Chaudhari A, Boutin R. Preoperative MRI of articular cartilage in the knee: A practical approach. J Knee Surg. 2020;33(11):1088-1099. doi: 10.1055/s-0040-1716719
  42. Potter H, Black B, Chong le R. New techniques in articular cartilage imaging. Clin Sports Med. 2009;28(1):77-94. doi: 10.4103%2F0971-3026.137028
  43. Chen X, Jiang C, Wang T, Zhu T, Li X, Huang J. Hyaluronic acid-based biphasic scaffold with layer-specific induction capacity for osteochondral defect regeneration. Mater Des. 2022;216. doi: 10.1016/j.matdes.2022.110550
  44. Schuurmans C, Mihajlovic M, Hiemstra C, Ito K, Hennink WE, Vermonden T. Hyaluronic acid and chondroitin sulfate (meth)acrylate-based hydrogels for tissue engineering: Synthesis, characteristics and pre-clinical evaluation. Biomaterials. 2021;268:120602. doi: 10.1016/j.biomaterials.2020.120602
  45. Agarwal G, Agiwa S, Srivastava A. Hyaluronic acid containing scaffolds ameliorate stem cell function for tissue repair and regeneration. Int J Biol Macromol. 2020; 165(Pt A):388-401. doi: 10.1016/j.ijbiomac.2020.09.107
  46. Amann E, Wolff P, Breel E, van Griensven M, Balmayor ER. Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater. 2017;52:130-144. doi: 10.1016/j.ijbiomac.2020.09.107
  47. da Silva LP, Santos T, Rodrigues D, et al. Stem cell-containing hyaluronic acid-based spongy hydrogels for integrated diabetic wound healing. J Invest Dermatol. 2017;137(7):1541-1551. doi: 10.1016/j.jid.2017.02.976
  48. Agrawal P, Pramanik K, Vishwanath V, et al. Enhanced chondrogenesis of mesenchymal stem cells over silk fibroin/ chitosan-chondroitin sulfate three dimensional scaffold in dynamic culture condition. J Biomed Mater Res B Appl Biomater. 2018;106(7):2576-2587. doi: 10.1002/jbm.b.34074
  49. Lafuente-Merchan M, Ruiz-Alonso S, Zabala A, et al. Chondroitin and dermatan sulfate bioinks for 3D bioprinting and cartilage regeneration. Macromol Biosci. 2022;22(3):e2100435. doi: 10.1002/mabi.202100435
  50. Tan G, Tabata Y. Chondroitin-6-sulfate attenuates inflammatory responses in murine macrophages via suppression of NF-kappaB nuclear translocation. Acta Biomater. 2014;10(6):2684-2692. doi: 10.1016/j.actbio.2014.02.025
  51. Wang D, Varghese S, Sharma B, et al. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nat Mater. 2007;6(5): 385-392. doi: 10.1038/nmat1890
  52. Kwon H, Brown W, Lee C, et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol. 2019;15(9):550-570. doi: 10.1038%2Fs41584-019-0255-1
  53. 53. Trengove A, Di Bella C, O’Connor A. The challenge of cartilage integration: Understanding a major barrier to chondral repair. Tissue Eng Part B Rev. 2022;28(1): 114-128. doi: 10.1089/ten.teb.2020.0244
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing