AccScience Publishing / IJB / Volume 9 / Issue 1 / DOI: 10.18063/ijb.v9i1.621
Submit to IJB
Cite this article
2
Download
109
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
RESEARCH ARTICLE

Formulation and evaluation of a bioink composed of alginate, gelatin, and nanocellulose for meniscal tissue engineering

Julia Anna Semba1,2 ,  Adam Aron Mieloch1 ,  Ewa Tomaszewska3 ,  Piotr Cywoniuk1 ,  Jakub Dalibor Rybka1*
Show Less
1 Center for Advanced Technology, Adam Mickiewicz University, Poznan, Poland
2 Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
3 Faculty of Mechanical Engineering, Poznan University of Technology, Poznan, Poland
ijb 2023, 9(1), 0621–0123;
© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Download PDF
Cite
XML
Abstract

Background: Neuroendocrine carcinoma of the cervix (NECC) is more prone to lymphatic infiltration, lymph node involvement, local recurrence, and distant metastasis. Using CCRT with or without adjuvant chemotherapy as the standard treatment for locally advanced NECCs and CCRT for patients with early lesions confined to the cervix. However, the prognosis of NECC patients treated with definitive radiotherapy (RT) is unknown. Immune checkpoint inhibitors are a promising therapeutic strategy for locally advanced cervical cancer. Some reports suggest that the expression of PD-L1 in solid tumors correlates with prognosis.
Aim: This study investigates prognostic factors for survival in patients with neuroendocrine cervical carcinoma (NECC) treated with definitive radiotherapy (RT) and the relationship between PD-L1 expression and prognosis in these patients.
Methods: This retrospective study included 66 patients with histologically confirmed NECC who received RT with or without chemotherapy. From January 2015 to December 2020, patients received routine extended-field irradiation (EFI), and PD-L1 expression was assessed by immunohistochemistry. The most commonly used chemotherapy agents were etoposide-platinum and paclitaxel-platinum.
Results: PD-L1 expression was positive in 17 of 45 (37.8%) patients. There were 52 cases of pure NECC and 14 cases of mixed carcinoma. Sixty stage IB-III patients received definitive RT. The 3- and 5-year progression-free survival (PFS) was 39.8% and 34.1%, and 3- and 5-year overall survival (OS) was 48.0% and 40.2%, respectively. There was no significant difference in 3 and 5-year PFS and 3 and 5-year OS between patients with pure and mixed carcinoma. Positive PD-L1 expression was associated with higher 3-year PFS in patients with mixed histology. Univariate analysis showed that LNM and FIGO stages predicted 3-and 5-year PFS in patients who received definitive RT. The median OS in patients receiving less than four cycles and at least four cycles of chemotherapy (CT) was 26.0 and 44.0 months, respectively (P=0.038); moreover, 3- and 5-year PFS was 34.1% and 25.7% in the former and 46.4% and 40.4% in the latter. There were no significant differences in OS and PFS between pelvic irradiation and prophylactic EFI in patients treated with definitive RT. There were no significant differences in para-aortic failure rate after concurrent chemoradiotherapy between patients who underwent pelvic irradiation or prophylactic EFI (p=0.147).
Conclusion: In patients with mixed NECC, positive PD-L1 expression is correlated with higher 3-year PFS. Chemoradiotherapy was effective for NECCs. The LNM and stage predicted PFS. Four or more cycles of chemotherapy improve prognosis. Prophylactic EFI did not significantly improve PFS and OS.
Relevance for patients: This study is relevant to patients as it confirms that chemoradiotherapy is effective for both early and locally advanced NECC, and that four or more cycles of chemotherapy improved prognosis. The regimen should be carefully evaluated to ensure that patients receive the most effective radiation therapy for the prophylactic of para-aortic lymph node metastasis. Potential risk factors for recurrence of radical radiotherapy should be fully understood to minimize these risks. This study observed that PD-L1 expression positive in patients with mixed NECC types is correlated with higher 3-year PFS.

 

GA.09.202304.23-00067.png

 

DOI: http://dx.doi.org/10.18053/jctres.09.202304.23-00067

Keywords
Meniscus
3D bioprinting
Bioink; Alginate
Gelatin
Carboxymethylated cellulose nanocrystal
References
  1. Pereira H, Varatojo R, Sevivas N, et al., 2016, Physiopathology of the meniscal lesions, in: Surgery of the Meniscus, Springer Berlin Heidelberg, 47–61. https://doi:10.1007/978-3-662-49188-1_5
  2. Doral MN, Bilge O, Huri G, et al., 2018, Modern treatment of meniscal tears. EFORT Open Rev, 3:260–268. https://doi.org/10.1302/2058-5241.3.170067
  3. Beaufils P, Becker R, Kopf S, et al., 2017, The knee meniscus: Management of traumatic tears and degenerative lesions. EFORT Open Rev, 2:195–203. https://doi.org/10.1302/2058-5241.2.160056
  4. Vaishya R, Patralekh MK, Vaish A, et al., 2018, Publication trends and knowledge mapping in 3D printing in orthopaedics. J Clin Orthop Trauma, 9:194–201. https://doi.org/10.1016/j.jcot.2018.07.006
  5. Semba JA, Mieloch AA, Rybka JD, 2020, Introduction to the state-of-the-art 3D bioprinting methods, design, and applications in orthopedics. Bioprinting, 18:e00070. https://doi.org/10.1016/j.bprint.2019.e00070
  6. Agarwal S, Saha S, Balla VK, et al., 2020, Current developments in 3D bioprinting for tissue and organ regeneration–A review. Front Mech Eng, 6:589171. https://doi.org/10.3389/fmech.2020.589171
  7. Luo W, Song Z, Wang Z, et al., 2020, Printability optimization of gelatin-alginate bioinks by cellulose nanofiber modification for potential meniscus bioprinting. J Nanomater. https://doi.org/10.1155/2020/3863428
  8. Stanco D, Urbán P, Tirendi S, et al., 2020, 3D bioprinting for orthopaedic applications: Current advances, challenges and regulatory considerations. Bioprinting, 20:e00103. https://doi.org/10.1016/j.bprint.2020.e00103
  9. Ma X, Liu J, Zhu W, et al., 2018, 3D bioprinting of functional tissue models for personalized drug screening and in vitro disease modeling. Adv Drug Deliv Rev, 132:235–251.
  10. Chae S, Lee SS, Choi YJ, et al., 2021, 3D cell-printing of biocompatible and functional meniscus constructs using meniscus‐derived bioink. Biomaterials, 267:120466. https://doi.org/10.1016/j.biomaterials.2020.120466
  11. Jian Z, Zhuang T, Qinyu T, et al., 2021, 3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering. Bioact Mater, 6:1711–1726. https://doi.org/10.1016/j.bioactmat.2020.11.027
  12. Mieloch AA, Semba JA, Rybka JD, 2022, CNT-type dependent cellular adhesion on 3D-printed nanocomposite for tissue engineering. Int J Bioprint, 8(2):548. https://doi.org/10.18063/ijb.v8i2.548
  13. Vahedi P, Jarolmasjed S, Shafaei H, et al., 2019, In vivo articular cartilage regeneration through infrapatellar adipose tissue derived stem cell in nanofiber polycaprolactone scaffold. Tissue and Cell 57:49–56. https://doi.org/10.1016/j.tice.2019.02.002
  14. Romanazzo S, Vedicherla S, Moran C, et al., 2018, Meniscus ECM-functionalised hydrogels containing infrapatellar fat pad-derived stem cells for bioprinting of regionally defined meniscal tissue. J Tissue Eng Regen Med, 12:e1826–e1835. https://doi.org/10.1002/term.2602
  15. Saldin LT, Cramer MC, Velankar SS, et al., 2017, Extracellular matrix hydrogels from decellularized tissues: Structure and function. Acta Biomaterialia 49:1–15
  16. Ng WL, Chua CK, Shen YF, 2019, Print me an organ! Why we are not there yet. Prog Polym Sci, 97:101145. https://doi.org/10.1016/j.progpolymsci.2019.101145
  17. Liu D, Nikoo M, Boran G, et al., 2015, Collagen and gelatin. Annu Rev Food Sci Technol, 6:527–557. https://doi.org/10.1146/annurev-food-031414-111800
  18. Ojansivu M, Rashad A, Ahlinder A, et al., 2019, Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabrication, 11:35010. https://doi.org/10.1088/1758-5090/ab0692
  19. Leite ÁJ, Sarker B, Zehnder T, et al., 2016, Bioplotting of a bioactive alginate dialdehyde-gelatin composite hydrogel containing bioactive glass nanoparticles. Biofabrication, 8:035005. https://doi.org/10.1088/1758-5090/8/3/035005
  20. Costantini M, Idaszek J, Szöke K, et al., 2016, 3D bioprinting of BM-MSCs-loaded ECM biomimetic hydrogels for in vitro neocartilage formation. Biofabrication, 8:035002. https://doi.org/10.1088/1758-5090/8/3/035002
  21.  
  22. Markstedt K, Mantas A, Tournier I, et al., 2015, 3D bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules, 16:1489–1496. https://doi.org/10.1021/acs.biomac.5b00188
  23. Ojansivu M, Rashad A, Ahlinder A, et al., 2019, Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabrication, 11:035010. https://doi.org/10.1088/1758-5090/ab0692
  24. Zaeri A, Cao K, Zhang F, et al., 2022, A review of the structural and physical properties that govern cell interactions with structured biomaterials enabled by additive manufacturing. Bioprinting, 26:e00201. https://doi.org/10.1016/j.bprint.2022.e00201
  25.  
  26. Zhao Z, Li Y, Wang M, et al., 2020, Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis. Journal of Cellular and Molecular Medicine, 24:5408–5419. https://doi.org/10.1111/jcmm.15204
  27. Möller T, Amoroso M, Hägg D, et al., 2017, In vivo chondrogenesis in 3D bioprinted human cell-laden hydrogel constructs. Plast Reconstr Surg—Glob Open, 5:e1227. https://doi.org/10.1097/GOX.0000000000001227
  28. Jiang T, Munguia-Lopez JG, Flores-Torres S, et al., 2019, Extrusion bioprinting of soft materials: An emerging technique for biological model fabrication. Appl Phys Rev, 6:011310. https://doi.org/10.1063/1.5059393
  29. Dravid A, McCaughey-Chapman A, Raos B, et al., 2022, Development of agarose-gelatin bioinks for extrusion-based bioprinting and cell encapsulation. Biomed Mater (Bristol), 17:055001. https://doi.org/10.1088/1748-605X/ac759f
  30. Li Z, Huang S, Liu Y, et al., 2018, Tuning alginate-gelatin bioink properties by varying solvent and their impact on stem cell behavior. Sci Rep, 8:8020. https://doi.org/10.1038/s41598-018-26407-3
  31. Zhuang P, Ng WL, An J, et al., 2019, Layer-by-layer ultraviolet assisted extrusion-based (UAE) bioprinting of hydrogel constructs with high aspect ratio for soft tissue engineering applications. PLoS ONE, 14:1–21. https://doi.org/10.1371/journal.pone.0216776
  32. Zaeri A, Zgeib R, Cao K, et al., 2022, Numerical analysis on the effects of microfluidic-based bioprinting parameters on the microfiber geometrical outcomes. Sci Rep, 12:1–16. https://doi.org/10.1038/s41598-022-07392-0
  33.  
  34. Li X, Liu B, Pei B, et al., 2020, Inkjet bioprinting of biomaterials. Chem Rev, 120:10793–10833. https://doi.org/10.1021/acs.chemrev.0c00008
  35. Ng WL, Huang X, Shkolnikov V, et al., 2022, Controlling droplet impact velocity and droplet volume: key factors to achieving high cell viability in sub-nanoliter droplet-based bioprinting. Int J Bioprint, 8:424. https://doi.org/10.18063/ijb.v8i1.424
  36. Xiong R, Zhang Z, Chai W, et al., 2017, Study of gelatin as an effective energy absorbing layer for laser bioprinting. Biofabrication, 9:024103. https://doi.org/10.1088/1758-5090/aa74f2
  37. Ng WL, Lee JM, Zhou M, et al., 2020, Vat polymerization-based bioprinting—process, materials, applications and regulatory challenges. Biofabrication, 12:022001. https://doi.org/10.1088/1758-5090/ab6034
  38. Li W, Mille LS, Robledo JA, et al., 2020, Recent advances in formulating and processing biomaterial inks for vat polymerization-based 3D printing. Adv Healthc Mater, 9:1–18. https://doi.org/10.1002/adhm.202000156
  39.  
  40. Pääkkönen T, Dimic-Misic K, Orelma H, et al., 2016, Effect of xylan in hardwood pulp on the reaction rate of TEMPO-mediated oxidation and the rheology of the final nanofibrillated cellulose gel. Cellulose, 23:277–293. https://doi.org/https://doi.org/10.1007/s10570-015-0824-7
  41. Jessop ZM, Al-Sabah A, Gardiner MD, et al., 2017, 3D bioprinting for reconstructive surgery: Principles, applications and challenges. J Plast Reconstr Aesthetic Surg, 70(9):1155–1170. https://doi.org/10.1016/j.bjps.2017.06.001
  42. Giuseppe M di, Law N, Webb B, et al., 2018, Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting. J Mech Behav Biomed Mater, 79:150–157. https://doi.org/10.1016/j.jmbbm.2017.12.018
  43. Ning L, Gil CJ, Hwang B, et al., 2020, Biomechanical factors in three-dimensional tissue bioprinting. Appl Phys Rev, 7:041319. https://doi.org/10.1063/5.0023206
  44. Kawabe S, Seki M, Tabata H, 2014, Investigation of the sol-gel transition of gelatin using terahertz time-domain spectroscopy. J Appl Phys, 115:143103. https://doi.org/10.1063/1.4870954
  45. Liu F, Chen Q, Liu C, et al., 2018, Natural polymers for organ 3D bioprinting. Polymers (Basel), 10:1278. https://doi.org/10.3390/polym10111278
  46. Kačarević ŽP, Rider PM, Alkildani S, et al., 2018, An introduction to 3D bioprinting: Possibilities, challenges and future aspects. Materials, 11:2199. https://doi.org/10.3390/ma11112199
  47. Dimitreli G, Thomareis AS, 2004, Effect of temperature and chemical composition on processed cheese apparent viscosity. J Food Eng, 64:265–271. https://doi.org/10.1016/j.jfoodeng.2003.10.008
  48.  
  49. Li MG, Tian XY, Chen XB, 2009, A brief review of dispensing-based rapid prototyping techniques in tissue scaffold fabrication: Role of modeling on scaffold properties prediction. Biofabrication, 1:032001. https://doi.org/10.1088/1758-5082/1/3/032001
  50.  
  51. Murphy S V., Atala A, 2014, 3D bioprinting of tissues and organs. Nat Biotechnol, 32:773–785. https://doi.org/10.1038/nbt.2958
  52. Jones N, 2012, Science in three dimensions: The print revolution. Nature, 487:22–23. https://doi.org/10.1038/487022a
  53. Rutz AL, Hyland KE, Jakus AE, et al., 2015, A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv Mater, 27:1607–1614. https://doi.org/10.1002/adma.201405076
  54. Blaeser A, Duarte Campos DF, Puster U, et al., 2016, Controlling shear stress in 3D bioprinting is a key factor to balance printing resolution and stem cell integrity. Adv Healthc Mater, 5:326–333. https://doi.org/10.1002/adhm.201500677
  55.  
  56. Jin Y, Zhao D, Huang Y, 2018, Study of extrudability and standoff distance effect during nanoclay-enabled direct printing. Bio-Des Manuf, 1:123–134. https://doi.org/10.1007/s42242-018-0009-y
  57. Markstedt K, Mantas A, Tournier I, et al., 2015, 3D bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules, 16:1489–1496. https://doi.org/10.1021/acs.biomac.5b00188
  58. Athukoralalage SS, Balu R, Dutta NK, et al., 2019, 3D bioprinted nanocellulose-based hydrogels for tissue engineering applications: A brief review. Polymers, 11(5):898. https://doi.org/10.3390/polym11050898
  59. Han C, Wang X, Ni Z, et al., 2020, Effects of nanocellulose on alginate/gelatin bio-inks for extrusion-based 3D printing. BioResources, 15:7357–7373. https://doi.org/10.15376/biores.15.4.7357-7373
  60. Fakhruddin K, Hamzah MSA, Razak SIA, 2018, Effects of extrusion pressure and printing speed of 3D bioprinted construct on the fibroblast cells viability. IOP Conf Ser: Mater Sci Eng, 440:012042. https://doi.org/10.1088/1757-899X/440/1/012042
  61. Liu Q, Hu X, Zhang X, et al., 2016, Effects of mechanical stress on chondrocyte phenotype and chondrocyte extracellular matrix expression. Sci Rep, 6:1–8. https://doi.org/10.1038/srep37268
  62.  
  63. He H, Li D, Lin Z, et al., 2020, Temperature-programmable and enzymatically solidifiable gelatin-based bioinks enable facile extrusion bioprinting. Biofabrication, 12. https://doi.org/10.1088/1758-5090/ab9906
  64.  
  65. Erkoc P, Uvak I, Nazeer MA, et al., 2020, 3D printing of cytocompatible gelatin-cellulose-alginate blend hydrogels. Macromol Biosci, 20:1–15. https://doi.org/10.1002/mabi.202000106
  66. Place ES, Rojo L, Gentleman E, et al., 2011, Strontium-and zinc-alginate hydrogels for bone tissue engineering. Tissue Eng Part A, 17:2713–2722. https://doi.org/10.1089/ten.tea.2011.0059
  67. Teti G, Focaroli S, Salvatore V, et al., 2018, The hypoxia-mimetic agent cobalt chloride differently affects human mesenchymal stem cells in their chondrogenic potential. Stem Cells Int, 2018: 3237253. https://doi.org/10.1155/2018/3237253
  68. Focaroli S, Teti G, Salvatore V, et al., 2016, Calcium/cobalt alginate beads as functional scaffolds for cartilage tissue engineering. Stem Cells Int, 2016:20–22. https://doi.org/10.1155/2016/2030478
  69. Nguyen D, Hgg DA, Forsman A, et al., 2017, Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Sci Rep, 7:658. https://doi.org/10.1038/s41598-017-00690-y
  70. Apelgren P, Amoroso M, Lindahl A, et al., (2017) Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS ONE, 12:e0189428. https://doi.org/10.1371/journal.pone.0189428
  71.  
  72. Grogan SP, Duffy SF, Pauli C, et al., 2018, Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering. J Orthop Res, 36:1947–1958. https://doi.org/10.1002/jor.23864
  73. Mackie EJ, Ahmed YA, Tatarczuch L, et al., 2008, Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol, 40:46–62. https://doi.org/10.1016/j.biocel.2007.06.009
  74. Folkesson E, Turkiewicz A, Rydén M, et al., 2020, Proteomic characterization of the normal human medial meniscus body using data-independent acquisition mass spectrometry. J Orthop Res, 38:1735–1745. https://doi.org/10.1002/jor.24602
  75. Francis SL, di Bella C, Wallace GG, et al., 2018, Cartilage tissue engineering using stem cells and bioprinting technology— barriers to clinical translation. Front Surg, 5:1–12. https://doi.org/10.3389/fsurg.2018.00070
  76. Sharma P, Kumar P, Sharma R, et al., 2019, Tissue engineering; current status & futuristic scope. J Med Life, 12:225–229. https://doi.org/10.25122/jml-2019-0032
  77.  
  78. Sathish PB, Gayathri S, Priyanka J, et al., 2022, Tricomposite gelatin-carboxymethylcellulose-alginate bioink for direct and indirect 3D printing of human knee meniscal scaffold. Int J Biol Macromol, 195:179–189. https://doi.org/10.1016/j.ijbiomac.2021.11.184
  79.  
  80. Dutta SD, Hexiu J, Patel DK, et al., 2021, 3D-printed bioactive and biodegradable hydrogel scaffolds of alginate/ gelatin/cellulose nanocrystals for tissue engineering. Int J Biol Macromol, 167:644–658. https://doi.org/10.1016/j.ijbiomac.2020.12.011
  81.  
  82. Ramakrishnan R, Kasoju N, Raju R, et al., 2022, Exploring the potential of alginate-gelatin-diethylaminoethyl cellulose-fibrinogen based bioink for 3d bioprinting of skin tissue constructs. Carbohydr Polym Technol Appl, 3:100184. https://doi.org/10.1016/j.carpta.2022.100184
  83. Somasekharan LT, Raju R, Kumar S, et al., 2021, Biofabrication of skin tissue constructs using alginate, gelatin and diethylaminoethyl cellulose bioink. Int J Biol Macromol, 189:398–409. https://doi.org/10.1016/j.ijbiomac.2021.08.114
Previous article in this issue
Next article in this issue
Share
Back to top
International Journal of Bioprinting, Print ISSN: 2424-8002, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept