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Cited by 2063D Printing in Biomedical ResearchAdditive Manufacturing and 3D Printing TechnologiesHydrogels: synthesis, properties, applications

Digital Light Processing Based Bioprinting with Composable Gradients

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Wang, Mian, Li, Wanlu, Mille, Luis S., Ching, Terry, Luo, Zeyu, Tang, Guosheng, Garciamendez, Carlos Ezio, Lesha, Ami +2 more·2022·Advanced Materials
DOI 10.1002/adma.202107038PMC PMC8741743
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Abstract

Recapitulation of complex tissues signifies a remarkable challenge and, to date, only a few approaches have emerged that can efficiently reconstruct necessary gradients in 3D constructs. This is true even though mimicry of these gradients is of great importance to establish the functionality of engineered tissues and devices. Here, a composable‐gradient Digital Light Processing (DLP)‐based (bio)printing system is developed, utilizing the unprecedented integration of a microfluidic mixer for the generation of either continual or discrete gradients of desired (bio)inks in real time. Notably, the precisely controlled gradients are composable on‐the‐fly by facilely by adjusting the (bio)ink flow ratios. In addition, this setup is designed in such a way that (bio)ink waste is minimized when exchanging the gradient (bio)inks, further enhancing this time‐ and (bio)ink‐saving strategy. Various planar and 3D structures exhibiting continual gradients of materials, of cell densities, of growth factor concentrations, of hydrogel stiffness, and of porosities in horizontal and/or vertical direction, are exemplified. The composable fabrication of multifunctional gradients strongly supports the potential of the unique bioprinting system in numerous biomedical applications.

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  • The combination of 90% amino substitution degree GelMA and 10% w/v concentration (GM90-10%) was selected for its optimal mechanical properties, biocompatibility, and photocrosslinking efficiency, which has become the mainstream choice for tissue engineering, 3D printing, and cell culture.

    “For GelMA hydrogel preparation, the combination of 90 % amino substitution degree GelMA and 10 % w/v concentration (GM90-10 %) was selected for its optimal mechanical properties, biocompatibility, and photocrosslinking efficiency, which has become the mainstream choice for tissue engineering, 3D printing, and cell culture [47,48].”

    From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [47]

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Research works printed but not linked: 56

  1. [1]Li C, Ouyang L, Armstrong JPK, Stevens MM, Trends Biotechnol 2020. 32650955
  2. [2]Wu J, Chen Q, Liu W, Lin JM, Lab Chip 2013 13(10) 1948– 54. 23538998
  3. [3]Bracaglia LG, Smith BT, Watson E, Arumugasaamy N, Mikos AG, Fisher JP, Acta Biomater 2017 56 3– 13. 28342878 PMC5544968
  4. [4]Singh M, Berkland C, Detamore MS, Tissue Eng Part B Rev 2008 14(4) 341– 66. 18803499 PMC2737593
  5. [5]Cheng A, Schwartz Z, Kahn A, Li X, Shao Z, Sun M, Ao Y, Boyan BD, Chen H, Tissue Eng Part B Rev 2019 25(1) 14– 29. 30079807 PMC6388715
  6. [7]Seidi A, Sampathkumar K, Srivastava A, Ramakrishna S, Ramalingam M, J Nanosci Nanotechnol 2013 13(7) 4647– 55. 23901487
  7. [8]Ilkhanizadeh S, Teixeira AI, Hermanson O, Biomaterials 2007 28(27) 3936– 43. 17576007
  8. [9]de Gans BJ, Schubert US, Langmuir 2004 20(18) 7789– 93. 15323532
  9. [10]Idaszek J, Costantini M, Karlsen TA, Jaroszewicz J, Colosi C, Testa S, Fornetti E, Bernardini S, Seta M, Kasarełło K, Biofabrication 2019 11(4) 044101. 31151123
  10. [11]Costantini M, Jaroszewicz J, Kozoń Ł, Szlązak K, Święszkowski W, Garstecki P, Stubenrauch C, Barbetta A, Guzowski J, Angewandte Chemie International Edition 2019 58(23) 7620– 7625. 30908850
  11. [12]Singh M, Haverinen HM, Dhagat P, Jabbour GE, Adv Mater 2010 22(6) 673– 85. 20217769
  12. [13]Placone JK, Engler AJ, Adv Healthc Mater 2018 7(8) e1701161. PMC5954828 29283220
  13. [14]Ma X, Qu X, Zhu W, Li Y-S, Yuan S, Zhang H, Liu J, Wang P, Lai CSE, Zanella F, Proceedings of the National Academy of Sciences 2016 113(8) 2206– 2211. PMC4776497 26858399
  14. [15]Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brock J, Graham L, Lu P, Sakamoto J, Marsala M, Chen S, Tuszynski MH, Nat Med 2019 25(2) 263– 269. 30643285 PMC6559945
  15. [16]Grigoryan B, Paulsen SJ, Corbett DC, Sazer DW, Fortin CL, Zaita AJ, Greenfield PT, Calafat NJ, Gounley JP, Ta AH, Science 2019 364(6439) 458– 464. 31048486 PMC7769170
  16. [17]Ligon SC, Liska R, Stampfl J, Gurr M, Mulhaupt R, Chem Rev 2017 117(15) 10212– 10290. 28756658 PMC5553103
  17. [18]Li W, Mille LS, Robledo JA, Uribe T, Huerta V, Zhang YS, Advanced Healthcare Materials 2020 2000156. PMC7473482 32529775
  18. [19]Schreurs M, Suttorp CM, Mutsaers HAM, Kuijpers-Jagtman AM, Von den Hoff JW, Ongkosuwito EM, Carvajal Monroy PL, Wagener F, Med Res Rev 2020 40(1) 9– 26. 31104334 PMC6972684
  19. [20]Lim KS, Galarraga JH, Cui X, Lindberg GC, Burdick JA, Woodfield TB, Chemical reviews 2020 120(19) 10662– 10694. 32302091
  20. [21]Zhang J, Hu Q, Wang S, Tao J, Gou M, International Journal of Bioprinting 2020 6(1) 242. 32782984 PMC7415858
  21. [22]Chan V, Zorlutuna P, Jeong JH, Kong H, Bashir R, Lab on a Chip 2010 10(16) 2062– 2070. 20603661
  22. [23]Miri AK, Nieto D, Iglesias L, Goodarzi Hosseinabadi H, Maharjan S, Ruiz-Esparza GU, Khoshakhlagh P, Manbachi A, Dokmeci MR, Chen S, Shin SR, Zhang YS, Khademhosseini A, Adv Mater 2018 30(27) e1800242. PMC6133710 29737048
  23. [25]Kim DS, Lee SW, Kwon TH, Lee SS, Journal of micromechanics and microengineering 2004 14(6) 798.
  24. [27]Li W, Wang M, Mille LS, Robledo Lara JA, Huerta V, Uribe Velazquez T, Cheng F, Li H, Gong J, Ching T, Murphy CA, Lesha A, Hassan S, Woodfield TBF, Lim KS, Zhang YS, Adv Mater 2021 33(35) e2102153. PMC8416928 34278618
  25. [28]Stroock AD, Dertinger SK, Ajdari A, Mezic I, Stone HA, Whitesides GM, Science 2002 295(5555) 647– 51. 11809963
  26. [29]Kim BS, Kwak BS, Shin S, Lee S, Kim KM, Jung H-I, Cho HH, International journal of heat and mass transfer 2011 54(1–3) 118– 125.
  27. [30]Lim KS, Levato R, Costa PF, Castilho MD, Alcala-Orozco CR, van Dorenmalen KMA, Melchels FPW, Gawlitta D, Hooper GJ, Malda J, Woodfield TBF, Biofabrication 2018 10(3) 034101. 29693552
  28. [31]Lee J, Kim KE, Bang S, Noh I, Lee C, International journal of precision engineering and manufacturing 2017 18(4) 605– 612.
  29. [33]Purcell EM, American journal of physics 1977 45(1) 3– 11.
  30. [34]Xia H, Wan S, Shu C, Chew Y, Lab on a Chip 2005 5(7) 748– 755. 15970968
  31. [35]Miri AK, Nieto D, Iglesias L, Goodarzi Hosseinabadi H, Maharjan S, Ruiz-Esparza GU, Khoshakhlagh P, Manbachi A, Dokmeci MR, Chen S, Advanced Materials 2018 30(27) 1800242. PMC6133710 29737048
  32. [36]Jadin KD, Wong BL, Bae WC, Li KW, Williamson AK, Schumacher BL, Price JH, Sah RL, J Histochem Cytochem 2005 53(9) 1109– 19. 15879579
  33. [37]Zhu D, Tong X, Trinh P, Yang F, Tissue Engineering Part A 2018 24(1–2) 1– 10. 28385124 PMC5770099
  34. [38]Sun Y, You Y, Jiang W, Wang B, Wu Q, Dai K, Sci Adv 2020 6(37). PMC11206535 32917692
  35. [39]Ren X, Wang F, Chen C, Gong X, Yin L, Yang L, BMC musculoskeletal disorders 2016 17(1) 301. 27439428 PMC4955200
  36. [40]Sant S, Hancock MJ, Donnelly JP, Iyer D, Khademhosseini A, Can J Chem Eng 2010 88(6) 899– 911. 21874065 PMC3160739
  37. [41]Byrne AM, Bouchier-Hayes DJ, Harmey JH, J Cell Mol Med 2005 9(4) 777– 94. 16364190 PMC6740098
  38. [42]Jeong GS, Han S, Shin Y, Kwon GH, Kamm RD, Lee SH, Chung S, Anal Chem 2011 83(22) 8454– 9. 21985643
  39. [43]Li C, Ouyang L, Pence IJ, Moore AC, Lin Y, Winter CW, Armstrong JPK, Stevens MM, Adv Mater 2019 31(17) e1900291. PMC6606439 30844123
  40. [44]Brandl F, Sommer F, Goepferich A, Biomaterials 2007 28(2) 134– 46. 17011028
  41. [45]Seidi A, Ramalingam M, Elloumi-Hannachi I, Ostrovidov S, Khademhosseini A, Acta Biomater 2011 7(4) 1441– 51. 21232635
  42. [47]Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A, Biomaterials 2015 73 254– 71. 26414409 PMC4610009
  43. [48]Gong J, Shuurmans C, Cao X, Van Genderen AM, Li W, Cheng F, He JJ, López A, Huerta V, Manríquez J, Li R, Li H, Delavaux C, Sebastian S, Wang H, Xie J, Yu M, Masereeuw R, Vermonden T, Zhang YS, Nature Communications 2020 11 1267. PMC7062888 32152307
  44. [49]Boontheekul T, Hill EE, Kong H-J, Mooney DJ, Tissue engineering 2007 13(7) 1431– 1442. 17561804
  45. [50]Loh QL, Choong C, Tissue Eng Part B Rev 2013 19(6) 485– 502. 23672709 PMC3826579
  46. [51]Ying GL, Jiang N, Maharjan S, Yin YX, Chai RR, Cao X, Yang JZ, Miri AK, Hassan S, Zhang YS, Adv Mater 2018 30(50) e1805460. PMC6402588 30345555
  47. [52]Ying G, Manriquez J, Wu D, Zhang J, Jiang N, Maharjan S, Hernandez Medina DH, Zhang YS, Mater Today Bio 2020 8 100074. PMC7508999 32995743
  48. [53]Ying G, Jiang N, Parra-Cantu C, Tang G, Zhang J, Wang H, Chen S, Huang NP, Xie J, Zhang YS, Advanced Functional Materials 2020 30(46) 2003740. PMC7941201 33708030
  49. [54]Li C, Ouyang L, Armstrong JPK, Stevens MM, Trends Biotechnol 2021 39(2) 150– 164. 32650955
  50. [56]Bose S, Roy M, Bandyopadhyay A, Trends Biotechnol 2012 30(10) 546– 54. 22939815 PMC3448860
  51. [57]Ryoo HM, Lee MH, Kim YJ, Gene 2006 366(1) 51– 7. 16314053
  52. [58]He X, Ma J, Jabbari E, Langmuir 2008 24(21) 12508– 16. 18837524
  53. [59]Huang W, Yang S, Shao J, Li YP, Front Biosci 2007 12 3068– 92. 17485283 PMC3571113
  54. [60]Liu W, Zhang YS, Heinrich MA, De Ferrari F, Jang HL, Bakht SM, Alvarez MM, Yang J, Li Y-C, Trujillo-de Santiago G, Miri AK, Zhu K, Khoshakhlagh P, Prakash G, Cheng H, Guan X, Zhong Z, Ju J, Zhu GH, Jin X, Shin SR, Dokmeci MR, Khademhosseini A, Adv. Mater. 2017 29 1604630. PMC5235978 27859710
  55. [61]Lim KS, Schon BS, Mekhileri NV, Brown GCJ, Chia CM, Prabakar S, Hooper GJ, Woodfield TBF, ACS Biomaterials Science & Engineering 2016 2(10) 1752– 1762. 33440473
  56. [62]Mangir N.i., Dikici S, Claeyssens F, MacNeil S, ACS Biomaterials Science & Engineering 2019 5(7) 3190– 3200. 33405582

Cited by

Sorted by citations

Authors
Wang, M., Li, W., Mille, L. S., Ching, T., Luo, Z., Tang, G., Garciamendez, C. E., Lesha, A., Hashimoto, M., & Zhang, Y. S.
Affiliations
  • Brigham and Women's Hospital (US)
  • Division of Engineering in Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Cambridge MA 02139 USA
  • Singapore University of Technology and Design (SG)
Corresponding author
Zhang, Yu Shrike
ORCID
Venue
Advanced Materials
Publisher
Wiley
Published
2021-10-23
Volume
34
Issue
1
Pages
e2107038-e2107038
ISSN
  • 0935-9648 (ISSN-L)
  • 1521-4095
DOI
10.1002/adma.202107038
PMC
PMC8741743
OpenAlex
W3203134233
Cited by
206
References
3
Citations by year
2026: 26 · 2025: 54 · 2024: 48 · 2023: 32 · 2022: 44 · 2021: 2
FWCI
9.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Materials (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R21EB025270, R00CA201603)
  • National Science Foundation (CBET‐EBMS‐123859)
  • Brigham Research Institute
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Automotive Engineering › Additive Manufacturing and 3D Printing Technologies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
digital light processing, 3D bioprinting, micromixer, growth factor gradients, cell density gradient, porosity gradient, 3D tissue constructs
MeSH terms
Ink, Hydrogels, Tissue Engineering, Tissue Scaffolds, Bioprinting, Printing, Three-Dimensional

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