Volume 1 Issue 1
March  2021
Turn off MathJax
Article Contents
Wentai Guo, Xiaocheng Wang, Chaoyu Yang, Rongkang Huang, Hui Wang, Yuanjin Zhao. Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing[J]. Materials Futures, 2022, 1(1): 015401. doi: 10.1088/2752-5724/ac446b
Citation: Wentai Guo, Xiaocheng Wang, Chaoyu Yang, Rongkang Huang, Hui Wang, Yuanjin Zhao. Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing[J]. Materials Futures, 2022, 1(1): 015401. doi: 10.1088/2752-5724/ac446b
Paper •

Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing

© 2022 The Author(s). Published by IOP Publishing Ltd on behalf of the Songshan Lake Materials Laboratory
Materials Futures, Volume 1, Number 1
  • Received Date: 2021-10-25
  • Accepted Date: 2021-12-16
  • Rev Recd Date: 2021-12-05
  • Publish Date: 2022-01-18
  • Biomimetic scaffolds with extracellular matrix (ECM)-mimicking structure have been widely investigated in wound healing applications, while insufficient mechanical strength and limited biological activity remain major challenges. Here, we present a microfluidic 3D printing biomimetic polyhydroxyalkanoates-based scaffold with excellent mechanical properties and hierarchical porous structures for enhanced wound healing. This scaffold is composed of poly(3-hydroxybutyrate-4-hydroxybutyrate) and polycaprolactone, endowing it with excellent tensile strength (2.99 MPa) and degradability (80% of weight loss within 7 d). The ECM-mimicking hierarchical porous structure allows bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to proliferate and adhere on the scaffolds. Besides, anisotropic composite scaffolds loaded with BMSCs and HUVECs can significantly promote re-epithelization, collagen deposition and capillary formation in rat wound defects, indicating their satisfactory in vivo tissue regenerative activity. These results indicate the feasibility of polyhydroxyalkanoates-based biomimetic scaffolds for skin repair and regeneration, which also provide a promising therapeutic strategy in diverse tissue engineering applications.
  • loading
  • Author contributions

    YJZ conceived the idea and designed the experiment; WTG and XCW conducted experiments and data analysis; CYY conducted software and visualization; RKH collected resources, verification, and supervision; HW conducted project administration and funding acquisition; WTG, XCW, and YJZ wrote the manuscript.

  • [1]
    Chen Y E, Fischbach M A, Belkaid Y 2018 Skin microbiota-host interactions Nature 553 427-36 doi: 10.1038/nature25177
    Lee J, et al 2020 Hair-bearing human skin generated entirely from pluripotent stem cells Nature 582 399-404 doi: 10.1038/s41586-020-2352-3
    Shi L X, Liu X, Wang W S, Jiang L, Wang S T 2019 A self-pumping dressing for draining excessive biofluid around wounds Adv. Mater. 31 e1804187 doi: 10.1002/adma.201804187
    Zhang X, Chen G, Liu Y, Sun L, Sun L, Zhao Y 2020 Black phosphorus-loaded separable microneedles as responsive oxygen delivery carriers for wound healing ACS Nano 14 5901-8 doi: 10.1021/acsnano.0c01059
    Guo X, Liu Y, Bera H, Zhang H, Chen Y, Cun D, Foder V, Yang M 2020 -lactalbumin-based nanofiber dressings improve burn wound healing and reduce scarring ACS Appl. Mater. Interfaces 12 45702-13 doi: 10.1021/acsami.0c05175
    Fiakos G, Kuang Z, Lo E 2020 Improved skin regeneration with acellular fish skin grafts Eng. Regener. 1 95-101 doi: 10.1016/j.engreg.2020.09.002
    Yang Z, et al 2021 Highly stretchable, adhesive, biocompatible, and antibacterial hydrogel dressings for wound healing Adv. Sci. 8 2003627 doi: 10.1002/advs.202003627
    Sun L, Fan L, Bian F, Chen G, Wang Y, Zhao Y 2021 MXene-integrated microneedle patches with innate molecule encapsulation for wound healing Research 2021 9838490 doi: 10.34133/2021/9838490
    Liu X, Liu Y, Du J, Li X, Yu J, Ding B 2021 Breathable, stretchable, and adhesive nanofibrous hydrogels as wound dressing materials Eng. Regen. 2 63-9 doi: 10.1016/j.engreg.2021.05.001
    Ahn S, Ardoa H A M, Campbell P H, Gonzalez G M, Parker K K 2019 Alfalfa nanofibers for dermal wound healing ACS Appl. Mater. Interfaces 11 33535-47 doi: 10.1021/acsami.9b07626
    Guo J, Yu Y, Zhang D, Zhang H, Zhao Y 2021 Morphological hydrogel microfibers with MXene encapsulation for electronic skin Research 2021 7065907 doi: 10.34133/2021/7065907
    Chen G, Yu Y, Wu X, Wang G, Gu G, Wang F, Ren J, Zhang H, Zhao Y 2019 Microfluidic electrospray niacin metal-organic frameworks encapsulated microcapsules for wound healing Research 2019 6175398 doi: 10.34133/2019/6175398
    Xu Y, et al 2020 ECM-inspired micro/nanofibers for modulating cell function and tissue generation Sci. Adv. 6 eabc2036 doi: 10.1126/sciadv.abc2036
    Huang G, Li F, Zhao X, Ma Y, Li Y, Lin M, Jin G, Lu T J, Genin G M, Xu F 2017 Functional and biomimetic materials for engineering of the three-dimensional cell microenvironment Chem. Rev. 117 12764-850 doi: 10.1021/acs.chemrev.7b00094
    Guo W, Yang Z, Qin X, Wei Y, Li C, Huang R, Zhou C, Wang H, Jin L, Wang H 2021 Fabrication, and characterization of the core-shell structure of poly(3-hydroxybutyrate-4-hydroxybutyrate) nanofiber scaffolds Biomed. Res. Int. 2021 8868431
    Marcano A, Bou Haidar N, Marais S, Valleton J M, Duncan A C 2017 Designing biodegradable PHA-based 3D scaffolds with antibiofilm properties for wound dressings: optimization of the microstructure/nanostructure ACS Biomater. Sci. Eng. 3 3654-61 doi: 10.1021/acsbiomaterials.7b00552
    Chen L, Zhang L, Zhang H, Sun X, Liu D, Zhang J, Zhang Y, Cheng L, Santos H A, Cui W 2021 Programmable immune activating electrospun fibers for skin regeneration Bioact. mater. 6 3218-30 doi: 10.1016/j.bioactmat.2021.02.022
    Arif U, Haider S, Haider A, Khan N, Alghyamah A A, Jamila N, Khan M I, Almasry W A, Kang I K 2019 Biocompatible polymers and their potential biomedical applications: a review Curr. Pharm. Des. 25 3608-19 doi: 10.2174/1381612825999191011105148
    Kong T, Shum H C, Weitz D A 2020 The fourth decade of microfluidics Small 16 e2000070 doi: 10.1002/smll.202000070
    Pi Q, et al 2018 Digitally tunable microfluidic bioprinting of multilayered cannular tissues Adv. Mater. 30 e1706913 doi: 10.1002/adma.201706913
    Vanaei S, Parizi M S, Vanaei S, Salemizadehparizi F, Vanaei H R 2021 An overview on materials and techniques in 3D bioprinting toward biomedical application Eng. Regen. 2 1-18 doi: 10.1016/j.engreg.2020.12.001
    Qiu J, Gao Q, Zhao H, Fu J, He Y 2017 Rapid customization of 3D integrated microfluidic chips via modular structure-based design ACS Biomater. Sci. Eng. 3 2606-16 doi: 10.1021/acsbiomaterials.7b00401
    Li R, McCarthy A, Zhang Y S, Xie J 2019 Decorating 3D printed scaffolds with electrospun nanofiber segments for tissue engineering Adv. Biosyst. 3 e1900137 doi: 10.1002/adbi.201900137
    Zhang H, Chen G, Yu Y, Guo J, Tan Q, Zhao Y 2020 Microfluidic printing of slippery textiles for medical drainage around wounds Adv. Sci. 7 2000789 doi: 10.1002/advs.202000789
    Zheng Y, Chen J C, Ma Y M, Chen G Q 2020 Engineering biosynthesis of polyhydroxyalkanoates (PHA) for diversity and cost reduction Metab. Eng. 58 82-93 doi: 10.1016/j.ymben.2019.07.004
    Zhang X, Lin Y, Wu Q, Wang Y, Chen G Q 2020 Synthetic biology and genome-editing tools for improving PHA metabolic engineering Trends Biotechnol. 38 689-700 doi: 10.1016/j.tibtech.2019.10.006
    VanItallie T B, Nufert T H 2003 Ketones: metabolism’s ugly duckling Nutrition Rev. 61 327-41 doi: 10.1301/nr.2003.oct.327-341
    Pereira J R, Arajo D, Marques A C, Neves L A, Grandfils C, Sevrin C, Alves V D, Fortunato E, Reis M A M, Freitas F 2019 Demonstration of the adhesive properties of the medium-chain-length polyhydroxyalkanoate produced by pseudomonas chlororaphis subsp. aurantiaca from glycerol Int. J. Biol. Macromol. 122 1144-51 doi: 10.1016/j.ijbiomac.2018.09.064
    Shishatskaya E I, Nikolaeva E D, Vinogradova O N, Volova T G 2016 Experimental wound dressings of degradable PHA for skin defect repair J. Mater. Sci. Mater. Med. 27 165 doi: 10.1007/s10856-016-5776-4
    Yu Y, Shang L, Guo J, Wang J, Zhao Y 2018 Design of capillary microfluidics for spinning cell-laden microfibers Nat. Protocols 13 2557-79 doi: 10.1038/s41596-018-0051-4
    Yu Y, Fu F, Shang L, Cheng Y, Gu Z, Zhao Y 2017 Bioinspired helical microfibers from microfluidics Adv. Mater. 29 201605765 doi: 10.1002/adma.201605765
    Shang L, Yu Y, Liu Y, Chen Z, Kong T, Zhao Y 2019 Spinning and applications of bioinspired fiber systems ACS Nano 13 2749-72 doi: 10.1021/acsnano.8b09651
    Guessasma S, Belhabib S, Nouri H 2019 Microstructure and mechanical performance of 3D printed wood-PLA/PHA using fused deposition modelling: effect of printing temperature Polymers 11 1778 doi: 10.3390/polym11111778
    Gao Q, Xie C, Wang P, Xie M, Li H, Sun A, Fu J, He Y 2020 3D printed multi-scale scaffolds with ultrafine fibers for providing excellent biocompatibility Mater. Sci. Eng. C 107 110269 doi: 10.1016/j.msec.2019.110269
    Hrynevich A, Elci B S, Haigh J N, McMaster R, Youssef A, Blum C, Blunk T, Hochleitner G, Groll J, Dalton P D 2018 Dimension-based design of melt electrowritten scaffolds Small 14 e1800232 doi: 10.1002/smll.201800232
    Chen Z, Cheng S, Xu K 2009 Block poly(ester-urethane)s based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and poly(3-hydroxyhexanoate-co-3-hydroxyoctanoate) Biomaterials 30 2219-30 doi: 10.1016/j.biomaterials.2008.12.078
    Liu M, Wang S, Jiang L 2017 Nature-inspired superwettability systems Nat. Rev. Mater. 2 17036 doi: 10.1038/natrevmats.2017.36
    Ueda E, Levkin P A 2013 Emerging applications of superhydrophilic-superhydrophobic micropatterns Adv. Mater. 25 1234-47 doi: 10.1002/adma.201204120
    Efremov A N, Stanganello E, Welle A, Scholpp S, Levkin P A 2013 Micropatterned superhydrophobic structures for the simultaneous culture of multiple cell types and the study of cell-cell communication Biomaterials 34 1757-63 doi: 10.1016/j.biomaterials.2012.11.034
    Ayala R, Zhang C, Yang D, Hwang Y, Aung A, Shroff S S, Arce F T, Lal R, Arya G, Varghese S 2011 Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation Biomaterials 32 3700-11 doi: 10.1016/j.biomaterials.2011.02.004
    Shin C S, et al 2021 3D-bioprinted inflammation modulating polymer scaffolds for soft tissue repair Adv. Mater. 33 e2003778 doi: 10.1002/adma.202003778
    Youm Y H, et al 2015 The ketone metabolite -hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease Nat. Med. 21 263-9 doi: 10.1038/nm.3804
    Shimazu T, et al 2013 Suppression of oxidative stress by -hydroxybutyrate, an endogenous histone deacetylase inhibitor Science 339 211-4 doi: 10.1126/science.1227166
    Pan B H, Zhang Q, Lam C H, Yuen H Y, Kuang S, Zhao X 2021 Petite miracles: insight into the nano-management of scarless wound healing Drug Discov. Today S1359-6446 00056-8
  • mfac446bsupp1.zip
  • 加载中



    Article Metrics

    Article Views(809) PDF downloads(123)
    Article Statistics
    Related articles from


    DownLoad:  Full-Size Img  PowerPoint