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Current Applied Polymer Science

Editor-in-Chief

ISSN (Print): 2452-2716
ISSN (Online): 2452-2724

Letter Article

Scaffolds Designing from Protein-loadable Coaxial Electrospun Fibermats of poly(acrylamide)-Co-poly(diacetone acrylamide) and Gelatin

Author(s): Yuji Tanikawa, Akiko Obata, Kenji Nagata, Toshihiro Kasuga and Toshihisa Mizuno*

Volume 4, Issue 2, 2021

Published on: 16 July, 2021

Page: [84 - 92] Pages: 9

DOI: 10.2174/2452271604666210716143235

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Aiming at in situ regenerative therapy, the tailored design of cytokine-releasing scaffolds is still one of the crucial issues to be studied. A core-shell fibermat is one of the attractive platforms for this purpose. But, very few detail the importance of choosing the right material for the shell units that can endow efficient release properties.

Objective: In this study, we characterized the effectiveness of core-shell fibermats that possess cross-linked gelatin (CLG) as the shell layer of constituent nanofibers, as a protein-releasing cell-incubation scaffold.

Methods: For the core nanofibers in the core-shell fibermats, we utilized a crosslinked copolymer of poly(acrylamide)-co-poly(diacetone acrylamide) (poly(AM/DAAM)) and adipic acid dihydrazide (ADH), poly(AM/DAAM)/ADH. By coaxial electrospinning and the subsequent crosslinking of the gelatin layer, we successfully constructed core-shell fibermats consisting of double-layered nanofibers of poly(AM/DAAM)/ADH and CLG. Using fluorescein isothiocyanate-labeled lysozyme (FITC-Lys) as a dummy guest protein, we characterized the release behavior of the coreshell fibermats containing a CLG layer. Upon loading basic fibroblast growth factor (bFGF) as cargo in our fibermats, we also characterized impacts of the released bFGF on proliferation of the incubated cells thereon.

Results: Although the single-layered poly(AM/DAAM)/ADH nanofiber fibermats did not adhere to the mammalian cells, the core-shell fibermat with the CLG shell layer exhibited good adherence and subsequent proliferation. A sustained release of the preloaded FITC-Lys over 24 days without any burst release was observed, and the cumulative amount of released protein reached over 65% after 24 days. Upon loading bFGF in our fibermats, we succeeded in promoting cell proliferation, and highlighting its potential for use in therapeutic applications.

Conclusion: We successfully confirmed that core-shell fibermats with a CLG shell layer around the constituent nanofibers, were effective as protein-releasing cell-incubation scaffolds.

Keywords: Fibermat, co-axial electrospinning, protein-encapsulation, gelatin, scaffold, growth factor, CLG shell layer.

Graphical Abstract
[1]
Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 2000; 97(21): 11307-12.
[http://dx.doi.org/10.1073/pnas.97.21.11307] [PMID: 11027332]
[2]
Smith JC, Price BMJ, Van Nimmen K, Huylebroeck D. Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A. Nature 1990; 345(6277): 729-31.
[http://dx.doi.org/10.1038/345729a0] [PMID: 2113615]
[3]
Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013; 499(7459): 481-4.
[http://dx.doi.org/10.1038/nature12271] [PMID: 23823721]
[4]
Zhang S, Wan Z, Kamm RD. Vascularized organoids on a chip: Strategies for engineering organoids with functional vasculature. Lab Chip 2021; 21(3): 473-88.
[http://dx.doi.org/10.1039/D0LC01186J] [PMID: 33480945]
[5]
Dash TK, Konkimalla VB. Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. J Control Release 2012; 158(1): 15-33.
[http://dx.doi.org/10.1016/j.jconrel.2011.09.064] [PMID: 21963774]
[6]
Holzwarth JM, Ma PX. 3D nanofibrous scaffolds for tissue engineering. J Mater Chem 2011; 21: 10243-51.
[http://dx.doi.org/10.1039/c1jm10522a]
[7]
Deshmukh K, Kovářík T, Křenek T, Docheva D, Stich T, Pola J. Recent advances and future perspectives of sol–gel derived porous bioactive glasses: A review. RSC Advances 2020; 10: 33782-835.
[http://dx.doi.org/10.1039/D0RA04287K]
[8]
Vallet-Regí M, Colilla M, González B. Medical applications of organic-inorganic hybrid materials within the field of silica-based bioceramics. Chem Soc Rev 2011; 40(2): 596-607.
[http://dx.doi.org/10.1039/C0CS00025F] [PMID: 21049136]
[9]
Schnettler R, Alt V, Dingeldein E, et al. Bone ingrowth in bFGF- coated hydroxyapatite ceramic implants. Biomaterials 2003; 24(25): 4603-8.
[http://dx.doi.org/10.1016/S0142-9612(03)00354-5] [PMID: 12951003]
[10]
Tao B, Deng Y, Song L, et al. BMP2-loaded titania nanotubes coating with pH-responsive multilayers for bacterial infections inhibition and osteogenic activity improvement. Colloids Surf B Biointerfaces 2019; 177: 242-52.
[http://dx.doi.org/10.1016/j.colsurfb.2019.02.014] [PMID: 30763789]
[11]
Bang S, Das D, Yu J, Noh I. Evaluation of mc3t3 cells proliferation and drug release study from sodium hyaluronate-1,4-butanediol diglycidyl ether patterned gel. Nanomaterials 2017; 7(10): 328.
[http://dx.doi.org/10.3390/nano7100328] [PMID: 29036920]
[12]
Yuasa M, Yamada T, Taniyama T, et al. Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2. PLoS One 2015; 10(2): e0116462.
[http://dx.doi.org/10.1371/journal.pone.0116462] [PMID: 25659106]
[13]
Yamamoto K, Kishida T, Nakai K, et al. Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal. Sci Rep 2018; 8(1): 8463.
[http://dx.doi.org/10.1038/s41598-018-26745-2] [PMID: 29855543]
[14]
Golchin A, Nourani MR. Effects of bilayer nanofibrillar scaffolds containing epidermal growth factor on full thickness wound healing. Polym Adv Technol 2020; 31: 2443-52.
[http://dx.doi.org/10.1002/pat.4960]
[15]
Carreira ACO, Zambuzzi WF, Rossi MC, Astorino Filho R, Sogayar MC, Granjeiro JM. Bone morphogenetic proteins: Promising molecules for bone healing, bioengineering, and regenerative medicine. Vitam Horm 2015; 99: 293-322.
[http://dx.doi.org/10.1016/bs.vh.2015.06.002] [PMID: 26279381]
[16]
Madry H, Rey-Rico A, Venkatesan JK, Johnstone B, Cucchiarini M. Transforming growth factor Beta-releasing scaffolds for cartilage tissue engineering. Tissue Eng Part B Rev 2014; 20(2): 106-25.
[http://dx.doi.org/10.1089/ten.teb.2013.0271] [PMID: 23815376]
[17]
Ji W, Sun Y, Yang F, et al. Bioactive electrospun scaffolds delivering growth factors and genes for tissue engineering applications. Pharm Res 2011; 28(6): 1259-72.
[http://dx.doi.org/10.1007/s11095-010-0320-6] [PMID: 21088985]
[18]
Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 2005; 26(15): 2603-10.
[http://dx.doi.org/10.1016/j.biomaterials.2004.06.051] [PMID: 15585263]
[19]
Lee SJ, Oh SH, Liu J, Soker S, Atala A, Yoo JJ. The use of thermal treatments to enhance the mechanical properties of electrospun poly(epsilon-caprolactone) scaffolds. Biomaterials 2008; 29(10): 1422-30.
[http://dx.doi.org/10.1016/j.biomaterials.2007.11.024] [PMID: 18096219]
[20]
Kenawy EIR, Abdel-Hay FI, EI-Newehy MH, Wnek GE. Processing of polymer nanofibers through electrospinning as drug delivery systems. Mater Chem Phys 2009; 113: 296-302.
[http://dx.doi.org/10.1016/j.matchemphys.2008.07.081]
[21]
Wu R, Gao G, Xu Y. Electrospun fibers immobilized with bmp-2 mediated by polydopamine combined with autogenous tendon to repair developmental dysplasia of the hip in a porcine model. Int J Nanomedicine 2020; 15: 6563-77.
[http://dx.doi.org/10.2147/IJN.S259028] [PMID: 32982218]
[22]
Qi H, Hu P, Xu J, Wang A. Encapsulation of drug reservoirs in fibers by emulsion electrospinning: Morphology characterization and preliminary release assessment. Biomacromolecules 2006; 7(8): 2327-30.
[http://dx.doi.org/10.1021/bm060264z] [PMID: 16903678]
[23]
Liu C, Wang C, Zhao Q, et al. Incorporation and release of dual growth factors for nerve tissue engineering using nanofibrous bicomponent scaffolds. Biomed Mater 2018; 13(4): 044107.
[http://dx.doi.org/10.1088/1748-605X/aab693] [PMID: 29537390]
[24]
Koeda S, Ichiki K, Iwanaga N, et al. Construction and characterization of protein-encapsulated electrospun fibermats prepared from a silica/poly(γ-glutamate) hybrid. Langmuir 2016; 32(1): 221-9.
[http://dx.doi.org/10.1021/acs.langmuir.5b02862] [PMID: 26681447]
[25]
Ido Y, Maçon ALB, Iguchi M, et al. Construction of enzyme-encapsulated fibermats from the cross-linkable copolymers poly(acrylamide)-co-poly(diacetone acrylamide) with the bi-functional cross-linker, adipic acid dihydrazide. Polymer (Guildf) 2017; 132: 342-52.
[http://dx.doi.org/10.1016/j.polymer.2017.10.057]
[26]
Tanikawa Y, Ido Y, Ando R, et al. Coaxial electrospun fibermat of poly(am/daam)/adh and PCL: Versatile platform for encapsulating functionally active enzymes. Bull Chem Soc Jpn 2020; 93: 1155-63.
[http://dx.doi.org/10.1246/bcsj.20200131]
[27]
Chou SF, Luo LJ, Lai JY, Ma DH. Role of solvent-mediated carbodiimide cross-linking in fabrication of electrospun gelatin nanofibrous membranes as ophthalmic biomaterials. Mater Sci Eng C 2017; 71: 1145-55.
[http://dx.doi.org/10.1016/j.msec.2016.11.105] [PMID: 27987671]
[28]
Zhao Y-Z, Tian X-Q, Zhang M, et al. Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction. J Control Release 2014; 186: 22-31.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.054] [PMID: 24815422]
[29]
Chao SC, Wang MJ, Pai NS, Yen SK. Preparation and characterization of gelatin-hydroxyapatite composite microspheres for hard tissue repair. Mater Sci Eng C 2015; 57: 113-22.
[http://dx.doi.org/10.1016/j.msec.2015.07.047] [PMID: 26354246]
[30]
Caliari SR, Burdick JA. A practical guide to hydrogels for cell culture. Nat Methods 2016; 13(5): 405-14.
[http://dx.doi.org/10.1038/nmeth.3839] [PMID: 27123816]
[31]
Wetter LR, Deutsch HF. Immunological studies on egg white proteins. IV. Immunochemical and physical studies of lysozyme. J Biol Chem 1951; 192(1): 237-42.
[http://dx.doi.org/10.1016/S0021-9258(18)55926-3] [PMID: 14917670]
[32]
Whalen GF, Shing Y, Folkman J. The fate of intravenously administered bFGF and the effect of heparin. Growth Factors 1989; 1(2): 157-64.
[http://dx.doi.org/10.3109/08977198909029125] [PMID: 2624780]
[33]
Zhang JD, Cousens LS, Barr PJ, Sprang SR. Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta. Proc Natl Acad Sci USA 1991; 88(8): 3446-50.
[http://dx.doi.org/10.1073/pnas.88.8.3446] [PMID: 1849658]

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