Microporous annealed particle hydrogel stiffness, void space size, and adhesion properties impact cell proliferation, cell spreading, and gene transfer.
Biocompatible Materials
/ pharmacology
Cell Adhesion
Cell Proliferation
Cell Survival
Cross-Linking Reagents
/ chemistry
Fibroblasts
/ cytology
Gene Transfer Techniques
Genetic Therapy
Humans
Hyaluronic Acid
/ chemistry
Hydrogels
/ chemistry
Integrins
/ chemistry
Ligands
Norbornanes
/ chemistry
Oligopeptides
/ chemistry
Oscillometry
Particle Size
Polyethylene Glycols
/ chemistry
Porosity
Regenerative Medicine
Rheology
Tissue Adhesions
Tissue Scaffolds
/ chemistry
Transgenes
Gene delivery
MAP hydrogel
Non-viral
Polyplex
Porous
Journal
Acta biomaterialia
ISSN: 1878-7568
Titre abrégé: Acta Biomater
Pays: England
ID NLM: 101233144
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
31
08
2018
revised:
21
02
2019
accepted:
21
02
2019
pubmed:
4
6
2019
medline:
12
8
2020
entrez:
3
6
2019
Statut:
ppublish
Résumé
Designing scaffolds for polyplex-mediated therapeutic gene delivery has a number of applications in regenerative medicine, such as for tissue repair after wounding or disease. Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing microgel particles to one another in situ to form a porous bulk scaffold. MAP gels have previously been shown to support and enhance proliferative and regenerative behaviors both in vitro and in vivo. Therefore, coupling gene delivery with MAP hydrogels presents a promising approach for therapy development. To optimize MAP hydrogels for gene delivery, we studied the effects of particle size and stiffness as well as adhesion potential on cell surface area and proliferation and then correlated this information with the ability of cells to become transfected while seeded in these scaffolds. We find that the void space size as well as the presentation of integrin ligands influence transfection efficiency. This work demonstrates the importance of considering MAP material properties for guiding cell spreading, proliferation, and gene transfer. STATEMENT OF SIGNIFICANCE: Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing spherical microgels together in situ, creating a porous scaffold from voids between the packed beads. Here we investigated the effects of MAP physical and adhesion properties on cell spreading, proliferation, and gene transfer in fibroblasts. Particle size and void space influenced spreading and proliferation, with larger particles improving transfection. MAP stiffness was also important, with stiffer scaffolds increasing proliferation, spreading, and transfection, contrasting studies in nonporous hydrogels that showed an inverse response. Last, RGD ligand concentration and presentation modulated spreading similar to non-MAP hydrogels. These findings reveal relationships between MAP properties and cell processes, suggesting how MAP can be tuned to improve future design approaches.
Identifiants
pubmed: 31154058
pii: S1742-7061(19)30400-3
doi: 10.1016/j.actbio.2019.02.054
pmc: PMC7444265
mid: NIHMS1531687
pii:
doi:
Substances chimiques
Biocompatible Materials
0
Cross-Linking Reagents
0
Hydrogels
0
Integrins
0
Ligands
0
Norbornanes
0
Oligopeptides
0
2-norbornene
2Q51FLS550
Polyethylene Glycols
3WJQ0SDW1A
arginyl-glycyl-aspartic acid
78VO7F77PN
Hyaluronic Acid
9004-61-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
160-172Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL110592
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS094599
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM067555
Pays : United States
Informations de copyright
Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Références
Biomaterials. 2011 Dec;32(36):9866-75
pubmed: 21924770
Tissue Eng Part B Rev. 2013 Dec;19(6):485-502
pubmed: 23672709
Acta Biomater. 2010 Sep;6(9):3436-47
pubmed: 20371304
Tissue Eng. 2001 Oct;7(5):557-72
pubmed: 11694190
J Gene Med. 2007 Aug;9(8):668-78
pubmed: 17533618
Biomaterials. 2013 May;34(16):3938-3947
pubmed: 23465825
Biomaterials. 2010 Jan;31(3):461-6
pubmed: 19819008
Langmuir. 2006 Sep 12;22(19):8151-5
pubmed: 16952255
Biomaterials. 2013 Jul;34(21):5070-7
pubmed: 23587444
Nat Mater. 2015 Jul;14(7):737-44
pubmed: 26030305
Bioconjug Chem. 2019 Feb 20;30(2):476-486
pubmed: 30513197
Tissue Eng Part A. 2011 Jan;17(1-2):139-50
pubmed: 20695776
Nano Lett. 2007 Jan;7(1):161-6
pubmed: 17212457
J Mech Behav Biomed Mater. 2015 Jun;46:318-30
pubmed: 25819199
J Theor Biol. 2015 Nov 7;384:19-32
pubmed: 26277735
Genes (Basel). 2017 Feb 10;8(2):
pubmed: 28208635
Nat Mater. 2005 Jun;4(6):460-4
pubmed: 15895097
Mol Pharm. 2011 Oct 3;8(5):1582-91
pubmed: 21823632
J Biol Eng. 2012 Sep 11;6(1):17
pubmed: 22967455
Tissue Eng Part A. 2015 Feb;21(3-4):486-97
pubmed: 25203687
Nat Rev Genet. 2014 Aug;15(8):541-55
pubmed: 25022906
Adv Mater. 2017 Aug;29(32):
pubmed: 28650574
Biomaterials. 2009 Feb;30(6):1089-97
pubmed: 19027948
Biotechnol Bioeng. 2009 Jul 1;103(4):655-63
pubmed: 19472329
Acta Biomater. 2014 Apr;10(4):1571-1580
pubmed: 23899481
Biomaterials. 2009 May;30(15):2956-65
pubmed: 19249094
Adv Mater. 2017 Aug;29(29):
pubmed: 28585393
PLoS One. 2012;7(9):e45297
pubmed: 23028915
Nat Mater. 2017 Sep;16(9):953-961
pubmed: 28783156
Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
pubmed: 15573414
Biomaterials. 2011 Jan;32(1):39-47
pubmed: 20933268
Gene Ther. 2000 Mar;7(5):401-7
pubmed: 10694822
J Vis Exp. 2016 Dec 13;(118):
pubmed: 28060331
Curr Med Chem. 2012;19(2):197-208
pubmed: 22320298
Biomacromolecules. 2013 Apr 8;14(4):949-53
pubmed: 23448682
IEEE Trans Biomed Eng. 2010 Apr;57(4):953-9
pubmed: 19822464
J Am Chem Soc. 2011 Sep 7;133(35):13828-31
pubmed: 21819063
Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Aug;90(2):022204
pubmed: 25215730