Granular hydrogels: emergent properties of jammed hydrogel microparticles and their applications in tissue repair and regeneration.

Granular hydrogels are emerging as a versatile and effective platform for tissue engineered constructs in regenerative medicine. The hydrogel microparticles (HMPs) that compose these materials exhibit particle jamming above a minimum packing fraction, which results in a bulk, yet dynamic, granular hydrogel scaffold. These injectable, microporous scaffolds possess self-assembling, shear-thinning, and self-healing properties. Recently, they have been utilized as cell cultures platforms and extracellular matrix mimics with remarkable success in promoting cellular infiltration and subsequent tissue remodeling in vivo. Furthermore, the modular nature of granular hydrogels accommodates heterogeneous HMP assembly, where varying HMPs have been fabricated to target distinct biological processes or deliver unique cargo. Such multifunctional materials offer enormous potential for capturing the structural and biofunctional complexity observed in native human tissue.

[1]  Lianqing Liu,et al.  High-Throughput Fabrication and Modular Assembly of 3D Heterogeneous Microscale Tissues. , 2017, Small.

[2]  K. Anseth,et al.  Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation , 2017, Advanced healthcare materials.

[3]  Sze Yi Mak,et al.  Controlled Electrospray Generation of Nonspherical Alginate Microparticles. , 2018, Chemphyschem : a European journal of chemical physics and physical chemistry.

[4]  S. Armes,et al.  Colloidosomes: synthesis, properties and applications. , 2015, Journal of colloid and interface science.

[5]  S. Carmichael,et al.  Injectable and Spatially Patterned Microporous Annealed Particle (MAP) Hydrogels for Tissue Repair Applications , 2018, Advanced science.

[6]  C. Armstrong,et al.  Na and Ca channels in a transformed line of anterior pituitary cells , 1984, The Journal of general physiology.

[7]  E. S. Bayrak,et al.  Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels. , 2015, Tissue engineering. Part C, Methods.

[8]  T. Desai,et al.  Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction. , 2018, Biomaterials.

[9]  D. Kaplan,et al.  Heparin-Modified Polyethylene Glycol Microparticle Aggregates for Focal Cancer Chemotherapy. , 2016, ACS biomaterials science & engineering.

[10]  Chengyang Wang,et al.  Droplet Microfluidics for the Production of Microparticles and Nanoparticles , 2017, Micromachines.

[11]  Antoinette Tordesillas,et al.  Self-assembly in a near-frictionless granular material: conformational structures and transitions in uniaxial cyclic compression of hydrogel spheres. , 2015, Soft matter.

[12]  Q. Han,et al.  Preformed gelatin microcryogels as injectable cell carriers for enhanced skin wound healing. , 2015, Acta biomaterialia.

[13]  Shiwei Zhao,et al.  Three-dimensional Voronoi analysis of monodisperse ellipsoids during triaxial shear , 2018 .

[14]  R. Reis,et al.  Chitosan microparticles as injectable scaffolds for tissue engineering , 2008, Journal of tissue engineering and regenerative medicine.

[15]  Nicolas Brodu,et al.  Spanning the scales of granular materials through microscopic force imaging , 2015, Nature communications.

[16]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[17]  Yan Shi,et al.  Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase. , 2017, Biomaterials.

[18]  Wei Chen,et al.  Injectable degradable PVA microgels prepared by microfluidic technology for controlled osteogenic differentiation of mesenchymal stem cells. , 2018, Acta biomaterialia.

[19]  Dino Di Carlo,et al.  Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. , 2015, Nature materials.

[20]  Nathaniel S. Hwang,et al.  Injectable multifunctional microgel encapsulating outgrowth endothelial cells and growth factors for enhanced neovascularization. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[21]  Shangjing Xin,et al.  Interplay Between Degradability and Integrin Signaling on Mesenchymal Stem Cell Function within Poly(ethylene glycol) Based Microporous Annealed Particle Hydrogels. , 2019, Acta biomaterialia.

[22]  David J Mooney,et al.  Injectable cryogel-based whole-cell cancer vaccines , 2015, Nature Communications.

[23]  Glenn H Fredrickson,et al.  The science of hyaluronic acid dermal fillers , 2008, Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology.

[24]  M. Zenobi‐Wong,et al.  Cartilage tissue formation through assembly of microgels containing mesenchymal stem cells. , 2018, Acta biomaterialia.

[25]  A. J. Putnam,et al.  Biofabrication of injectable fibrin microtissues for minimally-invasive therapies: application of surfactants , 2018, Biomedical materials.

[26]  Shangjing Xin,et al.  Assembly of PEG Microgels into Porous Cell‐Instructive 3D Scaffolds via Thiol‐Ene Click Chemistry , 2018, Advanced healthcare materials.

[27]  Xin Rong,et al.  Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus. , 2018, ACS applied materials & interfaces.

[28]  Rui L Reis,et al.  Morphology, mechanical characterization and in vivo neo-vascularization of chitosan particle aggregated scaffolds architectures. , 2008, Biomaterials.

[29]  Tingting Wang,et al.  Modulation of macrophage phenotype by cell shape , 2013, Proceedings of the National Academy of Sciences.

[30]  Dhananjay Dendukuri,et al.  Continuous-flow lithography for high-throughput microparticle synthesis , 2006, Nature materials.

[31]  S. Kundu,et al.  Silk sericin-alginate-chitosan microcapsules: hepatocytes encapsulation for enhanced cellular functions. , 2014, International journal of biological macromolecules.

[32]  J. D. Frost,et al.  Pore Size Distribution in Granular Material Microstructure , 2017, Materials.

[33]  D. Grijpma,et al.  Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation , 2016, Advanced science.

[34]  Tim R. Dargaville,et al.  Electrospraying, a Reproducible Method for Production of Polymeric Microspheres for Biomedical Applications , 2011 .

[35]  João Rodrigues,et al.  Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. , 2012, Chemical Society reviews.

[36]  James C. Weaver,et al.  Hydrogels with tunable stress relaxation regulate stem cell fate and activity , 2015, Nature materials.

[37]  Joe Tien,et al.  Molding of three-dimensional microstructures of gels. , 2003, Journal of the American Chemical Society.

[38]  Paul W. Cleary,et al.  Non-universal Voronoi cell shapes in amorphous ellipsoid packs , 2015, 1504.02737.

[39]  C. V. van Blitterswijk,et al.  Engineered Micro‐Objects as Scaffolding Elements in Cellular Building Blocks for Bottom‐Up Tissue Engineering Approaches , 2014, Advanced materials.

[40]  E. Weeks Soft jammed materials , 2007 .

[41]  Yichen Ding,et al.  Particle Hydrogels Based on Hyaluronic Acid Building Blocks. , 2016, ACS biomaterials science & engineering.

[42]  A. Gaharwar,et al.  Sequential Thiol-Ene and Tetrazine Click Reactions for the Polymerization and Functionalization of Hydrogel Microparticles. , 2016, Biomacromolecules.

[43]  Linyong Zhu,et al.  Tissue‐Integratable and Biocompatible Photogelation by the Imine Crosslinking Reaction , 2016, Advanced materials.

[44]  C. van Nostrum,et al.  Effect of particle size and charge on the network properties of microsphere-based hydrogels. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[45]  C T Laurencin,et al.  Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix. , 2004, The Journal of bone and joint surgery. British volume.

[46]  F. Calderon,et al.  Heparin crosslinked chitosan microspheres for the delivery of neural stem cells and growth factors for central nervous system repair. , 2013, Acta biomaterialia.

[47]  Lili Lin,et al.  Injectable Gel Constructs with Regenerative and Anti-Infective Dual Effects Based on Assembled Chitosan Microspheres. , 2018, ACS applied materials & interfaces.

[48]  N. Peppas,et al.  Physicochemical foundations and structural design of hydrogels in medicine and biology. , 2000, Annual review of biomedical engineering.

[49]  Öhrlund Jå,et al.  The Myth of the "Biphasic" Hyaluronic Acid Filler. , 2015 .

[50]  Dhananjay Dendukuri,et al.  Stop-flow lithography in a microfluidic device. , 2007, Lab on a chip.

[51]  Farren J. Isaacs,et al.  Photo‐Crosslinkable Unnatural Amino Acids Enable Facile Synthesis of Thermoresponsive Nano‐ to Microgels of Intrinsically Disordered Polypeptides , 2018, Advanced materials.

[52]  T. Sakai,et al.  Design of Hydrogels for Biomedical Applications , 2015, Advanced healthcare materials.

[53]  S. Carmichael,et al.  Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion , 2017, Advanced materials.

[54]  M. Plonska-Brzezinska,et al.  Hydrogels as Potential Nano-, Micro- and Macro-Scale Systems for Controlled Drug Delivery , 2020, Materials.

[55]  G. Weir,et al.  Core–Shell Hydrogel Microcapsules for Improved Islets Encapsulation , 2013, Advanced healthcare materials.

[56]  J. Burdick,et al.  Injectable Granular Hydrogels with Multifunctional Properties for Biomedical Applications , 2018, Advanced materials.

[57]  Karl-Heinz Krause,et al.  A 3D printed microfluidic device for production of functionalized hydrogel microcapsules for culture and differentiation of human Neuronal Stem Cells (hNSC). , 2016, Lab on a chip.

[58]  D. Hutmacher,et al.  The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth. , 2009, Biomaterials.

[59]  Julian R Jones,et al.  Quantifying the 3D macrostructure of tissue scaffolds , 2009, Journal of materials science. Materials in medicine.

[60]  Dong Liu,et al.  The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K/Akt pathways , 2015, Scientific Reports.

[61]  Xia Li,et al.  Micro-Macro Quantification of the Internal Structure of Granular Materials , 2009 .

[62]  Jonas C. Rose,et al.  Nerve Cells Decide to Orient inside an Injectable Hydrogel with Minimal Structural Guidance , 2017, Nano letters.