Bioinspired Robust Keratin Hydrogels for Biomedical Applications.

Although keratins are robust in nature, hydrogels producing their extracts exhibit poor mechanical properties due to the complicated composition and ineffective self-assembly. Here we report a bioinspired strategy to fabricate robust keratin hydrogels based on mechanism study through recombinant proteins. Homotypic and heterotypic self-assembly of selected type I and type II keratins in different combinations was conducted to identify crucial domain structures for the process, their kinetics, and relationship with the mechanical strength of hydrogels. Segments with best performance were isolated and used to construct novel assembling units. The new design outperformed combinations of native proteins in mechanical properties and in biomedical applications such as controlled drug release and skin regeneration. Our approach not only elucidated the critical structural domains and underlying mechanisms for keratin self-assembly but also opens an avenue toward the rational design of robust keratin hydrogels for biomedical applications.

[1]  U. Cengiz,et al.  Synthesis of Silica-Based Boron-Incorporated Collagen/Human Hair Keratin Hybrid Cryogels with the Potential Bone Formation Capability. , 2021, ACS applied bio materials.

[2]  A. Arockiarajan,et al.  Influence of water content on the mechanical behavior of gelatin based hydrogels: Synthesis, characterization, and modeling , 2021 .

[3]  M. Meyers,et al.  Engineering with keratin: A functional material and a source of bioinspiration , 2021, iScience.

[4]  Yilong Cheng,et al.  Bioactive skin-mimicking hydrogel band-aids for diabetic wound healing and infectious skin incision treatment , 2021, Bioactive materials.

[5]  Bochu Wang,et al.  Fabrication of ulcer-adhesive oral keratin hydrogel for gastric ulcer healing in a rat , 2021, Regenerative biomaterials.

[6]  Huali Nie,et al.  Glucose-Triggered in situ Forming Keratin Hydrogel for the Treatment of Diabetic Wounds. , 2021, Acta biomaterialia.

[7]  Jinghui Zhou,et al.  Biomimetic lignin/poly(ionic liquids) composite hydrogel dressing with excellent mechanical strength, self-healing properties, and reusability , 2020 .

[8]  Q. Wang,et al.  “All-in-one” hydrolyzed keratin protein-modified polyacrylamide composite hydrogel transducer , 2020 .

[9]  Myung Chul Choi,et al.  A bioinspired and hierarchically structured shape-memory material , 2020, Nature Materials.

[10]  Xiaoyan Li,et al.  Fabrication of mechanical robust keratin adsorbent by induced molecular network transition and its dye adsorption performance , 2020, Environmental Science and Pollution Research.

[11]  S. Hall,et al.  3D Structure and Mechanics of Silk Sponge Scaffolds Is Governed by Larger Pore Sizes , 2020, Frontiers in Materials.

[12]  Jiashing Yu,et al.  Effect of varied hair protein fractions on the gel properties of keratin/chitosan hydrogels for the use in tissue engineering. , 2020, Colloids and surfaces. B, Biointerfaces.

[13]  Xiaoyan Li,et al.  Fabrication of mechanical robust keratin film by mesoscopic molecular network reconstruction and its performance for dye removal. , 2020, Journal of colloid and interface science.

[14]  N. Muhammad,et al.  Keratin - Based materials for biomedical applications , 2020, Bioactive materials.

[15]  Bochu Wang,et al.  Study of Mechanisms of Recombinant Keratin Solubilization with Enhanced Wound Healing Capability , 2020 .

[16]  Bochu Wang,et al.  Nanoparticle encapsulated core-shell hydrogel for on-site BMSCs delivery protects from iron overload and enhances functional recovery. , 2020, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Xuanhe Zhao,et al.  Hydrogel machines , 2020 .

[18]  Min-Sung Kim,et al.  Structure–function analyses of a keratin heterotypic complex identify specific keratin regions involved in intermediate filament assembly , 2019, bioRxiv.

[19]  Bochu Wang,et al.  Thermo-sensitive keratin hydrogel against iron-induced brain injury after experimental intracerebral hemorrhage. , 2019, International journal of pharmaceutics.

[20]  Yu Cao,et al.  Tunable keratin hydrogel based on disulfide shuffling strategy for drug delivery and tissue engineering. , 2019, Journal of colloid and interface science.

[21]  Bochu Wang,et al.  Recombinant Human Hair Keratin Nanoparticles Accelerate Dermal Wound Healing. , 2019, ACS applied materials & interfaces.

[22]  Bochu Wang,et al.  Synthesis and fabrication of a keratin-conjugated insulin hydrogel for the enhancement of wound healing. , 2019, Colloids and surfaces. B, Biointerfaces.

[23]  J. Fisher,et al.  Development of keratin-based membranes for potential use in skin repair. , 2019, Acta biomaterialia.

[24]  E. Jabbari,et al.  Material properties and cell compatibility of poly (γ-glutamic acid)-keratin hydrogels. , 2020, International journal of biological macromolecules.

[25]  Bochu Wang,et al.  Recombinant human hair keratin proteins for halting bleeding , 2018, Artificial cells, nanomedicine, and biotechnology.

[26]  Jing Liu,et al.  Enhanced mechanical properties and gelling ability of gelatin hydrogels reinforced with chitin whiskers , 2018 .

[27]  Jianping Wu,et al.  Molecular mechanism and characterization of self-assembly of feather keratin gelation. , 2018, International journal of biological macromolecules.

[28]  M. V. Van Dyke,et al.  Homo‐ and heteropolymer self‐assembly of recombinant trichocytic keratins , 2017, Biopolymers.

[29]  David L. Kaplan,et al.  Enzymatically crosslinked silk-hyaluronic acid hydrogels. , 2017, Biomaterials.

[30]  Yiqi Yang,et al.  Keratin-Based Biocomposites Reinforced and Cross-Linked with Dual-Functional Cellulose Nanocrystals , 2017 .

[31]  H Zhao,et al.  Mechanically and Electrically Enhanced CNT-Collagen Hydrogels As Potential Scaffolds for Engineered Cardiac Constructs. , 2017, ACS biomaterials science & engineering.

[32]  E. Jabbari,et al.  Synthesis and Characterization of Photo-Cross-Linkable Keratin Hydrogels for Stem Cell Encapsulation. , 2017, Biomacromolecules.

[33]  Bochu Wang,et al.  Feather keratin hydrogel for wound repair: Preparation, healing effect and biocompatibility evaluation. , 2017, Colloids and surfaces. B, Biointerfaces.

[34]  B. Madhan,et al.  Fabrication of keratin-silica hydrogel for biomedical applications. , 2016, Materials science & engineering. C, Materials for biological applications.

[35]  J. Simcock,et al.  Keratin-based products for effective wound care management in superficial and partial thickness burns injuries. , 2016, Burns : journal of the International Society for Burn Injuries.

[36]  M. Meyers,et al.  Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration , 2016 .

[37]  J. Saul,et al.  Tunable Keratin Hydrogels for Controlled Erosion and Growth Factor Delivery. , 2016, Biomacromolecules.

[38]  Jesse K. Placone,et al.  Development and Characterization of a 3D Printed, Keratin-Based Hydrogel , 2016, Annals of Biomedical Engineering.

[39]  A. Sirivat,et al.  Electromechanical response of silk fibroin hydrogel and conductive polycarbazole/silk fibroin hydrogel composites as actuator material. , 2015, Materials science & engineering. C, Materials for biological applications.

[40]  David L. Kaplan,et al.  Transparent, Nanostructured Silk Fibroin Hydrogels with Tunable Mechanical Properties. , 2015, ACS biomaterials science & engineering.

[41]  J. Saul,et al.  Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery in tissue engineering applications. , 2015, Acta biomaterialia.

[42]  Weisi Lin,et al.  Culturing fibroblasts in 3D human hair keratin hydrogels. , 2015, ACS applied materials & interfaces.

[43]  Dany J. Munoz-Pinto,et al.  Characterization of sequential collagen-poly(ethylene glycol) diacrylate interpenetrating networks and initial assessment of their potential for vascular tissue engineering. , 2015, Biomaterials.

[44]  D. Weitz,et al.  Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks. , 2015, Current opinion in cell biology.

[45]  Shreyas S. Rao,et al.  Glioblastoma behaviors in three-dimensional collagen-hyaluronan composite hydrogels. , 2013, ACS applied materials & interfaces.

[46]  Thomas L. Smith,et al.  The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model. , 2013, Biomaterials.

[47]  A. Ragauskas,et al.  Improving the mechanical and thermal properties of gelatin hydrogels cross-linked by cellulose nanowhiskers. , 2013, Carbohydrate polymers.

[48]  M. Buehler,et al.  Structure and mechanical properties of human trichocyte keratin intermediate filament protein. , 2012, Biomacromolecules.

[49]  Diego Mantovani,et al.  Mechanical and biological performances of new scaffolds made of collagen hydrogels and fibroin microfibers for vascular tissue engineering. , 2012, Macromolecular bioscience.

[50]  Min-Sung Kim,et al.  Structural basis for heteromeric assembly and perinuclear organization of keratin filaments , 2012, Nature Structural &Molecular Biology.

[51]  L. P. Tan,et al.  Human keratin hydrogels support fibroblast attachment and proliferation in vitro , 2012, Cell and Tissue Research.

[52]  M. V. Van Dyke,et al.  Structure-property relationships of meta-kerateine biomaterials derived from human hair. , 2012, Acta biomaterialia.

[53]  M. V. Van Dyke,et al.  Mechanical and biological properties of keratose biomaterials. , 2011, Biomaterials.

[54]  G. Copello,et al.  In vitro studies and preliminary in vivo evaluation of silicified concentrated collagen hydrogels. , 2011, ACS applied materials & interfaces.

[55]  K. Tsumoto,et al.  Stepwise characterization of the thermodynamics of trichocyte intermediate filament protein supramolecular assembly. , 2011, Journal of molecular biology.

[56]  Markus J Buehler,et al.  Intermediate filament-deficient cells are mechanically softer at large deformation: a multi-scale simulation study. , 2010, Acta biomaterialia.

[57]  D. Parry,et al.  In Vitro Assembly and Structure of Trichocyte Keratin Intermediate Filaments , 2000, The Journal of cell biology.