Mussel-inspired cryogels for promoting wound regeneration through photobiostimulation, modulating inflammatory responses and suppressing bacterial invasion.

Wound healing is a complex and dynamic process, and involves a series of events, which create a unique microenvironment at the wound sites. It is highly desirable to develop multi-functional skin substitutes which can play their roles in the whole healing processes to enhance the final healing efficiency. Herein, we fabricated a mussel-inspired chitosan/silk fibroin cryogel functionalized with near-infrared light-responsive polydopamine nanoparticles (PDA-NPs), as a multifunctional platform to regulate the wound microenvironment and enhance efficient wound healing. The cryogel has an extracellular matrix-like macroporous structure, mimicking the natural tissue environment, which allows cell attachment and tissue ingrowth. The cryogel shows high anti-oxidative activity to eliminate overproduced reactive oxygen species during inflammatory responses. Furthermore, the cryogel exhibits photothermally assisted antibacterial activity to prevent bacterial invasion. Thus, by combining the photobiostimulation of infrared light, the cryogel realizes bio-chemo-photothermal synergistic therapy for accelerating the complete skin-thickness wound healing by simultaneously suppressing adverse events due to its antibacterial activity and anti-oxidative ability, and promoting cell activities and tissue regeneration. Our work therefore presents the great promise shown by this multifunctional biopolymer cryogel as a flexible wound dressing with combinatory therapy for accelerating wound healing.

[1]  A. Yu,et al.  Synthesis of Polydopamine Nanoparticles for Drug Delivery Applications , 2018, Microscopy and Microanalysis.

[2]  Pengfei Li,et al.  Mussel-inspired nanostructured coatings assembled using polydopamine nanoparticles and hydroxyapatite nanorods for biomedical applications , 2017 .

[3]  Hong Yang,et al.  Near-Infrared Chromophore Functionalized Soft Actuator with Ultrafast Photoresponsive Speed and Superior Mechanical Property. , 2017, Journal of the American Chemical Society.

[4]  A. Singer,et al.  Cutaneous wound healing. , 1999, The New England journal of medicine.

[5]  A. C. Jayasuriya,et al.  Current wound healing procedures and potential care. , 2015, Materials science & engineering. C, Materials for biological applications.

[6]  K. Pramanik,et al.  Optimization and evaluation of silk fibroin-chitosan freeze-dried porous scaffolds for cartilage tissue engineering application , 2016, Journal of biomaterials science. Polymer edition.

[7]  D. Ling,et al.  Promoting Angiogenesis in Oxidative Diabetic Wound Microenvironment Using a Nanozyme-Reinforced Self-Protecting Hydrogel , 2019, ACS central science.

[8]  H. Green,et al.  Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes , 1977, Nature.

[9]  Xingyu Jiang,et al.  Composites of Bacterial Cellulose and Small Molecule-Decorated Gold Nanoparticles for Treating Gram-Negative Bacteria-Infected Wounds. , 2017, Small.

[10]  Baolin Guo,et al.  Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. , 2017, Biomaterials.

[11]  Feng Chen,et al.  Silica-assisted incorporation of polydopamine into the framework of porous nanocarriers by a facile one-pot synthesis. , 2016, Journal of materials chemistry. B.

[12]  L. Fang,et al.  Protein‐Affinitive Polydopamine Nanoparticles as an Efficient Surface Modification Strategy for Versatile Porous Scaffolds Enhancing Tissue Regeneration , 2016 .

[13]  Jintu Fan,et al.  Intermolecular interactions between natural polysaccharides and silk fibroin protein. , 2013, Carbohydrate polymers.

[14]  Y. Yang,et al.  Improving pore interconnectivity in polymeric scaffolds for tissue engineering , 2009, Journal of tissue engineering and regenerative medicine.

[15]  A. A. Zaidan,et al.  An overview of laser principle, laser–tissue interaction mechanisms and laser safety precautions for medical laser users , 2011 .

[16]  B. Simionescu,et al.  Macroporous structures based on biodegradable polymers--candidates for biomedical application. , 2013, Journal of biomedical materials research. Part A.

[17]  Lehui Lu,et al.  Polydopamine and its derivative materials: synthesis and promising applications in energy, environmental, and biomedical fields. , 2014, Chemical reviews.

[18]  Yi Ren,et al.  Toward non-volatile photonic memory: concept, material and design , 2018 .

[19]  J. Boateng,et al.  Wound healing dressings and drug delivery systems: a review. , 2008, Journal of pharmaceutical sciences.

[20]  F. Ren,et al.  Bioadhesive Microporous Architectures by Self-Assembling Polydopamine Microcapsules for Biomedical Applications , 2015 .

[21]  B. Mandal,et al.  Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing. , 2017, Acta biomaterialia.

[22]  Shih-Hsin Chang,et al.  Tri-layered chitosan scaffold as a potential skin substitute , 2015, Journal of biomaterials science. Polymer edition.

[23]  Yong-Chien Ling,et al.  Graphene-based photothermal agent for rapid and effective killing of bacteria. , 2013, ACS nano.

[24]  M. Ribeiro,et al.  Thermoresponsive chitosan-agarose hydrogel for skin regeneration. , 2014, Carbohydrate polymers.

[25]  Lili Jiang,et al.  Biomimetic Mineralized Hierarchical Graphene Oxide/Chitosan Scaffolds with Adsorbability for Immobilization of Nanoparticles for Biomedical Applications. , 2016, ACS applied materials & interfaces.

[26]  T. K. Hunt,et al.  Human skin wounds: A major and snowballing threat to public health and the economy , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[27]  Tianhong Dai,et al.  Effect of red and near-infrared wavelengths on low-level laser (light) therapy-induced healing of partial-thickness dermal abrasion in mice , 2013, Lasers in Medical Science.

[28]  P. Gilbert,et al.  Biomechanical Origins of Muscle Stem Cell Signal Transduction. , 2016, Journal of molecular biology.

[29]  Jun Lin,et al.  Assembly of Au Plasmonic Photothermal Agent and Iron Oxide Nanoparticles on Ultrathin Black Phosphorus for Targeted Photothermal and Photodynamic Cancer Therapy , 2017 .

[30]  S. Werner,et al.  Injury-activated glial cells promote wound healing of the adult skin in mice , 2018, Nature Communications.

[31]  Xiong Lu,et al.  Polydopamine Nanoparticles Modulating Stimuli-Responsive PNIPAM Hydrogels with Cell/Tissue Adhesiveness. , 2016, ACS applied materials & interfaces.

[32]  B. Liu,et al.  Yolk-Structured Upconversion Nanoparticles with Biodegradable Silica Shell for FRET Sensing of Drug Release and Imaging-Guided Chemotherapy , 2017 .

[33]  Hamid Yeganeh,et al.  Stimulation of Wound Healing by Electroactive, Antibacterial, and Antioxidant Polyurethane/Siloxane Dressing Membranes: In Vitro and in Vivo Evaluations. , 2015, ACS applied materials & interfaces.

[34]  Bin Liu,et al.  Charge convertibility and near infrared photon co-enhanced cisplatin chemotherapy based on upconversion nanoplatform. , 2017, Biomaterials.

[35]  Youhong Tang,et al.  Mussel-Inspired Adhesive and Tough Hydrogel Based on Nanoclay Confined Dopamine Polymerization. , 2017, ACS nano.

[36]  G. Vunjak‐Novakovic,et al.  Stem cell-based tissue engineering with silk biomaterials. , 2006, Biomaterials.

[37]  Menghao Wang,et al.  Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils , 2018, Chemistry of Materials.

[38]  S. Singh,et al.  Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As) Augments Dermal Wound Healing in Immunosuppressed Rats , 2016, PloS one.

[39]  D. Kaplan,et al.  In vivo degradation of three-dimensional silk fibroin scaffolds. , 2008, Biomaterials.

[40]  S. Werner,et al.  Wound repair and regeneration , 1994, Nature.

[41]  S. MacNeil,et al.  Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. , 2017, Biomaterials.

[42]  A. Usumez,et al.  Effects of laser irradiation at different wavelengths (660, 810, 980, and 1,064 nm) on mucositis in an animal model of wound healing , 2014, Lasers in Medical Science.

[43]  Yuhua Shen,et al.  Chitosan/silk fibroin composite scaffolds for wound dressing , 2015 .

[44]  Lehui Lu,et al.  Dopamine‐Melanin Colloidal Nanospheres: An Efficient Near‐Infrared Photothermal Therapeutic Agent for In Vivo Cancer Therapy , 2013, Advanced materials.

[45]  Michele Henry,et al.  Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. , 2004, Mitochondrion.

[46]  N. Kotov,et al.  Three-dimensional cell culture matrices: state of the art. , 2008, Tissue engineering. Part B, Reviews.

[47]  P. Ma,et al.  Injectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing , 2018, Nature Communications.

[48]  N. Zheng,et al.  Core–Shell Pd@Au Nanoplates as Theranostic Agents for In‐Vivo Photoacoustic Imaging, CT Imaging, and Photothermal Therapy , 2014, Advanced materials.

[49]  Jianru Xiao,et al.  Multi-responsive photothermal-chemotherapy with drug-loaded melanin-like nanoparticles for synergetic tumor ablation. , 2016, Biomaterials.

[50]  Hsieh-Chih Tsai,et al.  Poly(N-isopropylacrylamide) hydrogels with interpenetrating multiwalled carbon nanotubes for cell sheet engineering. , 2013, Biomaterials.

[51]  Jun Peng,et al.  Photothermally Sensitive Poly(N‐isopropylacrylamide)/Graphene Oxide Nanocomposite Hydrogels as Remote Light‐Controlled Liquid Microvalves , 2012 .

[52]  Qiwei Tian,et al.  Multifunctional polypyrrole@Fe(3)O(4) nanoparticles for dual-modal imaging and in vivo photothermal cancer therapy. , 2014, Small.