Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.
Hydrogels/chemistry* ; Microfluidics/methods* ; Microspheres ; Regenerative Medicine ; Tissue Engineering/methods*

Cutaneous wounds are one of the commonest clinical diseases. At present, there are still many challenges in how to repair wounds quickly with high quality. With the rapid development and cross-integration of materials science and biomedicine, hydrogels that can integrate various excellent properties through flexible structural modification and combination of different functional components are widely applied in wound management and research. This paper attempted to summarize the role of hydrogel in promoting wound repair from the respects of matrix materials, special structures, and diverse functions of hydrogel.
Humans ; Hydrogels/chemistry* ; Wound Healing ; Soft Tissue Injuries

Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.
Chitosan/chemistry* ; Tissue Engineering ; Hydrogels/chemistry* ; Biocompatible Materials/chemistry* ; Cartilage ; Tissue Scaffolds/chemistry*

OBJECTIVES: To design and prepare silk fibroin/hyaluronic acid composite hydrogel. METHODS: The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by ¹H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope. RESULTS: The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good. CONCLUSIONS The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Hyaluronic Acid/chemistry* ; Biocompatible Materials/chemistry* ; Click Chemistry ; Sulfhydryl Compounds ; Silk/chemistry*

This study investigated the application of poly(N-isopropylacrylamide)-based interpenetrating network temperature-sensitive hydrogels (notation: IPNT) as the delivery vehicle for phage endolysin Lys84 and the potential of drug-loaded hydrogels as antimicrobial materials. Interpenetrating network temperature-sensitive hydrogels were prepared by free radical polymerization of sodium alginate and N-isopropylacrylamide. Drug-loaded hydrogels (IPNT-Lys84) were obtained by dry soaking method with the endolysin Lys84 of Staphylococcus aureus phage. The physical properties of the hydrogels with and without drug loading were characterized by infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The swelling and deswelling of the hydrogels as well as the release of endolysin Lys84 were investigated. Moreover, the antibacterial properties of IPNT-Lys84 hydrogels at different temperatures and concentrations of the drug solution were studied. The results showed that IPNT-Lys84 hydrogel had uniform pores and a low critical solubility temperature (LCST) of 32 ℃. The equilibrium swelling of the hydrogel was 30 g/g, and the water loss rate was 88% upon deswelling. The release rate of endolysin reached more than 70% within 6 h at 37 ℃. The bactericidal rate of IPNT-Lys84 hydrogel was over 99.9%. The research results showed the feasibility of using IPNT to deliver the endolysin Lys84, and IPNT-Lys84 hydrogel might be an effective antimicrobial material against multi-drug resistant Staphylococcus aureus.
Hydrogels/chemistry* ; Bacteriophages ; Methicillin-Resistant Staphylococcus aureus ; Temperature ; Anti-Infective Agents

The shortage of medical resources promotes medical treatment reform, and smart healthcare is a promising strategy to solve this problem. With the development of Internet, real-time health status is expected to be monitored at home by using flexible healthcare systems, which puts forward new demands on flexible substrates for sensors. Currently, the flexible substrates are mainly traditional petroleum-based polymers, which are not renewable. As a natural polymer, cellulose, owing to its wide range of sources, convenient processing, biodegradability and so on, is an ideal alternative. In this review, the application progress of nanocellulose in flexible sensors is summarized. The structure and the modification methods of cellulose and nanocellulose are introduced at first, and then the application of nanocellulose flexible sensors in real-time medical monitoring is summarized. Finally, the advantages and future challenges of nanocellulose in the field of flexible sensors are discussed.
Cellulose/chemistry* ; Hydrogels/chemistry* ; Polymers

Wound repair is a common clinical problem, which seriously affects the quality of life of patients and also brings a heavy burden to the society. Hydrogel-based multifunctional dressing has shown strong potential in the treatment of acute and chronic wounds. In addition to its good histocompatibility, cell adhesion, and biodegradability, methacrylic anhydride gelatin (GelMA) hydrogel has also attracted much attention due to its low cost, mild reaction conditions, adjustable physicochemical properties, and wide clinical applications. In this paper, the characteristics of GelMA hydrogel and its research progress in wound repair are introduced, and the future development of multifunctional GelMA hydrogel dressing for wound treatment is prospected.
Humans ; Gelatin/chemistry* ; Hydrogels ; Anhydrides ; Quality of Life ; Methacrylates/chemistry*

Novel hydrogel composed of both chondroitin sulfate (CS) and gelatin was developed for better cellular interaction through two step double crosslinking of N-(3-diethylpropyl)-N-ethylcarbodiimide hydrochloride (EDC) chemistries and then click chemistry. EDC chemistry was proceeded during grafting of amino acid dihydrazide (ADH) to carboxylic groups in CS and gelatin network in separate reactions, thus obtaining CS–ADH and gelatin–ADH, respectively. CS–acrylate and gelatin–TCEP was obtained through a second EDC chemistry of the unreacted free amines of CS–ADH and gelatin–ADH with acrylic acid and tri(carboxyethyl)phosphine (TCEP), respectively. In situ CS–gelatin hydrogel was obtained via click chemistry by simple mixing of aqueous solutions of both CS–acrylate and gelatin–TCEP. ATR-FTIR spectroscopy showed formation of the new chemical bonds between CS and gelatin in CS–gelatin hydrogel network. SEM demonstrated microporous structure of the hydrogel. Within serial precursor concentrations of the CS–gelatin hydrogels studied, they showed trends of the reaction rates of gelation, where the higher concentration, the quicker the gelation occurred. In vitro studies, including assessment of cell viability (live and dead assay), cytotoxicity, biocompatibility via direct contacts of the hydrogels with cells, as well as measurement of inflammatory responses, showed their excellent biocompatibility. Eventually, the test results verified a promising potency for further application of CS–gelatin hydrogel in many biomedical fields, including drug delivery and tissue engineering by mimicking extracellular matrix components of tissues such as collagen and CS in cartilage.
Amines ; Cartilage ; Cell Survival ; Chemistry ; Chondroitin Sulfates ; Chondroitin ; Click Chemistry ; Collagen ; Extracellular Matrix ; Gelatin ; Hydrogel ; Hydrogels ; In Vitro Techniques ; Spectrum Analysis ; Tissue Engineering ; Transplants

OBJECTIVES: To establish an experimental method for evaluating material permeability of type I collagen hydrogels. METHODS: Using BSA-FITC as an indicator, by combining BSA-FITC with PBS they were used as permeability media, and using transwell load hydrogen sample to detect BSA-FITC transparent rate. RESULTS: In the concentration range of 100 μg·mL~0.781 μg·mL, the standard curve ≥ 0.99, Lower Limit of Quantity (LLOQ) is 3.125 μg·mL, RSD <5%, detection recovery rate is in the range of 80%~120%. CONCLUSIONS In this study, we established an experimental method for evaluating material permeability of hydrogel. The BSA-FITC transparent rate of type I collagen hydrogel was 100% at 28 h.
Collagen Type I ; chemistry ; Hydrogels ; chemistry ; Materials Testing ; Permeability

BACKGROUND: The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state. METHODS: In this review, we present the recent developments of in situ hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels–Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions. RESULTS: The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and in situ injectable forms. CONCLUSION: Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in in situ 3D bioprinting for tissue or organ regeneration.
Biocompatible Materials ; Bioprinting* ; Click Chemistry ; Cycloaddition Reaction ; Hydrogel* ; Hydrogels* ; Ink* ; Regeneration ; Regenerative Medicine ; Tissue Engineering*