Hydrogels are three-dimensional networks of polymer chains containing large amounts of water in their structure. Hydrogels have received significant attention in biomedical applications owing to their attractive physicochemical properties, including flexibility, softness, biodegradability, and biocompatibility. Different natural and synthetic polymers have been intensely explored in developing hydrogels for the desired applications. Biopolymers-based hydrogels have advantages over synthetic polymers regarding improved cellular activity and weak immune response. These properties can be further improved by grafting with other polymers or adding nanomaterials, and they structurally mimic the living tissue environments, which opens their broad applicability. The hydrogels can be physically or chemically cross-linked depending on the structure. The use of different biopolymers-based hydrogels in biomedical applications has been reviewed and discussed earlier. However, no report is still available to comprehensively introduce the synthesis, advantages, disadvantages, and biomedical applications of biopolymers-based hydrogels from the material point of view. Herein, we systematically overview different synthesis methods of hydrogels and provide a holistic approach to biopolymers-based hydrogels for biomedical applications, especially in bone regeneration, wound healing, drug delivery, bioimaging, and therapy. The current challenges and prospects of biopolymers-based hydrogels are highlighted rationally, giving an insight into the progress of these hydrogels and their practical applications. 

Recent advances in biopolymer-based hydrogels and their potential biomedical applications

Chitosan is a promising naturally derived polysaccharide to be used in hydrogel forms for pharmaceutical and biomedical applications. The multifunctional chitosan-based hydrogels have attractive properties such as the ability to encapsulate, carry, and release the drug, biocompatibility, biodegradability, and non-immunogenicity. In this review, the advanced functions of the chitosan-based hydrogels are summarized, with emphasis on fabrications and resultant properties reported in literature from the recent decade. The recent progress in the applications of drug delivery, tissue engineering, disease treatments, and biosensors are reviewed. Current challenges and future development direction of the chitosan-based hydrogels for pharmaceutical and biomedical applications are prospected.

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Recent Development of Functional Chitosan-Based Hydrogels for Pharmaceutical and Biomedical Applications

The treatment of diseases, such as cancer, is one of the most significant issues correlated with human beings health. Hydrogels (HGs) prepared from biocompatible and biodegradable materials, especially biopolymers, have been effectively employed for the sort of pharmaceutical and biomedical applications, including drug delivery systems, biosensors, and tissue engineering. Chitosan (CS), one of the most abundant bio-polysaccharide derived from chitin, is an efficient biomaterial in the prognosis, diagnosis, and treatment of diseases. CS-based HGs possess some potential advantages, like high values of bioactive encapsulation, efficient drug delivery to a target site, sustained drug release, good biocompatibility and biodegradability, high serum stability, non-immunogenicity, etc., which made them practical and useful for pharmaceutical and biomedical applications. In this review, we summarize recent achievements and advances associated with CS-based HGs for drug delivery, regenerative medicine, disease detection and therapy. 

Advances in chitosan-based hydrogels for pharmaceutical and biomedical applications: A comprehensive review.

Diatom is a common single-cell microalgae with large species and huge biomass. Diatom biosilica (DB), the shell of diatom, is a natural inorganic material with a micro-nanoporous structure. Its unique hierarchical porous structure gives it great application potential in drug delivery, hemostat materials, and biosensors, etc. However, the structural diversity of DB determines its different biological functions. Screening hundreds of thousands of diatom species for structural features of DB that meet application requirements is like looking for a needle in a seaway. And the chemical modification methods lack effective means to control the micro-nanoporous structure of DB. The formation of DB is a typical biomineralization process, and its structural characteristics are affected by external environmental conditions, genes, and other factors. This allows to manipulate the micro-nanostructure of DB through biological regulation method, thereby transforming the screening mode of the structure function of DB from a needle in a seaway to biofabrication mode. This review focuses on the formation, biological modification, functional activity of DB structure, and its application in biomaterials field, providing regulatory strategies and research idea of DB from the perspective of biofabrication. It will also maximize the possibility of using DB as biological materials.

The Art of Exploring Diatom Biosilica Biomaterials: From Biofabrication Perspective.

Here, we developed a Ca2+ modified diatom biosilica-based hemostat (DBp-Ca2+) with a full scale hierarchical porous structure (pore sizes range from micrometers to nanometers). The unique porous size in stepped arrangement of DBp-Ca2+give it selective adsorption capacity during coagulation process, resulted in rapid hemorrhage control. Based on in vitro and in vivo studies, it was confirmed that the primary micropores of DBp-Ca2+gave it high porosity to hold water (water absorption: 78.46 ± 1.12 %) and protein (protein absorption: 83.7 ± 1.33 mg/g). Its secondary mesopores to macropores could reduce of water diffusion length to accelerate blood exchange (complete within 300 ms). The tertiary stacking pores of DBp-Ca2+ could absorb platelets and erythrocytes to reduce more than 50 % of thrombosis time, and provided enough contact between Ca active site and coagulation factors for triggering clotting cascade reaction. This work not only developed a novel DBs based hemostat with efficient hemorrhage control, but also provided new insights to study procoagulant mechanism of inorganic hemostat with hierarchical porous structure from selective adsorption to rapid hemostasis. 

The hierarchical porous structures of diatom biosilica-based hemostat: From selective adsorption to rapid hemostasis.

Pre-hospital control of bleeding is critical to save lives, however the development of hemostatic agents with efficient and safe performance is still a challenge. In this study, a hybrid hemostatic gauze (MG-PEG) with in-situ growth and tightly bound mesoporous silicon (MSN) was prepared by template method for hemorrhage control. This material integrated meso-porosity, blood coagulation and stability into flexible gauze fiber. The PEG in MG-PEG was not only used as template for the in-suit MSN growth, but also acted as joint connection between the gauze fibers and MSN. The MSN particles were firmly bound to the surface of gauze fibers with extremely low leakage after 3 min of sonication and displayed a comparable coagulant activity to untreated sample. The results of animal experiments confirmed that MG-PEG possessed superior hemostatic performance over silicates-based inorganic hemostasis-Combat Gauze, in terms of higher coagulant activity (in vivo clotting time <200 s), minimized loss of active components (liquids OD was only 3 % of CG), well biocompatibility (hemolysis ratio < 5 %, no cytotoxicity) and wider indications range for practical application. 

PEG-mediated hybrid hemostatic gauze with in-situ growth and tightly-bound mesoporous silicon.

Chitin whiskers enhanced methacrylated hydroxybutyl chitosan hydrogels as anti-deformation scaffold for 3D cell culture.

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PEG-mediated hybrid hemostatic gauze with in-situ growth and tightly-bound mesoporous silicon.

Chitin whiskers enhanced methacrylated hydroxybutyl chitosan hydrogels as anti-deformation scaffold for 3D cell culture.