Bioactive Glass in Tissue Regeneration: Unveiling Recent Advances in Regenerative Strategies and Applications.

Bioactive glass (BG) is a class of biocompatible, biodegradable, multifunctional inorganic glass materials, which is successfully used for orthopedic and dental applications, with several products already approved for clinical use. Apart from exhibiting osteogenic properties, BG is also known to be angiogenic and antibacterial. Recently, BG's role in immunomodulation has been gradually revealed. While the therapeutic effect of BG is mostly reported in the context of bone and skin-related regeneration, its application in regenerating other tissues/organs, such as muscle, cartilage, and gastrointestinal tissue, has also been explored recently. The strategies of applying BG have also expanded from powder or cement form to more advanced strategies such as fabrication of composite polymer-BG scaffold, 3D printing of BG-loaded scaffold, and BG-induced extracellular vesicle production. This review presents a concise overview of the recent applications of BG in regenerative medicine. Various regenerative strategies of BG will be first introduced. Next, the applications of BG in regenerating various tissues/organs, such as bone, cartilage, muscle, tendon, skin, and gastrointestinal tissue, will be discussed. Finally, summarizing clinical applications of BG for tissue regeneration will conclude, and outline future challenges and directions for the clinical translation of BG.

Preparation and characterization of antibacterial, antioxidant, and biocompatible p-coumaric acid modified quaternized chitosan nanoparticles.

To fabricate multifunctional nanoparticles (NPs) based on chitosan (CS) derivative, we first prepared quaternized CS (2-hydroxypropyltrimethyl ammonium chloride CS, HTCC) via a one-step approach, then synthesized p-coumaric acid (p-CA) modified HTCC (HTCC-CA) for the first time through amide reaction, and finally fabricated a series of NPs (HTCC-CA NPs) using HTCC-CAs with different substitution degrees and sodium tripolyphosphate (TPP) by ionic gelation. Newly-prepared HTCC and HTCC-CAs were characterized by FT-IR, 1H NMR, elemental analysis (EA), full-wavelength UV scanning, silver nitrate titration, and Folin-Ciocalteu methods. DLS and TEM results demonstrated that three selected HTCC-CA NPs had moderate size (< 350 nm), good dispersion (PDI < 0.4), and positive zeta potential (11-20 mV). The HTCC-CA NPs had high antibacterial activity against six bacterial strains, and the minimum inhibitory concentration (MIC) values were almost the same as the minimum bactericidal concentration (MBC) values (250-1000 µg/mL). Also, the HTCC-CA NPs had good antioxidation (radical scavenging ratio > 65 %) and low cytotoxicity (relative cell viability >80 %) to the tested cells. Totally, HTCC-CA NPs with high antibacterial activity, great antioxidation, and low cytotoxicity might serve as new biomedical materials for promoting skin wound healing.

Oral Delivery of Bioactive Glass-Loaded Core-Shell Hydrogel Microspheres for Effective Treatment of Inflammatory Bowel Disease.

Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro-inflammatory response of lipopolysaccharide (LPS)-stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate-based core-shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric-simulated environment while dissolved in an intestinal-simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.

Charge-dependent negative effects of polystyrene nanoplastics on Oryzias melastigma under ocean acidification conditions.

Marine nanoplastics (NPs) have attracted increasing global attentions because of their detrimental effects on marine environments. A co-existing major environmental concern is ocean acidification (OA). However, the effects of differentially charged NPs on marine organisms under OA conditions are poorly understood. We therefore investigated the effects of OA on the embryotoxicity of both positively and negatively charged polystyrene (PS) NPs to marine medaka (Oryzias melastigma). Positively charged PS-NH2 exhibited slighter aggregation under normal conditions and more aggregation under OA conditions than negatively charged PS-COOH. According to the integrated biomarker approach, OA reversed the toxicity of positively and negatively charged NPs towards embryos. Importantly, at environmental relevant concentrations, both types of PS-NPs could enter the embryos through chorionic pores and then transfer to the larvae. OA reversed the internalization of PS-NH2 and PS-COOH in O. melastigma. Overall, the reversed toxicity of PS-NH2 and PS-COOH associated with OA could be caused by the reversed bioavailability of NPs to O. melastigma, which was attributed to altered aggregation of the NPs in acidified seawater. This finding demonstrates the charge-dependent toxicity of NPs to marine fish and provides new insights into the potential hazard of NPs to marine environments under OA conditions that could be encountered in the near future.

Carboxymethyl chitosan and carboxymethyl cellulose based self-healing hydrogel for accelerating diabetic wound healing.

In this study, a new type of biodegradable, injectable, self-healing, and low-toxic CMCSH, formed by N, O-carboxymethyl chitosan-heparin (CMCS-Hep) and carboxymethyl cellulose-aldehyde (CMC-A), was designed to deliver drug for promoting the progress of the diabetic wound healing. CMCS was modified with Hep for the first time to synthesize CMCS-Hep, and CMC-A was synthesized by the periodate oxidation method. First, SOD encapsulated in the CMCSH was applied to the diabetic wound bed to moderate the microenvironment, then rhEGF retained in the CMCSH was sustainedly released to the wound area. These results indicated that the dual-drug delivery system had the ability to improve drug availability, promote cell migration and proliferation, reduce DNA damage, shorten the inflammatory period, and accelerate the deposition of collagen fibers and the formation of blood vessels in the model with diabetic skin injury, suggesting that CMCSH as drug carriers had positive effects on diabetic wound healing.

Antibacterial porous sponge fabricated with capric acid-grafted chitosan and oxidized dextran as a novel hemostatic dressing.

This work aims to fabricate multifunctional hemostatic sponges (C-ODs). Porous C-ODs were first constructed by using capric acid-modified chitosan (CSCA) and oxidized dextrans (ODs) with different oxidation degrees. Batches of experiments showed that (i) CSCA (33.39% of grafting degree), ODs, and C-ODs (100-200 µm in pore size) were synthesized, evidenced by FT-IR, 1H NMR, elemental analysis, hydroxylamine hydrochloride titration, and SEM results; (ii) among C-ODs, C-OD2 had appropriate porosity (85.0%), swelling (20 times its dry weight), absorption, water retention, water vapor transmission, and mechanical properties; (iii) C-OD2 possessed low toxicity (relative cell viability > 86%), low hemolysis rate (0.65%), suitable tissue adhesion (4.74 kPa), and strong antibacterial efficacy (five strains); and (iv) C-OD2's dynamic blood clotting was within 30 s. In three animal injury models, C-OD2's hemostasis time and blood loss were fairly lower than commercial gelatin sponge. Totally, C-OD2 might serve as an ideal hemostatic dressing.

Decanoic acid functionalized chitosan: Synthesis, characterization, and evaluation as potential wound dressing material.

Skin wound dressing materials, which can accelerate wound healing and have the synthetic advantages of simplicity, environmental safety, and resource abundance, are becoming a hot topic of research now. Following such a research trend, we prepared novel decanoic acid functionalized chitosan (CSDA) with good solubility by acylation via a facile one-step method. FTIR, 1H NMR, and UV-Vis results demonstrated that alkyl chains were successfully grafted onto C2 positions of chitosan (CS) skeleton through acylation. XRD patterns implied that the crystallinity of CSDA greatly declined due to the introduction of alkyl moieties, favorable for improving water solubility. Conductometric titration results showed that the degrees of substitution of CSDA, CSDA1, and CSDA2 were 41.42, 26.12, and 23.17%, respectively. MTT assay and hemolysis experiments illustrated that all the CSDA samples tested in this work possessed good hemocompatibility (hemolysis rate < 2%) and excellent cytocompatibility (relative cell viability >75%) toward L929 cells. Moreover, CSDA-soaked gauze dressings and full-thickness excisional wound models were employed to estimate the feasibility of CSDA as wound dressing material, and the results displayed that CSDA with the degree of substitution of 41.42% could enhance the wound healing rate to 100% on day 16. Altogether, CSDA might be potential material used as wound dressing.

Cr(VI) and Pb(II) capture on pH-responsive polyethyleneimine and chloroacetic acid functionalized chitosan microspheres.

PEI-ECH-CMCS microspheres (MPs) were first constructed via elaborately programmed procedures. Fourier transform infrared spectroscopy, conductometric titration, Brunauer-Emmett-Teller, X-ray diffraction, pH at zero point of charge (pHzpc), scanning electron microscopy, X-ray photoelectron spectroscopy, and swelling results demonstrated that chitosan-based adsorbent had ample -NH2 and -COOH, specific surface area of 29.040 m2/g, porous 3D architectures, pHzpc of 4.2, uniform spherical surfaces, narrow size distribution (19-33 µm), and pH-responsive swelling features, advantageous to Cr(VI) and Pb(II) capture. Adsorption parameters were obtained from batch experiments and pH 3 and 5 were chosen for Cr(VI) and Pb(II) capture. Pseudo-second-order kinetic and Liu isotherm models well interpreted adsorption behavior, and thermodynamic, isotherm, and kinetic studies revealed an exothermic, spontaneous, monolayer, and chemical adsorption process. Maximum adsorption capacity for Cr(VI) or Pb(II) was 331.32 or 302.56 mg/g, exceeding CS-based adsorbents reported. Excellent reusability and feasibility were evidenced by adsorption capacity loss < 12.10% and high removal efficiency for Cr(VI) (95.79%) and Pb(II) (91.40%) in synthetic effluents. Finally, potential adsorption mechanisms were proposed.

Characterization and antibacterial mechanism of poly(aminoethyl) modified chitin synthesized via a facile one-step pathway.

This work aims to synthesize poly(aminoethyl) modified chitin (PAEMC) and ascertain its antibacterial activity and mechanism. FTIR and 1H NMR results proved aminoethyl moieties were grafted to C6OH and C3OH on chitin backbone in the form of polymerization. XRD and TG/DTG analyses manifested its well-defined crystallinity and thermostability. PAEMC, with average molecular weight (MW) of 851.0 kDa, degree of deacetylation (DD) of 27.95%, and degree of substitution (DS) of 1.77, had good solubility in aqueous solutions over the pH range of 3-12, and also possessed high antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus proteus, and Klebsiella pneumoniae, commonly causing chronic wound infections. Nucleic acid release, protein leakage, increased inner membrane permeability, and decreased cell surface hydrophobicity implied bacterial cytomembranes were substantially compromised in the presence of PAEMC. Microscopically, PAEMC visually perturbed bacteria, illustrating deformed and even collapsed morphologies. Overall, PAEMC possessed good solubility, effectively destroyed bacteria via a membrane damage mechanism, and might serve as an antibacterial agent for treatments of chronic wound infections.

Biochemical characterization of a thermostable HNH endonuclease from deep-sea thermophilic bacteriophage GVE2.

His-Asn-His (HNH) proteins are a very common family of small nucleic acid-binding proteins that are generally associated with endonuclease activity and are found in all kingdoms of life. Although HNH endonucleases from mesophiles have been widely investigated, the biochemical functions of HNH endonucleases from thermophilic bacteriophages remain unknown. Here, we characterized the biochemical properties of a thermostable HNH endonuclease from deep-sea thermophilic bacteriophage GVE2. The recombinant GVE2 HNH endonuclease exhibited non-specific cleavage activity at high temperature. The optimal temperature of the GVE2 HNH endonuclease for cleaving DNA was 60-65 °C, and the enzyme retained its DNA cleavage activity even after heating at 100 °C for 30 min, suggesting the enzyme is a thermostable endonuclease. The GVE2 HNH endonuclease cleaved DNA over a wide pH spectrum, ranging from 5.5 to 9.0, and the optimal pH for the enzyme activity was 8.0-9.0. Furthermore, the GVE2 HNH endonuclease activity was dependent on a divalent metal ion. While the enzyme is inactive in the presence of Cu(2+), the GVE2 HNH endonuclease displayed cleavage activity of varied efficiency with Mn(2+), Mg(2+), Ca(2+), Fe(2+), Co(2+), Zn(2+), and Ni(2+). The GVE2 HNH endonuclease activity was inhibited by NaCl. This study provides the basis for determining the role of this endonuclease in life cycle of the bacteriophage GVE2 and suggests the potential application of the enzyme in molecular biology and biotechnology.