Multifunctional hydrogel dressing based on fish gelatin/oxidized hyaluronate for promoting diabetic wound healing.

Non-healing chronic diabetic wound treatment remains an unsolved healthcare challenge and still threatens patients' lives. Recently, hydrogel dressings based on natural biomaterials have been widely investigated to accelerate the healing of diabetic wounds. In this study, we introduce a bioactive hydrogel based on fish gelatin (FG) as a candidate for diabetic wound treatments, which is a recently emerged substitute for mammalian derived gelatin. The composite hydrogel simply fabricated with FG and oxidized hyaluronate (OHy) through Schiff base reaction could successfully accelerate wound healing due to their adequate mechanical stability and self-healing ability. In vitro studies showed that the fabricated hydrogels exhibited cytocompatibility and could reduce pro-inflammatory cytokine expression such as NO, IL-1ß, TNF-α, and PGE2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In addition, the production of reactive oxygen species (ROS), a key marker of free radicals producing oxidative stress, was also reduced by fabricated hydrogels. Furthermore, in vivo experiments demonstrated that the hydrogel could promote wound closure, re-epithelialization, collagen deposition, and protein expression of CD31, CD206, and Arg1 in diabetic mice models. Our study highlights the advanced potential of FG as a promising alternative material and indicates that FOHI can be successfully used for diabetic wound healing applications.

Poly(vinyl alcohol)/chitosan hydrogel incorporating chitooligosaccharide-gentisic acid conjugate with antioxidant and antibacterial properties as a potential wound dressing.

The design and development of wound dressing with antioxidant and antibacterial properties to accelerate wound healing remain challenging. In this study, we synthesize a chitooligosaccharide-gentisic acid (COS-GSA) conjugate using the free-radical grafting method, and fabricate a poly(vinyl alcohol) (PVA)/chitosan (CH)/COS-GSA (PVA/CH/CG) hydrogel using a freeze-thaw method. We characterize the synthesized COS-GSA conjugates using through polyphenol assay, absorbance, and 1H NMR spectroscopy and evaluate their antioxidant properties. The COS-GSA conjugates are successfully synthesized and exhibit better antioxidant properties than pristine COSs. Subsequently, the fabricated hydrogel is characterized based on its morphological analysis, rheological properties, water contact angle, swelling, degradation, water retention properties, and COS-GSA release profiles. Finally, the biocompatibility of the fabricated hydrogel is evaluated on HDF and HaCaT cells through indirect and direct cytotoxicity. The PVA/CH/CG hydrogel exhibited significantly higher antioxidant properties (DPPH, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydrogen peroxide (H2O2) scavenging activities) and antibacterial activities (Staphylococcus aureus and Pseudomonas aeruginosa) compared to other fabricated hydrogels such as PVA, PVA/CH, and PVA/CH/COS (PVA/CH/C). These results provide evidence that PVA/CH/CG hydrogels with antioxidant, antibacterial, and non-cytotoxic properties have great potential for wound-dressing applications.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Basic amino acid-mediated cationic amphiphilic surfaces for antimicrobial pH monitoring sensor with wound healing effects.

BACKGROUND: The wound healing process is a complex cascade of physiological events, which are vulnerable to both our body status and external factors and whose impairment could lead to chronic wounds or wound healing impediments. Conventional wound healing materials are widely used in clinical management, however, they do not usually prevent wounds from being infected by bacteria or viruses. Therefore, simultaneous wound status monitoring and prevention of microbial infection are required to promote healing in clinical wound management. METHODS: Basic amino acid-modified surfaces were fabricated in a water-based process via a peptide coupling reaction. Specimens were analyzed and characterized by X-ray photoelectron spectroscopy, Kelvin probe force microscopy, atomic force microscopy, contact angle, and molecular electrostatic potential via Gaussian 09. Antimicrobial and biofilm inhibition tests were conducted on Escherichia coli and Staphylococcus epidermidis. Biocompatibility was determined through cytotoxicity tests on human epithelial keratinocytes and human dermal fibroblasts. Wound healing efficacy was confirmed by mouse wound healing and cell staining tests. Workability of the pH sensor on basic amino acid-modified surfaces was evaluated on normal human skin and Staphylococcus epidermidis suspension, and in vivo conditions. RESULTS: Basic amino acids (lysine and arginine) have pH-dependent zwitterionic functional groups. The basic amino acid-modified surfaces had antifouling and antimicrobial properties similar to those of cationic antimicrobial peptides because zwitterionic functional groups have intrinsic cationic amphiphilic characteristics. Compared with untreated polyimide and modified anionic acid (leucine), basic amino acid-modified polyimide surfaces displayed excellent bactericidal, antifouling (reduction ~ 99.6%) and biofilm inhibition performance. The basic amino acid-modified polyimide surfaces also exhibited wound healing efficacy and excellent biocompatibility, confirmed by cytotoxicity and ICR mouse wound healing tests. The basic amino acid-modified surface-based pH monitoring sensor was workable (sensitivity 20 mV pH-1) under various pH and bacterial contamination conditions. CONCLUSION: Here, we developed a biocompatible and pH-monitorable wound healing dressing with antimicrobial activity via basic amino acid-mediated surface modification, creating cationic amphiphilic surfaces. Basic amino acid-modified polyimide is promising for monitoring wounds, protecting them from microbial infection, and promoting their healing. Our findings are expected to contribute to wound management and could be expanded to various wearable healthcare devices for clinical, biomedical, and healthcare applications.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.

A 3D-Printed Polycaprolactone/Marine Collagen Scaffold Reinforced with Carbonated Hydroxyapatite from Fish Bones for Bone Regeneration.

In bone tissue regeneration, extracellular matrix (ECM) and bioceramics are important factors, because of their osteogenic potential and cell-matrix interactions. Surface modifications with hydrophilic material including proteins show significant potential in tissue engineering applications, because scaffolds are generally fabricated using synthetic polymers and bioceramics. In the present study, carbonated hydroxyapatite (CHA) and marine atelocollagen (MC) were extracted from the bones and skins, respectively, of Paralichthys olivaceus. The extracted CHA was characterized using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, while MC was characterized using FTIR spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The scaffolds consisting of polycaprolactone (PCL), and different compositions of CHA (2.5%, 5%, and 10%) were fabricated using a three-axis plotting system and coated with 2% MC. Then, the MC3T3-E1 cells were seeded on the scaffolds to evaluate the osteogenic differentiation in vitro, and in vivo calvarial implantation of the scaffolds was performed to study bone tissue regeneration. The results of mineralization confirmed that the MC/PCL, 2.5% CHA/MC/PCL, 5% CHA/MC/PCL, and 10% CHA/MC/PCL scaffolds increased osteogenic differentiation by 302%, 858%, 970%, and 1044%, respectively, compared with pure PCL scaffolds. Consequently, these results suggest that CHA and MC obtained from byproducts of P. olivaceus are superior alternatives for land animal-derived substances.

Electrospun porous bilayer nano-fibrous fish collagen/PCL bio-composite scaffolds with covalently cross-linked chitooligosaccharides for full-thickness wound-healing applications.

The development of tissue-engineered biodegradable artificial tissue substitutes with extracellular matrix-mimicking properties that govern the interaction between the material and biological environment is of great interest in wound-healing applications. In the present study, novel bilayer nanofibrous scaffolds composed of fish collagen (FC) and poly(ε-caprolactone) (PCL) were fabricated using electrospinning, with the covalent attachment of chitooligosaccharides (COS) via carbodiimide chemistry. The architecture and fiber diameter of the non-cross-linked nanofibrous scaffolds remained consistent irrespective of the polymer ratio under different electrospinning conditions, but the fiber diameter changed after cross-linking in association with the FC content. Fourier-transform infrared spectroscopy analysis indicated that the blend of biomaterials was homogenous, with an increase in COS levels with increasing FC content in the nanofibrous scaffolds. Based on cytocompatibility analysis (i.e., the cellular response to the nanofibrous scaffolds and their interaction), the nanofibrous scaffolds with high FC content were functionally active in response to normal human dermal fibroblast­neonatal (NHDF-neo) and HaCaT keratinocyte cells, leading to the generation of a very effective tissue-engineered implant for full-thickness wound-healing applications. In addition to these empirical results, an assessment of the hydrophilicity, swelling, and mechanical integrity of the proposed COS-containing FC-rich FC/PCL (FCP) nanofibrous scaffolds confirmed that they have significant potential for use as tissue-engineered skin implants for rapid skin regeneration.

Characterization of an oxidized alginate-gelatin hydrogel incorporating a COS-salicylic acid conjugate for wound healing.

In the present study, chitooligosaccharide (COS) and salicylic acid (SA) conjugates were synthesized using H2O2-induced grafting polymerization and oxidized alginate (OA) and gelatin hydrogels were fabricated using Schiff's base reaction. To confirm the synthesis and improved activity of the COS-SA conjugates, polyphenol assays, ultraviolet absorbance, NMR, and antioxidant activity tests were all conducted. The results showed that the COS-SA conjugates were completely synthesized and improved antioxidant activity. OA was synthesized using a periodate method and a hydrogel was obtained at a mixed ratio of 3:7 via crosslinking between the aldehyde group of the OA and the amine groups of gelatin with COS-SA conjugates. In a cytotoxicity and wound healing model, the hydrogels with COS-SA conjugates did not exhibit cytotoxicity and exhibited wound healing activity in a mouse model. These results provide evidence that OA and gelatin hydrogels with a COS-SA conjugate can be successfully used for wound healing applications.