In silico assessment of biocompatibility and toxicity: molecular docking and dynamics simulation of PMMA-based dental materials for interim prosthetic restorations.

AIM: This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations. METHODOLOGY: Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets. RESULTS: The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles. CONCLUSION: This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance.

Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior.

Natural polymer-based hydrogels have demonstrated great potential as wound-healing dressings. They help to maintain a moist wound environment as well as promote faster healing. In this work, a multifunctional hydrogel was prepared using keratin, sodium alginate, and carboxymethyl chitosan with tannic acid modification. Micro-morphology of hydrogels has been performed by scanning electron microscopy. Fourier Transform Infrared Spectroscopy reveals the presence of hydrogen bonding. The mechanical properties of the hydrogels were examined using a universal testing machine. Furthermore, we investigated several properties of the modified hydrogel. These properties include swelling rate, water retention, anti-freezing properties, antimicrobial and antioxidant properties, hemocompatibility evaluation and cell viability test in vitro. The modified hydrogel has a three-dimensional microporous structure, the swelling rate was 1541.7%, the elastic modulus was 589.74 kPa, the toughness was 211.74 kJ/m3, and the elongation at break was 75.39%, which was similar to the human skin modulus. The modified hydrogel also showed inhibition of S. aureus and E. coli, as well as a DPPH scavenging rate of 95%. In addition, the modified hydrogels have good biological characteristics. Based on these findings, the K/SA/CCS hydrogel holds promise for applications in biomedical engineering.

Effects of bone surface topography and chemistry on macrophage polarization.

Surface structure plays a crucial role in determining cell behavior on biomaterials, influencing cell adhesion, proliferation, differentiation, as well as immune cells and macrophage polarization. While grooves and ridges stimulate M2 polarization and pits and bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, the impact of mimicking bone surface topography on macrophage polarization remains unknown. Understanding the synergistic sequential roles of M1 and M2 macrophages in osteoimmunomodulation is crucial for effective bone tissue engineering. Thus, exploring the impact of bone surface microstructure mimicking biomaterials on macrophage polarization is critical. In this study, we aimed to sequentially activate M1 and M2 macrophages using Poly-L-Lactic acid (PLA) membranes with bone surface topographical features mimicked through the soft lithography technique. To mimic the bone surface topography, a bovine femur was used as a model surface, and the membranes were further modified with collagen type-I and hydroxyapatite to mimic the bone surface microenvironment. To determine the effect of these biomaterials on macrophage polarization, we conducted experimental analysis that contained estimating cytokine release profiles and characterizing cell morphology. Our results demonstrated the potential of the hydroxyapatite-deposited bone surface-mimicked PLA membranes to trigger sequential and synergistic M1 and M2 macrophage polarizations, suggesting their ability to achieve osteoimmunomodulatory macrophage polarization for bone tissue engineering applications. Although further experimental studies are required to completely investigate the osteoimmunomodulatory effects of these biomaterials, our results provide valuable insights into the potential advantages of biomaterials that mimic the complex microenvironment of bone surfaces.

A short linear glucan nanocomposite hydrogel formed by in situ self-assembly with highly elastic, fatigue-resistant and self-recovery.

Polyacrylamide (PAM) hydrogels are widely used in wide-ranging applications in biology, medicine, pharmaceuticals and environmental sectors. However, achieving the requisite mechanical properties, fatigue resistance, self-recovery, biocompatibility, and biodegradability remains a challenge. Herein, we present a facile method to construct a nanocomposite hydrogel by integrating short linear glucan (SLG), obtained by debranching waxy corn starch, into a PAM network through self-assembly. The resulting composite hydrogel with 10 % SLG content exhibited satisfactory stretchability (withstanding over 1200 % strain), along with maximum compressive and shear strengths of about 490 kPa and 39 kPa at 90 % deformation, respectively. The hydrogel demonstrated remarkable resilience and could endure repeated compression and stretching. Notably, the nanocomposite hydrogel with 10 % SLG content exhibited full stress recovery at 90 % compression deformation after 20 s, without requiring specific environmental conditions, achieving an energy dissipation recovery rate of 98 %. Meanwhile, these hydrogels exhibited strong adhesion to various soft and hard substrates, including skin, glasses and metals. Furthermore, they maintain solid integrity at both 37 °C and 50 °C after swelling equilibrium, unlike traditional PAM hydrogels, which exhibited softening under similar conditions. We hope that this PAM-SLG hydrogel will open up new avenues for the development of multifunctional electronic devices, offering enhanced performance and versatility.

Evaluation of extruded starch foam for glucose-supplying biomaterials.

The survival rate of mesenchymal stem cells (MSC), a crucial factor in tissue engineering, is highly dependent on glucose supply. The purpose of this paper is to study the potential of starch foams as glucose suppliers. It is investigated through in vitro hydrolysis by amyloglucosidase in conditions that respect physiological constraints (37 °C and pH 7.4), including a duration of 21 days, and no stirring. Nine extruded starch foams with amylose contents ranging from 0 to 74 %, with various cell wall thicknesses (50 to 300 µm), and different crystallinities (0-30 %) were hydrolysed. These kinetics were fitted by a model which shows that the maximum rate of hydrolysis varies from 7 to 100 %, and which allows the rate of hydrolysis at 21 days to be calculated precisely. The results reveal the major role of amylose in glucose delivery kinetics, and the secondary roles of crystallinity and cell wall thickness of the foams. Additional hydrolysis of starch films revealed that thickness positively influences the amylose chain reorganisation during hydrolysis, which, in slows down and limits glucose delivery. A simple glucose delivery kinetics analysis procedure is proposed to select samples for testing as MSC glucose suppliers.

Engineered inulin-based hybrid biomaterials for augmented immunomodulatory responses.

Modified biopolymers that are based on prebiotics have been found to significantly contribute to immunomodulatory events. In recent years, there has been a growing use of modified biomaterials and polymer-functionalized nanomaterials in the treatment of various tumors by activating immune cells. However, the effectiveness of immune cells against tumors is hindered by several biological barriers, which highlights the importance of harnessing prebiotic-based biopolymers to enhance host defenses against cancer, thus advancing cancer prevention strategies. Inulin, in particular, plays a crucial role in activating immune cells and promoting the secretion of cytokines. Therefore, this mini-review aims to emphasize the importance of inulin in immunomodulatory responses, the development of inulin-based hybrid biopolymers, and the role of inulin in enhancing immunity and modifying cell surfaces. Furthermore, we discuss the various approaches of chemical modification for inulin and their potential use in cancer treatment, particularly in the field of cancer immunotherapy.

An introduction to injectable hydrogels.

Injectable hydrogels have emerged as intelligent and versatile materials that have been proven to possess huge potential for many biomedical applications including drug delivery, tissue engineering, and regenerative medicine. Hydrogels are a class of polymers with highly hydrated 3D networks that have microenvironmental properties such as oxygen/nutrient permeability that are similar to the native extracellular matrix. In addition to possessing the typical advantages of conventional hydrogels, injectable hydrogels offer extra unique features, enabling minimally invasive injectability and durability for irregularly shaped sites, and the possibility of processing these materials via, e.g., additive manufacturing techniques. As such, there has been a growing interest in using injectable hydrogels as scaffolds/carriers for therapeutic agents, including but not limited to drugs, cells, proteins, and bioactive molecules, targeted to treat chronic diseases including cancer, but also to facilitate the repair and regeneration of damaged organs/tissues. In this themed collection of Journal of Materials Chemistry B and Biomaterials Science, we include outstanding contributions covering recent developments in this rapidly evolving field of injectable hydrogels including emerging chemistries, synthesis pathways, fabrication methods, cell-material interaction, in vitro, ex vivo and in vivo performances, and subsequent targeted applications (drug delivery, tissue engineering and regenerative medicine) of injectable hydrogels.

Silanization Strategies for Tailoring Peptide Functionalization on Silicon Surfaces: Implications for Enhancing Stem Cell Adhesion.

Biomaterial surface engineering and the integration of cell-adhesive ligands are crucial in biological research and biotechnological applications. The interplay between cells and their microenvironment, influenced by chemical and physical cues, impacts cellular behavior. Surface modification of biomaterials profoundly affects cellular responses, especially at the cell-surface interface. This work focuses on enhancing cellular activities through material manipulation, emphasizing silanization for further functionalization with bioactive molecules such as RGD peptides to improve cell adhesion. The grafting of three distinct silanes onto silicon wafers using both spin coating and immersion methods was investigated. This study sheds light on the effects of different alkyl chain lengths and protecting groups on cellular behavior, providing valuable insights into optimizing silane-based self-assembled monolayers (SAMs) before peptide or protein grafting for the first time. Specifically, it challenges the common use of APTES molecules in this context. These findings advance our understanding of surface modification strategies, paving the way for tailoring biomaterial surfaces to modulate the cellular behavior for diverse biotechnological applications.

A morphological analysis of calcium hydroxylapatite and poly-l-lactic acid biostimulator particles.

Injectable fillers, pivotal in aesthetic medicine, have evolved significantly with recent trends favoring biostimulators like calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) and poly-l-lactic acid (PLLA; Sculptra Aesthetics, Galderma, Dallas, TX). This study aims to compare the particle morphology of these two injectables and examine its potential clinical implications. Utilizing advanced light and scanning electron microscopy techniques, the physical characteristics of CaHA-CMC and PLLA particles were analyzed, including shape, size, circularity, roundness, aspect ratio, and quantity of phagocytosable particles. The findings reveal several morphological contrasts: CaHA-CMC particles exhibited a smooth, homogenous, spherical morphology with diameters predominantly ranging between 20 and 45 µm, while PLLA particles varied considerably in shape and size, appearing as micro flakes ranging from 2 to 150 µm in major axis length. The circularity and roundness of CaHA-CMC particles were significantly higher compared to PLLA, indicating a more uniform shape. Aspect ratio analysis further underscored these differences, with CaHA-CMC particles showing a closer resemblance to circles, unlike the more oblong PLLA particles. Quantification of the phagocytosable content of both injectables revealed a higher percentage of phagocytosable particles in PLLA. These morphological distinctions may influence the tissue response to each treatment. CaHA-CMC's uniform, spherical particles may result in reduced inflammatory cell recruitment, whereas PLLA's heterogeneous particle morphology may evoke a more pronounced inflammatory response.

Heteroatom-doped carbon dots from medicinal plants as novel biomaterials for as-use biomedical applications in comparison with synthetic drug, zaltoprofen.

FN-doped carbon dots were synthesized using powdered leaves of Moringa oleifera L./Chromolaena odorata L./Tridax procumbens L./Tinospora cordifolia L./ and Lantana camara L., along with a precursor called 4,5-difluoro-1,2-benzenediamine (DFBD) and compared against the drug zaltoprofen derived carbon dots. They were assessed for their optical and structural characteristics using photoluminescence (optimal emission λ of 600 nm), vibrational (FTIR) spectroscopy (characteristic wave numbers of 1156 and 1269 cm-1 for C-F), as well as X-ray diffraction (XRD) (highest intensity at 27.56°) and high-resolution transmission electron microscopy (HR-TEM) (particles in the size range of 15-20 nm). Further, field emission scanning electron microscopy (FESEM) / energy dispersive spectroscopy (EDX) indicated FN doping of oval/oblong carbon dots. Membrane protection in percent is found to be 55.3 and 80.4 for FN-CDs and Z-FN-CDs respectively. The DPPH-free radical scavenging activity by FN-CDs was 69.4%, while with Z-FN-CDs, it was 54.2%. When tested on six bacterial strains (three each for gram-positive and gram-negative), the FN-CDs displayed a halo (ZOI) between 9 and 19 mm, whereas the Z-FN-CDs displayed a clearance zone between 9 and 17 mm. The FN-CDs showed significant emission-red-shift effects and demonstrated concentration-dependent biocompatibility and viability in neuroblastoma and beta-TC6-cell lines.

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy.

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.

A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels.

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.

Rationally designed ß-cyclodextrin-crosslinked polyacrylamide hydrogels for cell spheroid formation and 3D tumor model construction.

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of ß-cyclodextrin (ß-CD)-crosslinked polyacrylamide hydrogels with different ß-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of ß-CD-methacrylate (CD-MA) and a small amount of N,N'-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.

From lab to wearables: Innovations in multifunctional hydrogel chemistry for next-generation bioelectronic devices.

Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery.

BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. CONCLUSION: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

Characterization of Novel Cell-Adhesive Peptides for Biomaterial Development.

In previous studies, my group developed cell-adhesive peptide-polysaccharide complexes as biomaterials for tissue engineering. Having a wide variety of cell-adhesive peptides is important as the biological functions of peptide-polysaccharide complexes are highly dependent on the biological activity of peptides. This paper reviews the biological activities of two types of recently characterized cell-adhesive peptides. The first is peptides rich in basic amino acids originating from octaarginine. We analyzed the relationships between the amino acid composition of basic peptides and cell adhesion, elongation, and proliferation and identified the most suitable peptide for cell culture. The second was arginine-glycine-aspartic acid (RGD)-containing peptides that promote the adhesion of induced pluripotent stem cells (iPSCs). We identified the RGD-surrounding sequences necessary for iPSC adhesion, clarified the underlying mechanism, and improved cell adhesion by modifying the structure-activity relationships. The novel cell-adhesive peptides identified in our previous studies may aid in the development of novel peptide-based biomaterials.

Synthesis of Zwitterionic Phospholipid-Connected Silane Coupling Agents and Their Hybridization with Graphene Oxide.

The hybridization of lipids with graphene is expected to produce a promising, novel biomaterial. However, there are limited examples of the covalent introduction of lipid molecules, especially the immobilization of lipid molecules, onto graphene on a substrate. Therefore, we investigated the hybridization of a silane coupling agent having phospholipid moieties with graphene oxide on substrates prepared by photo-oxidation using chlorine dioxide. Three silane coupling agents with different carbon chain lengths (C4, C6, C8) were synthesized and phospholipid molecules were introduced onto graphene on a substrate. Phospholipid-immobilized graphene on a grid for TEM (transmission electron microscope) was used for EM analysis of proteins (glyceraldehyde 3-phosphate dehydrogenase and ß-galactosidase), enabling the observation of sufficient particles compared to the conventional graphene grid.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

A comprehensive review on recent progress in chitosan composite gels for biomedical uses.

Chitosan (CS) composite gels have emerged as promising materials with diverse applications in biomedicine. This review provides a concise overview of recent advancements and key aspects in the development of CS composite gels. The unique properties of CS, such as biocompatibility, biodegradability, and antimicrobial activity, make it an attractive candidate for gel-based composites. Incorporating various additives, such as nanoparticles, polymers, and bioactive compounds, enhances the mechanical, thermal, and biological and other functional properties of CS gels. This review discusses the fabrication methods employed for CS composite gels, including blending and crosslinking, highlighting their influence on the final properties of the gels. Furthermore, the uses of CS composite gels in tissue engineering, wound healing, drug delivery, and 3D printing highlight their potential to overcome a number of the present issues with drug delivery. The biocompatibility, antimicrobial properties, electroactive, thermosensitive and pH responsive behavior and controlled release capabilities of these gels make them particularly suitable for biomedical applications. In conclusion, CS composite gels represent a versatile class of materials with significant potential for a wide range of applications. Further research and development efforts are necessary to optimize their properties and expand their utility in pharmaceutical and biomedical fields.

Mild preparation of hyaluronic acid/silk fibroin sponges by modified crosslinking method.

The composites composed of hyaluronic acid (HA) and silk fibroin (SF) exhibit great potential in diverse biomedical applications. However, the utilization of commercial crosslinkers such as 1,4-butanediol diglycidyl ether (BDDE) for crosslinking HA typically necessitates harsh conditions involving strong alkaline, which greatly limits its potential applications. In this study, a mild modified approach was developed to fabricate HA/SF blend sponges crosslinked by BDDE without alkaline conditions. The blend solutions were cryo-concentrated to induce crosslinking reactions. The mechanism of freezing crosslinking was elucidated by investigating the effects of ice crystal growth and HA molecular weight on the degree of crosslinking. The results revealed that HA achieved efficient crosslinking when its molecular weight exceeds 1000 kDa and freezing temperatures ranged from -40 °C to -20 °C. After introducing SF, multiple crosslinks were formed between SF and HA chains, producing water-stable porous sponges. The SEM results demonstrated that the introduction of SF effectively enhanced the interconnectivity between macropores through creating subordinate holes onto the pores wall. Raising the SF content significantly enhanced compression strength, resistance to enzymatic degradation and cell viability of blend sponges. This study provides a novel strategy for designing bioactive HA/SF blend sponges as substitutes for tissue repair and wound dressing.