Postoperative anastomotic leakage (AL) and abdominal adhesions are two major complications after intestinal surgery, with an incidence of 2-25% for AL and 93% for adhesion. Until now, there is no method addressing AL and abdominal adhesions simultaneously. In this work, Bi-PEG-succinimidyl succinate (PEG-NHS), amino-gelatin (Agel) is combined with cefoperazone-sulbactam (SCF) to prepare a multifunctional bioadhesive (SCF/SEAgel) for the postoperative leakage and adhesion prevention. SCF/SEAgel possesses a great sealing capability for tissue, with a bursting pressure of 54 kPa. The loaded SCF endows the systems with good antibacterial properties. The in vivo antiadhesion experiments show that SCF/SEAgel possesses better anti-adhesion properties than the commercially used sodium hyaluronate gel. In the cecum leakage model, the SCF/SEAgel effectively seals the leakage with a survival rate of 100%, superior to commercial products (Sainaoning). Meanwhile, it significantly reduces tissue adhesion. Finally, the laparoscopic surgery with dogs shows that the SCF/SEAgel can be injected through minimally invasive surgery, demonstrating its ease of use. Combined with its great biocompatibility, SCF/SEAgel is very promising in intestinal surgery.

Protein adhesion and thrombosis formation caused by limited surface properties pose great challenges to biomedical implants. Although various hydrophilic coating or drug release coatings are reported, the single coating cannot cope with cases under the condition of complex physiological environment, which causes the coating effect is limited. In this study, a polyamino acid-derived zwitterionic coating is constructed to eliminate reactive oxygen species (ROS) in the microenvironment. It is demonstrated that the coating has excellent hydrophilicity, stability, and lubricity, and can obviously prevent protein adhesion. At the same time, the coating can eliminate hydrogen peroxide and maintain the stability of the microenvironment. The in vivo and in vitro experiments show that the coating has good biocompatibility, and inhibits thrombus. Amino acid zwitterion coating prevents protein deposition, alleviates the inflammatory process, inhibit of thrombosis, reduces the risk of implantable medical devices, and prolongs their service time. Hence, the work paves a new way to develop amino acid based zwitterionic polymer coating that can reduce the implant complications.

Periodontal diseases, if untreated, can cause gum recession and tooth root exposure, resulting in infection and irreversible damage. Traditional treatments using autologous grafts are painful and often result in postoperative complications. Scaffolds offer a less invasive alternative, promoting cell proliferation and healing without additional surgery, thus enhancing comfort for patients and doctors. This study developed Chitosan (Chit)/Collagen (Col) film surfaces and drug-loaded Polyvinyl Alcohol (PVA)/Amoxicillin (AMX) nanofibers using solvent casting and electrospinning methods, respectively. The surfaces are characterized by scanning electron microscopy (SEM), mechanical testing, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Biocompatibility and antimicrobial properties are assessed using NIH/3T3 fibroblast cells and bacterial cultures. SEM images confirmed the structural integrity of AMX-loaded 13% PVA nanofibers, while FTIR analysis validated the compositional integrity of PVA/AMX nanofibers and Chit/Col film hybrid surfaces. Cell studies showed over 90% viability for Chit/Col film + PVA/AMX nanofiber hybrid bilayer membranes, confirming their biocompatibility. The antimicrobial assessment indicated that the Chit/Col film + PVA/AMX (0.2%) nanofiber hybrid bilayer membrane exhibited superior efficacy against Streptococcus mutans. These findings suggest that this hybrid bilayer membrane can enhance cell growth, promote proliferation, and enable controlled drug release, offering significant promise for regeneration of gingival tissues.

Neurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 - 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 - 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.

As an exceptional carrier for localized drug delivery to tumors, hydrogels can achieve prolonged drug release through careful design and adjustments, effectively targeting cancer cells and minimizing side effects. This study investigates a novel dual-responsive hydrogel system designed for the delivery of nanomedicines, focusing on drug release and the local antitumor efficacy of SN-38-cholesterol nanoparticles (SN-38-chol NPs) and polydopamine NPs (PDA NPs)/poly(n-isopropylacrylamide) (pNIPAM) hydrogels. By combining the thermosensitive properties of pNIPAM with the near-infrared (NIR) responsiveness of PDA NPs, the hydrogel aims to enhance on-demand drug release. SN-38-chol NPs, known for their stability and small size, are incorporated into the hydrogel to improve drug release dynamics. The investigation reveals a drug release cycle of over three weeks, maintaining sensitivity to both temperature and NIR light for controlled drug release. In vivo studies demonstrate the high tumor growth inhibition performance of the system after photothermal treatment induced by 808 nm NIR light. These results suggest that the drug-carrying hydrogel system holds promise for diverse applications in chemical and physical therapies, including the treatment of malignant wounds, post-surgery wound healing, and direct tumor treatment. This study establishes the potential of SN-38-chol NPs and PDA NPs/pNIPAM hydrogels as effective platforms for chemo-phototherapy.

Alginate forms a hydrogel via physical cross-linking with divalent cations. In literature, Ca is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca-alginate hydrogels. On the other hand, Mg-alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg-alginate as the main component of a bio-ink for the first time to obtain 3D tumor models by magnetic bio-patterning technique. The bio-ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg-alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS-2, and SH-SY5Y cells. Long-term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F-actin expressions are observed successfully in 3D tumor models. Finally, the anti-cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio-patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg-alginate hydrogel is successfully used to form bio-patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.

Oral diseases represent a prevalent global health burden, profoundly affecting patients' quality of life. Given the involvement of oral mucosa and muscles in diverse physiological functions, coupled with clinical aesthetics considerations, repairing oral and maxillofacial soft tissue defects poses a formidable challenge. Wet-adhesive materials are regarded as promising oral repair materials due to their unique advantages in easily overcoming physical and biological barriers in the oral cavity. This review first introduces the intricate wet-state environment prevalent in the oral cavity, meticulously explaining the fundamental physical and chemical adhesion mechanisms that underpin adhesive materials. It then comprehensively summarizes the diverse types of adhesives utilized in stomatology, encompassing polysaccharide, protein, and synthetic polymer adhesive materials. The review further evaluates the latest research advancements in utilizing these materials to treat various oral and maxillofacial soft tissue diseases, including oral mucosal diseases, periodontitis, peri-implantitis, oral and maxillofacial skin defects, and maxillofacial tumors. Finally, it also highlights the promising future prospects and pivotal challenges related to stomatology application of multifunctional adhesive materials.

The interaction between proteins and RNA is crucial for regulating gene expression, with dysregulation often linked to diseases such as cancer. The RNA-binding protein (RBP) Lin28 inhibits the tumor suppressor microRNA (miRNA) let-7, making it a significant oncogenic factor in tumor progression and metastasis. In this study, a small molecule is used that binds Lin28 and blocks its inhibition of let-7. To enhance its efficay, the inhibitor is transformed into degraders via two degradation approaches: Proteolysis Targeting Chimera (PROTAC) and molecular glue. A series of PROTAC bifunctional molecules and molecular glues capable of degrading Lin28 in cells.is developed Both strategies significantly reduce overexpressed Lin28 and alleviate cancer cellular phenotypes. Notably, the molecular glue approach demonstrates exceptional potency, surpassing PROTAC in several aspects. This outcome underscores the superior efficiency of the molecular glue approach for targeted Lin28 degradation and highlights its potential for addressing associated diseases with small molecules. Innovative small molecule strategies such as molecular glue and PROTAC technology for targeted RBP degradation, hold promise for opening new avenues in RNA modulation and addressing related diseases.

A strategy for multifunctional biosurfaces exploiting multiblock copolymers and the antipolyelectrolyte effect is reported. Combining a polyzwitterionic/antifouling and a polycationic/antibacterial block with a central anchoring block for attachment to titanium oxide surfaces affords surface coatings that exhibit antifouling properties against proteins and allow for surface regeneration by clearing adhering proteins by employing a salt washing step. The surfaces also kill bacteria by contact killing, which is aided by a nonfouling block. The synthesis of block copolymers of 4-vinyl pyridine (VP), dimethyl 4-vinylbenzyl phosphonate (DMVBP), and 4-vinylbenzyltrimethyl ammonium chloride (TMA) is achieved on the multigram scale via RAFT polymerization with good end group retention and narrow dispersities. By polymer analogous reactions, poly(4-vinyl pyridinium propane sulfonate-block-4-vinylbenzyl phosphonic acid-block-4-vinylbenzyl trimethylammonium chloride) (P(VSP-b-PA-b-TMA)) is obtained. The antifouling properties against the model protein pepsin and the salt-induced surface regeneration are shown in surface plasmon resonance (SPR) experiments, while independently the antibacterial and antifouling properties of coated titanium substrates are successfully tested in preliminary microbiological assays against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This strategy may contribute to the development of long-term effective antibacterial implant surface coatings to suppress biomedical device-associated infections.

Existing methods for treating diabetic oral ulcers often fall short in clinical environments due to potential bacterial contamination, oxidative harm, and hindered angiogenesis throughout the healing process. Here, a hydrogel patch (HYG2) have been developed for local in situ application. HYG2 comprises oxidized pullulan, quaternized chitosan, and eumelanin nanoparticles derived from cuttlefish ink. These components work together to efficiently heal wounds associated with diabetic oral ulcers. Application begins with a simple local injection that quickly forms a protective barrier over the mucosa, effectively stopping bleeding and counteracting inflammatory agents. HYG2 is distinguished by its strong antibacterial properties and capacity to eliminate reactive oxygen species, promoting bacteria clearance and managing oxidative stress, which accelerates the healing phase from inflammation to tissue regeneration. Additionally, HYG2's 3D structure, incorporating elements from natural sources, offers exemplary support for structural and nutritional cell needs. This enhancement fosters cell adhesion, migration, and proliferation, along with further angiogenesis during mucosal remodeling. Ultimately, HYG2 is fully absorbed by the body after serving its therapeutic functions. Evidence from in vitro and in vivo studies shows that HYG2 hydrogel markedly accelerates mucosal wound repair, making it a promising treatment for diabetic oral ulcers.

Electrospun nanofibrous membranes made of chiral selectors (CSs) have shown their potential for efficient chiral resolutions via filtrations. It is thus of great importance to expand the number of electrospun membranes made of various CSs for the resolution of a wide range of chiral compounds. Here, the electrospinning of two benzyl carbamate derivatives of cellulose, namely cellulose benzyl carbamate (CBzC) and cellulose 4-chlorobenzyl carbamate (CCBzC), to form a new type of enantioselective membranes for chiral resolutions of racemic compounds, is reported. The morphology of the electrospun membranes is studied by optical microscopy and scanning electron microscopy in relation to the electrospinning process parameters. Liquid-liquid permeation experiments of the racemic compounds, (R,S)-1-(1-naphthyl)ethanol ((R,S)-NET), (R,S)-1,1'-bi-2-naphtol ((R,S)-BNP), (R,S)-naproxen ((R,S)-NAP), and (R,S)-benzoin ((R,S)-BNZ) through the membranes demonstrate preferable permeations of (R)- or (S)-enantiomers depending on the combinations between the CSs and the racemates. Molecular docking simulations indicate the differences in the binding type, number, and free energies between the CSs and the enantiomers.

Nanoparticles of zeolitic imidazole framework-8 (ZIF-8 NPs), which are the subclass of metal-organic frameworks consisting of Zn ion and 2-methylimidazole, have been identified as promising drug carriers since their large microporous structure is suited for encapsulating hydrophobic drug molecules. However, one of the limitations of ZIF-8 NPs is their low stability in physiological solutions, especially in the presence of water and phosphate anions. These molecules can interact with the coordinatively unsaturated Zn sites at the external surface to induce the degradation of ZIF-8 NPs. In this study, herein a facile approach is reported to enhance the chemical stability of ZIF-8 NPs by surface coating with polyacrylic acid (PAA). The PAA-coated ZIF-8 (PAA-ZIF-8) NPs are prepared by mixing ZIF-8 NPs and PAA in water. PAA coating inhibits the degradation of ZIF-8 NPs in water as well as phosphate-buffered saline over 6 days, which seems to be due to the coordination of carboxyl groups of PAA to the reactive Zn sites. Furthermore, the PAA-ZIF-8 NPs loaded with the anticancer drug doxorubicin (Dox) show cytotoxicity in human colon cancer cells. These results clearly show the feasibility of the PAA coating approach to improve the chemical stability of ZIF-8 NPs without impairing their drug delivery capability.

Cells coordinate their activity and regulate biological processes in response to chemical signals. Mimicking natural processes, control over the formation of artificial supramolecular materials is of high interest for their application in biology and medicine. Supramolecular material that can form in response to chemical signals is important for the development of autonomously responsive materials. Herein, a supramolecular hydrogel system is reported enabling in situ generation of hydrogelators in response to a specific chemical signal. Using self-immolative chemistry, spatial control over the formation of supramolecular hydrogel material and structured free-standing hydrogel objects via providing HO locally is demonstrated. In addition, a hybrid system is developed enabling in situ generation of the HO by the action of an enzyme and glucose, providing an extra handle for the development of an intelligent soft material. This generic design should enable the use of various (chemical)stimuli that can be obtained via coupling different stimuli and various chemical and/or biological markers and appears a versatile approach for the design of smart artificial soft materials that can find application in theranostic purposes.

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

Balloon-assisted enteroscopy (BAE) is highly invasive and carries a higher risk of complications such as pain and perforation during enteroscope insertion. Applying lubricants to the small intestinal mucosa and reducing the dynamic friction coefficient (DFC) between the small intestinal mucosa and endoscopic shaft (ES) (or overtube (OT)) can minimize the invasiveness of BAE. However, the ideal viscosity characteristics of these lubricants remain unknown. In this study, a model is developed to measure the DFC using human small intestines from forensic autopsies and determine the ideal viscosity of low-friction lubricants that exhibit a minimal DFC, thus reducing the pressure on the intestinal lining during the procedure. The results reveal that the DFC is strongly correlated to the lubricant's viscosity rather than its chemical composition. Low-friction lubricants with viscosities within 0.20-0.32 and 0.35-0.58 Pa·s (at shear rates of 10 s) for the OT and ES, respectively, can significantly reduce the DFC, yielding optimal results. These findings highlight the role of viscosity in minimizing the friction between the equipment and small intestinal mucosa. The ideal low-friction lubricants satisfying the aforementioned viscosity ranges can minimize the invasiveness of BAE by decreasing the friction between the equipment and intestinal lining.

Collagen (Col) is commonly used as a natural biomaterial for biomedical applications. Although Col I is the most prevalent col type employed, many collagen types work together in vivo to confer function and biological activity. Thus, blending collagen types can better recapitulate many native environments. This work investigates how hydrogel properties can be tuned through blending collagen types (col I/II and col I/III) and by varying polymerization temperatures. Col I/II results in poorly developed fibril networks, which softened the gels, especially at lower polymerization temperatures. Conversely, col I/III hydrogels exhibit well-connected fibril networks with localized areas of fine fibrils and result in stiffer hydrogels. A decreased molecular mass recovery rate is observed in blended hydrogels. The altered fibril morphologies, mechanical properties, and biological signals of the blended gels can be leveraged to alter cell responses and can be used as models for different tissue types (e.g., healthy vs fibrotic tissue). Furthermore, the biomimetic hydrogel properties are a tool that can be used to modulate the transport of drugs, nutrients, and wastes in tissue engineering applications.

White adipose tissue (WAT) plays a crucial role in energy homeostasis and secretes numerous adipokines with far-reaching effects. WAT is linked to diseases such as diabetes, cardiovascular disease, and cancer. There is a high demand for suitable in vitro models to study diseases and tissue metabolism. Most of these models are covered by 2D-monolayer cultures. This study aims to evaluate the performance of different WAT models to better derive potential applications. The stability of adipocyte characteristics in spheroids and two 3D gellan gum hydrogels with ex situ lobules and 2D-monolayer culture is analyzed. First, the differentiation to achieve adipocyte-like characteristics is determined. Second, to evaluate the maintenance of differentiated ASC-based models, an adipocyte-based model, and explants over 3 weeks, viability, intracellular lipid content, perilipin A expression, adipokine, and gene expression are analyzed. Several advantages are supported using each of the models. Including, but not limited to, the strong differentiation in 2D-monolayers, the self-assembling within spheroids, the long-term stability of the stem cell-containing hydrogels, and the mature phenotype within adipocyte-containing hydrogels and the lobules. This study highlights the advantages of 3D models due to their more in vivo-like behavior and provides an overview of the different adipose cell models.

Recent studies, leveraging click chemistry reactions, have significantly advanced the fields of biomaterials and drug delivery. Of these click reactions, the Diels-Alder cycloaddition is exceptionally valuable for synthetic organic chemistry and biomaterial design, as it occurs under mild reaction conditions and can undergo a retrograde reaction, under physiologically relevant conditions, to yield the initial reactants. In this review, potential applications of the Diels-Alder reaction are explored within the nexus of biomaterials and drug delivery. This includes an emphasis on key platforms such as polymers, nanoparticles, and hydrogels which utilize Diels-Alder for drug delivery, functionalized surfaces, bioconjugation, and other diverse applications. Specifically, this review will focus on the use of Diels-Alder biomaterials in applications of tissue engineering and cancer therapies, while providing a discussion of the advantages, platforms, and applications of Diels-Alder click chemistry.

The main objective of this study is to construct radially aligned PCL nanofibers reinforced with levan polymer and investigate their in vitro biological activities thoroughly. First Halomonas levan (HL) polysaccharide is hydrolyzed (hHL) and subjected to sulfation to attain Sulfated hydrolyzed Halomonas levan (ShHL)-based material indicating heparin mimetic properties. Then, optimization studies are carried out to produce coaxially generated radially aligned Poly(caprolactone) (PCL) -ShHL nanofibers via electrospinning. The obtained nanofibers are characterized with Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscopy with Energy Dispersive X-Ray (FESEM-EDX) analysis, and mechanical, contact angle measurement, biodegradability, and swelling tests as well. Afterward, cytotoxicity of artificial tympanic membranes is analyzed by MTT (3-(4,5-Dimethylthiazol-2-yl) -2,5 Diphenyltetrazolium Bromide) test, and their impacts on cell proliferation, cellular adhesion, wound healing processes are explored. Furthermore, an additional FESEM imaging is performed to manifest the interactions between fibroblasts and nanofibers. According to analytical measurements it is detected that PCL-ShHL nanofibers i) are smaller in fiber diameter, ii) are more biodegradable, iii) are more hydrophilic, and iv) demonstrated superior mechanical properties compared to PCL nanofibers. Moreover, it is also deciphered that PCL-ShHL nanofibers strongly elevated cellular adhesion, proliferation, and in vitro wound healing features compared to PCL nanofibers. According to obtained results it is assumed that newly synthetized levan and PCL mediated nanofibers are very encouraging for healing tympanic membrane perforations.

In this study, the fabrication and characterization of Zn-phthalocyanine/gelatin nanofibrous membranes is reported using the electrospinning technique. The membranes exhibit a homogeneous distribution of Zn-phthalocyanine within the gelatin matrix, maintaining the structural integrity and photosensitizing properties of the phthalocyanine. Scanning electron microscopy revealed that the electrospun fibers possess diameters ranging results as 100-300, 200-700, and 300-800 nm for Gel, ZnPc/Gel 1, and ZnPc/Gel 2, respectively. The addition of ZnPc does not decrease the hydrophilicity of the Gel membrane. The nanofibrous membranes showed good cytocompatibility, as indicated by the high viability of Vero cells exposed to membrane extracts. Furthermore, these composites supported cell adhesion and proliferation on their surfaces. The two Zn-phthalocyanine/gelatin nanofiber formulations exhibited significant antimicrobial activity toward Escherichia Coli (E. Coli) and Staphylococcus Aureus (S. Aureus) under visible light illumination, achieving reductions of 3.4 log and 3.6 log CFU mL for E. coli, and 3.9 log and 4.1 log CFU mL for S. aureus. These results demonstrate the potential of Zn-phthalocyanine/gelatin nanofibrous membranes as effective agents in antibacterial photodynamic therapy, providing a promising solution to control bacterial infections and antibiotic resistance.

Advancements in biomaterial-based spinal cord tissue engineering technology have profoundly influenced regenerative medicine, providing innovative solutions for both spinal cord organoid development and engineered spinal cord injury (SCI) repair. In spinal cord organoids, biomaterials offer a supportive microenvironment that mimics the natural extracellular matrix, facilitating cell differentiation and organization and advancing the understanding of spinal cord development and pathophysiology. Furthermore, biomaterials are essential in constructing engineered spinal cords for SCI repair. The incorporation of biomaterials with growth factors, fabrication of ordered scaffold structures, and artificial spinal cord assemblies are critical insights for SCI to ensure structural integrity, enhance cell viability, and promote neural regeneration in transplantation. In summary, this review summarizes the contribution of biomaterials to the spinal cord organoids progression and discusses strategies for biomaterial-based spinal cord engineering in SCI therapy. These achievements underscore the transformative potential of biomaterials to improve treatment options for SCI and accelerate future clinical applications.