Polyphenol-Reinforced Glycocalyx-Like Hydrogel Coating Induced Myocardial Regeneration and Immunomodulation.

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.

Hyaluronic acid-mediated epithelial-mesenchymal transition of human lens epithelial cells via CD44 and TGF-ß2.

PURPOSE: The epithelial-mesenchymal transition of human lens epithelial cells plays a role in posterior capsule opacification, a fibrotic process that leads to a common type of cataract. Hyaluronic acid has been implicated in this fibrosis. Studies have investigated the role of transforming growth factor (TGF)-ß2 in epithelial-mesenchymal transition. However, the role of TGF-ß2 in hyaluronic acid-mediated fibrosis of lens epithelial cell remains unknown. We here examined the role of TGF-ß2 in the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells. METHODS: Cultured human lens epithelial cells (HLEB3) were infected with CD44-siRNA by using the Lipofectamine 3000 transfection reagent. The CCK-8 kit was used to measure cell viability, and the scratch assay was used to determine cell migration. Cell oxidative stress was analyzed in a dichloro-dihydro-fluorescein diacetate assay and by using a flow cytometer. The TGF-ß2 level in HLEB3 cells was examined through immunohistochemical staining. The TGF-ß2 protein level was determined through western blotting. mRNA expression levels were determined through quantitative real-time polymerase chain reaction. RESULTS: Treatment with hyaluronic acid (1.0 µM, 24 h) increased the epithelial-mesenchymal transition of HLEB3 cells. The increase in TGF-ß2 levels corresponded to an increase in CD44 levels in the culture medium. However, blocking the CD44 function significantly reduced the TGF-ß2-mediated epithelial-mesenchymal transition response of HLEB3 cells. CONCLUSIONS: Our study showed that both CD44 and TGF-ß2 are critical contributors to the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells, and that TGF-ß2 in epithelial-mesenchymal transition is regulated by CD44. These results suggest that CD44 could be used as a target for preventing hyaluronic acid-induced posterior capsule opacification. Our findings suggest that CD44/TGF-ß2 is crucial for the hyaluronic acid-induced epithelial-mesenchymal transition of lens epithelial cells.

In Situ-Forming, Bioorthogonally Cross-linked, Nanocluster-Reinforced Hydrogel for the Regeneration of Corneal Defects.

Corneal defects can lead to stromal scarring and vision loss, which is currently only treatable with a cadaveric corneal transplant. Although in situ-forming hydrogels have been shown to foster regeneration of the cornea in the setting of stromal defects, the cross-linking, biomechanical, and compositional parameters that optimize healing have not yet been established. This, Corneal defects are also almost universally inflamed, and their rapid closure without fibrosis are critical to preserving vision. Here, an in situ forming, bioorthogonally cross-linked, nanocluster (NC)-reinforced collagen and hyaluronic acid hydrogel (NCColHA hydrogel) with enhanced structural integrity and both pro-regenerative and anti-inflammatory effects was developed and tested within a corneal defect model in vivo. The NCs serve as bioorthogonal nanocross-linkers, providing higher cross-linking density than polymer-based alternatives. The NCs also serve as delivery vehicles for prednisolone (PRD) and the hepatocyte growth factor (HGF). NCColHA hydrogels rapidly gel within a few minutes upon administration and exhibit robust rheological properties, excellent transparency, and negligible swelling/deswelling behavior. The hydrogel's biocompatibility and capacity to support cell growth were assessed using primary human corneal epithelial cells. Re-epithelialization on the NCColHA hydrogel was clearly observed in rabbit eyes, both ex vivo and in vivo, with expression of normal epithelial biomarkers, including CD44, CK12, CK14, α-SMA, Tuj-1, and ZO-1, and stratified, multilayered morphology. The applied hydrogel maintained its structural integrity for at least 14 days and remodeled into a transparent stroma by 56 days.

miR-21 attenuated inflammation targeting MyD88 in human chondrocytes stimulated with Hyaluronan oligosaccharides.

Inflammation is the body's response to injuries, which depends on numerous regulatory factors. Among them, miRNAs have gained much attention for their role in regulating inflammatory gene expression at multiple levels. In particular, miR-21 is up-regulated during the inflammatory response and reported to be involved in the resolution of inflammation by down-regulating pro-inflammatory mediators, including MyD88. Herein, we evaluated the regulatory effects of miR-21 on the TLR-4/MyD88 pathway in an in vitro model of 6-mer HA oligosaccharides-induced inflammation in human chondrocytes. The exposition of chondrocytes to 6-mer HA induced the activation of the TLR4/MyD88 pathway, which culminates in NF-kB activation. Changes in miR-21, TLR-4, MyD88, NLRP3 inflammasome, IL-29, Caspase1, MMP-9, iNOS, and COX-2 mRNA expression of 6-mer HA-stimulated chondrocytes were examined by qRT-PCR. Protein amounts of TLR-4, MyD88, NLRP3 inflammasome, p-ERK1/2, p-AKT, IL-29, caspase1, MMP-9, p-NK-kB p65 subunit, and IKB-a have been evaluated by ELISA kits. NO and PGE2 levels have been assayed by colorimetric and ELISA kits, respectively. HA oligosaccharides induced a significant increase in the expression of the above parameters, including NF-kB activity. The use of a miR-21 mimic attenuated MyD88 expression levels and the downstream effectors. On the contrary, treatment with a miR-21 inhibitor induced opposite effects. Interestingly, the use of a MyD88 siRNA confirmed MyD88 as the target of miR-21 action. Our results suggest that miR-21 expression could increase in an attempt to reduce the inflammatory response, targeting MyD88.

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.

An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.

Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.

Thermo-assisted fabrication of a novel shape-memory hyaluronic acid sponge for non-compressible hemorrhage control.

Hyaluronic acid (HA), a major component of skin extracellular matrix, provides an excellent framework for hemostatic design; however, there still lacks HA materials tailored with superior mechanical properties to address non-compressible hemorrhages. Here, we present a solvent-free thermal approach for constructing a shape-memory HA sponge for this application. Following facile thermal incubation around 130 °C, HA underwent cross-linking via esterification with poly(acrylic acid) within the sponge pre-shaped through a prior freeze-drying process. The resulting sponge system exhibited extensively interconnected macropores with a high fluid absorption capacity, excellent shape-memory property, and robust mechanical elasticity. When introduced to whole blood in vitro, the HA sponges demonstrated remarkable hemostatic properties, yielding a shorter coagulation time and lower blood clotting index compared to the commercial gelatin sponge (GS). Furthermore, in vivo hemostatic studies involving two non-compressible hemorrhage models (rat liver volume defect injury or femoral artery injury) achieved a significant reduction of approximately 64% (or 56%) and 73% (or 70%) in bleeding time and blood loss, respectively, which also outperformed GS. Additionally, comprehensive in vitro and in vivo evaluations suggested the good biocompatibility and biodegradability of HA sponges. This study highlights the substantial potential for utilizing the designed HA sponges in massive bleeding management.

Enhanced neuroprotective effect of verapamil-loaded hyaluronic acid modified carbon quantum dots in an in-vitro model of amyloid-induced Alzheimer's disease.

This study aims to investigate the molecular mechanisms and the neuroprotective effect of hyaluronic acid modified verapamil-loaded carbon quantum dots (VRH-loaded HA-CQDs) against an in-vitro Alzheimer's disease model induced by amyloid beta (Aß) in SH-SY5Y and Neuro 2a neuroblastoma cells. Briefly, different HA-CQDs were prepared using hydrothermal method and optimized by Box-Behnken design to maximize quantum yield and minimize particle size. Serum stable negatively charged VRH-loaded HA-CQDs was successfully prepared by admixing the optimized HA-CQDs and VRH with association efficiency and loading capacity of 81.25 ± 3.65 % and 5.11 ± 0.81 %, respectively. Cells were pretreated with VRH solution or loaded-HA-CQDs followed by exposure to Aß. Compared to the control group, amyloidosis led to reduction in cellular proliferation, mitochondrial membrane potential, expression of cytochrome P450, cytochrome c oxidase, CREB-regulated transcriptional coactivator 3, and mitotic index, along with marked increase in reactive oxygen species (ROS) and inflammatory cytokines. Pretreatment with VRH, either free or loaded HA-CQDs, enhanced cell survival, mitochondrial membrane potential, mitotic index, and gene expression. It also reduced inflammation and ROS. However, VRH-loaded HA-CQDs exhibited superior effectiveness in the measured parameters. These findings suggest that VRH-loaded HA-CQDs have enhanced therapeutic potential compared to free VRH in mitigating amyloidosis negative features.

Delivery of piperlongumine via hyaluronic acid/phenylboronic acid-mediated dual targetable polymersome for enhanced anticancer functionality against pancreatic tumor.

Pancreatic cancer cells highly resistance to conventional chemo drugs, resulting low survival rates. The aim of the study was to design and develop dual targeting polymersomes (DTPS) loaded with phyto alkaloid agent i.e., piperlongumine (PL) for effective pancreatic cancer treatment. Here, hyaluronic acid (HA) was functionalized with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG-NH2), poly(ethylene glycol) bis (amine) (PEG), and phenylboronic acid (PBA) moieties. The designed DTPS could selectively recognize CD44/sialic acid (SA) and deliver PL to MIA PaCa-2 pancreatic cancer cells, facilitated via HA-CD44 and PBA-SA interactions. Drug release and stability results implied sustained PL release profile and pH sensitivity. DTPS could be more efficiently bound with SA than other sugars based on fluorescence spectroscopy. The anticancer efficacy of designed polymersomes was tested with H6C7 normal pancreas cells and SA/CD44-overexpressed MIA PaCa-2 pancreatic cancer cells. DTPS showed both SA and CD44-mediated higher cellular uptake while single-targeted polymersomes showed CD44-mediated cellular uptake. The PL-loaded DTPS efficiently uptake by MIA PaCa-2 cancer cells, causing up to 80 % cell growth inhibition, reduced cell spheroids volume and increased dead cells by 58.3 %. These results indicate that the newly developed DTPS can effectively serve as a pH-responsive drug delivery system for efficient treatment of cancer.

Long-termin vitromaintenance of plasma cells in a hydrogel-enclosed human bone marrow microphysiological 3D model system.

Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g. in various malignant and non-malignant diseases such as multiple myeloma, primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived fromin vivostudies in mice, asin vitrostudies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survivalin vitrofor up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCsin vitro. Our innovative model system is suitable for in-depthin vitrostudies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.

Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging.

Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin.

Development of hyaluronic acid hydrogel containing prednisolone-encapsulated nonphospholipid liposomes for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) requires therapeutic approaches that alleviate symptoms and inhibit the progression of joint damage. Glucocorticoids (GCs) have been a cornerstone of RA treatment, yet their use is often limited by side effects. Recent advancements suggest that liposome-based delivery systems can improve GC biodistribution, minimizing toxicity. This study introduces an innovative tool for RA treatment using prednisone-encapsulated nonphospholipid liposomes (NPLs) in combination with a hyaluronic acid (HA) hydrogel. Our methodology involved incorporating prednisone (PR) with palmitic acid and cholesterol to formulate stable NPLs using a thin-film hydration technique. The synthesized PR-NPLs, characterized by a mean size of 150 nm, demonstrated uniform distribution and higher drug encapsulation in comparison with conventional phospholipid liposomes. In vitro assays revealed that PR-NPL markedly reduced inflammatory responses in macrophages. Additionally, we successfully incorporated PR-NPL into an HA hydrogel, employing a photoinitiated cross-linking process. This novel composite offered modulable PR release, governed by the degree of hydrogel cross-linking. The developed system presents a promising advancement in RA management, especially suited for intraarticular injections. It potentially enables targeted, controlled drug release with a reduced risk of side effects, signifying a significant improvement over existing RA therapies.

Application of In Situ Mucoadhesive Hydrogel with Anti-Inflammatory and Pro-Repairing Dual Properties for the Treatment of Chemotherapy-Induced Oral Mucositis.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent complication of chemotherapy and significantly affects the treatment process. However, effective treatment for CIOM is lacking due to the unique environment of the oral cavity and the single effect of current drug delivery systems. In this present study, we propose an innovative approach by combining a methacrylate-modified human recombinant collagen III (rhCol3MA) hydrogel system with hyaluronic acid-epigallocatechin gallate (HA-E) and dopamine-modified methacrylate-alginate (AlgDA-MA). HA-E is used as an antioxidant and anti-inflammatory agent and synergizes with AlgDA-MA to improve the wet adhesion of hydrogel. The results of rhCol3MA/HA-E/AlgDA-MA (Col/HA-E/Alg) hydrogel demonstrate suitable physicochemical properties, excellent wet adhesive capacity, and biocompatibility. Notably, the hydrogel could promote macrophage polarization from M1 to M2 and redress human oral keratinocyte (HOK) inflammation by inhibiting NF-κB activation. Wound healing evaluations in vivo demonstrate that the Col/HA-E/Alg hydrogel exhibits a pro-repair effect by mitigating inflammatory imbalances, fostering early angiogenesis, and facilitating collagen repair. In summary, the Col/HA-E/Alg hydrogel could serve as a promising multifunctional dressing for the treatment of CIOM.

Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing.

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly. Herein, we propose a HA-based composite hydrogel as the wound dressing based on oxidative coupling reaction. Tannic acid and dopamine-coated carbon particles (DCPs) containing abundant phenolic hydroxyl groups are incorporated into the HA-based hydrogel for increasing the number of crosslinking sites of oxidative coupling of the hydrogel and enhancing adhesion through the formation of covalent bonds and hydrogen bonds between hydrogel and wound sites. The composite hydrogel exhibits short gelation time (<6 s) and high adhesion strength (>8.1 kPa), which are superior to the references and commercial products of its kind. The in vitro experiments demonstrate that the hydrogel has low hemolytic reaction, negligible cytotoxicity, and the ability to promote fibroblast proliferation and migration. The in vivo full-thickness skin defect model experiments demonstrate that the hydrogel can accelerate wound healing under mild photothermal stimulation of DCPs by reducing inflammation, relieving tissue hypoxia, and promoting angiogenesis and epithelialization.

Hyaluron-Based Bionanocomposites of Silver Nanoparticles with Graphene Oxide as Effective Growth Inhibitors of Wound-Derived Bacteria.

Keeping wounds clean in small animals is a big challenge, which is why they often become infected, creating a risk of transmission to animal owners. Therefore, it is crucial to search for new biocompatible materials that have the potential to be used in smart wound dressings with both wound healing and bacteriostatic properties to prevent infection. In our previous work, we obtained innovative hyaluronate matrix-based bionanocomposites containing nanosilver and nanosilver/graphene oxide (Hyal/Ag and Hyal/Ag/GO). This study aimed to thoroughly examine the bacteriostatic properties of foils containing the previously developed bionanocomposites. The bacteriostatic activity was assessed in vitro on 88 Gram-positive (n = 51) and Gram-negative (n = 37) bacteria isolated from wounds of small animals and whose antimicrobial resistance patterns and resistance mechanisms were examined in an earlier study. Here, 69.32% of bacterial growth was inhibited by Hyal/Ag and 81.82% by Hyal/Ag/GO. The bionanocomposites appeared more effective against Gram-negative bacteria (growth inhibition of 75.68% and 89.19% by Hyal/Ag and Hyal/Ag/Go, respectively). The effectiveness of Hyal/Ag/GO against Gram-positive bacteria was also high (inhibition of 80.39% of strains), while Hyal/Ag inhibited the growth of 64.71% of Gram-positive bacteria. The effectiveness of Hyal/Ag and Hyal/Ag/Go varied depending on bacterial genus and species. Proteus (Gram-negative) and Enterococcus (Gram-positive) appeared to be the least susceptible to the bionanocomposites. Hyal/Ag most effectively inhibited the growth of non-pathogenic Gram-positive Sporosarcina luteola and Gram-negative Acinetobacter. Hyal/Ag/GO was most effective against Gram-positive Streptococcus and Gram-negative Moraxella osloensis. The Hyal/Ag/GO bionanocomposites proved to be very promising new antibacterial, biocompatible materials that could be used in the production of bioactive wound dressings.

Endogenous Hyaluronan Promotes Intestinal Homeostasis and Protects against Murine Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a complex, multifactorial gastrointestinal disorder predominantly affecting preterm infants. The pathogenesis of this condition involves a complex interplay between intestinal barrier dysfunction, microbial dysbiosis, and an altered immune response. This study investigates the potential role of endogenous hyaluronan (HA) in both the early phases of intestinal development and in the context of NEC-like intestinal injury. We treated neonatal CD-1 mouse pups with PEP1, a peptide inhibiting HA receptor interactions, from postnatal days 8 to 12. We evaluated postnatal intestinal developmental indicators, such as villi length, crypt depth, epithelial cell proliferation, crypt fission, and differentiation of goblet and Paneth cells, in PEP1-treated animals compared with those treated with scrambled peptide. PEP1 treatment significantly impaired intestinal development, as evidenced by reductions in villi length, crypt depth, and epithelial cell proliferation, along with a decrease in crypt fission activity. These deficits in PEP1-treated animals correlated with increased susceptibility to NEC-like injuries, including higher mortality rates, and worsened histological intestinal injury. These findings highlight the role of endogenous HA in supporting intestinal development and protecting against NEC.

The application of pH-responsive hyaluronic acid-based essential oils hydrogels with enhanced anti-biofilm and wound healing.

pH could play vital role in the wound healing process due to the bacterial metabolites, which is one essential aspect of desirable wound dressings lies in being pH-responsive. This work has prepared a degradable hyaluronic acid hydrogel dressing with wound pH response-ability. The aldehyde-modified hyaluronic acid (AHA) was obtained, followed by complex mixture formation of eugenol and oregano antibacterial essential oil in the AHA-CMCS hydrogel through the Schiff base reaction with carboxymethyl chitosan (CMCS). This hydrogel composite presents pH-responsiveness, its disintegration mass in acidic environment (pH = 5.5) is 4 times that of neutral (pH = 7.2), in which the eugenol release rate increases from 37.6 % to 82.1 %. In vitro antibacterial and in vivo wound healing investigations verified that hydrogels loaded with essential oils have additional 5 times biofilm removal efficiency, and significantly accelerate wound healing. Given its excellent anti-biofilm and target-release properties, the broad application of this hydrogel in bacteria-associated wound management is anticipated.

Evaluation of Interaction With Bio-absorbable Polyglycolic Acid Spacer and Anti-adhesive Agents Using a Rat Experimental Model.

BACKGROUND/AIM: Neskeep®, an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep® using rat models. MATERIALS AND METHODS: Animal experiments were performed using 60 rats, which underwent Neskeep® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm®, INTERCEED®, AdSpray®, and only Neskeep® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion. RESULTS: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep®, Seprafilm®, INTERCEED®, and AdSpray® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm® group on day 28. CONCLUSION: Seprafilm® may exhibit an anti-adhesive effect when used with Neskeep®.

Design and evaluation of a bilayered dermal/hypodermal 3D model using a biomimetic hydrogel formulation.

Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL. Cell viability, hemocompatibility, physicochemical, mechanical, and wound healing properties were investigated. Finally, a bilayered hydrogel loaded with fibroblasts and mesenchymal stromal cells was developed using the Ag-Col I-DS-HA-EL (ACDHE) formulation. The ACDHE hydrogel displayed the best in vitro results and acceptable physicochemical properties. Also, it behaved mechanically close to human native skin and exhibited good cytocompatibility. Environmental scanning electron microscopy (ESEM) analysis revealed a porous microstructure that allows the maintenance of cell growth and ECM-like structure production. These findings demonstrate the potential of the ACDHE hydrogel formulation for applications such as an injectable hydrogel or a bioink to create cell-laden structures for skin TE.

Conformal encapsulation of mammalian stem cells using modified hyaluronic acid.

Micro- and nanoencapsulation of cells has been studied as a strategy to protect cells from environmental stress and promote survival during delivery. Hydrogels used in encapsulation can be modified to influence cell behaviors and direct assembly in their surroundings. Here, we report a system that conformally encapsulated stem cells using hyaluronic acid (HA). We successfully modified HA with lipid, thiol, and maleimide pendant groups to facilitate a hydrogel system in which HA was deposited onto cell plasma membranes and subsequently crosslinked through thiol-maleimide click chemistry. We demonstrated conformal encapsulation of both neural stem cells (NSCs) and mesenchymal stromal cells (MSCs), with viability of both cell types greater than 90% after encapsulation. Additional material could be added to the conformal hydrogel through alternating addition of thiol-modified and maleimide-modified HA in a layering process. After encapsulation, we tracked egress and viability of the cells over days and observed differential responses of cell types to conformal hydrogels both according to cell type and the amount of material deposited on the cell surfaces. Through the design of the conformal hydrogels, we showed that multicellular assembly could be created in suspension and that encapsulated cells could be immobilized on surfaces. In conjunction with photolithography, conformal hydrogels enabled rapid assembly of encapsulated cells on hydrogel substrates with resolution at the scale of 100 µm.