F127 Hydrogel Research Articles

An injectable thermosensitive pluronic F127 loaded-nanohydroxyapatite / Polydopamine for promoting sciatic nerve repair after crush injury

Peripheral nerve injury (PNI) remains an urgent issue due to its huge financial burden and high rate of disability. Here, an injectable HAP/PDA thermosensitive Pluronic F127 hydrogel is proposed for peripheral nerve repair. We investigated the surface characteristics of HAP/PDA and evaluated biocompatibility, cellular proliferation, and apoptosis in vitro. After injecting the hydrogel into the injured site of rats, we recorded the recovery of motor function and judged the dregree of nerves through electrophysiological and morphological changes. The hydrogel was found to accelerate the nerve regeneration. Collectively, the HAP/PDA thermosensitive Pluronic F127 hydrogel has potential in promoting sciatic nerve repair.

Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications

Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.

Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes

Chronic nonhealing diabetic wounds are a critical clinical challenge. Regulatory T cells (Tregs) are immunosuppressive modulators affecting wound healing progression by controlling the inflammatory response. The current study attempted to investigate whether the exosomes derived from cord blood (CB) Tregs can accelerate the healing process. Exosomes were isolated from CB-Treg cultures using ultracentrifugation and validated with different specific markers of exosomes. The purified CB-Treg-derived exosomes were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes. The migration-promoting effect of CB-Treg-derived exosomes on fibroblasts and endothelial cells was investigated. We used thermosensitive Pluronic F-127 hydrogel (PF-127) loaded with CB-Treg-derived exosomes in a diabetic wound healing mouse model. CB-Treg-derived exosomes with 30–120 nm diameters revealed exosome-specific markers, such as TSG101, Alix, and CD63. CB-Treg-derived exosomes were mainly bound to the monocytes when co-cultured with PBMCs, and promoted monocyte polarization to the anti-inflammatory phenotype (M2) in vitro. CB-Treg-derived exosomes enhanced the migration of endothelial cells and fibroblasts. Furthermore, CB-Treg-derived exosomes treatment accelerated wound healing by downregulating inflammatory factor levels and upregulating the M2 macrophage ratio in vivo. Our findings indicated that CB-Treg-derived exosomes could be a promising cell-free therapeutic strategy for diabetic wound healing, partly by targeting monocytes.

Pluronic F127 composite hydrogel for the repair of contraction suppressed full-thickness skin wounds in a rabbit model

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

Imbalanced spectral data analysis using data augmentation based on the generative adversarial network

Spectroscopic techniques generate one-dimensional spectra with distinct peaks and specific widths in the frequency domain. These features act as unique identities for material characteristics. Deep neural networks (DNNs) has recently been considered a powerful tool for automatically categorizing experimental spectra data by supervised classification to evaluate material characteristics. However, most existing work assumes balanced spectral data among various classes in the training data, contrary to actual experiments, where the spectral data is usually imbalanced. The imbalanced training data deteriorates the supervised classification performance, hindering understanding of the phase behavior, specifically, sol-gel transition (gelation) of soft materials and glycomaterials. To address this issue, this paper applies a novel data augmentation method based on a generative adversarial network (GAN) proposed by the authors in their prior work. To demonstrate the effectiveness of the proposed method, the actual imbalanced spectral data from Pluronic F-127 hydrogel and Alpha-Cyclodextrin hydrogel are used to classify the phases of data. Specifically, our approach improves 8.8%, 6.4%, and 6.2% of the performance of the existing data augmentation methods regarding the classifier’s F-score, Precision, and Recall on average, respectively. Specifically, our method consists of three DNNs: the generator, discriminator, and classifier. The method generates samples that are not only authentic but emphasize the differentiation between material characteristics to provide balanced training data, improving the classification results. Based on these validated results, we expect the method’s broader applications in addressing imbalanced measurement data across diverse domains in materials science and chemical engineering.

Incorporation of Resveratrol-Hydroxypropyl-β-Cyclodextrin Complexes into Hydrogel Formulation for Wound Treatment.

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-β-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-β-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy.

Cupric-polymeric nanoreactors integrate into copper metabolism to promote chronic diabetic wounds healing

Given multifunction of copper (Cu) contributing to all stages of the physiology of wound healing, Cu-based compounds have great therapeutic potentials to accelerate the wound healing, but they must be limited to a very low concentration range to avoid detrimental accumulation. Additionally, the cellular mechanism of Cu-based compounds participating the healing process remains elusive. In this study, copper oxide nanoparticles (CuONPs) were synthesized to mimic the multiple natural enzymes and trapped into PEG-b-PCL polymersomes (PS) to construct cupric-polymeric nanoreactors (CuO@PS) via a direct hydration method, thus allowing to compartmentalize Cu-based catalytic reactions in an isolated space to improve the efficiency, selectivity, recyclability as well as biocompatibility. While nanoreactors trafficked to lysosomes following endocytosis, the released Cu-based compounds in lysosomal lumen drove a cytosolic Cu+ influx to mobilize Cu metabolism mostly via Atox1-ATP7a/b-Lox axis, thereby activating the phosphorylation of mitogen-activated protein kinase 1 and 2 (MEK1/2) to initiate downstream signaling events associated with cell proliferation, migration and angiogenesis. Moreover, to facilitate to lay on wounds, cupric-polymeric nanoreactors were finely dispersed into a thermosensitive Pluronic F127 hydrogel to form a composite hydrogel sheet that promoted the healing of chronic wounds in diabetic rat models. Hence, cupric-polymeric nanoreactors represented an attractive translational strategy to harness cellular Cu metabolism for chronic wounds healing.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. Statement of significanceF127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Rheology and printability of alumina-toughened zirconia pastes for high-density strong parts via direct ink writing

Direct ink writing (DIW) is a promising additive manufacturing technique for fabricating structural ceramics, including alumina-toughened zirconia (ATZ), heavily reliant on the rheological properties of the paste. The rheological properties of aqueous ATZ pastes with 25 wt% Pluronic® F127 hydrogel and solid loadings of 28–44 vol% were investigated, complemented by characterization of the parts, including relative density and shrinkage measurements, to assess the printability. The 42 vol% paste was identified as most suitable for producing high-density parts with minimal shrinkage. A controlled drying process gradually decreased humidity from 90% to 30% while raising temperature from 25 to 60°C over 4 days to prevent drying defects. Mechanical testing showed DIW-printed high-density (97.2±2.2%) parts with a mean flexural strength of 670±270 MPa, Vickers hardness of 13.6±2.8 GPa, and fracture resistance of 4.4±0.2 MPa, highlighting the potential for DIW to create high-density ATZ ceramic parts with favorable mechanical properties.

Multifunctional Cu2Se/F127 Hydrogel with SOD-Like Enzyme Activity for Efficient Wound Healing.

Free radicals are secreted following skin damage and cause oxidative stress and inflammatory reactions that increase the difficulty of wound healing. In this study, copper-based nanozyme Cu2Se nanosheets (NSs) are synthesized by an anion-exchange strategy and apply to wounds with F127 hydrogels to investigate the healing effect of this nanozyme composite hydrogels on wounds. Cu2Se NSs have a large number of catalytically active centers, are simple to synthesize, require few reaction conditions and have a short synthesis cycle. In vitro experiments have shown that Cu2Se NSs possess superoxide dismutase (SOD)-like activity and nitrogen radical scavenging activity and promote angiogenesis and fibroblast migration. The doping of Cu2Se NSs into the F127 hydrogel does not have a significantlyaffect on the properties of the hydrogel. This hybridized hydrogel not only adapts to the irregular and complex morphology of acute wounds but also prolongs the duration of nanozyme action on the wound, thus promoting wound healing. Transcriptomic analysis further reveals the potential therapeutic mechanism of the Cu2Se/F127 hydrogel in promoting acute wound healing. Animal experiments have shown that the Cu2Se/F127 hydrogel has good biosafety. The Cu2Se/F127 hydrogel provides an innovative idea for the development of hydrogel dressings for the treatment of acute wounds.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

Thermosensitive curcumin/silver/montmorillonite-F127 hydrogels with synergistic photodynamic/photothermal/silver ions antibacterial activity.

Bacterial infections and the emergence of super-resistant bacteria pose a significant risk to human health. Effective sterilization to prevent the development of bacterialdrug resistance remains a challenge. Herein, curcumin/silver/montmorillonite (Cur/Ag/Mt) was prepared through a green chemical reduction method with montmorillonite as the carrier, curcumin as the reducing agent and the capping agent, and citric acid as the structure guide agent. Then, a novel dual light-responsive and thermosensitive Pluronic F127-based hydrogel (CAM-F) was prepared by encapsulating Cur/Ag/Mt within the F127 hydrogel. The Cur/Ag/Mt showed strong absorption in the near-infrared region that efficiently converts light into heat for photothermal therapy when the molar ratio of curcumin to silver nitrate was 2 : 1. Specifically, triangular silver nanoparticles reduced by curcumin were immobilized on the Mt layers, which could enhance photodynamic therapy by the metal-enhanced singlet oxygen and metal-enhanced fluorescence mechanisms. Upon combining 405 nm and 808 nm laser irradiation, the CAM-F hydrogel could simultaneously generate reactive oxygen species, increase the local temperature, and sustain the release of Ag+, thus displaying excellent bactericidal performance against Gram-negative and Gram-positive bacteria. The antibacterial rates of CAM-F hydrogels were 99.26 ± 0.95% and 99.95 ± 0.98% for Escherichia coli and Staphylococcus aureus, respectively. The findings suggest the potential of the CAM-F hydrogel as a stable, biologically safe, and broad-spectrum antimicrobial material. The thermosensitive CAM-F hydrogels for synergetic phototherapy may provide a promising strategy for solving clinical problems caused by pathogenic infections.

Thermoresponsive and Injectable Pluronic F127 Hydrogel for Loading Adipose-Derived Mesenchymal Stem Cells.

Stem cell-based therapies display immense potential in regenerative medicine, highlighting the crucial significance of devising efficient delivery methods. This study centers on a pioneering approach that utilizes Pluronic F127 (PF127) as a thermoresponsive and injectable hydrogel designed for the encapsulation of adipose-derived mesenchymal stem cells (AdMSCs). The degradation profile, gelation time, and microstructure of the PF127 hydrogel were thoroughly examined. AdMSCs were isolated, expanded, and characterized based on their multi-lineage differentiation potential. AdMSCs from the third passage were specifically employed for encapsulation within the PF127 hydrogel. Subsequently, the cytotoxicity of the AdMSC-loaded PF127 hydrogel was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays. Characterized by scanning electron microscopy (SEM), the PF127 hydrogel exhibited a porous structure, indicating its suitability for accommodating AdMSCs and facilitating wound healing. The PF127 hydrogel demonstrated reversible phase transitions, rendering it suitable for in vivo applications. Studies on the gelation time of PF127 hydrogel unveiled a concentration-dependent decrease in gelation time, offering adaptability for diverse medical applications. Analysis of the degradation profile showcased a seven-day degradation period, leading to the decision for weekly topical applications. Cytotoxicity assessments confirmed that AdMSCs loaded into the PF127 hydrogel maintained heightened metabolic activity for up to one week, affirming the safety and appropriateness of the PF127 hydrogel for encapsulating cellular therapeutics. Furthermore, cell apoptosis assays consistently indicated low rates of apoptosis, emphasizing the viability and robust health of AdMSCs when delivered within the hydrogel. These findings underscore the vast potential of PF127 hydrogel as a versatile and biocompatible delivery system for AdMSCs in the realm of regenerative medicine. Boasting adjustable gelation properties and a remarkable capacity for cell encapsulation, this pioneering delivery system presents a promising path for applications in tissue engineering and wound healing. Ultimately, these advancements propel and elevate the landscape of regenerative medicine.

Interplay between yielding, 'recovery', and strength of yield stress fluids for direct ink writing: new insights from oscillatory rheology.

Formulation design and rheology are critical for successful manufacturing via direct ink writing (DIW), thus linking rheology and printability is a growing area of research amongst the DIW and rheology communities. This work provides an extensive rheological investigation into the material strength, yielding and 'recovery' properties of graphite (Gr)-hydrogel based formulations. Using state-of-the-art Large Amplitude Oscillatory Shear (LAOS) techniques, Fourier Transform (FT) rheology and sequence of physical process (SPP) analysis, and 3-step 'recovery' tests we provide new insights on the yielding phenomenon, energy transitions and microstructural changes that the formulations undergo. The insights from the rheology experiments are combined with in situ and continuous monitoring during the printing process. From these analyses, we select rheological metrics or descriptors to quantify flowability, recoverability, and material strength. There is a threshold concentration of Gr powders (30 wt%) at which there is a shift in the yielding process. Below this threshold (for the F127 hydrogel and mixtures with low Gr content), perfect plastic dissipation ratio (ϕ) values are close to 0 in the LVR and then steeply increase to close to 1 after the cross-over in a narrow strain (and stress) space. As Gr concentration increases, and print quality gets worse, ϕ values consistently increase in the LVR and at any given γ0, evidencing an increased energy dissipation throughout the flow transition region. Lissajous-Bowditch curves and SPP Cole-Cole plots illustrate these trends. The extent of the 'recovery' (quantified by the mutation time, λI, and the storage modulus 'recovered' after large deformations ) is also directly related to Gr content, with higher loading resulting in lesser recovery. Our findings provide a comprehensive set of metrics to characterise complex (yield stress) fluids for DIW using three property maps, one for each stage: flowability or yielding process, recoverability and material strength. The results demonstrate that considering these three maps holistically provides insightful trends to guide formulation design and assess performance in DIW.

Temperature-dependent yield stress and wall slip behaviour of thermoresponsive Pluronic F127 hydrogels.

This study explores the temperature-dependent dynamic yield stress of a triblock thermoresponsive polymer, Pluronic F127, with chemical structure (PEO)100(PPO)65(PEO)100, during the sol-gel transition. The yield stress can be defined as static, dynamic, or elastic, depending on the experimental protocol. We examine the dynamic yield stress estimation for this study, which usually entails utilizing non-Newtonian models like the Herschel-Bulkley (HB) or Bingham models to extrapolate the flow curve (shear rate against shear stress). Initially, we determine the yield stress using the HB model. However, apparent wall slip makes it difficult to calculate yield stress using conventional methods, which could lead to underestimates. To validate the existence of apparent wall slip in our trials, we carry out meticulous experiments in a range of rheometric geometries. To determine the true yield stress corrected for slip, we first use the traditional Mooney method, which requires labor-intensive steps and large sample sizes over various gaps in the parallel plate (PP) design. To overcome these drawbacks, we use a different strategy. We modify the Windhab model equation by adding slip boundary conditions to the HB equation, which allowed us to calculate the slip yield stress in addition to the true yield stress. In contrast to other typical thermoresponsive polymers like poly(N-isopropyl acrylamide) (PNIPAM), our findings demonstrate that PF127's yield stress obeys the Boltzmann equation and increases with temperature.

A tissue-adhesive F127 hydrogel delivers antioxidative copper-selenide nanoparticles for the treatment of dry eye disease

Dry eye disease (DED) is currently the most prevalent condition seen in ophthalmology outpatient clinics, representing a significant public health issue. The onset and progression of DED are closely associated with oxidative stress-induced inflammation and damage. To address this, an aldehyde-functionalized F127 (AF127) hydrogel eye drop delivering multifunctional antioxidant Cu2−xSe nanoparticles (Cu2−xSe NPs) was designed. The research findings revealed that the Cu2−xSe nanoparticles exhibit unexpected capabilities in acting as superoxide dismutase and glutathione peroxidase. Additionally, Cu2−xSe NPs possess remarkable efficacy in scavenging reactive oxygen species (ROS) and mitigating oxidative damage. Cu2−xSe NPs displayed promising therapeutic effects in a mouse model of dry eye. Detailed investigation revealed that the nanoparticles exert antioxidant, anti-apoptotic, and inflammation-mitigating effects by modulating the NRF2 and p38 MAPK signalling pathways. The AF127 hydrogel eye drops exhibit good adherence to the ocular surface through the formation of Schiff-base bonds. These findings suggest that incorporating antioxidant Cu2−xSe nanoparticles into a tissue-adhesive hydrogel could present a highly effective therapeutic strategy for treating dry eye disease and other disorders associated with reactive oxygen species. Statement of significanceA new formulation for therapeutic eye drops to be used in the treatment of dry eye disease (DED) was developed. The formulation combines copper-selenium nanoparticles (Cu2-xSe NPs) with aldehyde-functionalized Pluronic F127 (AF127). This is the first study to directly examine the effects of Cu2-xSe NPs in ophthalmology. The NPs exhibited antioxidant capabilities and enzyme-like properties. They effectively eliminated reactive oxygen species (ROS) and inhibited apoptosis through the NRF2 and p38 MAPK signalling pathways. Additionally, the AF127 hydrogel enhanced tissue adhesion by forming Schiff-base links. In mouse model of DED, the Cu2-xSe NPs@AF127 eye drops demonstrated remarkable efficacy in alleviating symptoms of DED. These findings indicate the potential of Cu2-xSe NPs as a readily available and user-friendly medication for the management of DED.

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

E2-Loaded Microcapsules and Bone Marrow-Derived Mesenchymal Stem Cells with Injectable Scaffolds for Endometrial Regeneration Application.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been recognized as new candidates for the treatment of serious endometrial injuries. However, owing to the local microenvironment of damaged endometrium, transplantation of BMSCs yielded disappointing results. In this study, Pectin-Pluronic® F-127 hydrogel as scaffolds were fabricated to provide three-dimensional architecture for the attachment, growth, and migration of BMSCs. E2 was encapsulated into the W/O/W microspheres to construct pectin-based E2-loaded microcapsules (E2 MPs), which has the potential to serve as a long-term reliable source of E2 for endometrial regeneration. Then, the BMSCs/E2 MPs/scaffolds system was injected into the uterine cavity of mouse endometrial injury model for treatment. At 4 weeks after transplantation, the system increased proliferative abilities of uterine endometrial cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive an embryo, suggesting that the BMSCs/E2 MPs/scaffolds system is a promising treatment option for endometrial regeneration. Furthermore, the mechanism of E2 in promoting the repair of endometrial injury was also investigated. Exosomes are critical paracrine mediators that act as biochemical cues to direct stem cell differentiation. In this study, it was found that the expression of endometrial epithelial cell (EEC) markers was upregulated in BMSCs treated by exosomes secreted from endometrial stromal cells (ESCs-Exos). Exosomes derived from E2-stimulated ESCs further promoted the expression level of EECs markers in BMSCs, suggesting exosomes released from ESCs by E2 stimulation could enhance the differentiation efficiency of BMSCs. Therefore, exosomes derived from ESCs play paracrine roles in endometrial regeneration stimulated by E2 and provide optimal estrogenic response.

Comparative Evaluation of Masson's Trichrome and Picrosirius Red Staining for Digital Collagen Quantification Using ImageJ in Rabbit Wound Healing Research

The therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for repairing full-thickness skin wounds was evaluated using a rabbit model. The rabbits were randomly divided into eight groups with six animals each and treatment was given as per the predetermined protocol (3 doses at one-week interval): Group A (Control), Group B (AdSVF), Group C (AdMSC), Group D (AdMSC-CM), Group E (PF127), Group F (AdSVF + PF127), Group G (AdMSC + PF127), and Group H (AdMSC-CM + PF127). Skin tissue samples were collected from the healing wounds on day 28 for staining and collagen quantification. Collagen density (Area %) was quantified using tissue sections stained with Masson's Trichrome (MT) and Picrosirius Red (PSR) stain using the Colour Deconvolution plugin of ImageJ and RGB stack method, respectively. These techniques function based on separating different colour channels in the stained tissue sections to isolate the collagen fibers and then quantifying them through thresholding and image analysis. Across the treatment groups, both staining methods generally showed a trend of increased collagen density compared to the control group. For most groups, PSR staining consistently indicated slightly lower collagen densities than MT staining. However, the overall trends were similar in both staining. The comparison between PSR and MT staining methods revealed that both techniques effectively assess collagen density in healing wounds. However, there were subtle differences in the absolute values obtained, with PSR staining tending to yield slightly lower collagen density measurements than MT. These differences can be attributed to the distinct mechanisms of these staining methods. Therefore, both staining methods can digitally quantify collagen density in wound healing research.

Engineered Microcystis aerugiosa Hydrogel as an Anti‐Tumor Therapeutic by Augmenting Tumor Immunogenicity and Immune Responses

AbstractCancer immunotherapy holds great promise but is generally limited by insufficient induction of anticancer immune responses. In this work, Microcystis aerugiosa (MA) is observed to act as an immune stimulator, which activates the cGAS‐STING and IRF‐signaling pathways of dendritic cells (DCs), induces immunostimulatory factors production, eventually resulting in the death of tumor cells by promoting cytotoxic CD8+ T cells infiltration. To further enhance the tumor immunogenicity, MA is engineered with polydopamine (PDA) and assembled in injectable Pluronic F127 hydrogels (denoted as MA@PDA‐F127). The introduction of PDA endows the MA@PDA‐F127 with photothermal therapy capability, which enhances the immunogenicity by in situ exposing damage‐associated molecular patterns and tumor antigens from dying tumor cells. Importantly, the surface‐rich reaction sites in thermosensitive MA@PDA‐F127 hydrogels capture antigens, facilitating long retention of antigens exposure and enhancing DCs maturation for advanced anti‐tumor immune response. Accordingly, in situ administration of MA@PDA‐F127 hydrogels in a single dose achieves efficient eradication of both primary and distant tumors in an orthotopic tumor metastasis model. Furthermore, this hydrogel can sensitize immune checkpoint inhibitor therapy and enhance T cell infiltration in a murine tumor model. Collectively, MA@PDA‐F127 hydrogel offers an effective anti‐tumor therapeutic by augmenting tumor immunogenicity and activating a systematic immune response.