Tissue Adhesives Research Articles

Conductive Hyaluronic Acid/Deep Eutectic Solvent Composite Hydrogel as a Wound Dressing for Promoting Skin Burn Healing Under Electrical Stimulation.

Burns can cause severe damage to the skin due to bacterial infection and severe inflammation. Although conductive hydrogels as electroactive burn-wound dressings achieve remarkable effects on accelerating wound healing, issues such as imbalance between their high conductivity and mechanical properties, easy dehydration, and low transparency must be addressed. Herein, a double-network conductive eutectogel is fabricated by integrating polymerizable deep eutectic solvents (PDESs)including acrylamide/choline chloride/glycerol (acrylamide-polymerization crosslink) and thiolated hyaluronic acid (disulfide-bonding crosslink). The introduction of PDESs provides the eutectogel with a conductivity (up to 0.25 S·m-1) and mechanical strength (tensile strain of 59-77%) simulating those of natural human skin, as well as satisfactory tissue adhesiveness, self-healing ability, and antibacterial properties. When combined with exogenous electrical stimulation, the conductive eutectogel exhibits the ability to reduce inflammation, stimulate cell proliferation and migration, promote collagen deposition and angiogenesis, and facilitate skin tissue remodeling. This conductive eutectogel shows great potential as a dressing for healing major burn wounds.

Effect of Tannic Acid Concentrations on Temperature-Sensitive Sol-Gel Transition and Stability of Tannic Acid/Pluronic F127 Composite Hydrogels.

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Cartilage Decellularized Extracellular Matrix-Based Hydrogel with Enhanced Tissue Adhesion and Promoted Chondrogenesis for Cartilage Tissue Engineering

Cartilage Decellularized Extracellular Matrix-Based Hydrogel with Enhanced Tissue Adhesion and Promoted Chondrogenesis for Cartilage Tissue Engineering

Protamine-grafted carboxymethyl chitosan based hydrogel with adhesive and long-term antibacterial properties for hemostasis and skin wound healing

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 μm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.

A Wood-Derived Periosteum for Spatiotemporal Drug Release: Boosting Bone Repair through Anisotropic Structure and Multiple Functions.

Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA)binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDAcoating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.

Synthesis and Analysis of Novel Hyaluronic Acid-Based Dual Photocrosslinkable Tissue Adhesive: An In Vitro Study.

Background Tissue adhesives are mainly used for aiding in the attachment of adjacent tissues or to nearby hard tissue surfaces. They promote the natural healing processes of the tissues, especially for less painful closure, simple application, no need for sutures following surgery, and localized drug release. This study aimed to synthesize and assess the properties of hyaluronic acid (HA)-based, dual photocrosslinkable tissue adhesive. Materials and methodology N-hydroxysuccinimide (NHS), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), HA, and polymethylmethacrylate, which served as a photoinitiator, were combined to synthesize a tissue adhesive. The prepared formulation was characterized, and its biocompatibility was assessed. Results Surface morphology, mechanical properties, and biological properties of the HA adhesive were comparable to those of conventional fibrin glue. Scanning electron microscopy (SEM) analysis showed the average size of the molecules, 10-25 mm in diameter, and also showed a smooth and nonporous surface. The specimens experienced maximum compressive stress of 0.06 ± 0.02 MPa, compressive strain of 3.07 ± 2.02, and a compressive displacement at break of 3.04 ± 1.23 mm, with a maximum force of 2.33 ± 0.07 N at break. The cytotoxicity assay results for HA and fibrin glue are almost equal. Conclusion HA-based photocrosslinkable tissue adhesive could be a potential biomaterial in various applications in the field of medicine, especially in soft tissue management.

Hemoadhican-Based Bioabsorbable Hydrogel for Preventing Postoperative Adhesions.

Postoperative peritoneal adhesions are a prevalent clinical issue following abdominal and pelvic surgery, frequently resulting in heightened personal and societal health burdens. Traditional biomedical barriers offer limited benefits because of practical challenges for doctors and their incompatibility with laparoscopic surgery. Hydrogel materials, represented by hyaluronic acid gels, are receiving increasing attention. However, existing antiadhesive gels still have limited effectiveness or carry the risk of complications in clinical applications. Herein, we developed a novel hydrogel using polysaccharide hemoadhican (HD) as the base material and polyethylene glycol diglycidyl ether (PEGDE) as the cross-linking agent. The HD hydrogels exhibit appropriate mechanical properties, injectability, and excellent cytocompatibility. We demonstrate resistance to protein adsorption and L929 fibroblast cell adhesion to the HD hydrogel. The biodegradability and efficacy against peritoneal adhesion are further evaluated in C57BL/6 mice. Our results suggest a potential strategy for anti-postoperative tissue adhesion barrier biomaterials.

Facile synthesis of mechanically robust and injectable tetra-polyethylene glycol/methacrylate chitosan double-network hydrogel cartilage repair

The development of advanced hydrogel scaffolds with good biocompatibility, mechanical strength and bioactive property is highly desirable in cell growth, proliferation, and differentiation for the cartilage tissue regeneration. Herein, we reported a simple, inexpensive, feasible, and environmentally benign strategy to synthesize a biocompatible polyethylene glycol-based methacrylate-modified chitosan (PCSMA) double network (DN) hydrogel via the reversible Schiff base reaction and successive photopolymerization between the tetra-poly (ethylene glycol) aldehyde (Tetra-PEG-CHO) and methacrylate-modified chitosan (CSMA) in mild conditions. The four-terminated CHO groups were hypothesized to not only construct the whole architectural network through the dynamic pH-responsive Schiff base but also contribute to the injectable behavior and good tissue adhesion, which may furnish the surgeon with the availability of injectable and shapeless ability to fill in the gaps. Compared to the single PCS hydrogel with the main similar components of the tetra-PEG-CHO and pure CS moieties, the post-fabrication of PCSMA DN hydrogel possessed slower degradation time, denser network, and stronger mechanical stability, which could facilitate the bone marrow mesenchymal stem cell (BMSCs) activity and promote the chondrogenic differentiation for facilitating cartilage regeneration. Our study highlights the positive effects on chondrogenic performance and supports the PCSMA hydrogel as a promising tissue-engineered scaffold for the cartilage defect repair.

STING Membrane Prevents Post-Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer.

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.

A Case Report of Superficial Solitary Fibrous Tumor in the Right Parotideomasseteric Region.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that occur in various soft tissues and organs throughout the body. Superficial SFTs in the head and neck region are uncommon and reports of such cases are limited. An elderly Japanese woman in her 80s presented to our clinic with a smooth mass in the right parotideomasseteric region. Ultrasonography and magnetic resonance imaging revealed a well-defined subcutaneous mass measuring 20 mm. For a definitive diagnosis and treatment, surgical resection was performed under local anesthesia. Intraoperatively, a brown-colored tumor was identified beneath the skin, without surrounding tissue adhesion, and was completely excised. Immunohistochemistry, revealing the expression of STAT6, confirmed the diagnosis of SFT. Based on the SFT risk classification, this case was classified into the low-risk group, and no recurrence occurred during the 4 year postoperative period. According to the 2020 World Health Organization Classification of Soft Tissue Tumors, SFTs belong to the intermediate category with recurrence potential. In previous studies, cases of positive margins and recurrence have been reported in superficial SFTs, and SFTs may show benign features on clinical presentation but require precise surgical manipulation. Therefore, it is crucial for otolaryngologists to gain a comprehensive understanding of this tumor for appropriate treatment.

Dual-layer conduit containing VEGF-A – Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significanceNerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair.This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.

A Nature-Derived, Hetero-Structured, Pro-Healing Bioadhesive Patch for High-Performance Sealing of Wet Tissues.

Tissue adhesives are promising alternatives to sutures and staples to achieve wound closure and hemostasis. However, they often do not work well on tissues that are soaked in blood or other biological fluids, and organs that are typically exposed to a variety of harsh environments such as different pH values, nonhomogeneous distortions, continuous expansions and contractions, or high pressures. In this study, a nature-derived multilayered hetero-bioadhesive patch (skin secretion of Andrias davidianus (SSAD)-Patch) based on hydrophilic/hydrophobic pro-healing bioadhesives derived from the SSAD is developed, which is designed to form pressure-triggered strong adhesion with wet tissues. The SSAD-Patch is successfully applied for the sealing and healing of tissue defects within 10 s in diverse extreme injury scenarios in vivo including rat stomach perforation, small intestine perforation, fetal membrane defect, porcine carotid artery incision, and lung lobe laceration. The findings reveal a promising new type of self-adhesive regenerative SSAD-Patch, which is potentially adaptable to broad applications (under different pH values and air or liquid pressures) in sutureless wound sealing and healing.

The Influence of Wound Closure Techniques after Surgical Decompression in Patients with Carpal Tunnel Syndrome on Sleep Disturbance and Life Quality: A Prospective Comparison of Surgical Techniques.

The compression of the median nerve within the carpal tunnel is the cause of carpal tunnel syndrome (CTS). Surgical decompression is successful in improving sleep and quality of life, but the effect of tissue adhesives as a material for wound closure has not been investigated. The objective of the study was to evaluate sleep disorders and health-related life quality by comparing two methods for wound closure after carpal surgery in participants who were randomized to receive tissue adhesives or transcutaneous sutures. The subjects, aged 61.56 ± 12.03 years, were randomized to receive either tissue adhesives (n = 50) or suture-based wound closure (n = 50) using the Glubran Tiss 2® skin adhesive after subcutaneous running sutures. The outcomes were assessed during the 12-month postoperative follow-up. The Pittsburgh Sleep Quality Index (PQSI) and Insomnia Severity Scale (ISI) were used for the sleep disturbance assessment, and for the health-related quality of life assessment, the total SF-36 (36-Item Short Form Survey) was used. The PQSI, ISI, and SF-36 were not statistically different between groups during the follow-up, except in the ISI score two weeks after surgery (9.40 ± 1.18 in the tissue adhesive group vs. 9.96 ± 1.09 in the suture-based group, p = 0.008). The PQSI, ISI, and SF-36 scores for all the subjects and groups were persistently improved at all the follow-up intervals after surgery. The total SF-36 score increased 12 months after surgery (49.84 ± 5.85 vs. 82.46 ± 5.68, p < 0.001). Cyanoacrylate-based adhesion material can be used for wound closure after open CTS decompression as a standard transcutaneous suture, and both techniques equally lead to improved sleep and life quality. The possible advantages of tissue adhesives include a faster reduction in the ISI.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Type of Prior Operation Does Not Predict Surgical Intervention for Small Bowel Obstruction.

Background: Patients with prior abdominal surgeries are at higher risk for intra-abdominal adhesive tissue formation and subsequently higher risk for small bowel obstruction (SBO).Purpose: In this study, we investigated whether surgical intervention for SBO was more likely following specific types of abdominal surgeries.Research Design: With retrospective chart review, we pooled data from 799 patients, ages 18 to 89, admitted with SBO between 2012 and 2019. Patients were evaluated based on whether they underwent surgery or were managed conservatively. They were further compared with regard to past surgical history by way of type of abdominal surgery (or surgeries) undergone prior to admission.Results: Of the 799 patients admitted for SBO, 206 underwent surgical intervention while 593 were managed nonoperatively. There was no significant difference in number of prior surgeries (2.07±1.56 vs 2.36±2.11,P = .07) or in number of comorbidities (2.39±1.97 vs 2.65±1.93,P= .09) for surgical vs non-surgical intervention. Additionally, of the operations evaluated, no specific type of abdominal surgery predicted need for surgical intervention in the setting of SBO. However, for both surgical and non-surgical intervention following SBO, pelvic surgery was the most common type of prior abdominal surgery (45% vs 43%). There are significantly more female pelvic surgeries in both the operative (91.4% vs 8.6%,P< .0001) and nonoperative groups (89.9% vs 10.2%,P< .0001).Conclusion: Ultimately, no specific type of prior operation predicted the need for surgical intervention in the setting of SBO.

Naturally Derived Injectable Dual-Cross-Linked Adhesive Hydrogel for Acute Hemorrhage Control and Wound Healing.

Developing biocompatible injectable hydrogels with high mechanical strength and rapid strong tissue adhesion for hemostatic sealing of uncontrolled bleeding remains a prevailing challenge. Herein, we engineer an injectable and photo-cross-linkable hydrogel based on naturally derived gelatin methacrylate (GelMA) and N-hydroxysuccinimide-modified poly(γ-glutamic acid) (γPGA-NHS). The chemically dual-cross-linked hydrogel rapidly forms after UV light irradiation and covalently bonds to the underlying tissue to provide robust adhesion. We demonstrate a significantly improved hemostatic efficacy of the hydrogel using various injury models in rats compared to the commercially available fibrin glue. Notably, the hydrogel can achieve hemostasis in porcine liver and spleen incision, and femoral artery puncture models. Moreover, the hydrogel is used for sutureless repair of the liver defect in a rat model with a significantly suppressed inflammatory response, enhanced angiogenesis, and superior healing efficacy compared to fibrin glue. Together, this study offers a promising bioadhesive for treating severe bleeding and facilitating wound repair.

Triple threat: how diabetes results in worsened bacterial infections.

Diabetes mellitus, characterized by impaired insulin signaling, is associated with increased incidence and severity of infections. Various diabetes-related complications contribute to exacerbated bacterial infections, including hyperglycemia, innate immune cell dysfunction, and infection with antibiotic-resistant bacterial strains. One defining symptom of diabetes is hyperglycemia, resulting in elevated blood and tissue glucose concentrations. Glucose is the preferred carbon source of several bacterial pathogens, and hyperglycemia escalates bacterial growth and virulence. Hyperglycemia promotes specific mechanisms of bacterial virulence known to contribute to infection chronicity, including tissue adherence and biofilm formation. Foot infections are a significant source of morbidity in individuals with diabetes and consist of biofilm-associated polymicrobial communities. Bacteria perform complex interspecies behaviors conducive to their growth and virulence within biofilms, including metabolic cross-feeding and altered phenotypes more tolerant to antibiotic therapeutics. Moreover, the metabolic dysfunction caused by diabetes compromises immune cell function, resulting in immune suppression. Impaired insulin signaling induces aberrations in phagocytic cells, which are crucial mediators for controlling and resolving bacterial infections. These aberrancies encompass altered cytokine profiles, the migratory and chemotactic mechanisms of neutrophils, and the metabolic reprogramming required for the oxidative burst and subsequent generation of bactericidal free radicals. Furthermore, the immune suppression caused by diabetes and the polymicrobial nature of the diabetic infection microenvironment may promote the emergence of novel strains of multidrug-resistant bacterial pathogens. This review focuses on the "triple threat" linked to worsened bacterial infections in individuals with diabetes: (i) altered nutritional availability in diabetic tissues, (ii) diabetes-associated immune suppression, and (iii) antibiotic treatment failure.

Multifunctional PDA/ZIF8 based hydrogel dressing modulates the microenvironment to accelerate chronic wound healing by ROS scavenging and macrophage polarization

An ideal wound dressing has both efficient antimicrobial and anti-inflammatory properties, as well as the potential to regulate the immune microenvironment for the treatment of chronically infected wounds. Herein, a novel multifunctional hydrogel wound dressing (HPZ8) was developed for wound healing by incorporating polydopamine Zeolite Imidazole Framework 8 (PDA-ZIF8) nanoparticles into a dynamic cross-linked network consisting of hydrazide-modified hyaluronic acid (HA-CDH) and oxidized hyaluronic acid (HA-CHO). The results suggested that the HPZ8 hydrogel could be injected into the wound to form a barrier, facilitating tissue adhesion and rapid hemostasis. After loaded with PDA-ZIF8 nanoparticles, the hydrogel exhibited excellent antioxidant and photothermal antimicrobial properties, which could effectively scavenge ROS, reduce oxidative stress and eliminate bacterial infections. Especially, near-infrared (NIR) irradiation strengthened the photothermal therapy (PTT). Besides, HPZ8 hydrogel could release zinc ions to promote cell migration, angiogenesis and M2 polarization of macrophages, accelerating macrophage transition from inflammation to proliferation stages, thus promoting infected wound healing. Therefore, the HPZ8 multifunctional hydrogel dressing has application prospects for the therapy of chronic infected wounds.

Abstract 6604: Spatial transcriptomics delineates tumor heterogeneity in NACT triple-negative breast cancer

Abstract BACKGROUND: Triple-Negative Breast Cancer (TNBC) is a highly aggressive subtype of breast cancer and only ~40% of TNBC patients achieve a pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Since molecular heterogeneity of TNBC may contribute to variable responses to NACT, we aimed to deconvolute TNBC’s histological and spatial transcriptomics (ST) patterns. METHODS: In total, 90 pre-treatment biopsies were collected from NACT-treated TNBC patients from archival samples and the ongoing FORCE (NCT03238144) clinical trial at Guy’s Hospital, London, UK. Of these, 38 achieved pCR (Responder), 46 had residual disease (Non-Responder) whilst 6 are currently undergoing NACT; 46 post-treatment surgical resections were collected from Non-Responders.Each sample was H&amp;E stained, imaged, and annotated by a pathologist. A 6-digit classifier was designed to capture the histology of each region of interest (ROI), characterizing the tumour region, epithelial type and immune cell localization, population, distribution, and abundance.H&amp;Es were used to guide ST profiling of serial sections which was performed on the GeoMx Digital Spatial Profiler. Tissues were stained with fluorescent antibodies against PanCK and CD45 to visualize the tissue, select ROIs and illuminate spatially resolved tumor and immune-enriched compartments, defined as PanCK+/CD45- and PanCK-/CD45+, respectively.Data analysis was performed in R 4.3.1 using the limma, dplyr, EdgeR, GeoMx Tools, GeoMx Workflows, RUV4, Spatial Experiment, SpatialDecon and GSVA packages, facilitating quality control, batch correction, differential and topographical gene expression, immune cell deconvolution and gene set enrichment analysis (GSEA), respectively. RESULTS: To date, we have performed ST profiling of 120 TNBC samples from 82 patients (46 Non-Responders; 36 Responders), totaling 3917 tumor or immune-cell enriched regions. Preliminary analyses revealed KEGG pathways involved in tissue adhesion are upregulated in tumor compartments of Non-Responders compared to Responders, whilst those involved in genomic integrity are suppressed. Unsupervised clustering of PanCK+CD45- regions in Non-Responders identified tumor clusters present in both pre- and post-NACT samples, suggesting potential chemo-resistant properties. Moreover, immune cell deconvolution of the PanCK-/CD45+ regions revealed spatially distinct patters of immune cell composition mapped to histological annotations identified by our ROI classifier. CONCLUSION: (S)Large scale ST of TNBC before and after NACT reveals novel patterns associated with response to treatment. We have designed a novel ROI classifier to spatially resolved transcriptomes of histological features, as such provide an in-depth characterization of the histo-genomics of TNBC. Citation Format: Isobelle Wall, Jelmar Quist, Sarah Pinder, KCL Cancer Biobank, Sheeba Irshad, Cheryl Gillet, Victoria Seewaldt, Kavitha Mukund, David Frankhouser, Shankar Subramaniam, Maddy Parsons, Anita Grigoriadis. Spatial transcriptomics delineates tumor heterogeneity in NACT triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6604.

ANALYSIS OF SKIN SCARRING WITH PRE-, INTRA- AND DELAYED SURGICAL INJECTION THERAPY: THE PRECLINICAL RESEARCH

Purpose: Experimental testing of injection therapy in the area of the upcoming skin incision in order to improve the quality of achieving the aesthetic appearance of the skin scarring process. Materials and methods: The study was carried out on the skin of the sternum and anterior abdominal wall on 2 closely related minipigs.3 series of operations were carried out synchronously on two individuals in a surgical operating room with preliminary specific markings in the form of rectangles and trapezoids, respectively; the nipple-areolar complexes served as a guide for drawing the figures. At each stage, the same type of geometric marking of the surgical field was used and repeated interventions were performed in the same areas of injection therapy and biopsy sampling. In the postoperative period, on the 30th and 120th days, biopsy specimens were taken to verify the ongoing reparative processes based on clinical, photometric and histological analysis. Results: Preoperative injection therapy contributed to the formation of a normotrophic scar in structure closer to normal skin compared to a scar during normal tissue healing, which allows it to be recommended for preoperative preparation and for research in humans. The selected technique allows for assessment of the classic primary wound, with the introduction of saline and botulinum toxin intraoperatively and delayed at 1 and 4 months with histological analysis of the results. At each stage of the experiment, the team achieved long-term survival of minipigs without compromising their vital functions. The same type of geometric marking of the surgical field was used and repeated interventions were performed in the same areas of injection therapy and biopsy sampling. Conclusion: The methodology allows to assess different methods of linear scar formation with or without the use of injection therapy during surgical access, as well as comparing tissue adhesion histologically and optimal scar formation. When the effectiveness of BTA therapy is achieved, injection therapy requires further research under conditions of tissue deficit or tension during wound closure.