Transforming growth factor beta 3 (TGF-β3) is a homodimeric cytokine with potential therapeutic applications in wound healing, tissue engineering and regenerative medicine. Production of recombinant TGF-β3 in Escherichia coli faces significant challenges due to TGF-β3's propensity for misfolding and aggregation, driven by a high disulfide bond content and low aqueous solubility. To address these limitations, the impacts of substituting non-conserved cysteine residues C7, C16 and C77 with serine on TGF-β3 folding, dimerization and activity were investigated. Whilst C7 and C16 form an intra-chain disulfide bond, C77 forms an inter-chain disulfide bond stabilizing dimer formation. Our results showed that the C7S, C16S double cysteine mutant protein exhibited reduced aggregation, increased dimer formation, and maintained wild-type biological activity in nano-luciferase reporter gene assay. In contrast, both C77S single and C7S, C16S, C77S triple mutants were purified predominantly in monomeric forms and displayed about 2.5-fold reduced activities. Our findings highlight the roles of the non-conserved C7, C16 and C77 cysteine residues in TGF-β3 folding and aggregation. The identification of the C7S, C16S mutant as a more soluble protein with wild-type TGF-β3 activity offers a promising strategy for improving recombinant TGF-β3 production to facilitate therapeutic applications. This study underscores the importance of targeted cysteine engineering to overcome the inherent challenges associated with the production of TGF-β3 and related complex disulfide-rich proteins.

Secondary cleft lip deformities (SCLD) are common, diverse, and individually unique due to their multifactorial etiology and varied clinical presentation. They are the result of postoperative complications of primary cleft lip repair, such as lip dehiscence, delayed wound healing, hematoma, infection, trauma, suture abscesses, poor operative planning, and inadequate surgical technique. The broad spectrum of these deformities and the absence of a standardized stratification framework necessitated the development of a comprehensive and universally applicable classification system. This system was designed to provide a simplified, consistent approach to identifying and categorizing residual cleft deformities. By doing so, it enhances communication among cleft care providers and facilitates the planning and execution of appropriate corrective procedures. The proposed classification organizes SCLD into 5 types (type I to V) based on the anatomic structures involved: skin, mucosa, orbicularis oris muscle, nose, and premaxilla. Each type corresponds to a specific pattern of tissue involvement and is associated with a tailored surgical approach described in this chapter. A careful preoperative assessment using this classification system significantly improves surgical planning, guides anesthetic considerations, ensures more accurate time and resource allocation, and promotes effective interdisciplinary communication.

β-Nicotinamide mononucleotide prevents senescence and lipid accumulation in hepatic stellate cells by restoring SIRT1 function.

Mesenchymal stem/stromal cells (MSCs) are known to secrete wound healing factors. However, the delivery of the MSCs and their secretomes remains a barrier to the development of a successful regenerative medicine. Therefore, we examined the content and paracrine activity of serum free MSC conditioned media (MSC CM) generated in routine tissue culture and when cultured on a plasma polymerized membrane previously used clinically in cell therapies for skin wounds. Serum free MSC CM from murine and human MSC cultures were subjected to proteomic analysis by mass spectrometry and quantitative immunoassays and their paracrine effects were tested on dermal fibroblasts in vitro. MSC CM contained multiple wound healing factors, including extracellular matrix proteins and soluble factors. MSC CM harvested from flask cultures and plasma polymerized membrane cultures significantly increased dermal fibroblast adhesion, proliferation, and scratch wound closure (for mouse MSC CM) compared to control media. This study has: (i) shown that MSC secreted factors increased dermal fibroblast activities seen in wound healing; (ii) identified target factors potentially responsible for these paracrine effects; (iii) shown that MSC secretomes generated on a plasma polymerized membrane used in skin cell therapies also have wound healing paracrine effects.

Phyto-fabricated gold nanoparticles and heterologous platelet-rich fibrin potentiates cutaneous wound healing dynamics in canines.

Post-traumatic wound management is a critical issue that needs to be addressed. Chitosan (CS) with inherent biocompatibility and biodegradability is widely applied in wound healing, but the products of CS often suffer from poor water solubility and mechanical strength. Herein, we developed new double-crosslinked CS-based cryogels. Firstly, glycidyl methacrylate (GMA) was used to modify CS for the crosslinking of double bonds, followed by further crosslinking with 1,4-butanediol diglycidyl ether (BDDE). A series of CS-based cryogels were prepared by adjusting the concentration of CS from 2wt% to 4wt% and the content of BDDE from 0.1vol% to 0.4vol%. The CS-based cryogels demonstrated enhanced mechanical properties as the concentration of CS increased, higher swelling capacity as the content of BDDE increased and potent antioxidant activity around 80%. The CS-based cryogels exhibited broad-spectrum antibacterial performance, with antibacterial rates over 90% against both S. aureus and E. coli. Cytotoxicity and hemolysis assays confirmed the biocompatibility and hemocompatibility of the cryogels. The CS-based cryogels reduced blood loss in mice tail amputation models and accelerated tissue regeneration in full-thickness wound models demonstrating potential for clinical application. Among them, the CS3-GB3 cryogel demonstrated the most effective promotion of wound healing.

Cell migration plays a fundamental role in numerous physiological processes, including embryonic development, wound healing, and cancer metastasis. While cell-cell adhesion is known to regulate motion by shaping cell morphology and intercellular force balance, its dynamic, rate-dependent contributions to tissue behavior remain poorly understood. In this study, we examine how the dissipative nature of cell-cell adhesion influences tissue dynamics and collective migration using an extended vertex model with explicit junctional viscosity. Our findings reveal a nontrivial interplay between two distinct components of adhesion: an interfacial adhesion energy (energetic, rate-independent) contribution, which sets the effective junctional tension, and a dissipative (rate-dependent) contribution, which controls resistance to relative motion during cell rearrangements. We show that increasing the energetic component promotes migration by modifying cell shape and lowering the barrier to neighbor exchanges, whereas strengthening the dissipative component induces jamming and suppresses cell motion. Linear rheological analysis further demonstrates that, in the unjammed regime, vertex-model tissues exhibit power-law viscoelastic behavior, with adhesion modulating the power-law exponent and thereby controlling the spread of relaxation timescales. Together, these findings clarify the dual role of adhesion in governing tissue mechanics and rheology and provide a mechanistic framework for understanding the balance between fluidity and rigidity in epithelial monolayers.

The aim of this study was to evaluate the novel rhein derivative Y01 for its anti-HCC activity and potential molecular mechanisms, thereby positioning it as a promising candidate for HCC therapy. CCK-8, EdU incorporation and clone formation assay were employed to assess the impact of Y01 on the cell viability and proliferation of HCC cells. While apoptosis was assessed through flow cytometry and western blotting techniques. Additionally, the impact of Y01 on cell mobility was evaluated via wound healing and transwell migration assays, with western blotting analyses providing further insights. Mechanistically, transcriptomics and western blotting assays were used to explore the potential signaling pathways. Y01 markedly suppressed the growth, colony formation, and migratory capacity of HCC cells, induced apoptosis and affected the expression of apoptosis-related proteins. Transcriptomics initially pointed toward the PI3K/AKT/mTOR pathway as a potential target, which was corroborated by western blotting results showing decreased levels of phosphorylated PI3K, AKT, and mTOR following Y01 treatment, highlighting its role in mediating the compound's anticancer effects. Y01 inhibited the proliferation, migration, and induced apoptosis of HCC cells possibly by blocking PI3K/AKT/mTOR signaling pathway.

On-demand degradation: A design principle for next-generation tissue adhesives.

Janus interfaces consist of chemically asymmetric surfaces that give rise to asymmetric wettability and interfacial transport phenomena. This literature review delves into the current state of Janus materials, encompassing their design principles and fabrication methods such as electrospinning, plasma treatment, dip coating, and spray coating, as well as the underlying mechanisms that govern their unique properties. We consider their innovative uses in the fields of biological medicine, including advanced wound dressings that help in wound healing through the interactive management of exudates, wearable sensors to track real-time sweat biomarkers, and personal thermal management fabrics. We also present the advanced applications of Janus materials in industrial studies, such as oil-water separation, fog harvesting, and desalination. These applications leverage asymmetric wettability to achieve selective permeability and improve interfacial interactions. Moreover, we address the existing issues in scalability and long-term stability and provide a vision for the future trends, such as real-world testing and cross-disciplinary collaborations. This review aims to integrate basic materials science knowledge and applied research to develop interdisciplinary innovations for sustainable, smart solutions in biomedical and industrial contexts.

A potent antioxidant and antimicrobial caffeic acid-Cu2+ crosslinked gelatin hydrogel for rapid hemostasis and inflammation-resolving wound healing.

Tissue fluidity regulates many critical biological processes, including embryonic development, wound healing, and cancer metastasis. In confluent epithelia, where cell packing fraction is effectively fixed, the prevailing paradigm postulates that transitions between solid-like jammed and fluid-like unjammed states are governed by a geometric cell shape index determined by the balance of cortical tension and intercellular adhesion. Here, we challenge this geometric framework by reporting a mode of fluidization in epithelial monolayers that is entirely shape-independent. We observe that reducing cell-cell adhesion triggers a substantial increase in fluidity, yet this occurs without any corresponding change in cell shape, cell density, substrate traction, or junctional line tension. This decoupling of shape and fluidity reveals that current vertex models, which treat adhesion solely as a contribution to interfacial tension, are incomplete. To reconcile these findings, we extend the theoretical framework to account for the dual nature of adhesion -- its thermodynamic role in setting interfacial adhesion energy at the cell-cell junctions and its kinetic role in generating viscous drag as cells slide past their neighbors. This generalized model quantitatively captures the experimental data, demonstrating that the interplay between adhesive energetics and dissipative friction is essential for a complete understanding of epithelial fluidity.

Halloysite and Zn2+-crosslinked gelatin/polyamidoxime-based hydrogel with immunoregulatory and antibacterial properties for promoting wound healing.

Research on wound-healing agents is a growing area in modern biomedical sciences, and oxidative stress plays a significant role in the challenges of chronic wound healing. These challenges include dry dressings that lack functionality and cause increased pain by adhering to wounds. Hydrogels are widely utilised for wound healing because they mimic the native extracellular matrix (ECM) and help maintain a moist environment. In silico docking studies revealed that lutein forms strong and stable interactions with proteins involved in ECM degradation, inflammation and oxidative stress. The optimised hydrogel formulations demonstrated excellent physicochemical stability and improved topical delivery of the drug. In vitro and ex vivo studies confirmed superior skin permeation and sustained release of lutein from the fermented hydrogel compared with controls. In vivo experiments using F2 formulation (0.5% lutein) on diabetic rat models demonstrated rapid wound contraction, achieving 92.1% closure by day 9 and complete healing by day 11, with minimal scarring and enhanced tissue regeneration. Histopathological analysis supported these results, revealing dense granulation tissue, minimal inflammatory infiltration and notable dermal remodelling in the treatment group. These findings suggest that lutein-loaded hydrogels are promising biotherapeutic options for the effective management of diabetic wounds.

Effective management of acute wounds, particularly those caused by burns and trauma,remainsa significant clinical challenge. Conventional formulations, such as ointments, creams, and hydrogels, often face challenges related to stability, portability, and patient compliance. To address these limitations, we developed a novel bi-layered skin tablet system using direct compression for immediate application to topical wounds. The upper protective layercontainskonjac glucomannan as a gelling agent and oleic acid as a permeability enhancer. The lower therapeutic layer includes a synergistic combination of clindamycin hydrochloride (CLC), benzalkonium chloride (BKC), and recombinant human mitsugumin 53 (rhMG53), a membrane repair protein. rhMG53 was repurposed for acute wound healing at a reduced dosage tomaintaintherapeutic efficacy while improving cost efficiency. The formulation wasoptimizedto achieve controlled release of rhMG53 for wound repair and of CLC and BKC for antibacterial activity. The synergistic interaction between CLC and BKC (Index 1.2) enhanced broad-spectrum antibacterial efficacy. The prepared tablets underwentin-vitrotesting for hardness, swelling index, content uniformity, drug release, and stability. The rhMG53containingformulationdemonstratedconsistent drug loading (98.5%, RSD < 6%), prolonged release, and effective wound healing in cell-based tests. The tablet form improves portability, stability, and ease of application compared with conventional remedies.This bi-layered skin tablet systemrepresentsa promising therapeutic strategy for acute wound management, particularly in emergency and military settings where lightweight, ready-to-use treatments are critically needed.

In burn-injured skin, the main goal is to accelerate wound healing and restore the barrier. In chemical burns, excessive inflammation and deep tissue damage complicate repair. Regenerative medicine approaches may modulate these processes. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (HucMSCs) and their exosomes (Exo-HucMSCs) on wound healing in a chemical burn model. A chemical burn was induced on the dorsal skin of 24 Wistar rats using 2 M sodium hydroxide. Rats were randomly assigned to three groups (n = 8): HucMSC-treated, Exo-HucMSC-treated and control. Wound closure and histopathological changes were evaluated and compared among groups. Wound closure was higher in the HucMSC group (78.15% ± 9.19) than in the Exo-HucMSC (66.11% ± 7.33) and control groups (57.35% ± 4.54) (p < 0.05). Histologically, treatment groups showed early inflammatory changes on days 1 and 3 (p < 0.01), enhanced striated muscle regeneration on day 7 (p < 0.01) and narrower non-epithelialized areas on day 21 (p < 0.05). Neoangiogenesis was greater in the Exo-HucMSC group on day 3 (p < 0.01). Both HucMSC and Exo-HucMSC treatment accelerated chemical burn healing. Exosomes promoted early-phase angiogenesis, whereas HucMSCs provided superior long-term wound closure.

Achilles tendon ruptures are recognized as one of the most widespread musculoskeletal injuries. Tendon injuries are a notable clinical challenge, primarily due to the restricted regenerative capacity of the tissue and the associated risks of fibrosis and incomplete functional recovery. Recent studies suggest that cell-free therapies, including stem cell-derived secretomes, may facilitate tendon regeneration. Additionally, mechanical stimulation through exercise can enhance tissue remodeling. This study aimed to investigate the combined effects of tendon-derived stem cell (TDSC) secretome and treadmill-based rehabilitation on Achilles tendon regeneration in a rat model. TDSCs were isolated from rat Achilles tendon and characterized using morphology, cytochemical staining, and flow cytometry. In vitro scratch assays were performed to assess cell migration and wound healing in a laboratory setting. The secretome was collected from fourth-passage TDSCs and incorporated into a collagen-based, injectable hydrogel. A total of 42 adult female Wistar rats were categorized into eight distinct experimental groups, including injury-only, treadmill-only, secretome-only, and treadmill + secretome groups. A surgical procedure was performed to induce a partial rupture of the Achilles tendon, followed by the injection of a secretome-loaded hydrogel at the site of injury. Subsequently, a structured treadmill training program was initiated post-surgery. Regenerative outcomes were evaluated using footprint analysis, histological staining (hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome), and biomechanical testing. In vitro scratch assays demonstrated that TDSCs treated with secretome exhibited enhanced migratory capabilities. Flow cytometry confirmed the identity of these mesenchymal stem cells (MSCs). In vivo studies showed that the combination therapy group (secretome-loaded hydrogel and treadmill training) achieved superior histological recovery. This group exhibited organized collagen bundles, aligned spindle-shaped tenocytes, minimal inflammation, and restored extracellular matrix integrity. PAS staining indicated reduced glycosaminoglycan degradation, while Masson's trichrome staining revealed partial collagen maturation. Additionally, footprint analysis showed improved functional performance, with the combination group achieving significantly higher Achilles functional index scores. Biomechanical testing confirmed enhanced tensile strength and elastic modulus, approaching values comparable to those of intact tendon healing. The synergistic application of TDSC-derived secretome along with treadmill training significantly improved tendon regeneration, matrix remodeling, and functional recovery. This cell-free, bioactive approach offers a promising therapeutic alternative for enhancing tendon recovery.

Dermatochalasis is characterized by age-related loss of upper eyelid skin elasticity leading to excess folds. The aim of our study is to discuss the possible neurogenic mechanisms of temporary and unilateral lagophthalmos developing after upper blepharoplasty performed only with skin excision in a case presenting with dermatochalasis. A 52-year-old female patient with no systemic disease underwent bilateral upper blepharoplasty under conscious sedation with local anesthesia. Dissection was performed at the subcutaneous level, preserving the orbicularis oculi muscle and orbital septum. Symmetry and complete closure were present in the early postoperative period. On the 5th day post-op, lagophthalmos developed on the right side; wound healing was normal, and no excessive skin excision or scar tissue was detected. After mechanical causes were ruled out, it was thought that the condition could be due to neurogenic dysfunction or sensorimotor coordination disorder in the temporary motor branches of the facial nerve. The patient was administered 1 mg/kg/day of intravenous methylprednisolone for 3 days; significant improvement was observed on the 10th day and complete recovery occurred within three weeks. Unilateral temporary lagophthalmos occurring after upper blepharoplasty performed with skin excision alone may not always be due to a mechanical cause. Neurogenic mechanisms such as the effect of local anesthetics, temporary facial nerve conduction disorders, or sensorimotor coordination loss may contribute. To avoid unnecessary surgical revisions in patients without mechanical pathology, neurogenic and functional processes must be considered; spontaneous recovery is expected in most cases with conservative management and close follow-up.

Prostate cancer represents a prevalent urological malignancy, but the molecular mechanisms underlying the differentiation of distinct tumor cell subtypes have not been fully elucidated. We conducted an analysis of paired single-cell RNA sequencing data from the public database on prostate cancer, and discovered differentially expressed genes between tumor cells and normal epithelial cells. We evaluated the expression of SCGB1A1 in prostate cell lines and tissue samples, and assessed migration, invasion, and proliferation through CCK-8, EdU, wound healing, and Transwell experiments. We performed pathway enrichment analysis to explore the downstream mechanism of SCGB1A1 (Secretoglobin Family 1A Member 1). Single-cell transcriptomic analysis revealed a marked reduction in SCGB1A1⁺ epithelial cells within tumor tissues, accompanied by an increased abundance of KLK3⁺ tumor epithelial cells. SCGB1A1 expression was significantly downregulated in both prostate cancer cell lines and tumor epithelial cells. Functional assays demonstrated that SCGB1A1 overexpression suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of prostate cancer cells. SCGB1A1 expression is negatively correlated with the activation of the MAPK signaling pathway, which may be associated with its tumor-suppressive effects. Our findings identify SCGB1A1 as a previously underappreciated tumor-suppressive role in prostate cancer and reveal its role in modulating MAPK signaling and EMT. The depletion of SCGB1A1⁺ epithelial cells characterizes the malignant epithelial phenotype, suggesting its potential as a candidate diagnostic biomarker and therapeutic target that requires further clinical validation.

Background: The oral cavity is sometimes referred to as a “diagnostic window” of systemic health, as even subtle systemic disturbances can manifest as changes in the oral mucosa. Coeliac disease, diabetes mellitus, and inflammatory bowel diseases (IBD) are chronic conditions that frequently present with oral mucosal lesions, which may precede or accompany the classical symptoms of these diseases. Aim: To systematically review and compare the oral mucosal changes reported in coeliac disease, diabetes mellitus, and IBD. The most common clinical manifestations are characterized, potential pathophysiological mechanisms are discussed, and the relevance of oral findings for early recognition and monitoring of these systemic diseases is evaluated. Materials and Methods: A systematic literature search was conducted in PubMed and Google Scholar using combinations of English keywords (including “oral mucosa,” “oral manifestations,” “coeliac disease,” “diabetes mellitus,” “inflammatory bowel disease,” “Crohn’s disease,” “ulcerative colitis,” “aphthous ulcers,” “xerostomia,” “oral microbiome,” and “oral–gut axis”). A total of 37 relevant peer-reviewed articles (clinical studies and reviews) were identified and analyzed. Results: The most frequently described oral manifestations in these conditions include recurrent aphthous stomatitis, inflammatory and atrophic changes of the tongue (such as geographic tongue and atrophic glossitis), angular cheilitis, xerostomia, and recurrent opportunistic infections (especially oral candidosis). In coeliac disease, oral lesions (aphthae, glossitis, cheilitis) and dental enamel defects often occur, sometimes even years before diagnosis, and tend to improve after the introduction of a strict gluten-free diet. Diabetes is associated with salivary gland dysfunction leading to dry mouth, elevated salivary glucose, and immune dysfunction – factors that contribute to candidosis, poor wound healing, burning mouth sensations, and an increased incidence of oral ulcers. IBD (Crohn’s disease and ulcerative colitis) can produce a broad spectrum of oral changes: Crohn’s disease in particular is characterized by specific granulomatous lesions (such as persistent lip swelling, mucosal “cobblestoning,” and deep linear ulcers) as well as nonspecific lesions (recurrent aphthae, pyostomatitis vegetans, glossitis, cheilitis). Oral manifestations of IBD are more common in Crohn’s disease and in pediatric patients and can precede intestinal symptoms or correlate with intestinal disease activity. Conclusions: Oral mucosal changes represent an important extraintestinal component of coeliac disease, diabetes, and IBD. They can serve as early warning signs of these disorders or indicators of disease activity and control. Recognition of characteristic oral lesions by dentists and physicians is crucial, as it can expedite diagnosis and prompt timely management (e.g. initiation of a gluten-free diet in coeliac disease or improved glycemic control in diabetes). Regular oral examinations should be an integral part of the care of patients with these conditions. Interdisciplinary collaboration – especially between dentists, gastroenterologists, and diabetologists – is essential for early detection, comprehensive monitoring, and improved patient outcomes.