Healing Response Research Articles

Transcriptomic analysis of circulating extracellular vesicles during the perioperative period of Fontan and Glenn surgery

Single-ventricle defects are treated with the Glenn and Fontan procedures, which offer lifesaving relief but result in lifelong complications. To address the lack of outcome predictors, we conducted an untargeted transcriptomic analysis to identify RNA biomarkers in serum and circulating sEVs from 25 Glenn or Fontan patients with three samples exclusively used for experimental assays. Unsupervised analysis revealed a distinction between pre-op and post-op samples in both surgical groups. Differential gene expression and pathway analysis showed enrichment for pro-angiogenic cargo in post-op sEVs compared to pre-op sEVs. Wound healing assays revealed post-op Fontan sEVs induce a stronger pro-angiogenic response than pre-op Fontan sEVs. A PLSR-guided approach revealed MAPK6, GLE1, hsa-miR-340-5p, and hsa-miR-199b-5p as key transcripts in the observed wound healing response. Lastly, EV-Origin revealed decreased secretion of sEV from cardiac tissue and increased secretion from brain tissue for both Fontan and Glenn samples. This work demonstrates the potential of sEV RNAs as biomarkers for patients with Fontan physiology, enabling quicker diagnosis for Fontan-associated complications.

Cancer Biology and the Perioperative Period: Opportunities for Disease Evolution and Challenges for Perioperative Care.

Efforts to deconvolve the complex interactions of cancer cells with other components of the tumor micro- and macro-environment have exposed a common tendency for cancers to subvert systems physiology and exploit endogenous programs involved in homeostatic control of metabolism, immunity, regeneration, and repair. Many such programs are engaged in the healing response to surgery which, together with other abrupt biochemical changes in the perioperative period, provide an opportunity for the macroevolution of residual disease. This review relates contemporary perspectives of cancer as a systemic disease with the overlapping biology of host responses to surgery and events within the perioperative period. With a particular focus on examples of cancer cell plasticity and changes within the host, we explore how perioperative inflammation and acute metabolic, neuroendocrine, and immune dyshomeostasis might contribute to cancer evolution within this contextually short, yet crucially influential timeframe, and highlight potential therapeutic opportunities within to further optimize surgical cancer care and its long-term oncological outcomes.

Donor site healing response to low-level laser therapy following skin graft surgery

IntroductionSkin grafting is an essential reconstructive technique for the healing of deep and extensive burns. Donor site problems are common complications after skin graft surgery. Speeding up the healing process at the donor site using low-level laser therapy helps avoid these problems. Objectives: The purpose of this research was to examine the efficacy of low-level laser therapy in promoting donor site healing in burn patients who underwent skin graft surgery.MethodsForty patients of both genders (16 male, 24 female) aged 20–40 years suffered full-thickness burns with a total body surface area varying from 20 to 35% and had undergone split-thickness skin graft surgery were selected randomly and divided into two equal groups. The low-level laser therapy group (study group) attended three sessions per week for three weeks, while the placebo group (control group) received sham laser treatments. All patients received conventional medical treatment and traditional wound care (dressing). Photography and J Image software were used to measure wound surface area before the treatment (day 1 post-operative), day 11 post-operative, and day 21 post-operative in both groups.ResultsThe study and control groups demonstrated a substantial reduction in wound surface area at day 11 and day 21 post-operative compared with day 1 (<i>p</i> < 0.001), with the percentage of improvement of 88.69% and 98.73% and 50.18% and 80.22%, respectively. On day 21 compared to day 11 (<i>p</i> < 0.001), the percentage of improvement was 88.81% and 60.30%, respectively. Between-group comparisons revealed a significant decrease in wound surface area at day 11 and day 21 post-operative in the study group compared to the control group (<i>p</i> < 0.001).ConclusionsLow-level laser therapy is an effective modality for enhancing wound healing of the donor site in burned patients undergoing skin graft surgery.

Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model.

Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel disease. But the epithelial-specific contribution to mucosal healing in vivo is poorly understood. We evaluated mucosal healing in an acute dextran sulfate sodium mouse model that shows an alleviated colitis response after epithelial-specific loss of Smad4. We find that enhanced epithelial wound healing alleviates the fibrotic response. Dextran sulfate sodium caused increased mesenchymal collagen deposition-indicative of fibrosis-within a week in the WT but not in the Smad4 KO colon. The fibrotic response correlated with decreased epithelial proliferation in the WT, whereas uninterrupted proliferation and an expanded zone of proliferation were observed in the Smad4 KO colon epithelium. Furthermore, the Smad4 KO colon showed epithelial extracellular matrix alterations that promote epithelial regeneration. Our data suggest that epithelium is a key determinant of the mucosal healing response in vivo, implicating mucosal healing as a strategy against fibrosis in inflammatory bowel disease patients.

CLINICAL PROFILE AND MANAGEMENT OF HYPERTROPHIC SCARS AT DR. SOETOMO GENERAL ACADEMIC HOSPITAL SURABAYA, INDONESIA

Highlights: Most hypertrophic scar patients were aged 17 to 25, mainly female, and the scars were mostly caused by burns on the face and upper extremities. Surgical techniques were the most common treatment, with most scars measuring 1 to 5 cm². Abstract: Introduction: Scars is a prevalent clinical concern that is often more complex than commonly perceived. Hypertrophic and keloid scars results from atypical wound healing responses following trauma, characterized by an excessive deposition of connective tissue. In Indonesia, there are remains a paucity of data on the clinical profile and management of hypertrophic scars. To address this gap, researchers conducted a descriptive study to systematically examine various variables associated with hypertrophic scars, aiming to enhance understanding and inform more effective management strategies. Methods: This research is a retrospective descriptive analysis utilizing secondary data from medical records of patients with hypertrophic scars treated at Dr. Soetomo General Academic Hospital in Surabaya during the 2019 – 2020 period. The data were collected and processed according to key variables, including age, gender, occupation, etiology, anatomical location of the hypertrophic scars, scar size, and therapeutic interventions. Results:The number of patients with hypertrophic scars at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from 2019 to 2020 was 68. Most patients were aged 17 to 25 years. The gender distribution was nearly equal, with 50% male and 50.9% female patients. Among the patients, 12.5% and 43% were students. Burns caused 37.5% and 25% of cases. The most common scar locations were the face (25%) and upper extremities (25%). Most scars measured 1 to 5 cm² (25%). The most common treatment was surgical techniques (80% and 48%). Conclusion: Most hypertrophic scar patients were aged 17 to 25 years, predominantly female, and students. The primary cause of the scars was burns, with the scars most commonly located on the face and upper extremities. The majority of scars measured between 1 and 5 cm², and surgical techniques were the most widely used therapy.

Urinary transforming growth factor beta-1 levels correlate with the effect of renorrhaphy on functional outcomes post-laparoscopic partial nephrectomy: A pilot-study

ABSTRACT Purpose Preservation of functional renal parenchyma is one of the main targets of partial nephrectomy. We investigated the effects of suture on renal parenchyma in tumor bed and on short-term renal function. Materials and Methods Patients with unilateral cT1 renal masses candidate for laparoscopic partial nephrectomy (PN) have been recruited. After tumor excision, medullary sutures were replaced by argon beam in Group 1, while Group 2 had conventional 2-layer renorrhaphy. Groups have been matched using propensity score. Transforming growth factor beta-1 (TGFb1) levels in urine have been measured at the 1st and 30th day post-PN. Glomerular filtration rate has been estimated (eGFR) at baseline and 3 months post-PN. Results Sixteen cases were matched in each group. There was no difference between groups regarding baseline, operative and perioperative data. Number of sutures in group 1 is nearly half that in group 2 (10 vs 19, respectively, p < 0.001). Group 1 showed lower urinary TGFb1 levels at the 1st and 30th day post-PN (p < 0.01 for each), higher eGFR after 3 months (p = 0.01), and less decline of eGFR from baseline (p = 0.046). Conclusion TGFb1 levels in urine after PN are related to the number of sutures. Reduced number of sutures in tumor bed has a positive effect on short term eGFR changes possibly by reducing tumor bed fibrogenic healing response as well as preserving renal parenchymal volume.

A multi-domain computational framework investigating the short- and long-term viability of bioabsorbable magnesium fixation for tibial fractures

This study presents a multi-domain computational framework to investigate the long-term performance of permanent and bioabsorbable magnesium fixation devices in orthopaedic fracture applications. The framework integrates a coupled model for bone fracture healing and remodeling, with an enhanced surface-based corrosion model to predict the performance of bioabsorbable magnesium devices. It was found that plated fracture fixation enabled fracture healing outcomes compare to non-plated models by facilitating direct fracture healing. During the fracture healing phase, it was found that the stiff titanium plate provided a better healing response compared to the less stiff bioabsorbable magnesium plates. However, in the longer-term remodeling phase, the titanium plate showed evidence of stress-shielding and inhibited bone remodeling. On the other hand, the magnesium plates showed that there was continued remodeling, which meant that the bone tissue gradually returned to the pre-fracture stress state. While the corrosion rate and pit severity heavily influenced the mechanical support provided by the corroding magnesium fixator, the results showed that fixation was only required to provide mechanical stability to the fracture region for approximately the first 30 days for successful fracture union to occur. This coupled computational framework provides a platform to investigate the role of a wide range of magnesium fixation devices and their design and optimisation in orthopaedic applications.

Contemporary Approach for Traumatic Dental Injuries in the Primary Dentition.

Management of traumatic dental injuries (TDI) is very complex, even under ideal circumstances. Children in the primary dentition have unique needs, and it is important that the diagnosis and treatment choices are offered to parents. The prevalence of TDI in the primary dentition is far greater than for any other age group. Education of parents and caregivers in prevention and emergency management of oral injuries is essential. When injuries occur, the dental professionals must also respond appropriately to establish correct diagnosis of the injuries and assist parents in making decisions for management while communicating realistic expectations for the future. Progress has been made in the diagnosis and management of dental injuries in the primary dentition based on the biological healing response of oral tissues following injury over time. Several factors influence critical decisions that must be made based on basic principles and guidelines to improve successful outcomes for the child. Managing co-operation must be balanced with the benefit of anticipated treatment need. The current evidence challenges previous dental interventions. The IADT guidelines updated the approach to management of TDI in children in the primary dentition. Encouraging a positive attitude to the dental setting early in the life course prepares the child to be a motivated dental attendee throughout their lifetime. This manuscript aimed to outline the critical issues and clinical choices for injuries to the primary dentition and to summarise recent guidance from the International Association of Dental Traumatology (IADT).

Histamine receptor agonism differentially induces immune and reparative healing responses in biomaterial-facilitated tissue repair

Tissue repair is a highly regulated process involving immune, stromal, vascular, and parenchymal cell responses. Mediators of cellular responses at different phases of the healing process stimulate transitions through the continuum of repair. Histamine is an early mediator of healing, which, in skin, is released by resident cells (e.g., mast cells) after cutaneous injury, and acts to stimulate diverse responses in multiple cell populations. Histamine signaling is regulated by four distinct cell surface G-protein coupled receptors (HRH1-4 in humans, Hrh1-4 in mice) which initiate different downstream signaling cascades upon activation, but the specific effect of each receptor on tissue repair is poorly understood. Here, we systematically investigated the effect of selective histamine receptor agonism in laser-activated sealing and tissue repair of incisional skin wounds in immunocompetent mice. Although all four histamine receptors exhibited wound responsiveness in the epidermis, we find that activation of Hrh1, Hrh2, and Hrh4 stimulate a pro-healing immune response characterized by increased pro-resolution macrophages, reduced pro-inflammatory macrophages, and suppressed neutrophil responses. Further, activation of Hrh1 and Hrh4 stimulate angiogenesis after injury. Lastly, although Hrh1 activation resulted in enhanced epidermal epithelial-to-mesenchymal transition (EMT) in vivo and epithelialization in vitro, activation of Hrh2 suppressed both epidermal EMT and epithelialization. Activation of Hrh3, primarily found on neuronal cells, had no effect on any measure in our study. Selective histamine receptor agonism, specifically of histamine receptors Hrh-1 and 4, is a potential reparative approach to promote the efficacy of biomaterial-mediated repair of tissues, including skin.

Multi-Layered Implant Approach for Hemilaryngectomy Reconstruction in a Porcine Model.

Partial laryngectomies result in voice, swallowing, and airway impairment for thousands of patients in the United States each year. Treatment options for dynamic restoration of laryngeal function are limited. Thus, there is a need for new reconstructive approaches. Here, we evaluated early (4 week) outcomes of multi-layered mucosal-myochondral (MMC) implants when used to restore laryngeal form and function after hemilaryngectomy in a porcine model. Six Yucatan minipigs underwent transmural hemilaryngectomies followed by reconstruction with customized MMC implants aiming to provide site-appropriate localization of regenerated laryngeal tissues, while supporting laryngeal function. All implants were fabricated from polymeric collagen, with a subset of muscle and cartilage implants containing motor endplate-expressing muscle progenitor cells or cartilage-like cells differentiated from adipose stem cells, respectively. Vocalization and laryngeal electromyography (L-EMG) measurements with nerve conduction studies were performed post-operatively and compared with baseline along with gross and histological analyses of the healing response. All animals (n = 6) survived and maintained airway patency, safe swallowing, and phonation, without the use of tracheostomy and/or gastrostomy tubes. Histological evaluation indicated no adverse tissue reaction or implant degradation, showing progressive regenerative remodeling with mucosa reformation and ingrowth of new muscle and cartilage. Preliminary L-EMG suggested weak but detectable motor unit action potentials. Although vocalization duration, frequency, and intensity decreased post-operatively, all animals retained vocal capacity and parameter recovery was evident over the study duration. Engineered collagen polymeric implants in the presence or absence of autologous cell populations may serve as a feasible reconstructive option to restore dynamic function after hemilaryngectomy. Long-term follow-up is needed to further assess functional outcomes. NA Laryngoscope, 2024.

Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

Non-Surgical Endodontic Management of Large Periapical Lesions After Traumatic Dental Injuries.

Traumatic dental injuries of permanent teeth result in multiple immediate and long-term consequences depending upon the severity of trauma, age of the patient, the status of root maturity, and the emergency care provided. The healing responses may get disturbed due to severe damage, loss of vascularity of the supporting structures, and infections. As a result, the prohealing mediators and pathways are overpowered by the destructive stimuli often manifested by an increased osteoclastic activity. Among the various late complications, the apical periodontitis or the periapical lesions are most worrisome for the patients and create clinical dilemma for the dentists. In the past, many such lesions were classified as cysts and subjected to surgical management. However, better understanding of lesion pathophysiology, three-dimensional imaging, and molecular pathways have established their inflammatory nature. The advancements in materials such as calcium silicates, and regenerative techniques have propelled the research related to non-surgical endodontic management as its clinical acceptability. The treatment largely follows the recommendations of regenerative medicine and is based on four principles: (a) establishing the drainage or an endodontic access to the area, (b) removal of most of the triggering agents such as necrosed pulp, toxins, and inflammatory mediators, (c) disinfection of the area, controlling inflammation and reversal of the acidic pH, and (d) maintenance of this infection/inflammation-free state for a long time through adequate sealing. This review aims to highlight the rationale of the approach, case selection, pathophysiology of the causation and healing, clinical protocols, and the limitations of non-surgical endodontic management of large periapical lesions secondary to traumatic dental injuries.

Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization

Epoxytiglianes are a novel class of diterpene esters. The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors. EBC-46 also consistently promotes wound re-epithelialization at the treatment sites, mediated via activation of classical protein kinase C (PKC) isoforms. We have previously shown that epoxytiglianes stimulate proliferative and wound repopulation responses in immortalized human skin keratinocytes (HaCaTs) in vitro, abrogated by pan-PKC inhibitor, bisindolylmaleimide-1. In this study, we further investigate the specific PKC isoforms responsible for inducing such wound healing responses, following HaCaT treatment with 1.51 nM-15.1 µM EBC-46 or analogue, EBC-211. Classical PKC inhibition by GӦ6976 (1 μM), significantly attenuated epoxytigliane induced, HaCaT proliferation and wound repopulation at all epoxytigliane concentrations. PKC-βI/-βII isoform inhibition by enzastaurin (1 μM), significantly inhibited HaCaT proliferation and wound repopulation responses induced by both epoxytiglianes, especially at 1.51–151 nM. PKC-α inhibitor, Ro 31–8220 mesylate (10 nM), exerted lesser inhibitory effects on HaCaT responses. Epoxytigliane changes in key keratin (KRT17) and cell cycle (cyclin B1, CDKN1A) protein levels were partly attenuated by GӦ6976 and enzastaurin. GӦ6976 also inhibited increases in matrix metalloproteinase (MMP-1, MMP-7, MMP-10) activities. Phospho-PKC (p-PKC) studies confirmed that epoxytiglianes transiently activated classical PKC isoforms (p-PKCα, p-PKC-βI/-βII, p-PKCγ) in a dose- and time-dependent manner. By identifying how epoxytiglianes stimulate classical PKCs to facilitate keratinocyte healing responses and re-epithelialization, these findings support further epoxytigliane development as topical therapeutics for clinical situations involving impaired re-epithelialization, such as non-healing wounds in skin.

Formulation of Asiatic acid-loaded polymeric chitosan-based hydrogel for effective MRSA infection control and enhanced wound healing in zebrafish models

BackgroundWound healing relies on a controlled inflammatory process vital for tissue regeneration. Chronic wounds, characterized by persistent inflammation and high infection risk, pose significant challenges in healthcare. Hydrogel dressings offer promise in wound care; however, the understanding of their role in managing inflammation and infection remains unclear. This study aimed to elucidate these processes and assess the efficacy of Asiatic acid (AA)-infused hydrogels in reducing inflammation and preventing infection. The unique properties of AA suggest its potential to modulate inflammation, promote tissue regeneration, and inhibit microbial colonization, thereby paving the way for specialized dressings that optimize healing outcomes. MethodsThe investigation encompassed the antibacterial, anti-biofilm, antioxidant activity, and biocompatibility of AA using a fibroblast cell line. A hydrogel incorporating AA was developed and characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle analysis, tensile testing, swelling capacity, and thermal stability assessments. Biodegradability was evaluated via enzymatic degradation, alongside controlled drug release and antibacterial efficacy against MRSA. In vivo studies using a zebrafish model examined wound healing and immune response. ResultsResults confirmed AA's potent antibacterial activity against MRSA and its effectiveness in disrupting mature biofilms. Additionally, AA exhibited strong antioxidant activity and biocompatibility. Morphological analysis revealed a pore structure conducive to wound healing, and the hydrogel demonstrated enhanced tensile strength, swelling properties, and thermal stability. In vivo, the AA-infused hydrogel accelerated wound closure, re-epithelialization, and immune response, supporting its potential for advanced wound care applications. In conclusion, the AA-infused chitosan hydrogel emerges as a promising candidate for advanced wound care therapies.

Impact of Dual-coated Silver Nanoparticle and Antibiotic Sutures on Wound Healing in Inflammatory Mouse Models.

The use of silver nanoparticles (AgNPs) in biomedicine has emerged in a big way owing to its antibacterial and anti-inflammatory properties. We hypothesize that combining the AgNPs with antibiotics for coating sutures will enhance the antibacterial property of sutures with the added advantage of the immunomodulatory effect of AgNPs on tissue healing. Polyglactin sutures were coated with AgNPs using the dip-coating method. The uniform coating and morphology of AgNPs on the suture surface were confirmed using scanning electron microscopy (SEM). Each type of suture - polyglactin plain, antibiotic coated (Triclosan), AgNP coated, and dually coated (antibiotic and AgNP) - was assessed for their antibacterial properties against Gram-positive bacteria, Gram-negative bacteria, and anaerobes. These sutures were utilized in an abdominal and systemic inflammatory mice model for ileal anastomosis. The intestinal tissue was evaluated for acute and chronic inflammation and collagen deposition to assess the healing and inflammatory response. The SEM and energy dispersive X-ray analysis showed successful coating of AgNPs on plain and antibiotic-coated sutures. In comparison with the other groups, the dually coated suture had the best in vitro antibacterial efficacy. The AgNP-coated sutures were able to decrease both acute and chronic inflammatory cell infiltration, but the collagen synthesis and deposition were enhanced. AgNPs can be coated on Polyglactin suture either alone or in combination with antibiotics with preserved antibacterial effects. The dual coating of sutures gives a synergistic antibacterial effect. The AgNP diminishes immune response in the presence of preserved extracellular matrix generation.

Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation

Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in implant-based breast reconstruction, and has shown to modulate the healing response. However, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective biomaterial integration requires regulating the immune response, fibrosis, and adipocyte-driven functionalization. Extracellular matrix (ECM) hydrogels have demonstrated utility in tissue regeneration, and decreasing inflammation and fibrosis in various tissues. Therefore, we hypothesized that a Decellularized Porcine Dermal (DPD) hydrogel to support ADM integration would prevent excessive fibrosis, regulate the macrophage response, and promote adipogenesis. Exploration of DPD hydrogel during ADM implantation in mice (healthy and radiated) revealed long-term effects of irradiation on implant wound healing. DPD hydrogel rescued radiation-induced fibrosis, restoring capsule thickness of healthy mice, and did not increase the fibroblast migration into the ADM. As a modulating soft tissue filler, DPD hydrogel also promoted adipocyte infiltration in healthy and irradiated mice. Detailed macrophage analysis showed that radiation led to the increase in pro-inflammatory, transition, and reparative markers. Despite relatively subtle effects on individual macrophage phenotype markers, multidimensional flow cytometry analysis revealed that DPD hydrogel temporally regulated two subpopulations. he presence of DPD resulted in significantly reduced CD9HiArg1HiCD301bLo and CD163HiCD38HiCD301bHi macrophages in healthy mice at one week, and a significant increase in CD9High macrophages with low expression of other markers at 6 weeks in irradiated mice. DPD hydrogel promotes a decreased fibrotic, and adipocyte-promoting coordination of wound healing in healthy and irradiated wound beds while not disrupting the immunomodulatory effects of ADM. Statement of significanceAcellular Dermal Matrix (ADM) provides mechanical and soft tissue support in post-mastectomy implant-based breast reconstruction, and positively affects wound healing. Following breast reconstruction, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective wound healing and biomaterial integration requires regulating the cellular immune response. Extracellular matrix hydrogels have demonstrated utility in tissue regeneration and decreasing inflammation and fibrosis in various tissues, but has yet to be utilized in the setting of breast reconstruction. Here, we demonstrated that a decellularized dermal hydrogel as an adjunct to ADM, decreases fibrosis and promotes adipogenesis during the coordination of wound healing in healthy and clinically relevant microenvironments that have received radiation therapy while not disrupting the immunomodulatory effects of implanted ADM.

Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision-cut liver slices.

Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision-cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking. In this study, PCLS prepared from male mouse liver tissue (mPCLS), healthy human liver tissue (hhPCLS), and cirrhotic human liver tissue (chPCLS) were cultured for 48 h with varying concentrations of the three compounds. Our findings indicate that NRG reduced collagen type 1 (COL1A1) expression in a concentration-dependent manner in both mPCLS and chPCLS, decreased fibrosis-related gene expression, and significantly lowered pro-collagen type 1 (PCOL1A1) levels in the culture medium by 54 ± 21% (mPCLS) and 78 ± 35% (chPCLS). Furthermore, NRG effectively inhibited IL-1β and TNF-α in mPCLS and IL-1β in chPCLS on both gene and protein levels. AA specifically reduced COL1A1 and PCOL1A1 in chPCLS, while ICA selectively downregulated Col1a1 and Acta2 gene expression in mPCLS. This study suggests NRG's potential as an effective antifibrotic agent, warranting further investigation into its mechanisms and therapeutic applications in liver fibrosis.

An advanced hydrogel dressing system with progressive delivery and layer-to-layer response for diabetic wound healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of significanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

ADVANCEMENTS IN REGENERATIVE MEDICINE: PRESENT APPROACHES, EMERGING STRATEGIES, AND FUTURE PERSPECTIVES

Background: Regenerative medicine is an evolving field with tremendous promise for treating various diseases and medical conditions. This innovative discipline encompasses various techniques, including the utilization of stem cells, tissue engineering, and gene therapy, to effectively regenerate or replace damaged tissues and organs. The rapid advancements in regenerative medicine over recent years have created new hope for patients who face otherwise untreatable conditions, showcasing the fields potential to transform healthcare. Objectives: The primary objective of this article is to provide a comprehensive overview of the current state of regenerative medicine. By delving into recent advancements and emerging technologies, this article aims to highlight the various FDA-approved therapies that have been developed to treat diverse pathologies. Additionally, it seeks to identify future directions for research and application within this dynamic field, ensuring that readers are informed about the latest breakthroughs and potential developments. Findings: To date, regenerative medicine has resulted in numerous FDA-approved therapies that target various pathologies. Extensive research has led to the creation of sophisticated grafts that leverage advanced scaffolding materials and cutting-edge cell manipulation technologies. These innovations allow for precise control over cell behavior and enhance tissue repair mechanisms. Strategies such as the controlled release of growth factors and vascular cell seeding are currently being developed to improve graft integration with both the host vasculature and the nervous system. Furthermore, there are ongoing efforts to stimulate and enhance the bodys healing response through immune system modulation, alongside the development of new cell sources for transplantation to address the persistent challenge of limited cell supply. Significance: The significance of regenerative medicine lies in its transformative potential to revolutionize the treatment of conditions that have long been deemed incurable. By providing insights into the advancements in graft technology, cell sourcing, and integration strategies, this article underscores the ultimate promise of regenerative medicine as a vital area of research. The findings and discussions presented here not only illuminate the current landscape but also pave the way for future innovations that could lead to groundbreakingtherapies, enhancing the quality of life for countless patients worldwide.[1][2].This article provides an overview and insights into the current state of the development of regenerative medicine and its various potential guiding into future directions.

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST elevation acute Coronary syndrome: a randomized optical coherence Tomography imaging study (EXPECT).

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200μm and 308μm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance.