Healing Model Research Articles

A continuous mode of action of nitric oxide in hard-to-heal wound healing.

Nitric oxide (NO) is one of the most studied molecules in medical science. The role of NO as an endogenous regulator of inflammation, as an antibacterial agent and as an endogenous gasotransmitter is well established. Even so, despite a plethora of excellent wound healing data, hard-to-heal (chronic) wounds are of epidemic proportions, and still growing in number. However, yet to be established and sorely needed is the identification of a single, continuous NO mechanism of action (MoA), where phase-to-phase variance in the complex sequence of cellular and molecular wound healing may elucidate the potential for placing hard-to-heal wounds on positive healing trajectories. Hence, the objectives of this review were to: identify salient MoAs for NO in each phase of skin wound healing; and to select and validate a single MoA that is both ubiquitous and continuous in NO across acute and hard-to-heal wound sequences, and which potentiates the ability to supplementally motivate and guide the recovery of a hard-to-heal wound onto a positive healing trajectory. The search began by selecting a detailed, multipart wound healing model. Next, as guided by the literature, was the identification of salient NO functionalities for each model segment. These modes of action were then be used to identify and validate a single NO MoA that is continuous across the healing spectrum. Finally, by using the principle of 'super position' of two continuous functions, this acute healing NO MoA solution was compared to a similar solution set describing a hard-to-heal or chronic wound. As both solution sets are continuous in a NO function, the resultant 'overlay' then helped to identify and guide the use of a NO MoA capable of placing any hard-to-heal wound on a positive healing trajectory.

Aging negatively affects postoperative recovery of biomechanical strength through decreased recruitment of Scx+/Sox9+ enthesis-related progenitors after rotator cuff repair in rats

BackgroundAlthough older adult patients have a higher retear rate after rotator cuff (RC) repair, the influence of aging on the healing process remains unclear. During mouse enthesis development, a multipotent progenitor co-expressing scleraxis (Scx) and SRY-box 9 (Sox9) contributes to enthesis formation. Scx+/Sox9+ cells may act as enthesis progenitors even during postnatal healing, and their number decreases with maturation. However, the pathophysiology of decreased RC healing ability due to aging remains unclear. We aimed to evaluate the effects of aging on tendon-to-bone healing after surgical RC repair in rats through biomechanical and histological analyses of Scx+ and Sox9+ progenitors in a ScxGFP transgenic rat model. MethodsThis was a controlled laboratory study. Adult Sprague-Dawley rats (n = 111) underwent unilateral surgery for supraspinatus tendon repair immediately after transection. The rats were divided into aged (95 weeks old) and control (12 weeks old) groups. The effects of aging were assessed using biomechanical tests at 6 weeks postoperatively and histologically at 2 and 6 weeks postoperatively. ScxGFP transgenic rats were used for the immunohistochemical assessment of Scx- and Sox9-expressing progenitors during the repair process. Sox9, Scx, and tenomodulin expression was assessed using real-time reverse transcription polymerase chain reaction. ResultsIn the biomechanical test at 6 weeks postoperatively, the aged group had lower ultimate load to failure (Control: 20.4 ± 6.1 N, Aged: 14.9 ± 6.6 N, P = 0.007), stiffness (Control: 16.1 ± 6.2 N/mm, Aged: 12.6 ± 5.5 N/mm, P = 0.023), and ultimate stress to failure (Control: 6.0 ± 3.4 N/mm2, Aged: 3.4 ± 2.5 N/mm2, P < 0.001) than the control group. The total histological score of the aged group was lower than that of the control group at 6 weeks postoperatively (Control: 8.8 ± 0.8, Aged: 5.8 ± 0.4, P = 0.029). Immunohistochemistry tests showed that the percentages of Sox9+ (Control: 6.6 ± 1.1, Aged: 2.0 ± 1.0, P = 0.029) and Scx+/Sox9+ (Control: 3.6 ± 0.8, Aged: 1.1 ± 0.6, P = 0.029) cells at the reparative site were lower in the aged group than in the control group at 2 weeks postoperatively. ConclusionIn a rat RC tendon-to-bone healing model, the decreased recruitment of Scx+/Sox9+ enthesis-related progenitor cells in the early phase may be associated with delayed reparative tissue remodeling in aging animals. These findings encourage the development of therapeutic strategies that biologically promote healing and reduce postoperative retears in older adult patients.

501 Next-generation in vitro testing: microfluidic models for aging, wound healing, and oral tissue analysis in safety, efficacy, and permeation studies

501 Next-generation in vitro testing: microfluidic models for aging, wound healing, and oral tissue analysis in safety, efficacy, and permeation studies

CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing

BackgroundDelayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds. MethodsIn vivo, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and Clec14a−/− diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. In vitro, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs. ResultsCLEC14A expression was suppressed in diabetic wounds. Deletion of the Clec14a inhibited angiogenesis and activated inflammatory responses in vivo. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels in vitro. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose. ConclusionCLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.

Exploration of the Topical Nanoemulgel Bearing with Ferulic Acid and Essential Oil for Diabetic Wound Healing

Aim: To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Methods: Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol® 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. Results: The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Conclusions: Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats.

Cavity self-healing mechanism at the interface of high-Cr ferritic steel/austenitic steel dissimilar diffusion-bonded joint during cyclic phase transformation treatment

In this work, cyclic phase transformation treatment (CPTT) was developed to achieve self-healing of interfacial voids in high-Cr ferritic steel/austenitic steel dissimilar diffusion-bonded joints. The evolution of voids was analyzed based on microstructural characteristics, and mechanical properties of joints were assessed through lap-shear tensile tests. The results indicate that, in contrast to isothermal heat treatment (IHT), CPTT significantly enhances efficiency of cavity healing, leading to substantial improvements in both interface bonded ratio and shear performance of joints. By considering equivalent interfacial internal stress, a kinetic model for cavity healing was proposed, incorporating coupled the interface and surface diffusion, and the power-law creep mechanism. Simulation results demonstrate that diffusion predominates during cavity healing with negligible contribution of plastic flow. The actual cavity healing can be divided into two stages: in initial stage the large penny-shaped cavities become shorter in length with negligible change of height, while in the final stage, nearly circular voids shrinkage with a significant decrease of void size due to the enhanced effect of local surface diffusion. Moreover, it suggests that tensile internal stresses can impede healing or even promote residual void growth. Conversely, normal compressive internal stresses within cavity healing zone induced by the cyclic α↔γ phase transformation during CPTT intensify chemical gradients around void neck. This promotes accelerated atomic diffusion adjacent to void neck region, thereby resulting in a notable reduction in the duration required for complete cavity healing.

Evaluating effects of community-based social healing model on Ubuntu, mental health and psychosocial functioning in post-genocide Rwanda: protocol for cluster randomized control trial

BackgroundThe community-based social healing (CBSH) model, developed by Ubuntu Centre for Peace, aims to support individuals with traumatic experiences and mental health challenges in achieving better mental health. CBSH combines BREATH-BODY-MIND™ (BBM) practices with collective narrative and rituals, facilitated by Community Healing Assistants in therapeutic groups. A previous pilot study involving 1889 Rwandan CBSH participants showed significant mental health improvements, including reductions in depression, anxiety, and PTSD, along with enhanced work productivity, and decreased intimate partner violence. The trial investigates the CBSH model’s impact on Ubuntu and mental health. Ubuntu, a concept that encompasses humanness, compassion, and interconnectedness, is deeply rooted in the African philosophy.Methods/designThis cluster randomized controlled trial will involve 54 villages randomly selected in the Kirehe district, with 1080 participants randomly allocated equally to the CBSH intervention or a wait-list control group. While the trial will be conducted at the village (cluster) level, both primary and secondary outcomes will be measured individually for participants within each cluster. The Primary outcome “Ubuntu” will be measured using a context-adapted Ubuntu measurement scale. Secondary outcomes include psychosocial indicators which will be assessed through standardized tools such as the Patient Health Questionnaire for depression (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Warwick-Edinburgh Mental Wellbeing scale (WEMWS), Connor-Davidson Resilience scale (CD-RISK-10), Somatic Symptom Severity Scale (PHQ-15), Revised Conflict Tactics scale (CTS2S), and Adapted Social Capital Assessment Tool (SASCAT).ConclusionThis trial aims to evaluate the CBSH model’s impacts on Ubuntu, mental health, and social functioning among trauma-affected Rwandans, including those impacted by the 1994 Genocide against the Tutsi, mass killings, sexual abuse, and domestic violence. The findings could be of value to the Ubuntu Centre for Peace, policymakers, healthcare practitioners, and other stakeholders, by highlighting the significance of promoting Ubuntu as a foundation for addressing mental health challenges and the consequences of psychosocial trauma.Trial registrationISRCTN ISRCTN17659369. Registered on February 09, 2024.

Impact of Aggregatibacter actinomycetemcomitans on epithelial repair

ABSTRACT: Normal wound healing occurs in four overlapping stages - hemostasis, inflammation, proliferation, and remodeling. In the oral cavity, these processes occur in an infectious environment. Among the pathogens found in the oral community, Aggregatibacter actinomycetemcomitans (Aa) constitutes a well-recognized periodontal pathogen responsible for expressing several virulence factors, which activate a host response. Aim: This study investigated whether Aa’s presence can interfere with oral keratinocyte tissue healing in an in vitro wound healing model. Methods: Two groups were defined: Group KO (n=5) and Group KO+Aa (n=5). The Aa (JP2 strains) were cultivated in anaerobiosis, and the total protein extract was obtained. The keratinocytes were cultivated with the medium of standard culture until their confluence. After confluence, plates were allocated to each group. With the pipette’s tip, a “scratch” was made in the middle of each well of the plate, and the cells were cultured at 37°C in a humidified atmosphere with 5% CO2. The cells received the stimulus according to groups, and, at times 0, 5, 10, 24, and 48 hours, the wound areas were visualized and standardly recorded using an inverted microscope. Results: When analyzing the timeframe, differences in wound measurements indicate a faster closure in the control group compared to the KO+Aa group, although not statistically significant. However, upon examining the wound closure measures, it was observed that the Aa protein extract significantly reduced wound closure at 10 and 48 hours (p&lt;0.05), negatively impacting the keratinocyte’s behavior. Conclusion: In summary, it was demonstrated that the pathogen Aa can interfere with the re-epithelization in vitro.

Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced - Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI).

Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can measure vascular perfusion. We investigated how a combined OE-DCE PAI protocol can measure vascular oxygenation and perfusion to a cutaneous healing model. We developed a cutaneous "punch" wound model and photographed the wounds to track healing for 9 days. We performed OE-DCE PAI on Day 0, 3, 6, and 9. OE PAI was performed with 21% O2 and 100% O2 breathing gases to measure oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (HbT), and oxygen saturation (%sO2), along with changes in these parameters caused by a change in breathing gas (ΔHb, ΔHbO2, ΔHbT, ΔsO2). To perform DCE PAI, indocyanine green (ICG) was administered intravenously while monitoring the PAI signal for 10min as the agent washed through the wound area, which was used to evaluate the wash-out rate. The average wound size was significantly smaller only by Day 6. For comparison, OE PAI measured a significant increase in HbO2, Hb, HbT, and %sO2 immediately after creating the wound, which significantly decreased by Day 3 and continued to decrease towards values for normal tissue by Day 9. The vascular wash-out rate significantly increased by Day 3, and continued to increase during the healing process. Notably, the wash-out rate can be assessed at a single PAI absorbance wavelength and by simply comparing signal amplitudes without advanced analysis, which may facilitate clinical translation. OE-DCE PAI can monitor significant changes in vascular perfusion and oxygenation prior to significant changes in cutaneous wound size. These results establish OE-DCE PAI as a tool for future pre-clinical wound healing studies and eventual clinical translation.

Prognostic bone fracture healing simulations in an ovine tibia model validated with in vivo sensors.

Bone fracture healing is a complex physiological process influenced by biomechanical and biomolecular factors. Mechanical stability is crucial for successful healing, and disruptions can lead to delayed healing or nonunion. Bone commonly heals itself through secondary fracture healing, which is governed by the mechanical strain at the fracture site. To investigate these phenomena, a validated methodology for capturing the mechanoregulatory process in specimen-specific models of fracture healing could provide insight into the healing process. This study implemented a prognostic healing simulation framework to predict healing trajectories based on mechanical stimuli. Sixteen sheep were subjected to a 3 mm transverse tibial mid-shaft osteotomy, stabilized with a custom plate, and equipped with displacement transducer sensors to measure interfragmentary motion over 8 weeks. Computed tomography scans were used to create specimen-specific bone geometries for finite element analysis. Virtual mechanical testing was performed iteratively to calculate strains in the callus region, which guided tissue differentiation and consequently, healing. The predicted healing outcomes were compared to continuous in vivo sensor data, providing a unique validation data set. Healing times derived from the in vivo sensor and in silico sensor showed no significant differences, suggesting the potential for these predictive models to inform clinical assessments and improve nonunion risk evaluations. This study represents a crucial step towards establishing trustworthy computational models of bone healing and translating these to the preclinical and clinical setting, enhancing our understanding of fracture healing mechanisms. Clinical significance: Prognostic bone fracture healing simulation could assist in non-union diagnosis and prediction.

Troxerutin associated with Agaricus blazei Murill polysaccharides in films improves full-thickness wound healing

The present study aimed to associate troxerutin (TRX) with polysaccharides from Agaricus blazei Murill mushroom (PolyAb) in alginate/PVA films and evaluate their effect on wound healing. The physicochemical, mechanical, morphological, and water vapor barrier properties of the films were studied, and their biological potential was analyzed in vivo using the full-thickness wound healing model. The association between TRX and PolyAb present in the polymeric film contributed to increased thermal stability, mechanical resistance, and elasticity when compared to films without TRX, which indicated good miscibility of the excipients. In the in vivo tests, the TRX films promoted greater collagen deposition and repair of epidermis and dermis layers. The 0.25 % TRX film showed an increase in reduced glutathione levels, while the 1.0 % TRX film reduced lipid peroxidation and production of the pro-inflammatory cytokine IL-1β, demonstrating the anti-inflammatory and antioxidant effect of TRX films. Therefore, it is estimated that the film containing 1 % TRX can be used as biocurative for wound dressing applications.

Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair

Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways. Among these, BMP-2 was identified as the key signaling protein responsible for this effect, as its expression was significantly upregulated during osteoblast differentiation. Moreover, integrin α2 deficiency led to earlier and elevated BMP-2 secretion at the cell surface during osteogenesis, which promoted accelerated osteoblast differentiation. This phenomenon likely contributes to enhanced matrix production in aging animals, providing a protective effect against osteoporosis.To explore the broader implications of this phenotype, we utilized a fracture healing model. In integrin α2-deficient 12 weeks old female mice, elevated serum levels of BMP-2 were detected during the early stages of fracture repair. This upregulation of BMP signaling within the fracture callus accelerated the healing process, resulting in faster formation and mineralization of the cartilaginous callus. Additionally, the elevated BMP-2 levels facilitated earlier differentiation of chondrocytic cells, evidenced by the premature appearance of collagen type II- and type X-positive cells during endochondral ossification. Despite the accelerated healing, the overall biomechanical integrity of the repaired fractures remained uncompromised.Thus, the modulation of integrin α2β1 presents a promising therapeutic target for enhancing fracture repair by regulating BMP-2 signaling in a physiologically relevant manner.

Evaluation effect of alginate hydrogel containing losartan on wound healing and gene expression.

Skin tissue engineering has become an increasingly popular alternative to conventional treatments for skin injuries. Hydrogels, owing to their advantages have become the ideal option for wound dressing, and they are extensively employed in a mixture of different drugs to accelerate wound healing. Sodium alginate is a readily available natural polymer with advantages such as bio-compatibility and a non-toxicological nature that is commonly used in hydrogel form for medical applications such as wound repair and drug delivery in skin regenerative medicine. Losartan is a medicine called angiotensin receptor blocker (ARB) that can prevent fibrosis by inhibiting AT1R (angiotensin II type 1 receptor). In this research, for the first time, three-dimensional scaffolds based on cross-linked alginate hydrogel with CaCl2 containing different concentrations of losartan for slow drug release and exudate absorption were prepared and characterized as wound dressing. Alginate hydrogel was mixed with 10, 1, 0.1, and 0.01mg/mL of losartan, and their properties such as morphology, chemical structure, water uptake properties, biodegradability, stability assay, rheology, blood compatibility, and cellular response were evaluated. In addition, the therapeutic efficiency of the developed hydrogels was then assessed in an in vitro wound healing model and with a gene expression. The results revealed that the hydrogel produced was very porous (porosity of 47.37 ± 3.76µm) with interconnected pores and biodegradable (weight loss percentage of 60.93 ± 4.51% over 14days). All hydrogel formulations have stability under various conditions. The use of CaCl2 as a cross-linker led to an increase in the viscosity of alginate hydrogels. An in vitro cell growth study revealed that no cytotoxicity was observed at the suggested dosage of the hydrogel. Increases in Losartan dosage, however, caused hemolysis. In vivo study in adult male rats with a full-thickness model showed greater than 80% improvement of the primary wound region after 2weeks of treatment with alginate hydrogel containing 0.1mg/mL Losartan. RT-PCR and immunohistochemistry analysis showed a decrease in expression level of TGF-β1 and VEGF in treatment groups. Histological analysis demonstrated that the alginate hydrogel containing Losartan can be effective in wound repair by decreasing the size of the scar and tissue remodeling, as evidenced by future in vivo studies.

Nervonic acid as novel therapeutics initiates both neurogenesis and angiogenesis for comprehensive wound repair and healing.

Rapid tissue reconstruction in acute and chronic injuries are challengeable, the inefficient repair mainly due to the difficulty in simultaneous promoting the regeneration of peripheral nerves and vascular, which are closely related. Main clinical medication strategy of tissue repair depends on different cytokines to achieve nerves, blood vessels or granulation tissue regeneration, respectively. However, their effect is still limited to single aspect with biorisk exists upon long-time use. Herein, for the first time, we have demonstrated that NA isolated from Malania oleifera has potential to simultaneously promote both neurogenesis and angiogenesis in vitro and in vivo. First, NA was identified by NMR and FTIR structural characterization analysis. In a model of oxidative stress in neural cells induced by hydrogen peroxide, the cells viability of RSC96 and PC12 were protected from oxidative stress injury by NA. Similarly, based on the rat wound healing model, effective blood vessel formation and wound healing can be observed in tissue staining under NA treatment. In addition, according to the identification of nerve and vascular related markers in the wound tissue, the mechanism of NA promoting nerve regeneration lies in the upregulation of the secretion NGF, NF-200 and S100 protein, and NA treatment was also able to up-regulate VEGF and CD31 to directly promote angiogenesis during wound healing. This study provides an important candidate drug molecules for acute or chronic wound healing and nerve vascular synchronous regeneration.

Three-dimensional anisotropic unified continuum model for simulating the healing of damaged soft biological tissues.

The soft biological tissues have the ability to heal and self-repair after damage or injury. During the healing process, damaged tissues are replaced by newly produced undamaged tissue to restore homeostasis. Computational modeling serves as an effective tool for simulating the healing process and understanding the underlying mechanisms. In previous work, we developed the first unified continuum damage model for the healing of soft biological tissues. However, the initial theory lacked generalizability to more realistic scenarios and applicability to biomechanical problems due to the simplicity of the isotropic constitutive model and two-dimensional simulations. Therefore, we further improve our approach by developing a three-dimensional anisotropic unified healing model to address more realistic challenges. By using the Holzapfel-Gasser-Ogden model as the hyperelastic term, the influence of the collagen fibers is considered and the reorientation of fibers in healing is simulated. Three numerical examples related to hypertension, aneurysm, and restenosis of the atherosclerotic artery after balloon angioplasty are presented to demonstrate the effectiveness of the proposed model. By comparing numerical solutions and reference solutions, we demonstrate the ability of the proposed model in simulating long-term tissue healing process and analyze the impact of anisotropic terms.

Aurelia aurita jellyfish collagen: Recovery properties

Wound and burn healing is a complex physiological process that can be facilitated by medications based on marine collagen. In this regard, biomass of the Aurelia aurita jellyfish is a promising alternative source of medical collagen. As the global incidence of burns and wounds continues to grow, new healing methods have become a relevant area of medical science. This study featured acetic acid as a means of marine collagen extraction from A. aurita biomass. The physical and chemical properties of jellyfish collagen were determined gravimetrically and included such indicators as water solubility and water holding capacity. The molecular weight was defined by gel electrophoresis. The spectral studies relied on the method of UV spectroscopy. The regenerative experiments included such parameters as cytotoxicity, antioxidant properties, adhesion, and wound healing rate, as well as a quantitative PCR analysis. The optimal conditions for maximal collagen yield were as follows: 0.5 M acetic acid and 48 h extraction time. However, the collagen yield was very low (≤ 0.0185%). The high water holding capacity showed good prospects for A. aurita collagen to be used as hemostatic sponge. The acid-soluble collagen sample had a molecular weight of 100–115 kDa, which made it possible to classify it as type I. A. aurita jellyfish collagen revealed no cytotoxic properties; it had no effect on adhesion, migration, and proliferation of keratinocytes, neither did it affect the expression of cell differentiation markers. The wound healing model proved that the marine collagen had regenerative properties as it was able to increase the wound healing rate by 24.5%. Therefore, collagen extracted from the biomass of A. aurita jellyfish d emonstrated good p rospects for cosmetology and regenerative medicine.

Synergistic effect of zinc oxide-cinnamic acid nanoparticles for wound healing management: in vitro and zebrafish model studies

Wound infections resulting from pathogen infiltration pose a significant challenge in healthcare settings and everyday life. When the skin barrier is compromised due to injuries, surgeries, or chronic conditions, pathogens such as bacteria, fungi, and viruses can enter the body, leading to infections. These infections can range from mild to severe, causing discomfort, delayed healing, and, in some cases, life-threatening complications. Zinc oxide (ZnO) nanoparticles (NPs) have been widely recognized for their antimicrobial and wound healing properties, while cinnamic acid is known for its antioxidant and anti-inflammatory activities. Based on these properties, the combination of ZnO NPs with cinnamic acid (CA) was hypothesized to have enhanced efficacy in addressing wound infections and promoting healing. This study aimed to synthesize and evaluate the potential of ZnO-CN NPs as a multifunctional agent for wound treatment. ZnO-CN NPs were synthesized and characterized using key techniques to confirm their structure and composition. The antioxidant and anti-inflammatory potential of ZnO-CN NPs was evaluated through standard in vitro assays, demonstrating strong free radical scavenging and inhibition of protein denaturation. The antimicrobial activity of the nanoparticles was tested against common wound pathogens, revealing effective inhibition at a minimal concentration. A zebrafish wound healing model was employed to assess both the safety and therapeutic efficacy of the nanoparticles, showing no toxicity at tested concentrations and facilitating faster wound closure. Additionally, pro-inflammatory cytokine gene expression was analyzed to understand the role of ZnO-CN NPs in wound healing mechanisms. In conclusion, ZnO-CN NPs demonstrate potent antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for wound treatment. Given their multifunctional properties and non-toxicity at tested concentrations, ZnO-CN NPs hold significant potential as a therapeutic agent for clinical wound management, warranting further investigation in human models.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

Revolutionizing cancer survivorship: Using human-centered design to build an innovative model for whole-person healing.

355 Background: The cancer care system has struggled for decades to deliver meaningful post-tx survivorship care, relying on patient uptake of clinical guidelines for surveillance, and SCPs for health promotion and managing late effects. On paper, we know how to support survivors. However, there is a lack of “comprehensive guidance on patient-centered practices that specifically address how cancer patients experience their care or how to personalize survivorship so that it meets patients’ unique needs” (Mead et al, 2020). Tofill this gap, we developed an evidence-based, community-delivered model for whole-person healing throughout acute and extended survivorship. Methods: We co-designed a new care model with 24 survivors, shaped by their lived experience &amp; unmet needs. The pilot comprised: A) 2-day in-person retreat to evaluate healing modalities (incl. yoga, journaling, group discussion, nutrition coaching, songwriting); B) a 3-hour human-centered design workshop defining “thriving,” mapping survivorship challenges/gaps &amp; crafting an ideal care map; C) 8-12 weeks of facilitated organic social engagement with their retreat cohort. We conducted the intervention 3x (6/2003-3/2024) with 7-9 participants aged 29-60. Pre-intervention &amp; 4-month post-intervention surveys measured QOL, symptoms &amp; self-efficacy. Participants also did a qualitative survey post-intervention, sharing preferences &amp; activity impact. Results: The model addresses cancer's proximal/distal psychological, emotional, physical &amp; existential impacts. It builds a connected survivor community &amp; drives long-term behavior change with group accountability. The intervention: A) reduced fears of recurrence &amp; preoccupation with functional concerns &amp; indicated positive changes in self-concept; B) improved social connectedness. 86% agreed/strongly agreed they felt seen &amp; understood; 100% strongly agreed that they can implement 1+ new wellness/healing tool in daily life; 80% increase in confidence keeping emotional distress from interfering with life; 40% reduction in perception of cancer/Tx causing negative changes in self-concept; 60% increase in confidence keeping fatigue from interfering with life. Conclusions: A new model of post-treatment survivorship care is needed that aligns with oncology and primary care delivery, builds on the modern wellness movement, and is able to be sustained in daily life. Survivorship can be delivered in the community leveraging in-person/virtual retreats, workshops, apps and social networks. This intervention shows potential to transform survivorship care delivery &amp; radically improve outcomes.

The syndemic effect of COVID-19 and racial discrimination on suicide risk for Black emerging adults: Examining a model of radical healing.

Suicide is a leading cause of death among Black emerging adults. The concurrent effect of the COVID-19 pandemic and racial discrimination were projected to exacerbate suicide vulnerability for Black Americans. The purpose of the present study was to utilize a risk-resilience model to examine the effects of racial discrimination and COVID-related stress on suicide risk for Black emerging adults, as well as the moderating effect of three central components of radical healing: critical consciousness, resilience, and cultural authenticity. Study participants included 521 Black emerging adults between the ages of 18 and 29 (51.6% male; Mage = 24.6, SD = 2.6) who completed measures evaluating symptoms of racial discrimination, COVID-related stress, suicide risk, and psychological well-being. After controlling for age, gender, socioeconomic status, and general stress, structural equation modeling analyses revealed unique and interactive effects of racial discrimination, COVID-related stress, and culturally relevant protective factors on suicide risk for Black emerging adults. These findings provide preliminary insight into novel risk and protective factors that influence suicide risk for Black emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).