Inhibition Of Scar Formation Research Articles

Mesenchymal stem cells paracrine proteins from three-dimensional dynamic culture system promoted wound healing in third-degree burn models.

Recovery of skin function remains a significant clinical challenge for deep burns owing to the severe scar formation and poor appendage regeneration, and stem cell therapy has shown great potential for injured tissue regeneration. Here, a cell-free therapy system for deep burn skin was explored using mesenchymal stem cell paracrine proteins (MSC-PP) and polyethylene glycol (PEG) temperature-sensitive hydrogels. A three-dimensional (3D) dynamic culture system for MSCs' large-scale expansion was established using a porous gelatin microcarrier crosslinked with hyaluronic acid (PGM-HA), and the purified MSC-PP from culture supernatant was characterized by mass spectrometric analysis. The results showed the 3D dynamic culture system regulated MSCs cell cycle, reduced apoptosis, and decreased lactic acid content, and the MSC-PP produced in 3D group can promote cell proliferation, migration, and adhesion. The MSC-PP + PEG system maintained stable release in 28 days of observation in vitro. The in vivo therapeutic efficacy was investigated in the rabbit's third-degree burn model, and saline, PEG, MSC-PP, and MSC-PP + PEG treatments groups were set. The in vivo results showed that the MSC-PP + PEG group significantly improved wound healing, inhibited scar formation, and facilitated skin appendage regeneration. In conclusion, the MSC-PP + PEG sustained-release system provides a potentially effective treatment for deep burn skin healing.

Aligned lovastatin-loaded electrospun nanofibers regulate collagen organization and reduce scar formation.

Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promotedskin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. STATEMENT OF SIGNIFICANCE: In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management.

Roles of bovine sialoglycoproteins for anti-skin aging and accelerating skin wound healing.

Fibroblasts are the most predominant cell subpopulation in the dermal layer of human skin, they play an important role in maintaining skin architecture and function. The senescence of fibroblasts is one of major causes of skin aging and chronic wound in the elderly, which is accompanied with a reduction of α2,6-sialylation on the cell surface. In this study, we investigated the effects of the bovine sialoglycoproteins on normal human dermal fibroblasts (NHDF). The results showed that bovine sialoglycoproteins could promote the proliferation and migration of NHDF cells, and accelerate the contraction of fibroblast-populated collagen lattice (FPCL). The average doubling time of NHDF cells treated with bovine sialoglycoproteins (0.5 mg/mL) was 31.1 ± 1.0 h whereas that was 37.9 ± 2.7 h for the control (p ˂ 0.05). Moreover, the expression of basic fibroblast growth factor (FGF-2) was upregulated, while that of transforming growth factor-beta 1 (TGF-β1) and human type I collagen (COL-I) were downregulated in treated NHDF cells. Furthermore, bovine sialoglycoproteins treatment significantly enhanced the α2,6-sialylation on the cell surfaces, which was consistent with the upregulation of α2,6-sialyltransferase I (ST6GAL1) expression. These results indicated that the bovine sialoglycoproteins might be developed as a reagent against skin aging in the cosmetic industry, or as a new candidate for accelerating skin wound healing and inhibiting scar formation.

Hydroxycamptothecin regulates scar formation of the filtration channel under scleral flap by inhibiting the proliferation of scleral fibroblasts.

To investigate the inhibitory effect of a hyaluronic acid hydrogel loaded with hydroxycamptothecin (HCPT) on scar formation after filtration surgery in a rabbit model. Scleral fibroblasts were isolated and extracted from rabbits' eyes. After treatment with different concentrations of HCPT, cytotoxicity was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and proliferation and extent of apoptosis were analysed using flow cytometry. Hydrogels loaded with different dosages of HCPT were prepared and placed under the scleral flap after the filtration surgery. One day, one week, and two weeks after surgery, follicular, conjunctival, corneal, and anterior chamber inflammation and iris and lens changes were observed. In vitro, compared with cells not treated with HCPT, cells treated with HCPT had decreased survival rate and proliferation, and the apoptosis level increased with increasing HCPT concentrations (p < 0.05). In vivo, the flattening time of filtering blebs in the three groups treated with different dosages of HCPT hydrogel was delayed. The degrees of oedema, inflammation, and bleeding were similar to those observed in the control group. The HCPT hydrogel effectively downregulated the expression of collagen 1 and 3 and tissue inhibitor of metalloproteinase 2 and upregulated the expression of matrix metalloproteinase 2 in a dose-dependent manner. HCPT significantly inhibited the growth of rabbits' scleral fibroblasts and effectively inhibited scar formation after filtering surgery by accelerating the degradation of extracellular matrix deposition.

Adhesive Hydrogel Patch-Mediated Combination Drug Therapy Induces Regenerative Wound Healing through Reconstruction of Regenerative Microenvironment.

Regenerative wound healing involves the scarless wound healing as observed in fetal skin. Multiple features of regenerative wound healing have been well studied; however, the practical application of pro-regenerative materials to recapitulate the regenerative wound healing in adult skins has not yet been achieved. In this study, the authors identified that their novel pro-regenerative material, pyrogallol-functionalized hyaluronic acid (HA-PG) patches in combination with protein transduction domain-fused Dishevelled (Dvl)-binding motif (PTD-DBM), a peptide inhibiting the CXXC-type zinc finger protein 5 (CXXC5)-Dvl interaction, promoted regenerative wound healing in mice. The HA-PG patches loaded with this competitor peptide and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor, significantly inhibited scar formation during wound healing. The HA-PG patches with PTD-DBM and/or VPA inhibit the expression of differentiated cell markers such as α-smooth muscle actin (α-SMA) while inducing the expression of stem cell markers such as CD105 and Nestin. Moreover, Collagen III, an important factor for regenerative healing, is critically induced by the HA-PG patches with PTD-DBM and/or VPA, as also seen in VPA-treated Cxxc5-/- mouse fibroblasts. Overall, these findings suggest that the novel regeneration-promoting material can be utilized as a potential therapeutic agent to promote both wound healing and scar attenuation.

MicroRNA let-7d attenuates hypertrophic scar fibrosis through modulation of iron metabolism by reducing DMT1 expression.

Hypertrophic scar is an unavoidable result of wound healing following burns and trauma, which remains a challenging problem for clinicians. Previously, we demonstrated that exosomal microRNAs (miRs) of human amniotic epithelial cells accelerated wound healing and inhibited scar formation. However, the underlying mechanism is still unclear. In this particular study, we found that miR-let-7d reduced collagen deposition, and this was accompanied by decreased level of iron content in myofibroblasts. Importantly, inhibition of miR-let-7d in myofibroblasts accelerated collagen deposition and promoted cell proliferation. In addition, bioinformatics prediction combined with classical dual-luciferase reporter gene assay demonstrated that the cellular iron importer divalent metal transporter 1 (DMT1) was a target gene of miR-let-7d, and the miR-let-7d mimics inhibited the expression of DMT1 in myofibroblasts. Moreover, silencing of DMT1 with small interfering RNA (siRNA) reduced the deposition of extracellular matrix. Consistent with the results in vitro, the miR-let-7d mimics effectively ameliorated hypertrophic scar fibrosis in a rabbit ear hypertrophic scar model. Taken together, our results indicated for the first time that miR-let-7d attenuated hypertrophic scar fibrosis through modulation of iron metabolism by reducing iron uptake through DMT1, which may provide a novel therapeutic strategy for hypertrophic scar.

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.

Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury.

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Ellipsoidal porous patch with anisotropic cell inducing ability for inhibiting skin scar formation

• An ellipsoidal porous patch is fabricated for inhibiting skin scar formation. • The anisotropic surface microstructure of patch showed dramatic capability in guiding cell growth and arrangement by reconstructing cell morphology. • The proliferation of fibroblasts growing on the stretched inverse opal patch was significantly suppressed without cell cytotoxicity. • The patch effectively reduce the scar formation by inhibiting excessive fibroblast proliferation of and type-I collagen deposition. Scar formation has always been a difficult point to overcome in the field of clinical wound care. Here, we present an ellipsoidal porous patch with cell inducing ability for inhibiting scar formation. The patch was prepared by stretching a poly (lactic-co-glycolic acid) (PLGA) inverse opal film at the glass transition temperature to form a neatly arranged three-dimensional ellipsoidal porous structure. Such anisotropic structure showed dramatic capability in directing cell growth and arrangement by reconstructing cell morphology. Besides, the proliferation of cells growing on the stretched patch was significantly suppressed without cell cytotoxicity. In addition, benefitting from the abundant and connected nanopores, the patch could be imparted with a potent ability to promote cell migration by encapsulating fibroblast growth factor 2 (FGF2) via the second filling of functional gelatin methacryloyl (GelMA) hydrogel into its scaffold. In a typical scar model, we have demonstrated that the resultant patch performed well in inhibiting scar formation characterized by inhibiting the excessive proliferation of fibroblasts, decreasing the deposition of type I collagen, reducing the scar index and achieved complete tissue reconstruction. These results indicate the anisotropic inverse opal patch has an excellent application prospect in inhibiting scar formation during wound repair.

Angiogenic gene characterization and vessel permeability of dermal microvascular endothelial cells isolated from burn hypertrophic scar

Hypertrophic scar (HTS) formation is a common challenge for patients after burn injury. Dermal microvascular endothelial cells (DMVECs) are an understudied cell type in HTS. An increase in angiogenesis and microvessel density can be observed in HTS. Endothelial dysfunction may play a role in scar development. This study aims to generate a functional and expression profile of HTS DMVECs. We hypothesize that transcript and protein-level responses in HTS DMVECs differ from those in normal skin (NS). HTSs were created in red Duroc pigs. DMVECs were isolated using magnetic-activated cell sorting with ulex europaeus agglutinin 1 (UEA-1) lectin. Separate transwell inserts were used to form monolayers of HTS DMVECs and NS DMVECs. Cell injury was induced and permeability was assessed. Gene expression in HTS DMVECS versus NS DMVECs was measured. Select differentially expressed genes were further investigated. HTS had an increased area density of dermal microvasculature compared to NS. HTS DMVECs were 17.59% less permeable than normal DMVECs (p < 0.05). After injury, NS DMVECs were 28.4% and HTS DMVECs were 18.8% more permeable than uninjured controls (28.4 ± 4.8 vs 18.8 ± 2.8; p = 0.11). PCR array identified 31 differentially expressed genes between HTS and NS DMVECs, of which 10 were upregulated and 21 were downregulated. qRT-PCR and ELISA studies were in accordance with the array. DMVECs expressed a mixed profile of factors that can contribute to and inhibit scar formation. HTS DMVECs have both a discordant response to cellular insults and baseline differences in function, supporting their proposed role in scar pathology. Further investigation of DMVECs is warranted to elucidate their contribution to HTS pathogenesis.

Research progress on role of Chinese medicinal materials and their topical preparations in wound healing by regulating cytokines and growth factors

Delayed-or non-healing wounds caused by trauma, surgical procedures, acute diseases, or chronic diseases, and proli-ferating scar have a serious impact on patients' quality of life and increase the economic and psychological burden on their families. Therefore, how to accelerate wound healing and obtain satisfactory aesthetic results is of great concern to researchers and is an urgent clinical problem to be solved. In recent years, the mechanisms of Chinese medicinal materials in accelerating wound healing and inhi-biting scar formation by regulating cytokines have been clarified, which provides a scientific basis for revealing the efficacy of Chinese medicinal materials against clinical trauma. This review focuses on the therapeutic effects of active ingredients, extracts, and topical preparations of Chinese medicinal materials through regulating cytokines in the inflammation, proliferation, and remodeling phases of wound healing. It is expected to provide evidence for the application of Chinese medicinal materials in wound therapy.

Different dimension ZnO nano materials in the rehabilitation of patients with limb fracture and injury

With the rapid development of industry and transportation in China, the incidence rate of open fracture caused by high energy injuries such as traffic accidents and falling height is increasing year by year. Based on the above background, the purpose of this paper is to study the application of ZnO nano materials with different dimensions in the rehabilitation of patients with limb fracture injury. In order to further solve the problem of limb fracture rehabilitation, zinc oxide nanomaterials are applied to fracture rehabilitation in this paper. The application of zinc oxide nanomaterials in fracture rehabilitation is realized by its strong antibacterial, high-efficiency stability and rich and colorful structure. In this paper, we propose to use the unique physical and chemical properties of ZnO nanomaterials to prepare artificial bone, bone cement, external fixation with good osteogenic performance and antibacterial performance, and carry antibiotics for the treatment of open fracture infection and bone defect. During the experiment, compared with other materials, the infection rate of external fixation was only 63%, and the inflammation index of artificial bone was only 2 mg/dl, which was far less than other materials. Moreover, using the excellent plasticity of ZnO nanomaterials, the oriented ZnO nanotube films were prepared, and the effect of inhibiting scar formation was confirmed through experimental research. In this paper, the unique physical, chemical and biological characteristics of zinc oxide nanomaterials were used to creatively introduce them into the treatment of infectious bone defect and injury rehabilitation caused by limb fracture. Through a series of in vitro and animal in vivo experiments, it was proved that zinc oxide nanomaterials can be used as ideal materials for the treatment of infectious bone defect, which provides new zinc oxide nanomaterials to solve clinical problems A new way of thinking.

The effects of GelMA hydrogel on nerve repair and regeneration in mice with spinal cord injury.

BackgroundTo determine the effects of gelatin methacryloyl (GelMA) hydrogel on nerve repair and regeneration in mice with spinal cord injury (SCI).MethodsA total of 30 ICR mice (6–8 weeks old) were randomly assigned into the control group, the model group, and the experimental group via the random digits table method. There were 10 mice in each group. All mice underwent a T8 laminectomy. For mice in the experimental group and the model group, after the T8 laminectomy, SCI models were constructed by clamping the mice spinal cord tissue for 1 minute using an aneurysm clip (25 g). Additionally, the SCI area of each mouse in the experimental group was locally injected with 0.05–0.7 mL GelMA hydrogel [10% (w/v)] and photocrosslinking was initiated under a blue light source with a wavelength of 405 nm. The exercise performance of each mouse was tested via the bedside mobility scale (BMS) on post-operative days 1, 3, 7, and 14. After 14 days, mice were sacrificed and the dorsal root ganglion (DRG) sensory neurons were isolated and cultured for 3 days in vitro. The axon lengths of the neurons were then evaluated. Immunohistochemical staining was performed to assess the development of syringomyelia in the area. Western blots (WB) and immunofluorescence staining were performed to quantify the expression of glial fibrillary acidic protein (GFAP), growth associated protein (GAP)43, and nestin in the DRG neurons from each group of mice.ResultsCompared with mice in the control group, mice in the SCI model group showed a notable decrease in exercise ability, while the exercise ability of mice in the experimental group recovered markedly after treatment with GelMA hydrogel. Administration of GelMA hydrogel lengthened the axon of DRG neurons in mice and reduced the area of syringomyelia. Furthermore, GelMA hydrogel inhibited scar formation and promoted the recovery of neurological function by upregulating GAP43 and nestin expression and downregulating GFAP expression.ConclusionsIn mice with SCI, local injection of GelMA hydrogel strongly inhibited scar formation, reduced the area of syringomyelia, and promoted nerve regeneration and recovery of limb movement function.

Curcumin/Fe-SiO2 nano composites with multi-synergistic effects for scar inhibition and hair follicle regeneration during burn wound healing

The scar formation and hair follicle regeneration are closely related in the healing process of skin burn wounds. Excessive pathological fibroblasts at the scar site severely hinders the migration of hair follicle stem cells to the damaged site. Therefore, it is of great clinical significance to develop wound dressings to inhibit scar formation and promote hair follicle regeneration. In this study, inspired by the bioactivity of SiO32−, Fe3+ and Cur, we designed a new type of nano composites, Cur-Fe-mesoporous silica nanoparticles (Cur-Fe-SiO2, MFSC). On the one hand, Fe3+ doping reduced the stability of mesoporous silica, so that it can effectively release biologically active SiO32− and Fe3+. On the other hand, Fe3+ ions released on the surface of the mesoporous silica pores chelated with the Cur in the solution and resulted in significantly improved loading of Cur and the chelates showed higher biological activity as compared to Cur or Fe alone. The released bioactive components such as SiO32−, Fe3+ and Fe-Cur chelates showed synergistic activity in both inhibiting scar hyperplasia and promoting hair follicle regeneration. Our results suggest that the synergistic effects between ions and flavonoids can be used to increase the bioactivity of biomaterials, and design of nano composites with bioactive ions and flavonoids might be an effective approach to prepare materials for tissue regeneration.

The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease.

Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Stem cell transplantation has become a promising approach for the treatment of IHD in recent decades. It is generally recognized that preclinical cell-based therapy is effective and have yielded encouraging results, which involves preventing or reducing myocardial cell death, inhibiting scar formation, promoting angiogenesis, and improving cardiac function. However, clinical studies have not yet achieved a desired outcome, even multiple clinical studies showing paradoxical results. Besides, many fundamental puzzles remain to be resolved, for example, what is the optimal delivery timing and approach? Additionally, limited cell engraftment and survival, challenging cell fate monitoring, and not fully understood functional mechanisms are defined hurdles to clinical translation. Here we review some of the current dilemmas in stem cell-based therapy for IHD, along with our efforts and opinions on these key issues.

Polyphenol and Cu2+ surface-modified chitin sponge synergizes with antibacterial, antioxidant and pro-vascularization activities for effective scarless regeneration of burned skin

Bacterial overgrowth and high oxidative stress often lead to burn wound infection, hyper-inflammation, and slowed wound healing, eventually causing scar formation. Wound dressings synergized with antibacterial, antioxidant, and pro-vascularization activities can effectively promote wound healing and inhibit scars formation. Herein, chitin sponge consisted of chitin fibers was modified by the coating of proanthocyanidins (PAs) – Cu2+ for effective scarless skin regeneration in a burn injury. The physicochemical characteristics indicated that PAs and Cu2+ successfully modified chitin sponges by the coordination between PAs and Cu2+. For one thing, PAs improved the antioxidant performance of sponges, and for another, with the help of PAs, Cu2+ effectively catalyzed S-nitrosothiols (RSNOs) to continuously generate nitric oxide (NO) in vitro/vivo for improving the inhibition of microorganisms and pro-vascularization activities. Also, Ch/PAs-Cu promoted proliferation of human umbilical vein endothelial cells (HUVECs) and rat fibroblasts (NIH-3T3), and the expression of angiogenic-related cytokines VEGF, eNOS, FGF, and MMP9. In animal experiments, Ch/PAs-Cu inhibited the accumulation of macrophages and neutrophils to regulate wound inflammation while up-regulating the expression of CD31 and α-SMA cytokines to promote angiogenesis. Ultimately, it promoted wound healing and inhibited scar formation. Therefore, Ch/PAs-Cu may be a promising dressing for the scarless repair of burned skin.

Collagen Peptides Derived from Sipunculus nudus Accelerate Wound Healing.

Marine collagen peptides have high potential in promoting skin wound healing. This study aimed to investigate wound healing activity of collagen peptides derived from Sipunculus nudus (SNCP). The effects of SNCP on promoting healing were studied through a whole cortex wound model in mice. Results showed that SNCP consisted of peptides with a molecular weight less than 5 kDa accounted for 81.95%, rich in Gly and Arg. SNCP possessed outstanding capacity to induce human umbilical vein endothelial cells (HUVEC), human immortalized keratinocytes (HaCaT) and human skin fibroblasts (HSF) cells proliferation and migration in vitro. In vivo, SNCP could markedly improve the healing rate and shorten the scab removal time, possessing a scar-free healing effect. Compared with the negative control group, the expression level of tumor necrosis factor-α, interleukin-1β and transforming growth factor-β1 (TGF-β1) in the SNCP group was significantly down-regulated at 7 days post-wounding (p < 0.01). Moreover, the mRNA level of mothers against decapentaplegic homolog 7 (Smad7) in SNCP group was up-regulated (p < 0.01); in contrast, type II TGF-β receptors, collagen I and α-smooth muscle actin were significantly down-regulated at 28 days (p < 0.01). These results indicate that SNCP possessed excellent activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to reducing inflammation, improving collagen deposition and recombination and blockade of the TGF-β/Smads signal pathway. Therefore, SNCP may have promising clinical applications in skin wound repair and scar inhibition.

The therapeutic effects of earthworm extract on deep second-degree burn wound healing.

To investigated the effect of earthworm extract (EE) on deep second-degree burn wound healing process. A burn wound model was created on the mice's skin and was subject to different treatments: the control group received no treatment; the Jingwanhong (JWH: a well-established, widely used external ointment for treating burn wounds) group was treated with 0.1 g of JWH cream and spray it on the wound surface; the EE group was treated with 0.1 mL of EE solution. All the mice were sacrificed at 3, 7, 11, and 15 days after injury (n=6/group/time point). Macroscopic observation, wound healing rate (WHR), wound healing time (WHT), water content (WC), hydroxyproline (Hyp) content, histological, and hematological analyses were performed at the burn wound sites. Better, faster burn wound healing in the JWH and EE groups than the control group at 15 days after injury were detected at the wound sites. Compared to the control group, the EE group had higher WHR, shorter WHT, lower WC, higher Hyp content, more fibroblasts, fibrocytes, and capillary endothelial cells; in addition, they showed greater capillary endothelial cell grouping at the wound sites during the healing process. This group also showed more platelets, white blood cells (WBCs), and neutrophilic granulocytes in serum at the early stages after burn injury. EE could effectively promote skin wound healing by decreasing edema, suppressing fibrosis, activating angiogenesis and epithelial regeneration, inhibiting scar formation, and reducing the risk of infection. Thus, it could be made into a promising healing agent for burn wound.

Review of interferon alpha-2b inhibiting scar formation

Review of interferon alpha-2b inhibiting scar formation

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

BackgroundTendon stem cells (TSCs) have been reported to hold promises for tendon repair and regeneration. However, less is known about the effects of exosomes derived from TSCs. Therefore, we aimed to clarify the healing effects of TSC-derived exosomes (TSC-Exos) on tendon injury.MethodsThe Achilles tendons of Sprague-Dawley male rats were used for primary culture of TSCs and tenocytes, and exosomes were isolated from TSCs. The proliferation of tenocytes induced by TSC-Exos was analyzed using an EdU assay; cell migration was measured by cell scratch and transwell assays. We used western blot to analyze the role of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. In vivo, Achilles tendon injury models were created in Sprague-Dawley rats. Rats (n = 54) were then randomly assigned to three groups: the TSC-Exos group, the GelMA group, and the control group. We used immunofluorescence to detect changes in the expression of inflammatory and apoptotic markers at 1 week after surgery. Histology and changes in expression of extracellular matrix (ECM)-related indices were assessed by hematoxylin-eosin (H&E) staining and immunohistochemistry at 2 and 8 weeks. The collagen fiber diameter of the healing tendon was analyzed at 8 weeks by transmission electron microscopy (TEM).ResultsTSC-Exos were taken up by tenocytes, which promoted the proliferation and migration of cells in a dose-dependent manner; this process may depend on the activation of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. At 1 week after surgery, we found that inflammation and apoptosis were significantly suppressed by TSC-Exos. At 2 and 8 weeks, tendons treated with TSC-Exos showed more continuous and regular arrangement in contrast to disorganized tendons in the GelMA and control groups, and TSC-Exos may help regulate ECM balance and inhibited scar formation. Further, at 8 weeks, the TSC-Exos group had a larger diameter of collagen compared to the control group.ConclusionsOur data suggest that TSC-Exos could promote high-quality healing of injured tendon, which may be a promising therapeutic approach for tendon injury.