Insulin modified Decellularized Adipose Tissue/Tremella Polysaccharide hydrogel loaded with ADSCs for skin wound healing.

Full-thickness skin wounds still represent a challenge for clinical treatment. Adipose-derived stem cells (ADSCs) therapy is a promising approach to achieve efficient healing in skin wounds. The excellent cell scaffold can promote proliferation, differentiation and paracrine of ADSCs in wound microenvironment, and is a key factor in ADSCs application. Herein, we first prepared the composite hydrogel with decellularized adipose tissue (DAT) and tremella polysaccharide (TPS), and loaded insulin (INS) into the DAT/TPS composite hydrogel (DAT/TPS-gel) to fabricate an efficient carrier for ADSCs in treating skin wound. Our study showed that INS modified DAT/TPS-gel (INS-DAT/TPS-gel) can promote the proliferation, differentiation and paracrine of ADSCs. INS-DAT/TPS-gel laden with ADSCs (ADSCs/INS-DAT/TPS-gel) effectively facilitated the skin wound healing in SD rats. These findings indicated that INS-DAT/TPS-gel was an effective scaffold for ADSCs transplantation, and ADSCs/INS-DAT/TPS-gel provides a potential strategy for the treatment of skin wounds.

Metasurface of deflection prism phases for generating non-diffracting optical vortex lattices.

A functional metasurface of both transparent medium slices and multiple deflection prisms is proposed, where phase retardations for generating non-diffracting vortex lattices are integrated and encoded as rotation angles of nano-apertures. Under plane-wave illumination, the transmitted waves from the thin flat metasurface act analogously as multiple beams, each with a designed propagating direction and pre-scribed phase shift, that generate an optical lattice within their overlapping region of space. By altering the design parameters of the metasurface, lattice type and size can be controlled. Both numerical simulations and experiments were conducted, verifying the possibility of the proposed method and the non-diffracting properties of the generated vortex lattices.

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques.

BACKGROUND/AIMS: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. METHODS: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. RESULTS: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP+/α-SMA+- and GFP+/VIM+-cell numbers decreased gradually with healing time, α-SMA+- and VIM+-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. CONCLUSION: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

CXCR4 antagonist delivery on decellularized skin scaffold facilitates impaired wound healing in diabetic mice by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing. ADM scaffolds were fabricated from nondiabetic mouse skin through decellularization processing and incorporated with AMD3100 to construct ADM-AMD3100 scaffold. Full-thickness cutaneous wound in streptozotocin (STZ)-induced diabetic mice were treated with ADM, AMD3100, or ADM-AMD3100. 21 days after treatment, wound closure in ADM-AMD3100-treated mice was more complete than ADM group and AMD3100 group, and it was accompanied by thicker collagen formation. Correspondingly, diabetic mice treated with ADM-AMD3100 demonstrated prominent neovascularization (higher capillary density and vascular smooth muscle actin), which were accompanied by up-regulated mRNA levels of SDF-1 and enhanced migration of CXCR4 in the granulation tissue. Our results demonstrate that ADM scaffold provide perfect niche for loading AMD3100 and ADM-AMD3100 is a promising method for diabetic wound healing mainly by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

Raman spectroscopy enables noninvasive biochemical identification of the collagen regeneration in cutaneous wound healing of diabetic mice treated with MSCs.

Mesenchymal stem cells (MSCs) had been reported as a novel therapeutic strategy for non-healing diabetic cutaneous wound mainly by promoting the formation of extracellular matrix (ECM) and neovasculature. Collagen regeneration is one of the key processes of ECM remodeling in wound healing. Accordingly, rapid assessment of the collagen content in a noninvasive manner can promptly provide objective evaluation for MSC therapy of cutaneous wound healing and strength evidence to adjust therapeutic regimen. In the present study, noninvasive Raman microspectroscopy was used for tracing the regeneration status of collagen during diabetic wound healing with MSCs. Wound tissues of normal mice, diabetic mice, and MSC-treated diabetic mice were subjected to Masson trichrome staining assay and submitted to spectroscopic analysis by Raman microspectroscopy after wounding 7, 14, and 21 days. Masson trichrome staining demonstrated that there was more collagen deposition in diabetic + MSCs group relative to diabetic group. The relative intensity of Raman collagen peak positions at 937, 1004, 1321, 1452, and 1662 cm-1 increased in MSC-treated diabetic group compared to diabetic group, although normal mice group had the highest relative intensity of collagen peak bands. Correlation analysis suggested that the spectral bands had a high positive correlation with the collagen intensity detected by Masson trichrome staining in wound tissues of three groups. Our results demonstrate that Raman microspectroscopy has potential application in rapidly and quantitatively assessing diabetic wound healing with MSCs by monitoring collagen variation, which may provide a novel method for the study of skin regeneration.

Smart windows based on ultraviolet-B persistent luminescence phosphors for bacterial inhibition and food preservation.

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12O19: Ce3+, Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage. Thus, the smart window with SrAl12O19: Ce3+, Sc3+/PDMS produces UVB PersL to efficiently inactivate Escherichia coli and Staphylococcus aureus. In addition, the presence of the smart window delays the critical point of pork decay, and greatly reduces the time of pork spoilage. It maximizes the convenience of eradicating bacteria and preserving food, thus offering a fresh perspective on the use of UV light for food sterilization and preservation.

PLGA@IL-8 nanoparticles-loaded acellular dermal matrix as a delivery system for exogenous MSCs in diabetic wound healing.

Diabetic chronic wounds are not only accompanied by inflammation and ulcers but also cause amputation when they develop into severe diabetic foot. Mesenchymal stem cells (MSCs) have been proven to ameliorate diabetic wound healing, however, the low survival rate of exogenous MSCs after transplantation into the highly proteolytic wound environment is a major obstacle to effective stem cell therapy. Herein, to improve the proliferation, differentiation, and anti-apoptosis ability of transplanted MSCs, we prepared Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with anti-inflammatory and angiogenic cytokine IL-8, then loaded the nanospheres on acellular dermal matrix to fabricate an efficient delivery medium (PLGA@IL-8/ADM) for exogenous MSCs. It was observed that, in the PLGA@IL-8-loaded ADM, MSCs presented significant proliferation and endothelial differentiation with a great survival rate. In addition, PLGA@IL-8/ADM laden with MSCs effectively induced the capillary construction, collagen deposition and wound healing in cutaneous wounds of streptozotocin-induced diabetic mice. Further immunofluorescence analysis indicated that proangiogenic factors (VEGF and α-SMA) were upregulated in regenerated tissue. Overall, our findings indicated that PLGA@IL-8/ADM-MSCs was a potential therapeutic dressing that may contribute to the therapy of diabetic wounds and the PLGA@IL-8/ADM scaffold would be a novel delivery system for exogenous cells for tissue regeneration.

A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing.

Inadequate angiogenesis in diabetic wound healing has been identified as one of the most difficult issues to treat. Copper ions (Cu2+) have been confirmed to stimulate angiogenesis; nevertheless, the rapid rise in non-physiological Cu2+ concentrations increases the danger of ion poisoning. For the first time, biotin was used to stabilize a copper-based metal-organic framework (HKUST-1) to change its hydrophobicity and achieve sustained release of Cu2+. The inability to offer a suitable area for the dynamic interaction between cells and growth factors still restricts the use of nanomaterials for the regeneration of injured skin in diabetes. Acellular dermal matrix (ADM) scaffolds are collagen fibers with natural spatial tissue that can create a biological "niche" for cell attachment and growth. In this study, biotin-stabilized HKUST-1 (B-HKUST-1) nanoparticles were modified with an ADM to form a novel scaffold (ADM-B-HKUST-1). Notably, Cu2+ and mesenchymal stem cells (MSCs) released by the composite scaffold may synergistically promote MSC adhesion, proliferation and endothelial differentiation by upregulating the expression of transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Overall, the ADM-B-HKUST1 scaffold combines the dual advantages of the sustained release of Cu2+ and creating a biological "niche" can provide a potential strategy for enhancing angiogenesis and promoting diabetic wound healing.

[Identification of Ginseng and its counterfeit by laser Raman spectroscopy].

The objective of the present study is to identify Ginseng and its false sample: Anthriscus sylvestris, Radix glehniae and balloonflower root by Laser Raman spectroscopy, second derivative Raman spectroscopy. The structural information of the samples indicated that Ginseng and its false samples contains a large amount of carbohydrates, since some characteristic vibration peaks of the carbohydrates, such 1 640, 1 432, 1 130, 1 086, 942, 483 cm(-'1) can be observed. The characteristic vibration peak of Radix glehniae which arouse at 2 206 cm(-1) in the aman spectra, totally different from the other three kinds of traditional Chinese medicines. Anthriscus sylvestris appeare the characteristic vibration peak in 1 050 cm(-1) and the corresponding 1 869 cm(-1) because of the chain ester compounds. The characteristic vibration peak of balloonflower root, such as 1 227, 691, 600 cm(-1) can be observed, significantly different from the other three herbs in the Raman spectra. Further more, the previous identification results can be verified again with second derivative Raman spectroscopy. This identification method is more fast, convenient, and keeping the integrity of the samples than the routine spectroscopic method.

Specificity of auricular acupoints in reflecting changes of qi and blood measured by diffuse reflectance spectroscopy.

OBJECTIVE: This study aimed to assess the specificity of auricular acupoints in responding to changes of qi and blood which, in traditional Chinese medicine, are considered as the fundamental substances in the human body for sustaining normal vital activity. METHODS: A miniature fiber optic system was used to invasively measure the diffuse reflectance spectra of three auricular acupoints, namely, Uterus (TF2), Gan (CO12) and Neifenmi (CO18), at different stages of menstruation, when the female body exhibits regular changes of qi and blood. The spectra of different acupoints were compared to find their difference in responding changes of qi and blood, especially the reflectivity of absorption peaks of hemoglobin. RESULTS: The reflectivity of the same auricular acupoint during menstruation is higher than that before and after menstruation, and this trend is more obvious for the Uterus point compared with the points Gan and Neifenmi. The average reflectivity of the Uterus point during menstruation was significantly higher than that before or after menstruation (P<0.01). The D-values during and after menstruation of the Uterus point were greater than those of the points Gan and Neifenmi at 544.06 and 577.47 nm, respectively (P<0.05). CONCLUSION: The diffuse reflectance light of auricular acupoints changes as qi and blood fluctuates, and there is relative specificity among different auricular acupoints in reflecting changes of qi and blood. The Uterus point may be the most sensitive auricular acupoint in reflecting uterus function and subsequent changes of qi and blood.

New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway.

Ceria-based nanomaterials have aroused major attentions among the biomedical application research field in recent years. Most of the researches have mainly focused on promoting the functional healing therapies of normal cells/organs with cerium oxide compounds, while the applications of ceria-based materials employed on cancer curing processes have been merely mentioned. To explore the possible capabilities of cerium oxide nanomaterials exterminating tumor cells, innovatively, we synthesized the eco-friendly pure cerium oxide nanodots (CNDs), proving the prominent ability of CNDs used in tumor chemotherapy (CDT) via Fenton reaction with the highly presence of H2O2 (acidic pH) in tumor tissues. CNDs reacted with the self-produced H2O2 of tumor cells, which generated piled up toxic hydroxyl radical (·OH). The accumulated virulent ·OH restrained the growth of cancer cells intensively. This peroxidase-like activity, provided a distinguished paradigm for effective cancer curing treatment. We also verified the biosafety of CNDs applied on normal cells. Notably, not only did CNDs be harmless to normal cells, but also it protected them from the damages of reactive oxygen species (ROS). In normal cells/tissues, under the microenvironment of neutral pH and low level of H2O2, the CNDs could effectively function as an annihilator inhibiting ROS. They reduced the damages caused by ROS, exhibiting catalase-like activity. The research we studied, which estimated CNDs thoroughly, has provided a new perspective to the future researches of the cerium oxide biomaterial applications.

Microscopic second harmonic generation (SHG) from tilt-placed collagen fibrils.

We report a theoretical study of second-harmonic generation (SHG) from the collagen fibrils which have a tilt angle Φ between their axes with the plane of the polarization angle α of the linearly polarized focused light. The effects of Φ as well as α on SHG emission have been investigated. Our results show that the total strength of SHG electrical field (E(2ω)) and power (P(2ω)) reach their maximal values as Φ locates at a certain angle, here it is around 27° under all demonstrated α. When Φ < 27°, E(2ω) and P(2ω) gradually increase to their maximal value, while when Φ > 27°, they quickly drops. Specially, E(2ω) and P(2ω) are almost undetectable when Φ ≥ 45°. Also, Φ influences the distribution pattern of E(2ω), P(2ω) and their parallel (E(2ω,p), P(2ω,p)) and perpendicular (E(2ω,s), P(2ω,s)) components, such as the number of emission lobes and shape. α has unevenly impact on E(2ω) and P(2ω), the far deviation of α from x axis induce much great decrease of E(2ω) and P(2ω). α = 45° has special influence on the distribution pattern of E(2ω,s), E(2ω), P(2ω,s) as well as P(2ω) compared to those of α = 0° and 90°.

[Influence of brightness value of supranasal point and apex nasi on dominant wavelength and excitation purity in complexion inspection of healthy adults].

OBJECTIVE: In this study, to analyze the influence of the brightness value of the supranasal point and the apex nasi on their dominant wavelength and excitation purity according to the spectrocolorimetry data of the supranasal point and the apex nasi in healthy adults that were collected based on optical spectrum colorimetry. METHODS: A total of 516 healthy adults were taken as the research subjects. The brightness, dominant wavelength and excitation purity values of the supranasal point and the apex nasi during the complexion inspection of subjects were calculated. This was based on the visible reflection spectrum, and the linear correlation/regression analysis between the brightness Y value and the dominant wavelength or excitation purity value. RESULTS: There was no correlation between the brightness Y value and the dominant wavelength of the normal supranasal point and the apex nasi; however, there was negative correlation between the brightness Y value and the excitation purity of the normal supranasal point and apex nasi. CONCLUSION: During the complexion inspection, the brightness Y value would not influence the dominant wavelength value, indicating that whiteness and/or blackness would not influence the normal individual complexion. However, the brightness Y value would influence the excitation purity of the supranasal point and the apex nasi, and the degree of saturation should be referred to as the brightness. This research provides a basic reference for diagnosing facial complexion in traditional Chinese medicine.

[Comparative study of reflectance spectroscopy of women's acupoints around menstruation].

Acupoint was reaction of viscera and its optical parameter was an important characteristic of tissue. In the present work, in order to discuss specificity of acupuncture on the response of qi and blood in human body, we compared the diffuse reflectance of Taichong (LV3), Taibai (SP3), and Chongyang (ST42) before, during and after menstruation. All the acupoints had the same shape of the spectrum and troughs were all at 423.16, 544.06 and 577.47 nm. The values of reflectance during menstruation were greater than before and after menstruation, especially for SP3 and ST42 (P < 0.05). SP3 and ST42 were more sensitive to the changes of qi and blood than LV3, and it was asymmetric and we found no evidence for the imbalance of the left side and right. These results indicated that acupoint diffuse reflectance changed with qi and blood, and that SP3 and ST42 had close relationship with menstruation. Diffuse reflectance may be possibly used in the quantitative analysis of qi and blood.

[Comparative study of reflectance spectroscopy of human laogong acupoint and non-acupoint tissues irradiated by near-infrared laser].

Characteristics and differences of reflectance spectroscopy of human Laogong acupoint and non-acupoint tissues before and after irradiation by different power of laser were studied in the spectral range from 400 to 1 000 nm. A wavelength 808 nm semiconductor laser was used for irradiation at the power of 20, 50 and 100 mW for ten minutes. Reflectance spectra of human Laogong acupoint and non-acupoint tissues were measured by using an AvaSpec-2048 optical fiber spectroscopy with an integrating sphere attachment. The result shows that before irradiation the shape of the reflectance spectra of Laogong acupoint and non-acupoint is similar, they have the same troughs at 423, 544, 577 and 980 nm, and the reflectance for Laogong acupoint and non-acupoint at these wavelengths is 17.1%, 26.1%, 25.9% and 35.0%, and 17.1%, 27.6%, 28.1% and 36.5% respectively. But from 475 to 1 000 nm, the reflectance of Laogong acupoint is smaller than that of non-acupoint. After being irradiated by semiconductor laser at the power of 20, 50 and 100 mW, there is a very significant decrease in the reflectance of Laogong acupoint compared to that before irradiation, and the higher the power, the lower the reflectance. But there is just a small decrease in the reflectance for non-acupoint compared to that before irradiation. From the above results, it is clearly seen that Laogong acupoint is different from non-acupoint on reflectance spectroscopy, and Laogong acupoint is more sensitive to laser irradiation than non-acupoint tissue.

Acidic pH and High-H2O2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition.

It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H2O2). These features of the tumor microenvironment may provide physiochemical conditions that are suitable for selective tumor therapy and recognition. Here, for the first time, we demonstrate that a type of graphene oxide nanoparticle (N-GO) can exhibit peroxidase-like activities (i.e., can increase the levels of reactive oxygen species (ROS)) under acidic conditions and catalyze the conversion of H2O2 to ROS-hydroxyl radicals (HO·) in the acidic microenvironment in Hela tumors. The concentrated and highly toxic HO· can then trigger necrosis of tumor cells. In the microenvironment of normal tissues, which has a neutral pH and low levels of H2O2, N-GOs exhibit catalase-like activity (scavenge ROS) that splits H2O2 into O2 and water (H2O), leaving normal cells unharmed. In the recognition of tumors, an inherent redox characteristic of dopamine is that it oxidizes to form dopamine-quinine under neutral (pH 7.4) conditions, quenching the fluorescence of N-GOs; however, this characteristic has no effect on the fluorescence of N-GOs in an acidic (pH 6.0) medium. This pH-controlled response provides an active targeting strategy for the diagnostic recognition of tumor cells. Our current work demonstrates that nanocatalytic N-GOs in an acidic and high-H2O2 tumor microenvironment can provide novel benefits that can reduce drug resistance, minimize side effects on normal tissues, improve antitumor efficacy, and offer good biocompatibility for tumor selective therapeutics and specific recognition.

Reduced Graphene Oxide Incorporated Acellular Dermal Composite Scaffold Enables Efficient Local Delivery of Mesenchymal Stem Cells for Accelerating Diabetic Wound Healing.

Chronic skin wounds caused by diabetes mellitus (DM) have been acknowledged as one of the most intractable complications. Local transplantation of mesenchymal stem cells (MSCs) is a promising method, but strategies for stabilizing and efficiently delivering active MSCs according to the wound circumstance with high proteolysis remain the main barrier. Hereon, the study demonstrates the feasibility of incorporating reduced graphene oxide (RGO) nanoparticles with an acellular dermal matrix (ADM) to improve physicochemical characteristics of natural scaffold material and fabricate a highly efficient local transplantation system for MSCs in diabetic wound healing. Under the influence of RGO nanoparticles, the ADM-RGO composite scaffolds achieved high stability and strong mechanical behaviors. In vitro, conductive ADM-RGO scaffolds demonstrated an admirable milieu for stem cells adhesion and proliferation. After having been cocultured with MSCs, the ADM-RGO-MSC composite scaffolds were transplanted into the full-thickness wound of a diabetic model that was induced by streptozotocin (STZ) to evaluate its effects. As a result, the ADM-RGO composite scaffold delivered with MSCs supported robust vascularization and collagen deposition as well as rapid re-epithelialization during diabetic wound healing. Overall, the versatile nature of the ADM-RGO composite scaffold makes it an efficient transplanting mediator for pluripotent stem cells in tissue engineering applications. The composite scaffold delivered with MSCs presents a promising approach for nonhealing diabetic wounds.

Ion exchange in KTiOPO4 crystals irradiated by copper and hydrogen ions.

Cs(+)-K+ ion exchanges were produced on KTiOPO4 crystals which is prior irradiated by Cu+ can H+ ions. The energy and dose of implanted Cu+ ions are 1.5 MeV and 0.5 x 10(14) ions/cm2, and that of H+ are 300 keV and 1 x 10(16) ions/cm2, respectively. The temperature of ions exchange is 430 degrees C, and the time range from 15 minutes to 30 minutes. The prism coupling method is used to measure the dark mode spectra of the samples. Compared with results of ion exchange on the sample without irradiations, both the number of guided mode and its corresponding effective refractive index are decreased. The experimental results indicate that the ion exchange rate closely related with the lattice damage and the damage layers formed in the depth of maximum nuclear energy deposition act as a barrier to block the ions diffuse into the sample and the concentration of defects can modify the speed of ion exchange..

Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signalling pathway.

The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischaemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the protein kinase C (PKC) signalling pathway. The performance of CTGF and CTGF + PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin-induced diabetic mice, was evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, whereas the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM + CTGF group, which produce FN, obviously promoted alpha-smooth muscle actin and transforming growth factor-beta expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF + PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signalling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing.

Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing.

BACKGROUND: Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair. METHODS: In this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline). RESULTS: In vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature TH1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of TH1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin. CONCLUSIONS: Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.