Beneficial Effects of Astragaloside IV-Treated and 3-Dimensional-Cultured Endothelial Progenitor Cells on Angiogenesis and Wound Healing.

INTRODUCTION: Astragaloside IV (AS-IV) is a natural herb extract and a popular compound used in traditional Chinese medicine because of its effect on multiple biological processes, such as promotion of cell proliferation, improvement in cardiopulmonary and vascular function, and promotion of angiogenesis around wounds, leading to accelerated wound healing. Vascular regeneration primarily results from the differentiation of endothelial progenitor cells (EPCs). Biomedical acceleration of angiogenesis and differentiation of EPCs around the wound remain challenging. MATERIALS AND METHODS: In this study, we treated human umbilical cord blood-derived EPCs with AS-IV and cultured them on 2-dimensional (tissue culture polystyrene) and 3-dimensional culture plates (3DPs). These cultured cells were then combined with human blood plasma gel and applied on the skin of nude mice in an attempt to repair full-thickness skin defects. RESULTS: The results show that using 3DP culture could increase vascular-related gene expression in EPCs. Furthermore, 12.5 µg/mL AS-IV-treaded EPCs were combined with plasma gels (P-3DP-EPC12.5) and showed enhanced vascular-related protein expression levels after 3 days of culture. Finally, P-3DP-EPC12.5s were used to repair full-thickness skin defects in nude mice, and we could register a wound healing rate greater than 90% by day 14. CONCLUSIONS: Based on these results, we concluded that we have developed a potential therapeutic approach for wound healing using plasma gel containing 3-dimensional surface-cultured AS-IV-treated EPCs.

Cryogel/hydrogel biomaterials and acupuncture combined to promote diabetic skin wound healing through immunomodulation.

Unhealed chronic wounds often deteriorate into multiple infection with several kinds of bacteria and excessive proteolytic wound exudate and remains one of the common healthcare issues. Here, the functional and antimicrobial hydrogel and cryogel biomaterials were prepared from glycol chitosan and a novel biodegradable Schiff base crosslinker difunctional polyurethane (DF-PU). The cryogel exhibited ~2730 ± 400% of water absorption with abundant macropores and 86.5 ± 1.6% of porosity formed by ice crystal as well as ~240% cell proliferation effect; while the hydrogel demonstrated considerable antimicrobial activity and biodegradability. As an optimized procedure to treat the diabetic skin wound in a rat model, the combined application of adipose stem cell-seeded cryogel/hydrogel biomaterials on the wound and acupuncture surrounding the wound may attain 90.34 ± 2.3% of wound closure and secure the formation of granulation tissue with sufficient microvessels and complete re-epithelialization in 8 days. The average increases in the superficial temperature of wounded animals after acupuncture were about 1-2 °C. Through the activation of C3a and C5a, the increased secretion of cytokines SDF-1 and TGFß-1, as well as the down-regulation of proinflammatory cytokines TNF-α and IL-1ß, the combined treatment of stem cell-seeded cryogel/hydrogel biomaterials and acupuncture on wounds produced synergistic immunomodulatory effects. The strategy using the combined treatment of biomaterials, stem cells, and acupuncture reveals a perspective new approach to accelerate the tissue regeneration.

Non-sticky and antimicrobial zwitterionic nanocomposite dressings for infected chronic wounds.

Zwitterionic poly(sulfobetaine acrylamide) (pSBAA)-based nanocomposite hydrogels impregnated with germicidal silver nanoparticles (AgNPs) were synthesized and implemented for the treatment of infected chronic wounds. The zwitterionic hydrogels exhibited excellent non-sticky properties and had reinforced mechanical properties by the addition of hectorite nanoclay and poly(ethylene glycol)dimethacrylate as physical and chemical crosslinkers, respectively. In addition, AgNPs were grown within the intercalated clay/polymer structure by in situ free radical reduction, as confirmed by UV-vis spectroscopy and transmission electron microscopy (TEM). The silver-containing pSBAA nanocomposite hydrogels (pSBAA/Ag) exhibited germicidal properties against Gram-positive S. epidermidis and Gram-negative P. aeruginosa. The zwitterionic hydrogels show higher water content than 2-hydroxyethyl methacrylate (pHEMA) hydrogels, owing to the strong hydration via ionic solvation. The negligible cytotoxicity of pSBAA/Ag hydrogels was assessed with human fibroblasts by the MTT assay. Moreover, the zwitterionic hydrogels demonstrated excellent resistance to the adsorption of bovine serum albumin (BSA). To evaluate the feasibility of the hydrogels for clinical application as wound dressings, we created infected diabetic rat models and compared with commercial wound dressings. The results show that pSBAA/Ag hydrogels did not adhere to the newly formed tissue, and were readily removed from the wounds after treatment for 3 days. Moreover, the healing recovery was evaluated by visual observation of infected dorsal wounds on rats with induction of diabetes by streptozotocin. The finding indicates complete healing with the pSBAA/Ag hydrogels after 15 days, faster than other dressings. A histological examination also proved that the zwitterionic hydrogels facilitated epithelialization and collagen distribution in the infected diabetic wounds. Consequently, these novel non-sticky and antimicrobial zwitterionic nanocomposite hydrogels can have high potential for the treatment of infected chronic wounds.

Adjunctive hyperbaric oxygen therapy in severe burns: Experience in Taiwan Formosa Water Park dust explosion disaster.

BACKGROUND: Despite major advances in therapeutic strategies for the management of patients with severe burns, significant morbidity and mortality is observed. Hyperbaric oxygen therapy (HBOT) increases the supply of oxygen to burn areas. The aim of this study was to determine whether HBOT is effective in the treatment of major thermal burns. METHODS: On June 27, 2015 in New Taipei, Taiwan, a mass casualty disaster occurred as fire erupted over a large crowd, injuring 499 people. Fifty-three victims (20 women and 33 men) were admitted to Tri-Service General Hospital. Thirty-eight patients underwent adjunctive HBOT (HBOT group), and 15 patients received routine burn therapy (control group). Serum procalcitonin (PCT) level, a sepsis biomarker, was measured until it reached normal levels (<0.5µg/L). The records of all patients from June 2015 to March 2016 were analyzed retrospectively. Outcome measures that were compared between the groups included the use of tracheostomy and hemodialysis, total body surface area (TBSA) and the number of skin graft operations, length of hospital stay, infection status, and mortality. RESULTS: The mean age of the patients was 22.4 years, and the mean TBSA was 43%. All the patients survived and were discharged without requiring limb amputation or being permanently disabled. Patient characteristics did not differ significantly between the groups. PCT levels returned to normal significantly faster (p=0.007) in the HBOT group. CONCLUSION: Multidisciplinary burn care combined with adjunctive HBOT improves sepsis control compared with standard treatment without HBOT. Prospective studies are required to define the role of HBOT in extensive burns.

Hyperbaric Oxygen Therapy for the Adjunctive Treatment of Pyoderma Gangrenosum: A Case Report.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by an ulcerative skin condition and confirmed through a diagnosis of exclusion. Management usually consists of systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Long-term use of these medications often has untold side effects. Hyperbaric oxygen therapy (HBOT) has been shown effective in the treatment of PG, reducing pain and tempering the need for medication. A case is presented of a 54-year-old woman with diabetes, hypertension, and a peptic ulcer who presented with painful, purulent ulcers on her buttocks, hands, and lower extremities of 2 weeks' duration. She was ultimately diagnosed with PG and provided 20 mg/day of oral prednisone for 1 week, tapered to 10 mg/day in the next week and then stopped. In addition, she received 12 sessions of HBOT - she breathed in 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes over 2 weeks. Her wounds healed without scarring. This excellent outcome including good wound healing, decreased pain, and reduced doses of systemic corticosteroids warrants additional study of the adjunctive use of HBOT for PG.

Histochemical and functional improvement of adipose-derived stem cell-based tissue-engineered cartilage by hyperbaric oxygen/air treatment in a rabbit articular defect model.

Cartilage is exposed to compression forces during joint loading. Therefore, exogenous stimuli are frequently used in cartilage tissue engineering strategies to enhance chondrocyte differentiation and extracellular matrix (ECM) secretion. In this study, human adipose-derived stem cells were seeded on a gelatin/polycaprolactone scaffold to evaluate the histochemical and functional improvement of tissue-engineered cartilage after hyperbaric oxygen/air treatment in a rabbit articular defect model. Behavior tests showed beneficial effects on weight-bearing and rear leg-supporting capacities after treatment of tissue-engineered cartilage with 2.5 ATA oxygen or air. Moreover, positron emission tomography images and immunohistochemistry staining demonstrated hydroxyapatite formation and increased ECM synthesis, respectively, at the tissue-engineered cartilage graft site after high pressure oxygen/air treatment. Based on these results, we concluded that hyperbaric oxygen and air treatment can improve the quality of tissue-engineered cartilage in vivo by increasing the synthesis of ECM.

Ascorbigen induces dermal papilla cell proliferation in vitro, but fails to modulate chemotherapy-induced alopecia in vivo.

Ascorbigen (ABG) is the predominant indole-derived compound from Brassica vegetables. In this study, we attempted to evaluate the effects of ABG on hair growth. To this end, we examined the proliferation of isolated human dermal papilla (DP) cells and keratinocytes after incubation in various concentrations (0-1.25 mM) of ABG. Furthermore, hair shaft regrowth was monitored in a mouse model of chemotherapy-induced alopecia (CIA), and hematoxylin and eosin staining was performed for histological analyses. We found that 1.25 mM ABG induced a 1.2-fold increase in the growth of DP cells, but not keratinocytes. However, ABG did not exert significant protective effects against CIA in the mouse model. These findings suggest that ABG may not be able to counteract CIA and that further investigation of the therapeutic potential of ABG in disease models is required.

The effect of hyperbaric oxygen and air on cartilage tissue engineering.

There is an urgent need to develop tissue-engineered cartilage for patients experiencing joint malfunction due to insufficient self-repairing capacity of articular cartilage. The aim of this research was to explore the effect of hyperbaric oxygen and air on tissue-engineered cartilage formation from human adipose-derived stem cells seeding on the gelatin/polycaprolactone biocomposites. The results of histological analyses indicate that under hyperbaric oxygen and air stimulation, the cell number of chondrocytes in cartilage matrix was not significantly increased, but the 1,9-dimethylmethylene blue assay showed that the glycosaminoglycans syntheses markedly increased compared to the control group. In quantification real-time polymerase chain reaction results, the chondrogenic-specific gene expression of SOX9, aggrecan, and COL2A1 were compared respectively. Within the limitation of this study, it was concluded that 2.5 atmosphere absolute oxygen and air may provide a stress environment to help cartilage tissue engineering development.