Nanofat: A therapeutic paradigm in regenerative medicine

Diabetes is closely connected with skeletal muscle dysfunction. Ellagic acid (EA) possesses a variety of bio-effects and is applied to the improvement of diabetes. The purpose of this study was to explore the potential improvement effect and mechanisms of EA in streptozotocin (STZ)-induced diabetic muscle atrophy. The model of diabetic mice was established by intra-peritoneal STZ to evaluate treatment effect of EA (100 mg/kg/d for 8 weeks) on muscle atrophy. Our data exhibited that EA enhanced fiber size and weight of gastrocnemius, and promoted grip strength to relieve STZ-induced muscle lesions. In serum, the levels of Creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) were inhibited, while high-density lipoprotein cholesterol (HDL) level was enhanced by EA treatment in diabetic mice. In gastrocnemius, EA decreased Atrogin-1 and MuRF-1 expressions to relieve STZ-induced muscle atrophy. Moreover, EA increased NRF-1 and PGC-1alpha expressions to alleviate mitochondrial disorder. Meanwhile, EA suppressed CHOP and GRP-87 levels to relieve ER stress. Lastly, EA inhibited BAX expressions and enhanced BCL-2 expressions to mitigate apoptosis. In conclusion, EA is preventing the event of STZ-induced gastrocnemia by amelioration of mitochondrial dysfunction, ER stress and apoptosis, and could be used in the protection and therapeutic of muscle atrophy in diabetes.

/pdf/ellagic-acid-attenuates-muscle-atrophy-in-stz-induced-3gk88zoj.pdf

Ellagic acid attenuates muscle atrophy in STZ-induced diabetic mice.

Since the initial introduction by Tonnard in 2013, numerous studies have reported positive findings after employing nanofat; however, concerns exist regarding its effects and mechanisms, and various methods to generate nanofat also remain unclear. The systematic review was conducted to evaluate the efficacy of sole nanofat grafting in plastic and reconstructive surgery.The MEDLINE, Embase, Cochrane Central, Web of Science, and Scopus databases were searched for studies related to sole nanofat grafting in plastic and reconstructive surgery (November 23rd, 2022). Outcomes of interest were all clinical results on humans or animals.Twelve studies were included, and no meta-analysis was conducted due to the clinical heterogeneity of the studies. In general, included studies had a low level of evidence. Six studies (n=253) showed significant improvements in scar characteristics via evaluation of the POSAS scales, FACE-Q scale, physician assessment, patient satisfaction, or VSS scale. Four studies described its benefits in skin rejuvenation (wrinkles, fine rhytides, pigmentation, or discoloration) via photographs, questionnaires, or indentation indices. Histological evaluation illustrated overall increases of skin thickness, collagen, and elastic fibers. Three experimental studies showed beneficial effects of nanofat on fat grafting, diabetic wound healing, and hair growth with compelling histological evidence. No severe complication was reported.Sole nanofat grafting shows potential benefits in scar treatment and anti-aging with conclusive histological evidence. Clinical studies about fat grafting, wound healing, or hair growth should be conducted, based on the foundation in this systematic review. Nanofat grafting could be a practical and safe procedure. 

Effects of Nanofat in Plastic and Reconstructive Surgery: A Systematic Review.

OBJECTIVE
The aim of this study was to explore the effect of concentrated growth factor (CGF) on the wound healing potential of human epidermal cells (HaCaT) in vitro and in vivo.


METHODS
CGF was extracted from venous blood using the centrifugal separation method. The CGF-conditioned medium was prepared from CGF gel immersed in Dulbecco's Modified Eagle medium. Crystal violet staining and wound healing assay were used to evaluate the proliferation and migration of HaCaT cells, respectively. Lipopolysaccharide (LPS) was used to test the anti-inflammatory function of CGF. An ELISA kit was employed to detect the concentration of growth factors and interleukins in CGF medium. mRNA and protein levels of angiogenic biomarkers (Angiopoietin-1 (ANGPT-1), vascular endothelial growth factor-A (VEGF-A) and Angiopoietin-2 (ANGPT-2) ) were determined by quantitative polymerase chain reaction (qPCR) and Western blot, respectively. A dorsal excisional wound model was recruited to test the wound healing effect of CGF in mice.


RESULTS
Three-day treatment of HaCaT cells with CGF significantly promoted cell proliferation, which was followed by an increase in Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) levels in the medium. Cytokines (IL-6, IL-8 and TNF-α) were increased in LPS-stimulated HaCaT cells after 3 days, and CGF slightly inhibited the mRNA expression of these cytokines. The RAS signaling pathway was activated upon CGF treatment. Both RAS knockdown and an inhibitor of RAS (zoledronic acid) could block the migration of HaCaT cells after CGF treatment. Protein expressions of CD31, ANGPT-1, and VEGF-A were up-regulated in a dose-dependent manner upon CGF exposure. The protein level of ANGPT-2 was down-regulated after CGF treatment. CGF could promote wound healing in vivo, as demonstrated using the full skin defect model in nude mice.


CONCLUSIONS
CGF was shown to promote wound repair in vitro and in vivo. The RAS cell signaling pathway was responsible for CGF stimulating the wound healing potential of HaCaT cells.

Concentrated Growth Factor Promotes Wound Healing Potential of HaCaT Cells by Activating the RAS Signaling Pathway.

Concentrated Growth Factor (CGF): The Newest Platelet Concentrate and Its Application in Nasal Hyaluronic Acid Injection Complications

This investigation studied the effect of concentrated growth factor and nanofat on aging skin of nude mice induced by D-Galactose. BALB/c mice were randomly divided into five groups: 5 mice in the control group were fed normally without any intervention, 9 mice were treated with concentrated growth factor (CGF), 9 mice were treated with nanofat (NF), 9 mice were treated with CGF + NF, and 9 mice in the model group (no treatment after subcutaneous injection of D-galactose). Relevant indicators are measured and recorded. In skin and serum, SOD and GSH content in the model group were significantly lower than those in other groups (P<0.05), and the MDA of the three treatment groups was significantly lower than that of the model group (P<0.05). Compared with the control group, the contents of total collagen, type I collagen and type III collagen in the NF group and model group were decreased in different degrees (P<0.05); the contents of elastin and elastic fiber in the skin of nude mice in the model group and NF group were significantly decreased. Compared with the model group, he number of CD31 and VEGF in the treatment group was significantly increased (P<0.01); the skin AGE content of three treatment groups was significantly lower (P<0.05). These findings suggest that concentrated growth factor and nanofat may have a significant effect on delaying aging skin induced by D-Galactose in nude mice.

/pdf/effects-of-concentrated-growth-factor-and-nanofat-on-aging-1ewu145y3b.pdf

Effects of concentrated growth factor and nanofat on aging skin of nude mice induced by D-galactose.

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Effects of concentrated growth factor and nanofat on aging skin of nude mice induced by D-galactose.