Abstract
In this study, we sought to investigate the impact of photobiomodulation and adipose-derived stem cells (ADS), alone and in combination, on the maturation step of wound healing in an ischemic infected delayed healing wound model in rats with type 2 diabetes mellitus (DM2). We randomly divided 24 adult male rats into 4 groups (n = 6 per group). DM2 plus an ischemic delayed healing wound were induced in all rats. The wounds were infected with methicillin-resistant Staphylococcus aureus. Group 1 was the control (placebo) group. Group 2 received only photobiomodulation (890 nm, 80 Hz, 0.324 J/cm2, and 0.001 W/cm2). Group 3 received only the allograft ADS. Group 4 received allograft ADS followed by photobiomodulation. On days 0, 4, 8, 12, and 16, we performed microbiological examination (colony forming units, [CFU]), wound area measurement, wound closure rate, wound strength, and histological and stereological examinations. The results indicated that at day 16, there was significantly decreased CFU (Analysis of variance, p = 0.001) in the photobiomodulation + ADS (0.0 ± 0.0), ADS (1350 ± 212), and photobiomodulation (0.0 ± 0.0) groups compared with the control group (27250 ± 1284). There was significantly decreased wound area (Analysis of variance, p = 0.000) in the photobiomodulation + ADS (7.4 ± 1.4 mm2), ADS (11 ± 2.2 mm2), and photobiomodulation (11.4 ± 1.4 mm2) groups compared with the control group (25.2 ± 1.7). There was a significantly increased tensiometeric property (stress maximal load, Analysis of variance, p = 0.000) in the photobiomodulation + ADS (0.99 ± 0.06 N/cm2), ADS (0.51 ± 0.12 N/cm2), and photobiomodulation (0.35 ± 0.15 N/cm2) groups compared with the control group (0.18 ± 0.04). There was a significantly modulated inflammatory response in (Analysis of variance, p = 0.049) in the photobiomodulation + ADS (337 ± 96), ADS (1175 ± 640), and photobiomodulation (69 ± 54) treatments compared to control group (7321 ± 4099). Photobiomodulation + ADS gave significantly better improvements in CFU, wound area, and wound strength compared to photobiomodulation or ADS alone. Photobiomodulation, ADS, and their combination significantly hastened healing in ischemic methicillin-resistant Staphylococcus aureus infected delayed healing wounds in rats with DM2. Combined application of photobiomodulation plus ADS demonstrated an additive effect.
Highlights
Type 2 diabetes mellitus (DM2) is an important worldwide health problem with a high prevalence in the United States[1]
There was a significant increase in body weight after feeding with fructose followed by a significant increase in blood sugar levels and a significant decrease in body weight after treatment with Streptozotocin (Table 1)
The blood sugar level increased one week after Streptozotocin administration, there was no significant difference in the blood sugar levels among the different groups
Summary
Type 2 diabetes mellitus (DM2) is an important worldwide health problem with a high prevalence in the United States[1]. The repair of injured skin (skin wound healing) is a physiological reaction towards interruption of skin integrity that needs coordinated regulation of different cells and growth factors. This complex course of healing is susceptible to imbalance by DM and the consequences of ischemia[2]. Protective and therapeutic approaches to stimulate healing include the application of antibacterial substances, wet absorbent dressings, bioengineered gauzes, vacuum-assisted closure, Regranex PDGF gel, and unloading[13] None of these approaches has consistently demonstrated an advantage, and the cure of chronic wounds and DFUs is a prolonged, and difficult process[13]. Autologous stem cell therapy approaches can be limited by the decreased function of stem cells obtained from patients with DM18,19
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