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Negative pressure wound therapy (NPWT) is a wound-dressing system that applies sub-atmospheric pressure on the surface of a wound to promote healing. An evolution of this technology, NPWT with solution instillation and dwell time (NPWTi-d), is increasingly being used to maximise wound closure and reduce failure rates. However, there is still a lack of evidence concerning its use in orthoplastic surgery. Therefore, the aim of this study is to compare NPWTi-d with NPWT and standard of care for wound management in orthoplastic surgery. A comprehensive literature search using PubMed, Web of Science, and Cochrane databases up to 15 March 2022 was performed, including studies describing the outcomes of NPWTi-d for traumatic/orthopaedic injuries. A meta-analysis on the number of surgical debridements, as well as the rate of complete wound closure and complications was carried out, although for other outcomes, a descriptive statistic was applied. Risk of bias and quality of evidence were assessed using the DownsBlack's Checklist for Measuring Quality. Thirteen studies with a total number of 871 patients were included, in which NPWTi-d demonstrated significantly higher primary wound closure and lower complication rates (P .05). No difference in the number of surgical procedures required for final wound healing was observed. Moreover, five out of six studies showed better results for NPWTi-d when the change of the bioburden and bacterial count of the wound were analysed. A singular study investigating the length of the hospital stay of patients treated with NPWTi-d showed a reduction in the latter. The present meta-analysis proves that NPWTi-d is superior to NPTW or conventional dressings in orthoplastic wound care management, in terms of complete wound closure rate and the reduced number of complications. Still, the limited quality of the studies analysed shows that future randomised studies are needed to confirm the benefits and to identify the most appropriate recommendations for using NPWTi-d in orthoplastic surgery, as well as to investigate the cost-effectiveness of this wound-dressing system.

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound-healing phases in a dose-dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound-healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.

Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß-tricalcium-phosphate (ß-TCP) and porous poly(L-lactide-co-glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen-coated, and additionally VEGF-loaded PLGA and ß-TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed repeatedly during a 14-day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß-TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß-TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß-TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß-TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte-endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß-TCP and PLGA scaffolds. Our study demonstrates that ß-TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF.

Lymphocyte homing to peripheral lymph nodes is governed by adhesion molecules, including lymphocyte function-associated antigen 1 (LFA-1). Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and exert anti-inflammatory effects, e.g. inhibition of LFA-1. It is still not known whether statin compounds are capable of inhibiting lymphocyte homing in vivo. We used a cervical lymph node preparation to study the effects of simvastatin on lymphocyte adhesion to high endothelial venules (HEVs) by means of intravital fluorescence microscopy (IVM). IVM revealed that firm adhesion of lymphocytes to HEV endothelium critically depends on the adhesive function of LFA-1. The number of firmly adherent lymphocytes was reduced by 58% in LFA-1-deficient mice (P < 0·05 versus wild-type controls). As in mutant mice, acute treatment with simvastatin (i.p. injection at 2 hr prior to IVM) inhibited the firm adhesion of lymphocytes to HEV endothelium of wild-type animals by 63% (P < 0·05 versus vehicle-treated wild-type controls). In addition, acute treatment with the synthetic statin-derivate LFA878 also reduced firm lymphocyte adhesion in HEVs by 63% (P > 0·05 versus placebo-treated controls). Histological analysis after a 10-day treatment with simvastatin showed reduced cellularity of cervical lymph nodes, as indicated by a reduction of the relative area of haematoxylin-stained cell nuclei in cervical lymph node cross-sections from 94 ± 0% in vehicle-treated controls to 77 ± 3% in simvastatin-treated mice (P < 0·05). We conclude that statin compounds are capable of inhibiting lymphocyte homing to murine peripheral lymph nodes in vivo. This may have novel implications for the treatment of adaptive immune responses, e.g. transplant rejection.

Objective Recent findings have attested to EPO tissue-protective effects in ischemically challenged tissues. Therefore, the study aimed at elaborating the effect of systemic pre- and postconditioning using EPO in a mouse model of persistent ischemia of the skin. Methods Three groups of nine C57Bl/6-mice each were analyzed. The experimental groups consisted of untreated controls, EPO preconditioning, and EPO postconditioning (500 IU EPO/kg bw/day for 10 days). Critically perfused skin flaps undergoing necrosis, if kept untreated, were mounted into dorsal skinfold chambers. Intravital epi-fluorescence microscopy was performed for 10 days to assess tissue necrosis, microcirculation, inflammation, and angiogenesis. Protein expression analysis of eNOS was performed. Hematocrit analyses were carried out separately in eight animals. Results Only EPO preconditioning was able to significantly reduce necrosis, when compared with controls. This correlated with a significantly increased CD in the critically perfused tissue. Administration of EPO only slightly increased eNOS expression at day 10, when compared with controls. EPO induced angiogenesis and increased hematocrit. Finally, EPO significantly reduced leukocytic inflammation in arterioles in all EPO receiving mice. Conclusions EPO preconditioning effectively reduces skin necrosis predominantly by capillary maintenance and reperfusion, as well as improved tissue regeneration. Thus, EPO preconditioning might represent a promising, non-invasive approach to reduce complications in ischemically challenged skin.