Adipose-Derived Stem Cells for Regenerative Wound Healing Applications: Understanding the Clinical and Regulatory Environment.

There is growing interest in the regenerative potential of adipose-derived stem cells (ADSCs) for wound healing applications. ADSCs have been shown to promote revascularization, activate local stem cell niches, reduce oxidative stress, and modulate immune responses. Combined with the fact that they can be harvested in large numbers with minimal donor site morbidity, ADSC products represent promising regenerative cell therapies. This article provides a detailed description of the defining characteristics and therapeutic potential of ADSCs, with a focus on understanding how ADSCs promote tissue regeneration and repair. It summarizes the current regulatory environment governing the use of ADSC products across Europe and the United States and examines how various adipose-derived products conform to the current UK legislative framework. Advice is given to clinicians and researchers on how novel ADSC therapeutics may be developed in accordance with regulatory guidelines.

Suboptimal identification of patient-specific risk factors for poor wound healing can be improved by simple interventions.

Poor wound healing is an important surgical complication. At-risk wounds must be identified early and monitored appropriately. Wound surveillance is frequently inadequate, leading to increased rates of surgical site infections (SSIs). Although the literature demonstrates that risk factor identification reduces SSI rates, no studies have focused on wound management at a junior level. Our study assesses documentation rates of patient-specific risk factors for poor wound healing at a large district general hospital in the UK. It critically evaluates the efficacy of interventions designed to promote surveillance of high-risk wounds. We conducted a full-cycle clinical audit examining medical records of patients undergoing elective surgery over 5 days. Interventions included education of the multidisciplinary team and addition of a Wound Healing Risk Assessment (WHRA) checklist to surgical admissions booklets. This checklist provided a simple stratification tool for at-risk wounds and recommendations for escalation. Prior to interventions, the documentation of patient-specific risk factors ranged from 0·0% to 91·7% (mean 42·6%). Following interventions, this increased to 86·4-95·5% (mean 92·5%), a statistically significant increase of 117·1% (P < 0·01). This study demonstrates that documentation of patient-specific risk factors for poor wound healing is inadequate. We have shown the benefit of introducing interventions to increase risk factor awareness.

A Systematic Review of Autologous Fat Grafting in the Treatment of Acute and Chronic Cutaneous Wounds.

There is a growing interest in the regenerative potential of autologous fat. Adipose-derived stem cells, within the stromal vascular fraction of lipoaspirate samples, demonstrate anti-inflammatory, immunomodulatory, and angiogenic properties. This systematic review aimed to determine the efficacy and safety of autologous fat therapies for wound healing, with an evaluation of the quality of evidence provided by the literature. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched Ovid Medline, Embase, and Cochrane Library databases from inception to November 2018. We included all human studies where wounds were treated with lipotransfer, cell-assisted lipotransfer, stromal vascular fraction products, or isolated adipose-derived stem cells. Study screening and data extraction were performed by 2 authors. The quality of evidence was evaluated using the GRADE approach. RESULTS: The search strategy returned 5027 citations. From these, 10 observational case series were included in the qualitative synthesis; there were no randomized controlled trials. Patient characteristics, wound etiology, and intervention type differed markedly between studies, precluding formal meta-analysis. Autologous fat grafting was associated with satisfactory wound healing in all studies with low complication rates. However, the quality of evidence was consistently very low. CONCLUSIONS: Autologous fat grafting is an emerging therapeutic option for challenging wounds, although there is insufficient evidence to conclusively demonstrate its effectiveness and adverse event profile. Based on the literature to date, it is unclear whether one type of autologous fat therapy is superior. Well-designed, blinded, prospective randomized controlled trials with adequate methodologic details and objective outcome measure reporting are essential. PROSPERO ID: CRD42017081499.

Allogeneic Skin Substitutes Versus Human Placental Membrane Products in the Management of Diabetic Foot Ulcers: A Narrative Comparative Evaluation of the Literature.

Outcomes following standard wound care (SWC) for diabetic foot ulcers (DFUs) remain suboptimal. Supplementing SWC with tissue engineered allogeneic cellular wound therapies represents an emerging treatment strategy. This review aimed to evaluate the efficacy and safety of allogeneic skin substitutes and human placental membrane allografts in the management of DFUs. Ovid MEDLINE and Embase databases were searched from inception to October 2017. Any randomized controlled trial (RCT) with an allogeneic skin substitute or placental membrane allograft intervention group was included. Our primary outcome measure was the proportion of completely healed ulcers. Secondary outcome measures included time to complete wound healing and local adverse event rates. Each study was assessed for risk of bias and the quality of evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Moderate quality evidence from 11 included RCTs demonstrated that both allogeneic cellular approaches improve the proportion of completely healed ulcers at 6 and 12 weeks. One RCT showed that a placental membrane allograft was superior to an allogeneic skin substitute, although this has yet to be repeated in other studies. The addition of allogeneic cellular wound products to SWC improves DFU outcomes. Further studies are required to conclusively establish if placental membrane allografts are superior to allogeneic skin substitutes.

Protocol for a systematic review of autologous fat grafting for wound healing.

BACKGROUND: Autologous fat grafting is an emerging therapeutic option for cutaneous wounds. The regenerative potential of autologous fat relates to the presence of adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF). ADSCs are capable of differentiating into fibroblasts and keratinocytes, as well as secreting soluble mediators with angiogenic and anti-inflammatory properties. However, to date, there has been no comprehensive assessment of the wound healing literature in humans. This systematic review aims to critically evaluate the efficacy and safety of autologous fat grafting in acute and chronic cutaneous wounds with an appraisal of the quality of evidence available. METHODS: Following PRISMA guidelines, MEDLINE, Embase and Cochrane Library databases will be searched from inception to December 2017. All primary clinical studies in which wounds are treated with lipotransfer, cell-assisted lipotransfer (CAL), SVF products or isolated ADSCs will be eligible for inclusion. Study screening and data extraction will be conducted by two authors in duplicate. Our primary outcome measure will be the proportion of completely healed wounds at 12 weeks. Secondary outcome measures will include the proportion of partially healed wounds at 12 weeks; the mean wound surface area reduction at 12 weeks; the mean time to wound healing; and adverse event rates. The quality of evidence for each summary outcome measure will be assessed using the GRADE approach. DISCUSSION: In light of the growing popularity of autologous fat grafting for wound healing, a systematic appraisal of the available evidence is timely. If autologous fat grafting is associated with a positive treatment effect, we will compare these outcomes to those achieved using alternative wound management strategies. This review also aims to determine if one or more autologous fat grafting techniques are superior and whether this varies according to patient- and wound-specific factors. We anticipate that these results will guide future research and inform clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017081499.

Demonstration of the Effectiveness of Augmented Reality Telesurgery in Complex Hand Reconstruction in Gaza.

Augmented reality (AR) is defined as "a technology that superimposes a computer-generated image on a user's view of the real world, thus providing a composite view."1 This case report describes how emerging AR telesurgery technologies may be used to facilitate international surgeon-surgeon collaboration and training. Here, we illustrate how a remote surgeon in Beirut, Lebanon, was able to offer assistance to a surgeon in Gaza, Palestine, during a complex hand reconstruction case following a bomb-blast injury in an 18-year-old male. We discuss the implications of AR technology on the future of global surgery and how it may be used to reduce structural inequities in access to safe surgical care.

A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation Methods.

BACKGROUND: The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies. METHODS: In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data. RESULTS: From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios. CONCLUSIONS: Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice.

Conservative management of migrated percutaneous endoscopic colostomy tube.

A 68-year-old male nursing home resident presented following dislodgement of a percutaneous endoscopic colostomy (PEC) tube originally sited to prevent recurrent sigmoid volvulus. Computed tomography demonstrated tube migration into the lumen of the recto-sigmoid junction, where it remained for 12 days before passing spontaneously. During this period, the patient remained asymptomatic; the residual colocutaneous fistula functioned as a decompressive valve. Originally, the patient was due to be discharged with early flexible sigmoidoscopy follow-up. However, complex social issues delayed discharge. During his admission, a second PEC tube was successfully inserted next to the previous colostomy site without complication. This is an unusual case and no similar episodes of asymptomatic PEC migration have been reported. We demonstrate that such cases may be offered an appropriate trial of conservative management. Here, we describe our experience and critically appraise the literature.

Paintball-related traumatic liver injury.

Paintball is a popular recreational sport played at both amateur and professional level. Ocular injuries are well recognised, although there is a growing body of literature documenting superficial vascular as well as deep solid organ injuries. An 18-year-old man presented with signs and symptoms consistent with acute appendicitis. Intraoperatively, a grade III liver injury was identified and packed before a relook at 48 h. No further active bleeding was identified; however, follow-up ultrasound at 3 weeks demonstrated non-resolution of a large subcapsular haematoma. The patient was readmitted for a short period of observation and discharged with repeat ultrasound scheduled for 3 months. This represents the first report of paintball-related blunt traumatic injury to the liver. Solid organ injuries of this nature have only been reported three times previously-all in the urological setting. This case also highlights issues surrounding the use of routine follow-up imaging in blunt liver trauma and provides a concise discussion of the relevant literature.