Wide-Awake Hand Trauma Surgery: Designing Strategies to Optimise Patient Experience.

INTRODUCTION: The regional hand trauma service in Greater Manchester, United Kingdom, underwent significant reorganisation early in the COVID-19 pandemic, with a shift from predominantly general anaesthesia (GA) procedures to the adoption of a Wide-Awake Local Anaesthetic No Tourniquet (WALANT) technique. We implemented strategies targeted towards optimising patient experience, largely applicable to most healthcare settings. METHODS: Four domains were explored: (i) compliance in timing to nationally agreed treatment guidelines, (ii) the role of patient information leaflets, (iii) the introduction of a post-operative analgesia protocol, and (iv) broadly evaluating the environmental impact following the implementation of a same-day 'see and treat' service. RESULTS: Following reorganisation to a predominantly WALANT service, we observed an increase in compliance with nationally agreed standards for the treatment of common hand injuries. Patient education and peri-operative counselling reduced anxiety, whereas post-operative pain was better managed with the introduction of an analgesic protocol. Using a travel carbon calculator, it can be inferred that there are significant reductions in carbon emissions generated when patients are evaluated and treated on the same day as their clinical presentation. CONCLUSIONS: It is widely acknowledged that WALANT benefits patients and the healthcare system. We contemplated whether further incremental changes in clinical practice could further improve patient experience. Given our findings, we advocate a multi-modal approach with a greater focus on patient outcomes (trials are currently underway, e.g., WAFER) supplemented by universally accepted validated patient-reported outcome measures (PROMs).

Current perspectives on peripheral nerve repair and management of the nerve gap.

From the first surgical repair of a nerve in the 6th century, progress in the field of peripheral nerve surgery has marched on; at first slowly but today at great pace. Whether performing primary neurorrhaphy or managing multiple large nerve defects, the modern nerve surgeon has an extensive range of tools, techniques and choices available to them. Continuous innovation in surgical equipment and technique has enabled the maturation of autografting as a gold standard for reconstruction and welcomed the era of nerve transfer techniques all while bioengineers have continued to add to our armamentarium with implantable devices, such as conduits and acellular allografts. We provide the reader a concise and up-to-date summary of the techniques available to them, and the evidence base for their use when managing nerve transection including current use and applicability of nerve transfer procedures.

A pilot prospective cohort study using experimental quantification of early peripheral nerve regeneration with high-frequency three-dimensional tomographic ultrasound (HFtUS).

Quantification of peripheral nerve regeneration after injury relies upon subjective outcome measures or electrophysiology assessments requiring fully regenerated neurons. Nerve surgeons and researchers lack objective, quantifiable information on the site of surgical repair and regenerative front. To address this need, we developed a quantifiable, visual, clinically available measure of early peripheral nerve regeneration using high-frequency, three-dimensional, tomographic ultrasound (HFtUS). We conducted a prospective, longitudinal study of adult patients with ulnar and/or median nerve injury of the arm undergoing direct epineurial repair within 5 days of injury. Assessment of morphology, volumetric and 3D grey-scale quantification of cross-sectional views were made at baseline up to 15 months post-surgery. Sensory and motor clinical outcome measures and patient reported outcome measures (PROMs) were recorded. Five participants were recruited to the study. Our data demonstrated grey-scale values (an indication of axonal density) increased in distal stumps within 2-4 months after repair, returning to normal as regeneration completed (4-6 months) with concomitant reduction in intraneural volume as surgical oedema resolved. Two patients with abnormal regeneration were characterized by increased intraneural volume and minimal grey-scale change. HFtUS may quantify early peripheral nerve regeneration offering a window of opportunity for surgical intervention where early abnormal regeneration is detected.

Treatment of Symptomatic Lymphedema in the Hand with Omental Flow-through Flap.

Vascularized lymph node transfer (VLNT) is a surgical option to improve physiologic lymphatic drainage. This technique transfers healthy vascularized lymphatic tissue from various available donor sites to the existing lymphatics of the affected area. Here, we present a successful case halting the size progression and reversing lymphedema symptoms in a patient treated with vascularized omental lymph node transfer. A 56-year-old man presented with stage III malignant sarcoma of his left medial upper arm. Two-years after excision, flap reconstruction, and radiation brachytherapy, worsening diffuse left arm edema developed, causing pain, decreased range of motion, and paresthesia. A vascularized omental lymph node transfer was performed. The omental flap required a flow-through design, requiring anastomosis of both gastroepiploic arteries to obtain Dopplerable signals. The patient experienced progressive relief of lymphedema symptoms after this transfer. Treatment outcomes with the use of VLNT have been largely encouraging; however, objective measures of improvement and timing of neolymphangiogenesis in recipient lymph node sites still need to be defined. Understanding omental VLNT flow dynamics and expected time point changes during the postoperative course will define expected outcomes and allow for treatment of a greater number of patients affected by lymphedema.

Glomerulonephritis.

Glomerulonephritis (GN) encompasses several disorders that cause glomerular inflammation and injury through an interplay of immune-mediated mechanisms, host characteristics, and environmental triggers, such as infections. GN can manifest solely in the kidney or in the setting of a systemic illness, and presentation can range from chronic and relatively asymptomatic hematuria to fulminant renal failure. Classic acute GN is characterized by hematuria, edema, and hypertension, the latter 2 of which are the consequence of sodium and water retention in the setting of renal impairment. Although presenting signs and symptoms and a compatible clinical history can suggest GN, serologic and urinary testing can further refine the differential diagnosis, and renal biopsy can be used for definitive diagnosis. Treatment of GN can include supportive care, renin-angiotensin-aldosterone system blockade, immunomodulatory therapy, and renal transplant. Prognosis is largely dependent on the underlying cause of GN and can vary from a self-limited course to chronic kidney disease. This review focuses on lupus nephritis, IgA nephropathy, IgA vasculitis, and postinfectious GN.

Breast-Q sensory outcomes of non-neurotized, autologous, unilateral breast reconstruction with a minimum of 3-year follow-up.

INTRODUCTION: Sensory reinnervation of autologous breast tissue after free flap reconstruction is highly variable. There is no long-term follow-up data exploring spontaneous reinnervation and how this affects patients' quality of life nor the nerve-related symptoms they experience. To address this issue, we invited patients with a minimum of 3 years after non-neurotized, free flap breast reconstruction to complete patient-reported outcome measures exploring sensation, quality of life and breast-related symptoms. METHODS: We performed a retrospective cohort study of patients undergoing unilateral Muscle-Sparing Transverse Rectus Abdominus Muscle (MS-TRAM) or deep inferior epigastric artery perforator (DIEP) flap breast reconstruction between 01-01-2015 and 31-12-2019 in the Department of Plastic and Reconstructive Surgery at Manchester University NHS Foundation Trust. We invited participants to complete the recently developed Breast-Q© Breast Sensation Module. RESULTS: All patients had undergone unilateral immediate (n = 85) or delayed (n = 82) breast reconstruction after mastectomy using either a free DIEP (n = 150) or TRAM (n = 17) flap reconstruction a minimum of 3 years prior. The median age at operation was 48. Sensation after reconstruction was significantly reduced in the reconstructed breast compared with the contralateral breast (P < 0.0001) with a reduction in reported quality of life (immediate (68.0 [54.0, 89.0]) and delayed (68.0 [62.0, 83.8])). The sensation was significantly better in immediate vs delayed procedures (P = 0.024). Sensory scores after reconstruction increased with age (P = 0.036). DISCUSSION: Breast sensation after non-neurotized reconstruction with autologous tissue is significantly reduced at long-term follow-up with a reduction in quality of life. A minimum outcome set for quantification of breast sensation is required and future research into the cost-benefit of neurotized, autologous breast reconstruction is needed.

The incidence and management of peripheral nerve injury in England (2005-2020).

Peripheral nerve injury (PNI) is a significant health problem that confers lifelong impact on those injured. Current interventions are purely surgical; however, outcomes remain poor. There is a lack of high-quality epidemiological data that is needed to identify populations involved, current healthcare demands, and ensure resources are distributed to the greatest effect, to reduce the injury burden. METHODS: Anonymized hospital episode statistical (HES) data on admitted patient care was obtained from NHS Digital for all National Health Service (NHS) patients sustaining PNI of all body regions between 2005 and 2020. Total numbers of finished consultant episodes (FCEs) or FCEs/100,000 population were used to demonstrate changes in demographic variables, anatomical locations of injury, mechanisms of injury, speciality, and main operation. RESULTS: There was a mean national incidence of 11.2 (95% CI 10.9, 11.6) events per 100,000 population per year. Males were at least twice as likely (p < 0.0001) to sustain a PNI. Upper limb nerves at or distal to the wrist were most commonly injured. Knife injuries increased (p < 0.0001), whereas glass injuries decreased (p < 0.0001). Plastic surgeons increasingly managed PNI (p = 0.002) as opposed to orthopaedic surgeons (p = 0.006) or neurosurgeons (p = 0.001). There was an increase in neurosynthesis (p = 0.022) and graft procedures (p < 0.0001) during the study period. DISCUSSION: PNI is a significant national healthcare problem predominantly affecting distal, upper limb nerves of men of working age. Injury prevention strategies, improved targeted funding and rehabilitation pathways are needed to reduce the injury burden and improve patient care.

Urology case report: Multifactorial bladder dysfunction in the setting of down syndrome.

A 16-year-old male patient with Down syndrome diagnosed with AKI and urinary tract infection was treated with meropenem for ESBL-positive E. coli in urine culture. Persistently elevated creatinine and persistent post-void residual (PVR) of >300 mL led to further testing, which revealed urethral stricture and a lower sacral Tarlov cyst. Due to no complete improvement with urethral dilatation, he underwent laminectomy and Tarlov cyst fenestration. Creatinine normalized, with increased urine output and robust flow. Due to a PVR of >100 mL, he received behavioral therapy, including sitting and timed voiding, and the PVR was reduced to <5 mL.

Transretroperitoneal Pedicled Omental Flap for Coverage of Traumatic Sacral Defect: A Case Report.

The greater omentum is a reliable choice for salvage soft-tissue reconstruction. Benefits include consistent anatomy, long pedicle length, and a high concentration of lymphatic tissue that is resistant to infection. We report the case of a 46-year-old man with a complex traumatic sacral wound resulting in severe limitation of reconstructive options. A pedicled greater omentum flap was transposed through the retroperitoneum via the lumbosacral triangle, resulting in durable soft-tissue coverage.

Negative pressure wound therapy for surgical wounds healing by primary closure.

BACKGROUND: Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). Existing evidence for the effectiveness of NPWT on postoperative wounds healing by primary closure remains uncertain. OBJECTIVES: To assess the effects of NPWT for preventing SSI in wounds healing through primary closure, and to assess the cost-effectiveness of NPWT in wounds healing through primary closure. SEARCH METHODS: In January 2021, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries and references of included studies, systematic reviews and health technology reports. There were no restrictions on language, publication date or study setting. SELECTION CRITERIA: We included trials if they allocated participants to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with another. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trials using predetermined inclusion criteria. We carried out data extraction, assessment using the Cochrane risk of bias tool, and quality assessment according to Grading of Recommendations, Assessment, Development and Evaluations methodology. Our primary outcomes were SSI, mortality, and wound dehiscence. MAIN RESULTS: In this fourth update, we added 18 new randomised controlled trials (RCTs) and one new economic study, resulting in a total of 62 RCTs (13,340 included participants) and six economic studies. Studies evaluated NPWT in a wide range of surgeries, including orthopaedic, obstetric, vascular and general procedures. All studies compared NPWT with standard dressings. Most studies had unclear or high risk of bias for at least one key domain. Primary outcomes Eleven studies (6384 participants) which reported mortality were pooled. There is low-certainty evidence showing there may be a reduced risk of death after surgery for people treated with NPWT (0.84%) compared with standard dressings (1.17%) but there is uncertainty around this as confidence intervals include risk of benefits and harm; risk ratio (RR) 0.78 (95% CI 0.47 to 1.30; I2 = 0%). Fifty-four studies reported SSI; 44 studies (11,403 participants) were pooled. There is moderate-certainty evidence that NPWT probably results in fewer SSIs (8.7% of participants) than treatment with standard dressings (11.75%) after surgery; RR 0.73 (95% CI 0.63 to 0.85; I2 = 29%). Thirty studies reported wound dehiscence; 23 studies (8724 participants) were pooled. There is moderate-certainty evidence that there is probably little or no difference in dehiscence between people treated with NPWT (6.62%) and those treated with standard dressing (6.97%), although there is imprecision around the estimate that includes risk of benefit and harms; RR 0.97 (95% CI 0.82 to 1.16; I2 = 4%). Evidence was downgraded for imprecision, risk of bias, or a combination of these. Secondary outcomes There is low-certainty evidence for the outcomes of reoperation and seroma; in each case, confidence intervals included both benefit and harm. There may be a reduced risk of reoperation favouring the standard dressing arm, but this was imprecise: RR 1.13 (95% CI 0.91 to 1.41; I2 = 2%; 18 trials; 6272 participants). There may be a reduced risk of seroma for people treated with NPWT but this is imprecise: the RR was 0.82 (95% CI 0.65 to 1.05; I2 = 0%; 15 trials; 5436 participants). For skin blisters, there is low-certainty evidence that people treated with NPWT may be more likely to develop skin blisters compared with those treated with standard dressing (RR 3.55; 95% CI 1.43 to 8.77; I2 = 74%; 11 trials; 5015 participants). The effect of NPWT on haematoma is uncertain (RR 0.79; 95 % CI 0.48 to 1.30; I2 = 0%; 17 trials; 5909 participants; very low-certainty evidence). There is low-certainty evidence of little to no difference in reported pain between groups. Pain was measured in different ways and most studies could not be pooled; this GRADE assessment is based on all fourteen trials reporting pain; the pooled RR for the proportion of participants who experienced pain was 1.52 (95% CI 0.20, 11.31; I2 = 34%; two studies; 632 participants). Cost-effectiveness Six economic studies, based wholly or partially on trials in our review, assessed the cost-effectiveness of NPWT compared with standard care. They considered NPWT in five indications: caesarean sections in obese women; surgery for lower limb fracture; knee/hip arthroplasty; coronary artery bypass grafts; and vascular surgery with inguinal incisions. They calculated quality-adjusted life-years or an equivalent, and produced estimates of the treatments' relative cost-effectiveness. The reporting quality was good but the evidence certainty varied from moderate to very low. There is moderate-certainty evidence that NPWT in surgery for lower limb fracture was not cost-effective at any threshold of willingness-to-pay and that NPWT is probably cost-effective in obese women undergoing caesarean section. Other studies found low or very low-certainty evidence indicating that NPWT may be cost-effective for the indications assessed. AUTHORS' CONCLUSIONS: People with primary closure of their surgical wound and treated prophylactically with NPWT following surgery probably experience fewer SSIs  than people treated with standard dressings but there is probably no difference in wound dehiscence (moderate-certainty evidence). There may be a reduced risk of death after surgery for people treated with NPWT compared with standard dressings but there is uncertainty around this as confidence intervals include risk of benefit and harm (low-certainty evidence). People treated with NPWT may experience more instances of skin blistering compared with standard dressing treatment (low-certainty evidence). There are no clear differences in other secondary outcomes where most evidence is low or very low-certainty. Assessments of cost-effectiveness of NPWT produced differing results in different indications. There is a large number of ongoing studies, the results of which may change the findings of this review. Decisions about use of NPWT should take into account surgical indication and setting and consider evidence for all outcomes.

Nephrotic Syndrome.

Nephrotic syndrome (NS) encompasses a variety of disease processes leading to heavy proteinuria and edema. Minimal change disease (MCD) remains the most common primary cause of NS, as well as the most responsive to pharmacologic treatment with often minimal to no chronic kidney disease. Other causes of NS include focal segmental glomerulosclerosis, which follows MCD, and secondary causes, including extrarenal or systemic diseases, infections, and drugs. Although initial diagnosis relies on clinical findings as well as urine and blood chemistries, renal biopsy and genetic testing are important diagnostic tools, especially when considering non-MCD NS. Moreover, biomarkers in urine and serum have become important areas for research in this disease. NS progression and prognosis are variable and depend on etiology, with corticosteroids being the mainstay of treatment. Other alternative therapies found to be successful in inducing and maintaining remission include calcineurin inhibitors and rituximab. Disease course can range from recurrent disease relapse with or without acute kidney injury to end-stage renal disease in some cases. Given the complex pathogenesis of NS, which remains incompletely understood, complications are numerous and diverse and include infections, electrolyte abnormalities, acute kidney injury, and thrombosis. Pediatricians must be aware of the presentation, complications, and overall long-term implications of NS and its treatment.

One-stage combined "fix and flap" approach for complex open Gustilo-Anderson IIIB lower limbs fractures: a prospective review of 102 cases.

BACKGROUND: Management of open fractures is challenging and requires a multidisciplinary team approach. This study aims to evaluate outcomes of open Gustilo-Anderson IIIB fractures managed at a single Ortho-Plastic centre following One-stage "Fix and Flap" approach. METHODS: Prospective data review for patients presenting with Gustilo-Anderson IIIB Fractures to our centre and managed with one-stage "Fix and Flap" approach. Postoperative outcomes are presented only for the patients who had a minimum of 12 months postoperative follow-up. RESULTS: 120 patients were included (83 males and 37 females). Mean age was 43 years (10-96). Tibia diaphysis was the most common site of injury (60%). 55.9% of injuries were road traffic accidents (RTA). 102 out of 120 patients had a minimum of 12 months follow-up (mean follow-up duration 25 months). Meantime from injury until definitive surgery was 7.71 days. Primary union achieved in 86.73%. Delayed union was encountered in 10.20%. 3.06% of patients had non-union. Limb salvage rate was 97.05% and Deep infection rate was only 0.98%. CONCLUSION: Our results showed that low infection rate, high limb salvage rate, and high union rate can be achieved in these complex injuries with meticulous technique, combined Ortho-Plastic (Fix and Flap) approach, and MDT input.

Association of socioeconomic status with 30- and 90-day readmission following open and laparoscopic hernia repair: a nationwide readmissions database analysis.

BACKGROUND: Socioeconomic disparities have been associated with outcomes in many medical conditions. The association of socioeconomic status (SES) with readmissions after ventral and inguinal hernia repair has not been well studied on a national level. This study aims to evaluate the association of SES with readmission as a significant outcome in patients undergoing ventral and inguinal hernia repair. METHODS: A retrospective cohort study was performed evaluating patients undergoing ventral hernia and inguinal hernia repair with 1:1 propensity score matching using the Nationwide Readmissions Database (2016-2017). Both 30- and 90-day readmissions were examined. After matching, a multivariate logistic regression analysis was performed using confounding variables including hospital setting, comorbidities, urgency of repair, sociodemographic status, and payer. Likelihood of readmission was reported in odds ratio form. RESULTS: Readmission rates were 11.56% (24,323 out of 210,381) and 17.94% (30,893 out of 172,210) for 30- and 90-day readmissions, respectively. Patients with Medicaid and in the lower income quartile were more likely to present in an emergent fashion for hernia repair. After matching, a multivariate logistic regression analysis showed socioeconomic status (OR 1.250 and 1.229) was a statistically significant independent predictor of readmission at 30 and 90 days, respectively. Inversely, factors associated with the least likely chance of readmission were a laparoscopic approach (OR 0.646 and 0.641), elective admission (OR 0.824 and 0.779), and care in a teaching hospital (OR 0.784 and 0.798). CONCLUSION: SES is an independent predictor of readmission at 30 and 90 days following open and laparoscopic ventral and inguinal hernia repair. Patients with a lower socioeconomic status were more likely to undergo hernia repair in the emergent setting. Efforts toward mitigating SES disparities by potentially promoting MIS techniques, enhancing access to elective cases, and systematic approaches to perioperative care for this disadvantaged population can potentially enhance overall hernia outcomes.

An Epidermal-Specific Role for Arginase1 during Cutaneous Wound Repair.

Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized. ARG1 is also expressed by keratinocytes; however, ARG1 function in these critical wound repair cells is not understood. We characterized ARG1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal ARG1 expression was decreased in both human and murine delayed healing wounds. We therefore generated a keratinocyte-specific ARG1-null mouse model (K14-cre;Arg1fl/fl) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration, and differentiation, was significantly delayed in K14-cre;Arg1fl/fl mice. Similarly, using the arginase inhibitor N(omega)-hydroxy-nor-L-arginine, human in vitro and ex vivo models further confirmed this finding, revealing the importance of the downstream polyamine pathway in repair. Indeed, restoring the balance in ARG1 activity through the addition of putrescine proved beneficial in wound closure. In summary, we show that epidermal ARG1 plays, to our knowledge, a previously unreported intrinsic role in cutaneous healing, highlighting epidermal ARG1 and the downstream mediators as potential targets for the therapeutic modulation of wound repair.

Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure.

Hearing loss (HL) is the most common sensory disorder in the world population. One common cause of HL is the presence of vestibular schwannoma (VS), a benign tumor of the VIII cranial nerve, arising from Schwann cell (SC) transformation. In the last decade, the increasing incidence of VS has been correlated to electromagnetic field (EMF) exposure, which might be considered a pathogenic cause of VS development and HL. Here, we explore the molecular mechanisms underlying the biologic changes of human SCs and/or their oncogenic transformation following EMF exposure. Through NGS technology and RNA-Seq transcriptomic analysis, we investigated the genomic profile and the differential display of HL-related genes after chronic EMF. We found that chronic EMF exposure modified the cell proliferation, in parallel with intracellular signaling and metabolic pathways changes, mostly related to translation and mitochondrial activities. Importantly, the expression of HL-related genes such as NEFL, TPRN, OTOGL, GJB2, and REST appeared to be deregulated in chronic EMF exposure. In conclusion, we suggest that, at a preclinical stage, EMF exposure might promote the transformation of VS cells and contribute to HL.

Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors.

Neuromuscular junction (NMJ) research is vital to advance the understanding of neuromuscular patho-physiology and development of novel therapies for diseases associated with NM dysfunction. In vivo, the micro-environment surrounding the NMJ has a significant impact on NMJ formation and maintenance via neurotrophic and differentiation factors that are secreted as a result of cross-talk between muscle fibers and motor neurons. Recently we showed the formation of functional NMJs in vitro in a co-culture of immortalized human myoblasts and motor neurons from rat-embryo spinal-cord explants, using a culture medium free from serum and neurotrophic or growth factors. The aim of this study was to assess how functional NMJs were established in this co-culture devoid of exogenous neural growth factors. To investigate this, an ELISA-based microarray was used to compare the composition of soluble endogenously secreted growth factors in this co-culture with an a-neural muscle culture. The levels of seven neurotrophic factors brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and vascular endothelial growth factor (VEGF) were higher (p < 0.05) in the supernatant of NMJ culture compared to those in the supernatant of the a-neural muscle culture. This indicates that the cross-talk between muscle and motor neurons promotes the secretion of soluble growth factors contributing to the local microenvironment thereby providing a favourable regenerative niche for NMJs formation and maturation.

Graphene Oxide Substrate Promotes Neurotrophic Factor Secretion and Survival of Human Schwann-Like Adipose Mesenchymal Stromal Cells.

Mesenchymal stromal cells from adipose tissue (AD-MSCs) exhibit favorable clinical traits for autologous transplantation and can develop 'Schwann-like' phenotypes (sAD-MSCs) to improve peripheral nerve regeneration, where severe injuries yield insufficient recovery. However, sAD-MSCs regress without biochemical stimulation and detach from conduits under unfavorable transplant conditions, negating their paracrine effects. Graphene-derived materials support AD-MSC attachment, regulating cell adhesion and function through physiochemistry and topography. Graphene oxide (GO) is a suitable substrate for human sAD-MSCs incubation toward severe peripheral nerve injuries by evaluating transcriptome changes, neurotrophic factor expression over a 7-days period, and cell viability in apoptotic conditions is reported. Transcriptome changes from GO incubation across four patients are minor compared to biological variance. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) gene expression is unchanged from sAD-MSCs on GO substrates, but NGF and GDNF protein secretion increase at day 3 and 7. Secretome changes do not improve dorsal root ganglia neuron axon regeneration in conditioned media culture models. Fewer sAD-MSCs detach from GO substrates compared to glass following phosphate buffer saline exposure, which simulates apoptotic conditions. Overall, GO substrates are compatible with sAD-MSC primed for peripheral nerve regeneration strategies and protect the cell population in harsh environments.

The angiogenic potential of CD271+ human adipose tissue-derived mesenchymal stem cells.

BACKGROUND: Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat grafts with adipose tissue-derived mesenchymal stem cells (AD-MSCs) improves graft survival-however, AD-MSCs represent a heterogeneous population. Selection of subpopulations of AD-MSCs would allow the targeting of specific AD-MSCs that may benefit fat graft survival more than the general AD-MSC population. METHODS: Human AD-MSCs were selected for the surface marker CD271 using magnetic-activated cell sorting and compared to the CD271 negative phenotype.  These subpopulations were analysed for gene expression using Real-Time qPCR and RNA sequencing; surface marker characteristics using immunostaining; ability to form tubules when cultured with endothelial cells; and gene and protein expression of key angiogenic mediators when cultured with ex-vivo adipose tissue. RESULTS: Human AD-MSCs with the surface marker CD271 express angiogenic genes at higher levels, and inflammatory genes at lower levels, than the CD271- AD-MSC population. A greater proportion of CD271+ AD-MSCs also possess the typical complement of stem cell surface markers and are more likely to promote effective neoangiogenesis, compared to CD271- AD-MSCs. CONCLUSION: Enriching grafts with the CD271+ AD-MSC subpopulation holds potential for the improvement of reconstructive and aesthetic surgeries involving adipose tissue.