GFP-labeled Schwann cell-like cells derived from hair follicle epidermal neural crest stem cells promote the acellular nerve allografts to repair facial nerve defects in rats.

BACKGROUND: Acellular nerve allografts (ANAs) have been successfully applied to bridge facial nerve defects, and transplantation of stem cells may enhance the regenerative results. Up to now, application of hair follicle epidermal neural crest stem cell-derived Schwann cell-like cells (EPI-NCSC-SCLCs) combined with ANAs for bridging facial nerve defects has not been reported. METHODS: The effect of ANAs laden with green fluorescent protein (GFP)-labeled EPI-NCSC-SCLCs (ANA + cells) on bridging rat facial nerve trunk defects (5-mm-long) was detected by functional and morphological examination, as compared with autografts and ANAs, respectively. RESULTS: (1) EPI-NCSC-SCLCs had good compatibility with ANAs in vitro. (2) In the ANA + cells group, the GFP signals were observed by in vivo imaging system for small animals within 8 weeks, and GFP-labeled EPI-NCSC-SCLCs were detected in the tissue slices at 16 weeks postoperatively. (3) The facial symmetry at rest after surgery in the ANA + cells group was better than that in the ANA group (p < 0.05), and similar to that in the autograft group (p > 0.05). The initial recovery time of vibrissal and eyelid movement in the ANA group was 2 weeks later than that in the other two groups. (4) The myelinated fibers, myelin sheath thickness and diameter of the axons of the buccal branches in the ANA group were significantly worse than those in the other two groups (P < 0.05), and the results in the ANA + cells group were similar to those in the autograft group (p > 0.05). CONCLUSIONS: EPI-NCSC-SCLCs could promote functional and morphological recovery of rat facial nerve defects, and GFP labeling could track the transplanted EPI-NCSC-SCLCs in vivo for a certain period of time. These may provide a novel choice for clinical treatment of peripheral nerve defects.

Modulating endothelial cell dynamics in fat grafting: the impact of DLL4 siRNA via adipose stem cell extracellular vesicles.

In the context of improving the efficacy of autologous fat grafts (AFGs) in reconstructive surgery, this study delineates the novel use of adipose-derived mesenchymal stem cells (ADSCs) and their extracellular vesicles (EVs) as vehicles for delivering delta-like ligand 4 (DLL4) siRNA. The aim was to inhibit DLL4, a gene identified through transcriptome analysis as a critical player in the vascular endothelial cells of AFG tissues, thereby negatively affecting endothelial cell functions and graft survival through the Notch signaling pathway. By engineering ADSC EVs to carry DLL4 siRNA (ADSC EVs-siDLL4), the research demonstrated a marked improvement in endothelial cell proliferation, migration, and lumen formation, and enhanced angiogenesis in vivo, leading to a significant increase in the survival rate of AFGs. This approach presents a significant advancement in the field of tissue engineering and regenerative medicine, offering a potential method to overcome the limitations of current fat grafting techniques.NEW & NOTEWORTHY This study introduces a groundbreaking method for enhancing autologous fat graft survival using adipose-derived stem cell extracellular vesicles (ADSC EVs) to deliver DLL4 siRNA. By targeting the delta-like ligand 4 (DLL4) gene, crucial in endothelial cell dynamics, this innovative approach significantly improves endothelial cell functions and angiogenesis, marking a substantial advancement in tissue engineering and regenerative medicine.

Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries.

The availability of grafts to replace small-diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue-engineered vascular graft that aims to match the natural structure of small-size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co-electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell-laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi-automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post-implantation. These promising data open a new avenue to developing an artery-like product for reconstructing small-diameter blood vessels.

Comparison of bridging stent grafts in branched endovascular aortic repair.

BACKGROUND: Endovascular treatment of thoracoabdominal aortic aneurysms has become common, with satisfactory results. Nevertheless, long-term durability remains an issue mainly because of target visceral vessel (TVV) instability. Currently, no covered stent has been approved as a bridging stent graft (BSG), demanding continuous research on this topic. METHODS: This was a multicenter observational retrospective cohort study comparing the midterm results of the Bard Covera Plus and Gore VBX as BSGs during branched endovascular aneurysm repair. The primary outcome was the comparison of the target vessel instability between the two groups. Primary patency, freedom from branch-related type I and III endoleaks and reintervention, and technical and clinical success were considered secondary outcomes. Logistic regression analysis was used to assess the association between selected baseline factors and TVV instability. TVV instability during follow-up was then evaluated using the Kaplan-Meier cumulative function. RESULTS: Three hundred forty-five TVVs in 106 patients were considered suitable for the analysis. Two hundred twenty vessels were stented with the Covera stent graft (64%) and 125 with VBX (36%). Two hundred ninety-nine TVVs received a single BSG, 45 two BSGs, and only 1 three BSGs. Bare metal stent relining was required in 36% of TVVs, mostly in the Covera group (89 [41%] vs 36 [29%]) (P = .030). The primary technical success rate was 96% (331/345), and the assisted primary technical success rate was 99% (342/345). The TVV instability rate within 30 days was 2% (one Covera and five VBX; P = .015). Three BSG occlusions (one Covera and two VBX) and three type Ic endoleaks (three VBX) were detected. The median follow-up was 13.9 months (range, 5.8-25.5 months). Sixteen TVV instabilities were detected during the follow-up. Twelve BSG occlusions (six Covera and six VBX), three type Ic endoleaks (one Covera and two VBX), and one type IIIc endoleak (VBX). The overall target vessel instability rate was 5% (16/342). TVV instability was associated with the use of Gore VBX in the univariable logistic regression (odds ratio, 3.0; 95% confidence interval, 1.1-8.0; P = .027). Aneurysm rupture and aneurysm diameter were also associated with TVV instability in the univariable analysis (P = .002 and P = .008, respectively). The only factor predisposing to TVV instability in the multivariable logistic regression analysis was the use of Gore VBX as a BSG (odds ratio, 2.9; 95% confidence interval, 1.0-8.0; P = .043). Kaplan-Meier analysis showed a significantly higher risk of TVV instability in the VBX group (P < .001). CONCLUSIONS: Overall midterm outcomes in this cohort were satisfactory. Patency rates were similar between the two stents. Nevertheless, VBX seems to be associated with worse TVV instability. These results may be correlated with a higher incidence of type Ic endoleaks, which require an extensive learning curve for correct stent selection and deployment.

Anatomical suitability for branched endovascular aortic arch repair and balloon-expandable bridging stent grafts in a cohort of patients previously treated with a hybrid approach.

OBJECTIVE: We assessed the suitability of two triple branch arch devices (aBranch) (Terumo aortic and Cook Medical) and a balloon-expandable covered stent (VBX, W. L. Gore & Associates, Johnson & Johnson) to incorporate the brachiocephalic trunk (BCT) in a cohort previously treated with hybrid thoracic endovascular repair (TEVAR). METHODS: This is a single-center, retrospective, all-comers, preclinical suitability study. We conducted an analysis of preoperative computed tomography scans in surgical patients between 1999 and 2022 in a single vascular surgery unit. The primary outcome was the aortic suitability of aBranch devices and VBX as mating stent for BCT in previous hybrid TEVAR. Hybrid repair of the aortic arch included TEVAR, fenestrated or branched TEVAR associated with any surgical debranching of the supra-aortic trunks and chimney TEVAR with proximal landing in zones 0 to 2. Secondary outcomes included (i) suitability assessment when excluding minor instruction for use (IFU) criteria, (ii) a comparison of suitable and nonsuitable patients, (iii) risk factors analysis for nonsuitability, and (iv) a description of the exclusion causes. RESULTS: During the study period, 120 patients were treated. Among elective patients (n = 73), the suitability of any aBranch was 82.2% (60/73) and VBX was suitable in 64.4% of BCTs (47/73). The aBranch suitable patients had a significantly longer sinotubular-BCT length (P = .017) and smaller distal ascending aorta (P = .043) as compared with nonsuitable ones. The suitability of Terumo Aortic and Cook Medical devices was 52.1% (38/73) and 46.6% (34/73), respectively. When minor IFU criteria were ignored, suitability increased to 82.2% (60/73) and 63.0% (46/73), respectively. Left common carotid artery diameter and sinotubular-BCT length were significant nonsuitability risk factors for Terumo Aortic aBranch in multivariable analysis. No associations were found for Cook Medical device. The outcomes were tested in the entire cohort demonstrating a global suitability of 82.9%, increasing to 86.3% when ignoring minor IFUs. VBX was anatomically suitable to use in BCT in 73.2% of patient BCTs. CONCLUSIONS: aBranch devices are anatomically suitable in a vast majority of patients (86%) undergoing hybrid TEVAR. The innominate artery seems eligible for incorporation with VBX in almost two-thirds of patients. This mating stent may help to overcome some minor IFU restrictions.

Long-term outcomes of chimney endovascular aneurysm repair procedure for complex abdominal aortic pathologies.

OBJECTIVE: The aim of this study was to update our earlier experience and to evaluate long-term outcomes of chimney endovascular aortic repair performed for selected cases with complex abdominal aortic aneurysm. METHODS: A single-center retrospective cohort study was conducted on 51 consecutive patients who underwent chimney endovascular aortic repair procedure, deemed unfit for open surgical repair and fenestrated endovascular aneurysm repair, from October 2009 to November 2019. Kaplan-Meier analyses were used to assess the estimated overall survival, freedom from aneurysm related mortality, freedom from reintervention, freedom from target vessel instability, and freedom from type Ia endoleaks. RESULTS: Fifty-one patients (mean age, 77.1 ± 7.5 years) with a mean preoperative maximum aneurysm diameter of 74.2 ± 20.1 mm were included. Mean follow-up duration was 48.6 months (range, 0-136 months). Estimated overall survival at 5 and 7 years was 36.3% ± 7.1% and 18.3% ± 6.0%, respectively. Freedom from aneurysm-related mortality was 88.6% ± 4.9% at 7 years. Estimated freedom from type Ia endoleaks at 7 years was 91.8% ± 3.9%. A total of 21 late reinterventions were performed in 17 patients (33%). Most of them were performed to treat type II endoleaks with sac growth (47.6%; n = 10) and type Ib endoleak (23.8%; n = 5). Estimated freedom from reintervention at 7 years was 56.3% ± 7.9%. Estimated freedom from target vessel instability at 7 years was 91.5% ± 4.1%. CONCLUSIONS: The 7-year results of chimney endovascular aortic repair procedures performed in our center confirm the long-term safety and effectiveness of this technique in a series of high-risk patients with large aneurysms. The present study has, to the best of our knowledge, the longest follow-up for patients treated with chimney endovascular aortic repair, and it provides data to the scarce literature on the long-term outcomes of this procedure, showing acceptable to good long-term results.

Three-year outcomes of off-the-shelf Gore thoracoabdominal multibranch endoprosthesis and physician-modified endografts for complex abdominal and thoracoabdominal aortic aneurysms.

OBJECTIVE: Fenestrated-branched endovascular aortic repair (FB-EVAR) has shown favorable outcomes for repair of complex aneurysms and thoracoabdominal aortic aneurysms. Physician-modified endografting (PMEG) and the Gore thoracoabdominal multibranch endoprosthesis (TAMBE) provide custom and off-the-shelf devices for FB-EVAR, respectively. This study compares the outcomes of TAMBE and PMEG at a single institution. METHODS: A retrospective review of patients who underwent TAMBE as part of the multicenter pivotal trial or PMEG as part of a prospective physician-sponsored investigational device exemption at a single institution between 2020 and 2022 were completed. Patient demographics, characteristics, and perioperative and midterm outcomes were compared. RESULTS: A total of 68 patients were included, with 12 in the TAMBE group and 56 in the PMEG group. Baseline characteristics were comparable between groups. Aneurysm type was most often thoracoabdominal aortic aneurysm in both groups (58% TAMBE and 52% PMEG). TAMBE had a higher rate of upper extremity access (100% vs 63%; P = .013) and longer mean procedure time (247 ± 36 minutes vs 189 ± 49 minutes; P < .001). Other intraoperative metrics were similar between groups. Technical success was 100% in TAMBE and 95% in PMEG (P = .412). There was no 30-day mortality in either group. No major adverse events occurred with TAMBE, whereas in PMEG cases, 2% had respiratory failure, 2% required dialysis, and 4% experienced spinal cord ischemia. Although the overall endoleak rates were similar (50% of TAMBE vs 41% of PMEG; P = .57), type II endoleaks accounted for all of the endoleaks in the TAMBE group, whereas type I or III endoleaks were seen in 11% of PMEG patients. At a median follow-up of 26.7 months for the TAMBE group and 21.2 months for the PMEG group, target vessel instability was seen in 10.4% of TAMBE, and 6.9% of PMEG targeted branches (P = .401). Reintervention was required in 33% of TAMBE patients and 27% of PMEG patients (P = .646). Estimated freedom from reintervention rates at 3 years were similar (56% TAMBE vs 62% PMEG, log-rank P = .910). Freedom from visceral renal target vessel instability at 3 years was 89% for both groups (log-rank P = .459). The Kaplan-Meier 3-year estimated survival was 100% for patients in the TAMBE group and 77% for patients in the PMEG group (log-rank P = .157). CONCLUSIONS: At experienced centers, FB-EVAR can be completed with PMEG or TAMBE with comparable, excellent perioperative and midterm outcomes. Reinterventions are frequently needed for both TAMBE and PMEG.

Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APPV717I mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.

Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APPV717I mutation after cell injection into the mouse forebrain. APPV717I mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aß42 production, elevated phospho-tau, and impaired neurite outgrowth in APPV717I neurons. Two months after transplantation, APPV717I and control neural cells showed robust engraftment but at 12 months post-injection, APPV717I grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and tangle pathology were not seen. Single-nucleus RNA-sequencing of micro-dissected grafts, performed 2 months after cell injection, identified significantly altered transcriptome signatures in APPV717I iPSC-derived neurons pointing towards dysregulated synaptic function and axon guidance. Interestingly, APPV717I neurons showed an increased expression of genes, many of which are also upregulated in postmortem neurons of AD patients including the transmembrane protein LINGO2. Downregulation of LINGO2 in cultured APPV717I neurons rescued neurite outgrowth deficits and reversed key AD-associated transcriptional changes related but not limited to synaptic function, apoptosis and cellular senescence. These results provide important insights into transcriptional dysregulation in xenografted APPV717I neurons linked to synaptic function, and they indicate that LINGO2 may represent a potential therapeutic target in AD.

A Scoping Review of Definitions of Success in Endovascular Aortic Arch Repair.

INTRODUCTION: The present standard of care to treat aortic arch pathologies is open surgical repair with cardiopulmonary bypass and deep hypothermic arrest. With approaches for total endovascular and extra-anatomic cervical debranching hybrid arch repair becoming more diverse, understanding what is considered a successful operation is prerequisite for a rigorous comparison of techniques. This review describes the specific outcomes reported, the rates of success, and the definitions of technical and clinical success in total endovascular and extra-anatomic cervical debranching hybrid aortic arch repair. METHODS: A comprehensive search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed. Studies with patients undergoing total endovascular or hybrid extra-anatomic cervical debranching repair of the aortic arch were included. Any publications including only patients with Ishimaru zone 2 or distal repairs were excluded from this review. Studies with less than 5 patients were excluded. Data extraction was performed by one author. Data items included were study design, procedure type, procedural details, underlying pathology, type of cervical debranching, type of endograft repair, surgical outcomes, definition of cerebrovascular events, technical success, and the definition of technical success. RESULTS: Of 1754 studies screened for review, 85 studies with 5521 patients were included. By frequency, the included studies examined the following interventions: fenestrated devices, branched devices, parallel grafting. Most studies were retrospective single-institution studies. There were no randomized controlled trials. Short-term mortality and cerebrovascular events were nearly universally reported, present in 99% and 95% of studies reviewed, respectively. Only 27% of studies provided an explicit definition for cerebrovascular events. While 75% of studies reported a technical success rate, only 45% of those studies provided explicit criteria. Clinical success rates were infrequently reported, present in only 5.9% of studies reviewed. CONCLUSION: The definitions of technical success that were provided fell short of analogous defined reporting standards in nearly all studies, inflating technical success rates. Definitions of cerebrovascular events and technical success require stringent criteria to uniformly compare various methods of endovascular aortic arch repair. A societal consensus document for reporting standards of endovascular aortic arch repair would allow for higher-quality outcomes research. CLINICAL IMPACT: Total endovascular and extra-anatomic cervical debranching hybrid operations are being increasingly utilized for complex aortic arch repair. These techniques, however, can be associated with serious complications. Currently, there is no accepted metric to define technical or report clinical outcomes. Due to the paucity of high-quality data, use of these approaches may be limited in clinical practice. This study emphasizes the need for the development of standards for reporting outcomes in endovascular aortic arch repair. Future studies can then utilize these benchmarks, whcih will allow for improved efficacy and safety in these techniques.

Anatomical Feasibility of the "Canaud Technique" for Physician-Modified Thoracic Endovascular Grafts for the Treatment of Aortic Arch Disease.

PURPOSE: Thoracic endovascular aortic repair (TEVAR), originally conceived for deployment distal to the left subclavian artery (LSA), has been recently extended to more proximal landing zones. Among total endovascular solutions, the "Canaud technique" for Physician-Modified Thoracic Endovascular Grafts (C-PMEGs) has gained acceptance with good early results. The aim of this study is to report the proportion of patients with zone 0, 1, and 2 aortic arch lesions that could theoretically be treated with a C-PMEG. MATERIALS AND METHODS: Computed tomography angiography (CTA) of all consecutive patient candidates to open, hybrid, or endovascular arch repair from January 2009 to July 2023 at our Institution were analyzed. The assessment of feasibility of C-PEMG was conducted following previously extensively described anatomical criteria. RESULTS: During the study period, 209 consecutive patients were candidates for an open, hybrid, or endovascular aortic arch repair. Of them, 164 patients had a preoperative CTA scan eligible for analysis. One hundred twenty-six patients were male (76.8 %), with a mean age of 67 ± 10.8 years. Ninety-four patients (57.3%) were affected by atherosclerotic aneurysms, 48 post-dissecting aneurysms (29.3%) and 22 penetrating aortic ulcers (PAUs) (13.4%). Twenty patients (12.2%) were suitable for double-fenestrated C-PMEG, and 34 patients (20.7%) for single-fenestrated C-PMEG, totaling 32.9% of the entire cohort. The combination of supra-aortic trunks (SAT) bypass or the use of covered stent in IA or left common carotid artery (LCCA) as adjunctive maneuvers, would extend the C-PMEGs feasibility to 69 patients (42.1%). The use of an iliac graft conduit in 3 (1.8%) patients with inadequate ileo-femoral accesses would increase the C-PMEG suitability to 72 patients (43.9%). The main reason for exclusion was excessive ascending aortic diameter in 78 patients (47.6%). CONCLUSIONS: The use of C-PMEG was shown to be theoretically feasible in a percentage of patients ranging from 32.9 to 43.9% affected by aortic arch aneurysms, dissections, and PAU. The main reason for exclusion was the dimension of the ascending aorta. The C-PMEG technique is a viable option in aortic arch lesions endovascular treatment. An off-the-shelf device with similar characteristics could also be used in emergency, avoiding the limitations of physician modifications (such as time for back-table procedure, sterility, off-label use). CLINICAL IMPACT: Thoracic endovascular aortic repair (TEVAR) has been extended to more proximal landing zones for the treatment of aortic arch aneurysm, dissections, penetrating aortic ulcers. Among total endovascular solutions, the "Canaud technique" for Physician-Modified Thoracic Endovascular Grafts (C-PMEGs) has gained acceptance with good early results. The anatomical feasibility in 164 consecutive patients was 69 patients (42.1%), with the combination of supra-aortic trunks (SAT) bypass or the use of covered stent in IA or left common carotid artery (LCCA) as adjunctive maneuvers, showing that the C-PMEG technique is a viable option in aortic arch lesions endovascular treatment.

The Impact of Target Vessel Anatomy and Bridging Stent Geometry on Branched Endovascular Aortic Repair Outcomes.

OBJECTIVE: This study aimed to evaluate the impact of target vessel anatomy and bridging stent geometry on target vessel instability in branched endovascular aortic repair (B-EVAR). METHODS: This retrospective, single centre cohort study included all consecutive B-EVARs performed between September 2018 and December 2022 for thoraco-abdominal aortic aneurysm (TAAA) or complex abdominal aortic aneurysm (CAAA). The primary endpoints were target vessel instability and related re-interventions at 12 months. Secondary endpoints were 30 day results, including target vessel instability and re-interventions. Target vessel instability analysis consisted of assessment of target vessel anatomy, including diameter, aortic trunk to branch angle, and tortuosity. Post-operative parameters included change of clock position/horizontal misalignment, bridging length (gap), sealing length, tortuosity, post-stenting angle, and oversizing ratio. RESULTS: A total of 69 patients (TAAA: n = 56, 81%; CAAA: n = 13, 19%) and 271 (133 visceral and 138 renal) target vessels were included. The cumulative incidence of target vessel instability was 4.8%, 6.4%, and 7.9% at one, two, and three years, respectively. In the renal target vessel group, vessel diameter ≤ 4 mm (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.116 - 2.54; p = .022) and a bridging length ≥ 25 mm (HR 1.320, 95% CI 1.066 - 1.636; p = .011) were associated with increased target vessel instability. In visceral vessels, a change in clock position/horizontal misalignment ≥ 70 minutes (HR 1.072, 95% CI 1.026 - 1.121; p = .002) showed a significant association with target vessel instability. CONCLUSION: Target vessel diameter, bridging length (gap), and horizontal misalignment seemed to be associated with adverse target vessel outcomes. This may be solved with more customised endograft solutions to reduce the negative impact of the latter parameter.

Physician Made Bovine Pericardial Tube Grafts in Aortic Infection: A European Multicentre Study.

OBJECTIVE: This study examines outcome and durability of physician made bovine pericardial tube grafts in aortic infections in all anatomical locations. METHODS: This was a retrospective and prospective international multicentre study. Peri-operative and long term outcomes of patients undergoing in situ aortic reconstruction for native or graft infections with physician made bovine pericardial tube grafts between January 2008 and December 2020 in four European tertiary referral centres were analysed. The primary endpoint was recurrent aortic infection. Secondary endpoints were persistent infection, aortic re-operation for infection, graft related complications, and death. RESULTS: One hundred and sixty eight patients (77% male, mean age 67 ± 11 years) were identified: 38 (23%) with native and 130 (77%) with aortic graft infection. The thirty day mortality rate was 15% (n = 26) overall, 11% (n = 4), and 17% (n = 22) for native and aortic graft infections, respectively (p = .45). Median follow up was 26 months (interquartile range [IQR] 10, 51). Estimated survival at one, two, three, and five years was 64%, 60%, 57%, and 50%, and significantly better for native (81%, 77%, 77%, and 69%) than for graft infections (58%, 55%, 51%, and 44%; p = .011). Nine patients (5.3%) had persistent infection and 10 patients (6%) had aortic re-infection after a median of 10 months (IQR 5, 22), resulting in an estimated freedom from re-infection at one, two, three, and five years of 94%, 92%, 90%, and 86%. Estimated freedom from graft complications at one, two, three, and five years was 91%, 89%, 87%, and 87%. CONCLUSION: This multicentre study demonstrates low re-infection rates when using physician made bovine pericardial tube grafts, comparable to those of other biological grafts. The rate of graft complications, mainly anastomotic aneurysms and stenoses, was low, while graft degeneration was absent. Physician made bovine pericardial tube grafts are an excellent tool for in situ reconstruction in the setting of native aortic infection or aortic graft infection.

Autologous versus synthetic midurethral transobturator sling: A systematic review and meta-analysis of outcomes.

INTRODUCTION: There have been concerns around the use of synthetic mesh for stress urinary incontinence (SUI) surgery with a renewed interest in the use of autologous tissues. Recently, an autologous transobturator sling (aTOT) has been described, but the comparative data with synthetic transobturator sling (sTOT) is limited. The objective of this systematic review and meta-analysis was to assess the outcome of aTOT and compare it with sTOT. METHODS: A systematic search of PubMed, Scopus, and Web of Science databases was performed and all articles available up to December 31, 2023 were screened. Studies reporting on the outcomes of aTOT and those comparing aTOT with sTOT were included. This review was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Eleven studies evaluating 323 patients that met the criteria were included in the final analysis, of which 6 were single arm (155 patients) and 5 were comparative. In single-arm studies, the pooled success rate, defined as negative cough stress test at 12 months follow-up was 96.8%, 3.8% had postoperative urinary retention, 6.1% had graft site-related complications and 7.6% required additional intervention for persistent SUI. The overall complication rate was 20.6% and there were no Clavien III-V complications. aTOT had similar success and complication rates when compared with sTOT but had a significantly longer operative time (weighted mean difference: 22.35 min, p < 0.00001) and superior sexual function outcomes. CONCLUSIONS: aTOT, at short-term follow-up (12 months), has similar efficacy and complication rates when compared to sTOT. However, given that the data is limited and not of very good quality, and the fact that long-term follow-up is not available, further studies are required to better define the role of aTOT in the management of female patients with SUI.

Long-term stability of gingival margin and periodontal soft-tissue phenotype achieved after mucogingival therapy: A systematic review.

BACKGROUND: The aim of this systematic review was two-fold: (i) to evaluate the long-term (≥5 years) stability of the gingival margin position, keratinized tissue width (KTW) and gingival thickness (GT) in sites that underwent root coverage (RC) or gingival augmentation (GA); and (ii) to assess the influence of different local variables on the long-term stability of dental and gingival tissues. MATERIALS AND METHODS: Randomized controlled trials (RCTs) and non-RCTs reporting short-term (i.e., 6-12 months after baseline surgical intervention) and long-term (≥5 years) follow-up data after surgical treatment of adult patients presenting single or multiple mucogingival deformities, defined as sites presenting gingival recession defects (GRDs) and/or (KTW) deficiency (i.e., <2 mm), were considered eligible for inclusion. MEDLINE-PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases were searched for articles published up to 15 May 2023. Mixed-effects multiple linear regression was used to assess the association between KTW, type of surgical procedure and time (i.e., independent variables) on the stability of the gingival margin in sites that received RC or GA therapy. RESULTS: Of the 2569 potentially eligible records, 41 (reporting 40 studies) met the eligibility criteria. Graphical estimates including data from all RC procedures found an upward trend in recession depth (RD) increase over time. Conversely, it was observed that in 63.63% of RC studies and in 59.32% of RC treatment arms KTW increased over time, particularly in sites treated with subepithelial connective tissue grafts (SCTGs). Conversely, sites that underwent GA procedures generally exhibited an overall reduction of KTW over time. However, sites treated with free gingival grafts (FGGs) showed a decrease in RD after 10 years of follow-up. Three main findings derived from the pooled estimates were identified: (i) Gingival margin stability was associated with the amount of KTW present during short-term assessment (i.e. the greater the KTW at 6-12 months after treatment, the more stable the gingival margin). (ii) The use of autogenous soft-tissue grafts was associated with lower RD increase over time. (iii) Treatment approaches that contribute to the three-dimensional enhancement of the gingival phenotype, as clearly demonstrated by FGG, were associated with gingival margin stability. CONCLUSIONS: The extent of apical migration of the gingival margin appears to be directly related to the amount of KTW and GT upon tissue maturation. Interventions involving the use of autogenous grafts, either SCTG or FGG, are associated with greater short-term KTW gain and lower RD increase over time.

Sacrocolpopexy: Alternatives to Mesh Grafts.

INTRODUCTION AND HYPOTHESIS: The ongoing pelvic mesh controversy, coupled with a regulatory pause in using pelvic mesh in some countries, has created a need for mesh-free alternatives for sacrocolpopexy (SCP). This article provides an overview of mesh-free alternatives for SCP. METHODS: MEDLINE and PubMed searches were conducted to identify studies reporting on autologous and non-autologous biologic grafts for SCP. Identified studies were reviewed by two of the authors (CY and MR). RESULTS: Emerging evidence on autologous fascia lata (AFL) and rectus sheath (ARS) for SCP is promising, with low donor site morbidity. Non-autologous biologic grafts for SCP are mostly reported to be inferior to mesh. CONCLUSIONS: Emerging evidence suggests that AFL and ARS might be safe and effective alternative options to mesh SCP. The main advantages of AFL for SCP over ARS are laparoscopy or robot-assisted laparoscopy approaches, and that a larger graft can be safely harvested. The benefits of utilising allografts and xenografts are limited by their reduced durability compared with mesh and patient acceptability.

Critical-size defects reconstruction with four different bone grafts associated with e-PTFE membrane: A histomorphometric experimental in vivo study.

OBJECTIVES: The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical-size defects, associated or not with the non-resorbable membrane. MATERIALS AND METHODS: Two calvaria critical-size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e-PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed-effects model with multiple comparisons (significance level, p < .05). RESULTS: A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non-significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups. CONCLUSIONS: The best results were found in the autogenous group, with higher resorption and integration; non-significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e-PTFE barrier did not present significant results on new bone formation.

Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

Hypothermic Oxygenated machine PErfusion for high-risk liver grafts for transplantation: A systematic review and meta-analysis.

BACKGROUND: Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high-risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts. METHODS: This study includes all papers comparing HOPE to static cold storage for high-risk ECD and DCDD grafts. Systematic searches of Medline, Embase, and Scopus were completed using the terms "HOPE" OR "hypothermic oxygenated machine perfusion" AND "liver transplantation". Data were extracted and analyzed using IBM SPSS to perform the meta-analysis. RESULTS: A total of 2286 records were identified, with 10 meeting the inclusion criteria. Overall, the quality of evidence is heterogenous with many papers relying on retrospective controls. However, pooled analysis demonstrates HOPE to significantly reduce the rate of early allograft dysfunction, 12-month graft failure, re-transplantation, total biliary complications, and non-anastomotic strictures for high-risk grafts. CONCLUSIONS: There is good evidence that HOPE improves outcomes following liver transplantation across a number of biochemical and clinical endpoints for high-risk grafts. Of note, the reduction in biliary complications and re-transplantation is particularly significant given the morbidity associated with these endpoints. However, further, high-quality prospective trials with contemporary controls and clinically relevant primary endpoints are needed to better define the impact of HOPE for this cohort of grafts.

Adipose-derived stem cells transplantation improves survival and alleviates contraction of skin grafts via promoting macrophages M2 polarization.

BACKGROUND: Full-thickness skin grafts are widely used in plastic and reconstructive surgery. The main limitation of skin grafting is the poor textural durability and associated contracture, which often needs further corrective surgery. Excessive inflammation is the main reason for skin graft contractions, which involve overactivation of myofibroblasts. These problems have prompted the development of new therapeutic approaches, including macrophage polarization modulation and stem cell-based therapies. Currently, adipose-derived stem cells (ASCs) have shown promise in promoting skin grafts survival and regulating macrophage phenotypes. However, the roles of ASCs on macrophages in decreasing skin grafts contraction remain unknown. MATERIALS AND METHODS: Rat adipose-derived stem cells (rASCs) were isolated from rat inguinal adipose tissues. Full-thickness skin graft model was constructed on male rats divided into control group and rASCs treatment group. Skin graft was assessed for concentration, elasticity modulus and stiffness. Rat bone marrow-derived macrophages (rBMDMs) were isolated from rat femurs, and subsequent RT-qPCR and coculture assays were carried out to explore the cellular mechanisms. Immunohistochemical and immunofluorescence staining were used to verify mechanisms in vivo. RESULTS: In vivo results showed that after injection of ASCs, improved texture, increased survival and inhibited contraction of skin grafts were seen. Vascularization was also improved as illustrated by laser perfusion image and vascular endothelial growth factor (VEGF) concentration. Histological analysis revealed that ASCs injection significantly reduced expression of pro-inflammatory cytokines (TNF-a, IL-1ß) and increased expression of anti-inflammatory (IL-10) and pro-healing cytokines (IGF-1). At cellular level, after co-culturing with rASCs, rat bone marrow derived macrophages (rBMDMs) favored M2 polarization even under inflammatory stimulus. CONCLUSION: ASCs treatment enhanced vascularization via angiogenic cytokines secretion and alleviated inflammatory environment in skin grafts by driving M2 macrophages polarization, which improved survival and decreased skin grafts contraction. Our work showed that ASCs transplantation can be harnessed to enhance therapeutic efficacy of skin grafting in cutaneous defects treatment.

Iliac crest bone graft versus cell-based grafts to augment spinal fusion: a systematic review and meta-analysis.

INTRODUCTION: Despite successful fusion rates with iliac crest bone graft (ICBG), donor-site morbidity and increased operating time remain a considerable limitation and drive the search for alternatives. In this systematic review, grafts with additional cellular supplementation were compared with ICBG for spinal arthrodesis. We compared safety, efficacy and long-term outcomes, thus providing the current and relevant evidence for orthopaedic surgeons to make informed choices regarding this rapidly developing field. METHODS: An electronic literature search was conducted according to the PRISMA guidelines by two independent reviewers for articles published up to 1st March 2023 using PubMed, EMBASE and the Cochrane Central Register of Controlled Trial. Cellular allografts were not included. The following data were extracted: Number of patients, type of graft, fusion assessment method, follow-up duration, fusion rates, clinical outcomes and complications. The methodological quality of evidence (MQOE) was assessed using the Risk of Bias 2 (RoB-2) tool and Risk of Bias In Non-Randomised Studies (ROBINS) tool developed by Cochrane for evaluating bias in randomised and non-randomised studies. RESULTS: Ten studies fulfiled the inclusion criteria, including 465 patients. The mean number of patients per study was 43.8 (std dev. 28.81, range 12-100). Two studies demonstrated cell-based therapy to be significantly more successful in terms of fusion rates compared to ICBG. However, the remaining eight demonstrated equivocal results. No study found that cell-based therapy was inferior. No difference was seen between the two groups in three studies who focused on degenerative cohorts. No difference in functional outcome scores was seen between the groups. A number of different preparation techniques for cell-based grafts were used throughout the studies. CONCLUSION: Cell-based therapy offers a promising alternative to ICBG in spinal fusion surgery, which could help reduce the associated morbidity to patients. This review found that cell-based therapy is non-inferior to iliac crest bone graft and may offer patients an alternative treatment option with fewer complications and reduced post-operative pain. However, the literature to date is limited by heterogeneity of the cell preparation and grafting process. Future research with a unified approach to the cell preparation process is required to fully delineate the potential advantages of this technology.