Functionalised biomaterials as synthetic extracellular matrices to promote vascularisation and healing of diabetic wounds.

Diabetic foot ulcers (DFU) are a type of chronic wound that constitute one of the most serious and debilitating complications associated with diabetes. The lack of clinically efficacious treatments to treat these recalcitrant wounds can lead to amputations for those worst affected. Biomaterial-based approaches offer great hope in this regard, as they provide a template for cell infiltration and tissue repair. However, there is an additional need to treat the underlying pathophysiology of DFUs, in particular insufficient vascularization of the wound which significantly hampers healing. Thus, the addition of pro-angiogenic moieties to biomaterials is a promising strategy to promote the healing of DFUs and other chronic wounds. In this review, we discuss the potential of biomaterials as treatments for DFU and the approaches that can be taken to functionalise these biomaterials such that they promote vascularisation and wound healing in pre-clinical models.

Micro to macro scale anatomical analysis of the human hippocampal arteries with synchrotron hierarchical phase-contrast tomography.

PURPOSE: To date, no non-invasive imaging modality has been employed to profile the structural intricacies of the hippocampal arterial microvasculature in humans. We hypothesised that synchrotron-based imaging of the human hippocampus would enable precise characterisation of the arterial microvasculature. METHODS: Two preserved human brains from, a 69-year-old female and a 63-year-old male body donors were imaged using hierarchical phase-contrast tomography (HiP-CT) with synchrotron radiation at multiple voxel resolutions from 25.08 µm down to 2.45 µm. Subsequent manual and semi-automatic artery segmentation were performed followed by morphometric analyses. These data were compared to published data from alternative methodologies. RESULTS: HiP-CT made it possible to segment in context the arterial architecture of the human hippocampus. Our analysis identified anterior, medial and posterior hippocampal arteries arising from the P2 segment of the posterior cerebral artery on the image slices. We mapped arterial branches with external diameters greater than 50 µm in the hippocampal region. We visualised vascular asymmetry and quantified arterial structures with diameters as small as 7 µm. CONCLUSIONS: Through the application of HiP-CT, we have provided the first imaging visualisation and quantification of the arterial system of the human hippocampus at high resolution in the context of whole brain imaging. Our results bridge the gap between anatomical and histological scales.

Low-level laser therapy combined with scleral graft transplantation in the treatment of contracted socket: a clinical study.

OBJECTIVE: To analyse the efficacy of the therapeutic use of low-level laser therapy (LLLT) on the tissue repair process of allogeneic scleral grafts in patients with contracted sockets by analysing the speed of graft vascularisation and fornice depth of contraction percentage. METHODS: A retrospective chart review was performed from April 2015 to April 2021 including 39patients with socket contraction. Allogeneic scleral grafts were used to repair the sockets in all patients. They were randomly enrolled into two groups. The laser group included 18 patients treated with LLLT after the surgery, whereas the control group included 21 patients without LLLT after the surgery who healed naturally. The LLLT equipment used in the research had a wavelength of 650 nm, 10 mW power, and 3.8 J/cm2 dosimetry, and the procedure was performed once daily for 5 min over 7 days, beginning 1 week postoperatively. All patients were followed up over 6 months to examine the changes in the size of the area of the non-vascularised graft and upper and inferior fornice depth. RESULTS: The laser group presented a significantly increased speed of conjunctival vascularisation compared with the control group (P = 0.003). The fornice depth of contraction percentage was more apparent in the control group than that in the laser group (P = 0.000). CONCLUSION: LLLT accelerates conjunctival vascularisation, stimulates conjunctival incision healing within a short period, shortens the tissue repair process, reduces the local inflammatory response, and causes no significant shrinkage of the conjunctival sac.

Understanding the mechanisms of spontaneous and skin-grafted wound repair: the path to engineered skin grafts.

Spontaneous wound repair is a complex process that involves overlapping phases of inflammation, proliferation and remodelling, co-ordinated by growth factors and proteases. In extensive wounds such as burns, the repair process would not be achieved in a timely fashion unless grafted. Although spontaneous wound repair has been extensively described, the processes by which wound repair mechanisms mediate graft take are yet to be fully explored. This review describes engraftment stages and summarises current understanding of molecular mechanisms which regulate autologous skin graft healing, with the goal of directing innovation in permanent wound closure with skin substitutes. Graftability and vascularisation of various skin substitutes that are either in the market or in development phase are discussed. In doing so, we cast a spotlight on the paucity of scientific information available as to how skin grafts (both autologous and engineered) heal a wound bed. Better understanding of these processes may assist in developing novel methods of wound management and treatments.

Angiogenesis and flap-related research: A bibliometric analysis.

Adequate blood supply, a prerequisite for flap survival after grafting, makes angiogenesis of the flap the biggest problem to be solved. Researches have been conducted around vascularisation in correlation with flap grafting. However, bibliometric analyses systematically examining this research field are lacking. As such, we herein sought to conduct comprehensive comparative analyses of the contributions of different researchers, institutions, and countries to this research space in an effort to identify trends and hotspots in angiogenesis and vascularisation in the context of flap grafting. Publications pertaining to angiogenesis and vascularisation in the context of flap grafting were retrieved from the Web of Science Core Collection. References were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. In total, 2234 papers that were cited 40 048 times (17.63 citations/paper) were included in this analysis. The greatest number of studies were from the United States, with these studies exhibiting both the highest number of citations (13 577) and the greatest overall H-index (60). For The institutions that published the greatest number of studies were WENZHOU MEDICAL UNIVERSITY (681), while UNIVERSITY OF ERLANGEN NUREMBERG has the highest number of citations (1458), and SHANGHAI JIAO TONG UNIVERSITY holds the greatest overall H-index (20). The greatest number of studies in this research space were published by Gao WY, while Horch RE was the most commonly cited researcher in the field. The VOS viewer software clustered relevant keywords into three clusters, with clusters 1, 2, 3, and 4 corresponding to studies in which the keywords 'anatomy', 'survival', 'transplantation', 'therapy' most frequently appeared. The most promising research hotspot-related terms in this field included 'autophagy', 'oxidative stress', 'ischemia/reperfusion injury', which exhibited a most recent average appearing year (AAY) of 2017 and after. Generally speaking, the results of this analysis indicate that the number of articles exploring angiogenesis and flap-related research has risen steadily, with the United States and China being the two countries publishing the greatest proportion of studies in this field. The overall focus of these studies has shifted away from 'infratest and tissue engineering' towards 'mechanisms'. In the future, particular attention should be paid to emerging research hotspots, which include 'ischemia/reperfusion injury' and treatments for promoting vascularization, such as 'platelet-rich plasma'. In light of these findings, funding agencies should continue increasing their investment in the exploration of the concrete mechanisms and interventional therapeutic relevance of angiogenesis during flap transplantation.

The effect of aerobic exercise on tumour blood delivery: a systematic review and meta-analysis.

PURPOSE: Tumour blood vessels are structurally and functionally abnormal, resulting in areas of hypoxia and heterogeneous blood supply. Aerobic exercise may modulate tumour blood flow and normalise the tumour microenvironment to improve chemotherapy delivery. This systematic review and meta-analysis aimed to evaluate the effect of the aerobic exercise mode on tumour hypoxia, vascularisation and blood flow. METHODS: Four online databases were searched. Preclinical and clinical randomised controlled trials examining the effects of aerobic exercise training on hypoxia, vascularisation or blood flow in solid tumours were included. The risk of bias was assessed and a meta-analysis performed. RESULTS: Seventeen preclinical studies and one clinical study met criteria. Eleven studies assessed hypoxia, 15 studies assessed vascularisation and seven evaluated blood flow. There was large variability in measurement methods, tumour types and exercise program designs. The overall risk of bias was unclear in clinical and preclinical studies, owing to poor reporting. There was no significant effect of aerobic exercise on hypoxia (SMD = -0.17; 95% CI = -0.62, 0.28; I2 = 60%), vascularisation (SMD = 0.07; 95% CI = -0.40, 0.55; I2 = 71%) or blood flow (SMD = 0.01; 95% CI = -0.59, 0.61; I2 = 63%). CONCLUSION: There is heterogeneity in methodology, resulting in evidence that is inconsistent and inconclusive for the effects of aerobic exercise on hypoxia, vascularisation and blood flow. Most evidence of aerobic exercise effects on tumour blood flow is in animal models, with very limited evidence in humans.

Intra-operative assessment of the vascularisation of a cross section of the meniscus using near-infrared fluorescence imaging.

PURPOSE: The purpose of this study was to assess whether the vascularisation of the meniscus could be visualised intra-operatively using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) in patients undergoing total knee arthroplasty (TKA). METHODS: The anterior horn (i.e., Cooper classification: zones C and D) of the meniscus that was least affected (i.e., least degenerative) was removed during TKA surgery in ten patients to obtain a cross section of the inside of the meniscus. Thereafter, 10 mg of ICG was injected intravenously, and vascularisation of the cross section of the meniscus was assessed using the Quest spectrum NIRF camera system. We calculated the percentage of patients in whom vascularisation was observed intra-operatively using NIRF imaging compared to immunohistochemistry. RESULTS: Meniscal vascularisation using NIRF imaging was observed in six out of eight (75%) patients in whom vascularisation was demonstrated with immunohistochemistry. The median extent of vascularisation was 13% (interquartile range (IQR) 3-28%) using NIRF imaging and 15% (IQR 11-23%) using immunohistochemistry. CONCLUSION: This study shows the potential of NIRF imaging to visualise vascularisation of the meniscus, as vascularisation was observed in six out of eight patients with histologically proven meniscal vascularisation. LEVEL OF EVIDENCE: IV.

Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance.

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.

[Anatomical basis of gluteus maximus and application as a pedicled cover flap for pelvic tumor resections]. / Bases anatomiques du gluteus maximus et application comme lambeau pédiculé de couverture pour les résections de tumeurs du bassin.

OBJECTIVES: The resection of malignant bone tumors of the pelvis causes significant loss of substances making covering procedures difficult. The gluteus maximus pedicled flap allows some reconstructions, but its use in vascular sacrifice is not clearly established. The objective of our study was to study its vascularization in order to assess the possibility of vascular sacrifice during carcinological resection of a pelvic tumor. METHOD: We first performed a vascular mapping of the gluteus maximus muscle using 3-dimensional (3D) models from CT angiography in patients with Leriche syndrome. These models were compared to a cadaveric dissection of 2 injected muscles. A second 3D modeling from postoperative scans was performed in patients who had a gluteus maximus flap after pelvic carcinological surgery. RESULTS: Ten patients with Leriche syndrome had a 3D model from their scanners. Three distinct arterial systems were identified. Seven patients had a flap from the gluteus maximus muscle, including 3 cases of an Inverted pedicled Hemi Gluteus maximus flap (HGI). According to the modeling, the richness of the vascular network would allow the sacrifice of the superior gluteal pedicle without compromising the viability of this flap. CONCLUSION: Our study made it possible to confirm the richness of the vascular network of the gluteus maximus muscle and to consider the theoretical possibility of sacrificing the superior gluteal pedicle without endangering an HGI pedicled muscle flap.

Analysis of vascularization in thyroid gland nodes with superb microvascular imaging (SMI) and CD34 expression histology: a pilot study.

BACKGROUND: The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. METHODS: We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. RESULTS: Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). CONCLUSION: We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes.

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.

Vascular anatomy of the first metatarsal bone and surgical implications according to the severity of hallux valgus deformity: A cadaveric study.

BACKGROUND: Vascular injury after hallux valgus surgery is a rare condition but serious complications can ensue. METHODS: We performed an anatomical study using 26 cadaveric lower extremities. We enhanced first metatarsal bone's (FMB) vascularization by injecting latex. Each specimen was classified according to the severity of hallux valgus deformity (HVD). Then we measured two distances: one between the first tarsometatarsal joint (FTMJ) to the first dorsal branch's origin, the other between the first metatarsophalangeal joint (MTP) to the dorsal plexus's origin. RESULTS: The distance between the FTMJ and the first dorsal branch to the FMB ranges from 10 mm in normal feet to 15 mm in severe deformed feet. The distance between the MTP and the dorsal plexus' origin ranges from 20 mm in normal feet to 25 mm in severe deformed feet. CONCLUSIONS: Understanding the foot's vascular anatomy has allowed us to adapt surgical landmarks to the severity of the HVD and to avoid post-operative complications.

Recruited fibroblasts reconstitute the peri-islet membrane: a longitudinal imaging study of human islet grafting and revascularisation.

AIMS/HYPOTHESIS: Rapid and adequate islet revascularisation and restoration of the islet-extracellular matrix (ECM) interaction are significant factors influencing islet survival and function of the transplanted islets in individuals with type 1 diabetes. Because the ECM encapsulating the islets is degraded during islet isolation, understanding the process of revascularisation and engraftment after transplantation is essential and needs further investigation. METHODS: Here we apply a longitudinal and high-resolution imaging approach to investigate the dynamics of the pancreatic islet engraftment process up to 11 months after transplantation. Human and mouse islet grafts were inserted into the anterior chamber of the mouse eye, using a NOD.ROSA-tomato.Rag2-/- or B6.ROSA-tomato host allowing the investigation of the expansion of host vs donor cells and the contribution of host cells to aspects such as promoting the encapsulation and vascularisation of the graft. RESULTS: A fibroblast-like stromal cell population of host origin rapidly migrates to ensheath the transplanted islet and aid in the formation of a basement membrane-like structure. Moreover, we show that the vessel network, while reconstituted by host endothelial cells, still retains the overall architecture of the donor islets. CONCLUSIONS/INTERPRETATION: In this transplantation situation the fibroblast-like stromal cells appear to take over as main producers of ECM or act as a scaffold for other ECM-producing cells to reconstitute a peri-islet-like basement membrane. This may have implications for our understanding of long-term graft rejection and for the design of novel strategies to interfere with this process.

[Indocyanine green fluorescence to visualize the ureteric vascularization of kidney transplants: An exploratory study]. / Visualiser la vascularisation urétérale des transplants rénaux par fluorescence au vert d'indocyanine : étude exploratoire.

INTRODUCTION: Urinary complications after kidney transplantation are common and can compromise renal function. While they are mainly attributed to ischemic lesions of the ureter, there is no existing method to evaluate its vascularization during surgery. The aim of the study was to evaluate if indocyanine green, revealed by infra-red light andused to visualize tissue perfusion, could provide an appreciation of the ureter's vascularization during kidney transplantation. METHODS: This feasibility study was conducted over one month, on eleven consecutive kidney transplants. During transplantation, an injection of indocyanine green enabled the surgeon to visualize in real time with an infra-red camera the ureter fluorescence. Its intensity was reported on a qualitative and semi-quantitative scale. Occurrence of urinary complications such as stenosis or ureteral fistula were collected during 6 months. RESULTS: In all of the 11 cases (100%), the last centimeters of the ureters were not fluorescent. Three (27%) ureters were poorly or partiallly fluorescent. Out of these three cases, only one case of urinary fistula occurred, followed by ureteric stenosis. In the series, two fistulas (18%) and two ureteric stenoses (18%) occurred. No side effects were observed. The low number of events did not allow statistical analysis. CONCLUSION: Infra-red fluorescence of indocyanine green could be a simple and innovative way to appreciate the transplant's ureteric vascularization during kidney transplantation. It could help surgeons to identify the level of ureter section and to decide the anastomosis technique, in order to limit urinary complications. LEVEL OF EVIDENCE: 3.

The many secret lives of adipocytes: implications for diabetes.

Adipose tissue remains a cryptic organ. The ubiquitous presence of adipocytes, the different fat pads in distinct anatomical locations, the many different types of fat, in each case with their distinct precursor populations, and the ability to interchange into other types of fat cells or even de-differentiate altogether, offers a staggering amount of complexity to the adipose tissue organ as a whole. Adipose tissue holds the key to improving our understanding of systemic metabolic homeostasis. As such, understanding adipose tissue physiology offers the basis for a mechanistic understanding of the pathophysiology of diabetes. This review presents some of the lesser known aspects of this fascinating tissue, which consistently still offers much opportunity for the discovery of novel targets for pharmacological intervention.

Hybrid procedure of right ventricle outflow tract stenting in small infants with pulmonary atresia and ventricular septal defect: early and mid-term results from a single centre.

IntroductionPulmonary atresia, ventricular septal defect, major aorto-pulmonary collateral arteries, and pulmonary arteries hypoplasia are rare and complex congenital defects that require early interventions to relieve cyanosis and enhance the growth of native pulmonary arteries. The treatment of these patients is still controversial. Surgical techniques require cardiopulmonary bypass which is poorly tolerated by small infants. Percutaneous techniques such as radiofrequency perforation can be challenging. The hybrid technique consists of perventricular stenting of the right ventricle outflow tract through medial sternotomy, to restore native pulmonary flow. METHODS: We retrospectively reviewed the cardiovascular database of our centre in order to analyse our experience in hybrid procedure. We detected six patients who underwent hybrid first approach between November 2007 and December 2015. We report our early results and mid-term outcomes. RESULTS: Median age at the procedure was 26 days, median weight was 3150 g, and median Nakata index was 52 mm2/m2. All procedures were successful except for one: this patient underwent a surgical shunt. No immediate and early deaths or major complications occurred and oxygen saturation levels increased in all the patients. Patients were followed up for a period of 12-103 months, and four of them underwent a procedure of unifocalisation at the mean age of 12.5 months. CONCLUSIONS: We reported data from the largest series of patients who underwent this hybrid procedure. Our experience demonstrated encouraging results to expand the use of this approach to bridge high-risk patients with diminutive pulmonary arteries to a second step of surgical repair.

Abdominoplasty with simultaneous laparoscopic umbilical hernia repair: A practical approach to preserve the umbilical vascularization.

BACKGROUND: Umbilical necrosis is a well-known complication of abdominoplasty, the risk of this complication can be increased when an associated umbilical hernia requires further dissection in peri-umbilical region, potentially leading to umbilical devascularisation. Multiple minimally invasive open techniques were described to avoid this problem. The combined approach of abdominoplasty with laparoscopic umbilical hernia repair is one promising solution to avoid devascularising the umbilicus. METHODS: A retrospective evaluation of patients who underwent concomitant abdominoplasty with laparoscopic umbilical hernia repair from 2007 to 2017 was carried out. All patients were followed up and evaluated for complications, including the incidence of umbilical skin necrosis. RESULTS: A total of 47 patients were included in this study. The average operative duration was 3.3hours with an average hospital stay of 2.5 days. No cases of postoperative umbilical necrosis were encountered. A mean follow-up period was 2.4 years showed no cases of hernia or rectus abdominis diastasis recurrence. Minor complications included 4 cases of dehiscence, one hematoma. There was no major complications. CONCLUSION: The concomitant use of laparoscopic umbilical hernia repair and abdominoplasty is a feasible approach to reduce the risks of umbilical devascularization. Especially in larger hernias and in patients with higher risk of recurrence.

Study of the intra-prostatic arterial anatomy and implications for arterial embolization of benign prostatic hyperplasia.

INTRODUCTION: Prostatic arterial embolization (PAE) is an experimental therapy for benign prostatic hyperplasia. Its feasibility is based on the knowledge of the pelvic arterial anatomy, and more specifically the prostate. The aim of this study was to describe the prostatic arterial supply: origins, distribution and variability. MATERIAL AND METHODS: We reviewed retrospectively, with two radiologists, 40 arteriographies of patients who underwent PAE in our center. With these observations of 80 hemipelvics, we described the number of prostatic arteries, their origins, their distributions and eventually their anastomoses with other pelvic arteries. RESULTS: There was one prostatic artery in 70% of the cases. It came from a common trunk for the prostate and the bladder in 55% of the cases, from the obturator artery in 17.5% of the cases, from the pudendal artery in 25% of the cases, from the intern iliac artery in 1% of the cases, and from the superior gluteal artery in 1% of the cases. The prostatic artery splitted in two branches (medial and lateral), with no anastomoses in 37% of the cases. Anastomoses with penile and rectal arteries were observed in 29% of the cases. CONCLUSIONS: For our 40 patients, we observed many variations of arterial prostatic anatomy. We proposed a classification in order to increase security and efficacy of PAE, and it should be validated with more patients. LEVEL OF EVIDENCE: 2.

Controlled release of insulin-like growth factor 1 enhances urethral sphincter function and histological structure in the treatment of female stress urinary incontinence in a rat model.

OBJECTIVES: To determine the effects of controlled release of insulin-like growth factor 1 (IGF-1) from alginate-poly-L-ornithine-gelatine (A-PLO-G) microbeads on external urethral sphincter (EUS) tissue regeneration in a rat model of stress urinary incontinence (SUI), as SUI diminishes the quality of life of millions, particularly women who have delivered vaginally, which can injure the urethral sphincter. Despite several well-established treatments for SUI, growth factor therapy might provide an alternative to promote urethral sphincter repair. MATERIALS AND METHODS: In all, 44 female Sprague-Dawley rats were randomised into four groups: vaginal distension (VD) followed by periurethral injection of IGF-1-A-PLO-G microbeads (VD + IGF-1 microbeads; 1 × 104 microbeads/1 mL normal saline); VD + empty microbeads; VD + saline; or sham-VD + saline (sham). RESULTS: Urethral function (leak-point pressure, LPP) was significantly lesser 1 week after VD + saline [mean (sem) 23.9 (1.3) cmH2 O] or VD + empty microbeads [mean (sem) 21.7 (0.8) cmH2 O) compared to the sham group [mean (sem) 44.4 (3.4) cmH2 O; P < 0.05), indicating that the microbeads themselves do not create a bulking or obstructive effect in the urethra. The LPP was significantly higher 1 week after VD + IGF-1 microbeads [mean (sem) 28.4 (1.2) cmH2 O] compared to VD + empty microbeads (P < 0.05), and was not significantly different from the LPP in sham rats, demonstrating an initiation of a reparative effect even at 1 week after VD. Histological analysis showed well-organised skeletal muscle fibres and vascular development in the EUS at 1 week after VD + IGF-1 microbeads, compared to substantial muscle fibre attenuation and disorganisation, and less vascular formation at 1 week after VD + saline or VD + empty microbeads. CONCLUSION: Periurethral administration of IGF-1-A-PLO-G microbeads facilitates recovery from SUI by promoting skeletal myogenesis and revascularisation. This therapy is promising, but detailed and longer term studies in animal models and humans are needed.

Optical coherence tomography angiography: a review of current and future clinical applications.

Optical coherence tomography angiography is a non-invasive imaging technique that now allows for simultaneous in vivo imaging of the morphology as well as the vasculature in the eye. In this review, we provide an update on the existing clinical applications of optical coherence tomography angiography technology from the anterior to posterior segment of the eye. We also discuss the limitations of optical coherence tomography angiography technology, as well as the caveats to the interpretation of images. As current optical coherence tomography angiography systems are optimized for the retina, most studies have focused on interpreting images from conditions such as age related macular degeneration and retinal vascular diseases. However, the interpretation of these optical coherence tomography angiography images should be taken in consideration with other multi-modal imaging to overcome the limitations of each technique. In addition, there are a growing variety of clinical applications for optical coherence tomography angiography imaging in optic nerve head evaluation for glaucoma and optic neuropathies. Further developments in anterior optical coherence tomography angiography have now allowed for evaluation of anterior segment pathology such as glaucoma, ocular surface diseases, corneal vascularisation, and abnormal iris vasculature. Future developments in software could allow for improved segmentation and image resolution with automated measurements and analysis.