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Biomaterials need to be vigorously tested at every stage of preclinical development. As demand for in vivo culture environments continues to increase, traditional animal models are often technically complex, ethically undesirable, time-consuming, and resource intensive and thus present a barrier to high throughput screening. The chick chorioallantoic membrane (CAM) assay has long been used to study the effects of drugs on angiogenesis in vivo, providing researchers with a readily available, accessible, self-sustaining, and high throughput screen without requiring animal facilities. It has also been recognized as an in vivo assay to test initial tissue response to biomaterials; however it has not yet gained widespread acceptance. This could be due to lack of specific protocols on how to optimize this assay to specifically test biomaterials. Here we describe how the ex ovo (shell-less) CAM assay can be effectively used to study the angiogenic potential and initial tissue response to biomaterials. In comparison to alternative in vivo approaches, this technique provides additional advantages to the researcher as it allows better visualization of implanted biomaterials and the ability to implant several samples simultaneously enabling combinatorial biomaterial assays to be conducted.

In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients' tissues and merit further study in physiologically relevant animal models.

This study shows the angiogenic potential of estradiol-releasing PU scaffolds with appropriate strength and elasticity desirable to support the pelvic floor.

Aim:In this study, we explored the angiogenic potential and proangiogenic concentration ranges of 2deoxy-D-ribose (2dDR) and -Estradiol (E2) in comparison with vascular endothelial growth factor (VEGF). 2dDR and E2 were then loaded into tissue engineering (TE) scaffolds to investigate their proangiogenic potential when released from fibres. Materials and Methods: Ex-ovo chick chorioallantoic membrane (CAM) assay was used to evaluate angiogenic activity of 2dDR and E2. Both factors were then introduced into scaffolds via electrospinning to assess their angiogenic potential when released from fibres. Results: Both factors were approximately 80% as potent as (VEGF) and showed a dose-dependent angiogenic response. The sustained release of both agents from the scaffolds stimulated neovascularisation over 7 days in the CAM assay. Conclusion: We conclude that both 2dDR and E2 provide attractive alternatives to VEGF for the functionalisation of TE scaffolds to promote angiogenesis in vivo. Graphical abstract:

Graphical abstract

Vaginal meshes used in the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) have produced highly variable outcomes causing life-changing complications in some patients while providing others with effective, minimally invasive treatments. The issue surrounding the risk:benefit ratio when using the vaginal meshes is complex in which a combination of several factors, including the inherent incompatibility of the mesh material with some applications in pelvic reconstructive surgeries and the lack of appropriate regulatory approval processes at the time of premarket clearance of these products , have contributed to occurrence of complications caused by vaginal mesh. Surgical mesh used in hernia repair has evolved over many years from metal implants to knitted polymer meshes that were adopted for use in the pelvic floor for treatment of POP and SUI. The evolution of the material and textile properties of the surgical mesh was guided by clinical feedback from hernia repair procedures, which were also being modified to obtain the best outcomes with use of the mesh. Current evidence shows how surgical mesh fails biomechanically when used in pelvic floor and materials with improved performance can be developed using modern material processing and tissue engineering techniques. [H1] IntroductionVaginal meshes that are currently used in the surgical treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) can result in life-changing complications in some women who have vaginal mesh implants 1 . These adverse outcomes are now considered a major public health problem; New Zealand becoming the first country in the world to ban the use of transvaginal POP mesh products while still allowing transvaginal SUI meshes (except minislings) in December 2017 2 . In the UK, two public enquiries performed by the Scottish (in 2015) 3 and English (in 2017) 4 governments, in part, as a result of pressure from patient groups led to suspension of vaginal mesh products, both for SUI and POP, from July 2018 onwards 5 . The newest guidance by the National Institute of Health and Care Excellence (NICE) in the UK recommends that retropubic sling materials can be offered to women with SUI if nonsurgical management has failed 6 . In response, the British Society of Urogynaecologists expressed strong disagreement with the decision to suspend the use of vaginal mesh for SUI, but not POP, stating that this decision would deprive many women of an effective and safe treatment option as demonstrated by level I evidence 7 8 . Mesh manufacturers are currently facing lawsuits in the USA and Europe 9 . The issue with mesh repairs for SUI and POP is complex, as the vaginal mesh is implanted in the female pelvic floor in several different ways with very different outcomes in efficacy and complication outcomes. When used as a tape to treat SUI, many patients are effectively cured with the benefits outweighing the risks 10,11 , whereas when used for transvaginal POP repair, complications are more frequent 12 with...

In this best practice document, we propose recommendations for the use of LASER for gynaecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia and lichen sclerosus based on a thorough literature review. Most of the available studies are limited by their design; for example they lack a control group, patients are not randomized, follow up is short term, series are small, LASER is not compared with standard treatments, and most studies are industry sponsored. Due to these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration following LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, while short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. Therefore, at this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent and audit.