Sheila MacNeil

Suburethral polypropylene mesh tapes for women were initially introduced into clinical practice for the treatment of stress urinary incontinence without being tested in an appropriate animal model. The goal of this work has been to establish and evaluate a suitable animal model for the assessment of suburethral tape grafts. Allowing for the anatomical similarities between ewes and women and recognizing the inevitable differences in posture, but recognizing prior work, this report presents a step-by-step description of the surgery involved in an animal model that simulates the implantation of support materials for treating stress urinary incontinence in women. Seven ewes with a mean weight of 27.7 SD 5.1 kg underwent surgery. In the lithotomy position, a ventral vaginal wall incision was made. In five animals, using an introducer, a polyurethane implant was placed underneath the urethra and fixed with absorbable sutures. The incision was closed, and a betadine vaginal pack was placed after 24 h. Two animals received transvaginal polypropylene mesh using similar surgical steps but no fixation sutures. After surgery, all animals urinated freely and had regular bowel movements. No animals showed signs of vaginal erosion or graft infection during the three-month follow-up. This large animal model accurately reproduces the surgical technique used in women, thereby providing a valuable platform for evaluating new materials for stress urinary incontinence treatment.

Skin contracts during wound healing to facilitate wound closure. In some patients, skin contraction can lead to the formation of skin contractures that limit movement, impair function, and significantly impact well-being. Current treatment options for skin contractures are burdensome for patients, and there is a high risk of recurrence. Autologous fat grafting can improve the structure and function of scarred skin; however, relatively little is known about the effect of fat on skin contraction. In this study, an in vitro tissue-engineered model of human skin was used to test the effects of adipose tissue and adipose-derived stromal cells on skin contraction. Untreated tissue-engineered skin contracted to approximately 60% of the original area over 14 days in culture. The addition of adipose tissue reduced this contraction by 50%. Adipose tissue, which was emulsified or concentrated and high doses of adipose-derived stromal cells (ADSC) were able to inhibit contraction to a similar degree; however, lower doses of ADSC did not show the same effect. In conclusion, the subcutaneous application of adipose tissue has the potential to inhibit skin contraction. This study provides in vitro evidence to support the use of autologous fat grafting to prevent skin contraction in patients most at risk.

Introduction. Interspecies differences in human, pig and sheep corneal thickness may affect the Pseudomonas aeruginosa colonization. Currently, there is no research investigating the impact of these differences, along with variable storage and culture conditions on infection in ex vivo cornea models. These factors could significantly influence utilizing ex vivo models for drug testing research. Aim. In this study, we aim to compare the relevance of sheep and pig cornea infection models to human. Methodology. The corneas were stored in McCarey-Kaufman medium or Eagle’s Minimum Essential Medium or Dulbecco’s Modified Eagle’s Medium/Mixture F-12 Ham medium (incubator) and then infected after varying storage durations. The effect of added foetal bovine serum (FBS) to media and continuous shaking mimicking rinsing with tears on infection was also investigated. The infection outcome was evaluated by comparing c.f.u. between conditions. Results. The study found that storage conditions, culture media, FBS and continuous rinsing of corneas with media had no significant effect on infection progression in ex vivo keratitis models across selected species. Conclusions. Pig and sheep models yield results comparable to human corneas. These findings support the interchangeability of ex vivo human, pig and sheep keratitis models for P. aeruginosa infection studies, emphasizing their relevance and reliability in research contexts. This interchangeability is particularly useful for research groups where one particular animal model may not be available. The media in this ex vivo keratitis model can be free of animal components by the removal of FBS, which reduces the reliance on animal-derived products, aligning with ethical considerations and promoting more sustainable and humane scientific practices. This study advances the understanding of ex vivo keratitis models, demonstrating their robustness and potential for broader application in ophthalmic research and drug testing.

Background: Understanding vascular development and the key factors involved in regulating angiogenesis—the growth of new blood vessels from pre-existing vasculature—is crucial for developing therapeutic approaches to promote wound healing. Computational techniques offer valuable insights into improving angiogenic strategies, leading to enhanced tissue regeneration and improved outcomes for chronic wound healing. While chorioallantoic membrane (CAM) models are widely used for examining fundamental mechanisms in vascular development, they lack quantification of essential parameters such as blood flow rate, intravascular pressure, and changes in vessel diameter. Methods: To address this limitation, the current study develops a novel two-dimensional mathematical model of angiogenesis, integrating discrete and continuous modelling approaches to capture intricate cellular interactions and provide detailed information about the capillary network’s structure. The proposed hybrid meshless-based model simulates sprouting angiogenesis using the in vivo CAM system. Results: The model successfully predicts the branching process with a total capillary volume fraction deviation of less than 15% compared to experimental data. Additionally, it implements blood flow through the capillary network and calculates the distribution of intravascular pressure and vessel wall shear stress. An adaptive network is introduced to consider capillary responses to hemodynamic and metabolic stimuli, reporting structural diameter changes across the generated vasculature network. The model demonstrates its robustness by verifying numerical outcomes, revealing statistically significant differences with deviations in key parameters, including diameter, wall shear stress (p < 0.05), circumferential wall stress, and metabolic stimuli (p < 0.01). Conclusion: With its strong predictive capability in simulating intravascular flow and its ability to provide both quantitative and qualitative assessments, this research enhances our understanding of angiogenesis by introducing a biologically relevant network that addresses the functional demands of the tissue.

Background: Following the severe complications widely reported in some women following polypropylene suburethral mesh implantation for the treatment of stress urinary incontinence, it has become clear that careful preclinical study in an appropriate animal model is essential. The preclinical model described here allows the postoperative clinical and histochemical assessment of material implanted in the sheep vagina and represents a model that allows prediction of the potential vaginal tissue responses to suburethral mesh implantation before implantation into humans.Objectives: To develop and evaluate a relevant preclinical animal model to mimic suburethral implantation of support materials for stress urinary incontinence.Material: Fourteen parous ewes of 30–40 kg were used. Under general anesthetic, animals were placed in the lithotomy position. A 12‐French Foley catheter was inserted. The ventral vaginal wall was longitudinally incised. The space between the vaginal wall and the urethra was developed, with lateral retropubic dissection. Either a standard transvaginal polypropylene tape (seven animals) or a fascia mimetic microfibre spun polyurethane tape (seven animals) were inserted using an introducer either via a suprapubic (seven animals) or a transvaginal approach (seven animals) into the suburethral and retropubic space. The incisions were closed, and the catheter was removed. A betadine vaginal pack was placed and removed after 24 h. Postoperatively, the animals were observed carefully for pain and complications and allowed access to water and food under continuous veterinary supervision adhering to USA‐approved protocols.Results: On the second postoperative day, all the animals passed urine freely and had regular bowel motions. No procedure related complications were observed.Conclusion: This is the first large animal model which has been designed for suburethral implantation. and which can be effectively used for the preoperative evaluation of novel materials designed for suburethral implantation. We believe that this technique in this large animal model accurately reproduces the surgical technique used to treat stress urinary incontinence in women. It provides a new and effective in vivo model for the objective evaluation of new materials to treat female stress incontinence.

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Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%–90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson’s trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%–90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established.