EVALUATION COMMITTEE

The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture: 

• Dr. Marco Castagnetti, Urology, Chief of the Pediatric Urology Unit, Department of Women’s and Children’s Health, University-Hospital of Padova, Italy
• Prof. Magdalena Fossum,  Department of Pediatric Surgery, Center for Organ Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, Denmark
• Dr. Tue Bjerg Bennike, Health Science and Technology, Aalborg University, Denmark (Chairman).

Moderator:
Dr. Cristian Pablo Pennisi, HST, Aalborg University

ABSTRACT

Hypospadias is a congenital malformation of the male external genitalia in which the meatal opening is located at the ventral portion of the penis, affecting approximately 1 in 125 boys. There are a variety of surgical treatments for hypospadias, where the aim is to position the urethral opening at the tip of the glans and straighten the penis. Urethroplasty treatments usually involve the use of grafts, which may consist of the native urethral plate, autologous tissue, or tissue engineered constructs. The development of improved grafts for the treatment of hypospadias involves preclinical testing in animal models. With the goal of addressing some of the current challenges in the management of hypospadias, a series of studies were conducted in this PhD work.

The first series of studies focused on standardizing the evaluation of hypospadias abnormalities. Objective and reproducible tools for evaluating the severity of hypospadias anomaly were proposed, including methods to assess the quality of the urethral plate and to measure the degree of associated penile curvature. These methods utilized noninvasive imaging techniques based on ultrasound and state-of-the-art artificial intelligence. The studies have led to the development and validation of objective tools to assess these anatomic variables, which may be useful in personalized patient care and future research evaluating the outcomes of hypospadias treatment.

The second series of studies focused on the development and fabrication of grafts using tissue engineering concepts. Acellular scaffolds consisting of a three-layer structure of poly(lactic acid) and chitosan nanofibers were developed and tested in vitro. The scaffolds exhibited better water absorption, mechanical and biological properties compared to single-layer structures. In perspective, the proposed scaffolds appear to support the microenvironmental needs of different urethral cell types and adequate mechanical integrity, which should promote urethral formation in vivo.

Finally, the third series of studies focused on evaluating the advantages and limitations of the rabbit model currently used in the development of urethroplasty approaches. Guidelines from ARRIVE were used to generate systematic reviews that were helpful in identifying critical aspects of preclinical research that were not adequately addressed in the published studies. Considering the limitations identified, a paradigm for urethroplasty research was proposed that may help improve future research in this field.

Overall, the results of this work are expected to contribute significantly to the improvement of hypospadias management by providing a set of objective diagnostic tools, treatment modalities, and practical principles for the design of preclinical studies in hypospadias research.