Use of Acellular Dermal Matrix for Urethroplasty Coverage in Proximal Hypospadias Repair: a Pilot Study

This non-randomized study enrolled 35 patients (age range 15–60 months) with proximal hypospadias who underwent ADM operations between September 2018 and March 2019 at Beijing Children’s Hospitals (Beijing, China). Patient outcomes were compared with those of 80 non-matched control patients with proximal hypospadias who underwent the same procedure with dartos as a covering layer. The main inclusion criteria of the ADM group and dartos group were as follows: (i) primary male patients with proximal hypospadias with severe chordee (> 30°); (ii) hypospadias repair by transverse preputial island flap (TPIF) technique; (iii) written informed consent from patients’ parents following explanation of the nature of hypospadias and various methods of treatment; (iv) ability and willingness to regularly visit the hospital for follow-up during the study period. The main exclusion criteria of the ADM group and dartos group were as follows: (i) presence of distal hypospadias, recurrent hypospadias, and/or disorder of sex development, or receipt of preoperative topical androgen therapy; (ii) history of life-threatening allergic or immune-mediated reaction; (iii) clinically significant abnormalities in routine laboratory examinations; (iv) no use of the TPIF technique in hypospadias repair; (v) participation in any other clinical trials within 3 months before enrollment in this study; (vi) poor compliance with study requirements. The clinical study was approved by the ethics committee of Beijing Children’s Hospital (IEC-C-006-A03-V.05). All procedures performed in studies involving human participants were performed in accordance with the ethical standards of Beijing Children’s Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from parents to participate in the study and publish the results.

ADM (collagen type I) was derived from bovine skin and prepared by Zhenghai Biotechnology (Shandong, China); it exhibited a porous stereoscopic structure, as previously reported [12]. The ADM was sterilized by 12 kGy Co⁶⁰ irradiation. The surface morphology of collagen membranes was analyzed using a scanning electron microscope (Model S-2500; Hitachi), as well as by hematoxylin and eosin staining [13].

Acute toxicity, chronic toxicity, pyrogen reaction, allergen detection, genetic toxicity, intradermal irritation, cytotoxicity, hemolytic toxicity, and degradability characteristics of the ADM were evaluated by the National Institute of Food and Drug Control, in accordance with the Chinese Criterion of Medical Device GB16886.

All patients underwent hypospadias repair using the TPIF technique. Prophylactic preoperative intravenous antibiotic cefamandole (50 mg/kg) was routinely administered to all patients, 30 min prior to surgery. General anesthesia was induced in all patients; they were then placed in the supine position. After sterilization and draping had been performed, a glans stay suture was placed in the midline along the long axis of the penis. After complete degloving and excision of fibrotic tissue in the ventral aspect had been performed, the urethral plate was sectioned transversely at the position with severe chordee. Dorsal midline plication was performed to completely correct the chordee and rotational deformity. The dorsal preputial island flap was harvested and tubularized with an 8F silicon catheter (Fig. 1a, b). The length of the reconstructed tube was meticulously measured with a vernier caliper. The new tubularized urethral tube was sutured to the proximal urethral meatus and the tip of the glans (Fig. 1c). The single-layer pedicle dartos flap was used to cover the neo-urethra (Fig. 1d). An ADM sheet was trimmed to fit the length and width of the neo-urethral. The average width and length of the ADM were 1.5 cm and 3 cm, respectively. ADM was applied after completing single-layer dartos covering and secured by Mono-vicryl 6/0 (Ethicon, USA) (Fig. 1e); the skin was then sutured directly without any other covering layers.

The control group included 80 patients with proximal hypospadias of similar severity; for all control patients, surgery was performed by the same surgeon and postoperative care was identical to that provided for patients in the ADM group. For control patients, a single-layer pedicle dartos flap was used to cover the urethroplasty.

For all patients in this study, the wound was covered with soft permeable dressing that allowed absorption of any minor bleeding from the wound. The compressive dressing was removed for all patients on the fifth postoperative day. An indwelling transurethral catheter was kept for 21 days to reduce the incidence of urethral stricture. The urinary stream was evaluated in all patients after catheter removal.

All patients underwent follow-up for a maximum of 15 months; the mean follow-up duration was 11.56 months (range 9–15 months). Outpatient clinical assessment was performed at the time of catheter removal, as well as at 6 and 9 months after surgery. The outcomes of the patients were assessed by two of the authors with respect to operative time, postoperative complications, urinary stream, and cosmetic appearance. Complications were defined as fistula, urinary stricture, glandular dehiscence, and tissue infection. Cosmetic outcomes were evaluated by parents and based on the Pediatric Penile Perception Score (PPPS); the cosmetic parameters evaluated were normal meatus appearance and parental satisfaction. Success was defined as a lack of complications requiring re-intervention, with good cosmetic results. A functional outcome was defined as the presence of a normal voiding stream [14].