Autologous Fat Grafting Beneath Penile Split Thickness Skin Graft Placement During Penile Reconstruction

Assessing Possible Improvements to Cosmetic and Functional Outcomes of Penile Split Thickness Skin Grafting With Autologous Fat Graft

The goal of this randomized interventional clinical trial is to learn if placement of a thin layer of fatty tissue (fat graft) beneath a split-thickness skin graft on the surface of the penis improved outcomes of surgery in men who are scheduled to undergo reconstructive surgery on their penis and genitals. This is a randomized study, meaning that half of participants will receive the fat graft with their standard-of-care surgery, and half will have their standard-of-care surgery alone. Fat grafting underneath split-thickness skin grafts in other parts of the body has been shown to improve healing of the skin graft. Both study groups will be followed for specific outcomes through outpatient clinic visits for the first 12 months after their surgery, as well as chart review.

Questions the investigators hope to answer include:

• Does fat grafting improve the pliability and feel of the penile skin after grafting
• Does fat grafting change the penile length after surgery
• Does fat grafting improve sexual function, urinary function, and genital self-image after surgery
• Are there any unforeseen complications related to the fat grafting procedure

Participants will be asked to complete questionnaires related to sexual, urinary, and genital self-image questionnaires before surgery, 3 months after surgery, and 12 months after surgery. Noninvasive testing of the penile skin will also be performed at participants' routine appointments.

The investigators seek to study a novel adipose-based therapeutic strategy to improve cosmetic and function outcomes at the time of penile split-thickness skin graft (STSG) application during penile reconstruction. This entails a therapeutic repurposing of commonly utilized fat and skin grafting protocols to provide a fat-first reconstruction to address each of these limitations in one simple, economical, and widely accessible treatment for point-of-care penile reconstruction. Autologous adipose tissue is ideal as an adjunct to penile split-thickness skin grafting because it: 1) provides immediate, biologic soft tissue coverage with minimal to no donor site burden; 2) remains viable in poorly vascularized wound beds and can be placed as a biologic dressing without specialized microsurgical care; 3) enhances angiogenesis to mitigate risk of infection of deeper structures; 4) mitigates adhesions to underlying structures; and 5) can be used as immediate platform for rapid restoration of cutaneous integrity. By leveraging these techniques, the investigators seek to provide a safe, effective, and available option to augment standard-of-care reconstruction techniques.

Multiple conditions can lead to a need for penile reconstruction. Penile trauma, including burns, penetrating injury, blast injury, and friction injury can irreversibly damage penile skin, leading to a need to resurface the shaft and/or glans of the penis with local tissue flaps or autologous grafts. Infectious processes, most notably Fournier's gangrene, can also lead to loss of penile skin. Finally, adult-acquired buried penis (AABP) disease, a condition wherein the penis becomes trapped by adjacent soft tissues leading to chronic inflammation and loss of penile epithelial integrity, can require surgical excision of penile skin as part of a multicomponent repair. In all of these cases, STSG of the penile shaft is considered standard of care if local flaps, such as scrotal flaps, are not available for reconstruction due to overlapping disease processes. STSGs are commonly utilized to allow for rapid, definitive closure and restoration of the integument.

While STSG graft take on the penis following these processes is successful >95% of the time with restoration of urinary outcomes, patients who have undergone the procedure typically report dissatisfaction with the cosmetic appearance of their penile skin. This is due to adhesion of the STSG to the fixed Buck's deep fascia of the penis, which occurs due to the loss of the mobile Dartos fascia during the time of initial insult/injury. The combination of adhesion and graft contracture/fibrosis can lead to a "plasticky" feeling of the penile skin, which is especially bothersome given the expansile nature of the deep cavernosal bodies during sexual arousal. While current sexual outcomes in patients undergoing penile reconstruction are superior to patients who do not undergo reconstruction, there exists significant room for improvement. There currently exist no off-the-shelf products with proven efficacy in improving outcomes.

Adipose tissue is a prime candidate for this application due to its autologous origin, ease of procurement with minimal-to-no additional donor site morbidity, and abundant availability in patients, alongside its unique reconstructive and regenerative capacities. The use of autologous adipose in delayed tissue reconstruction is well established. However, the full therapeutic potential of adipose tissue remains underexploited. Fat grafting provides immediate soft tissue bulk, enhances angiogenesis, is both immunomodulatory and enhances immunologic homing, and supplies mesenchymal cells for soft tissue healing. Fat grafting is viable in hostile recipient beds including infected/contaminated and poorly vascularized wounds such as the diabetic foot ulcer, irradiated skin, and burn scars.

Grafting of autologous fat tissue is a minimally invasive surgical technique that starts with the harvest of small particles (2-5 mm) of fat tissue from the abdomen or using liposuction. Sometimes, fat graft can be harvested from tissue that is removed for other reasons. This technique utilizes incisions smaller than 5 mm in length and rapid intraoperative processing allowing for immediate transplantation of a patient's own tissue in a single operative procedure. Autologous fat can also be obtained from adipose tissue removed intraoperatively, which is a standard component to AABP repair, and processed intraoperatively for immediate use. This follows a standard fat grafting preparation protocol currently being used for standard of care cases.

A multitude of data exist to support the utility of autologous fat grafting for other disease processes at a variety of anatomic sites. Applications that have been subject to rigorous prior study include:

• Improvement in soft tissue volume, pliability, and skin quality after autologous fat grafting of atrophic amputation stumps
• Improvement in tissue pliability in a porcine burn model
• Improvement in human burn patients when autologous fat grafting was performed beneath a STSG overlying tendon in a burn patient

In the study described herein, participants will undergo the standard-of-care baseline reconstructive surgery for their primary disease process. This will include any necessary debridement, penile degloving, and soft tissue excision of the penis, genitals, and surrounding tissues as indicated by their primary traumatic, infectious, or other disease process. Post-operative wound care will proceed along standard-of-care pathways and will not be altered for the purposes of this protocol.

It is important to recognize that no cell extraction or isolation will be performed in this trial. The fat graft is regulated as a standard surgical procedure with no more than minimal manipulation of the fat tissue. Fat graft injection has been widely adopted by plastic surgeons, dermatologists, and ophthalmologists in clinical practice. Because these are autologous fat grafts that undergo minimal manipulation, they are regulated as a standard surgical procedure and are well-tolerated by patients with minimal safety risks. Only simple processing will be performed with the fat tissue to improve its texture and compliance as is already the standard of care and commonly performed. As autologous fat grafting is well known to soften scarring from trauma, surgical manipulation/incisions, and radiation fibrosis, the investigators believe this approach will be efficacious and well-tolerated due to the common anatomic factors seen in the penis and other parts of the body.

Inclusion Criteria:

• Ability to participate in informed consent
• Loss of penile skin necessitating split-thickness skin grafting for reconstruction
• Willingness to undergo the study interventions and comply with required study procedures
• Is a medical and surgical candidate to undergo standard-of-care split-thickness skin graft reconstruction of the penis after standard preoperative optimization

Exclusion Criteria:

• History of neophallus creation
• A diagnosed disorder of connective tissue or collagen deposition/formation
• The inability to obtain sufficient fat from the surgical specimen or separate lipoharvest donor site to allow the autologous fat tissue processing
• Any medical condition that would preclude safe conduct of the lipoharvest and/or injection procedure per investigator discretion