Clinical trial NCT03548610: Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects
Official title: Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects: A Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Wound of Skin
Non-melanoma Skin Cancer
Skin Graft Complications
Wound of Lower Leg
Wound of Knee
Keywords: nanofat
tumor defect
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-06-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Nanofat is obtained via lipoaspiration of 10cc of fat from abdomen under moderate local tumescent anesthesia w/ saline. Cannula access point is anesthetized by local lidocaine infiltration. Lipoaspirate is processed into the nanofat using the Tonnard method, after 3-minute decantation. Aspiration is performed using a multihole 3mm cannula. Wound margin + bed is treated w/ topical \& local injections of nanofat, then covered w/ a biological scaffold, the inferior surface of which is soaked in nanofat; scaffold is fixed w/ external dressings or resorbable sutures; external covering includes polyurethane film \& 3 layers of dressings. Topical application creates a fine \<1mm nanofat layer. Scaffold (Puracol Plus) is left in place to integrate w/ surrounding skin, while external dressings changed at 7 \& 15 days. Lipoaspirate donor site needs mild to moderate compression for 24 hours \& suture removal (if not absorbed) at 7 days.
Primary purpose: TREATMENT

Brief summary: Large full-thickness skin defects, such as those resulting from trauma, large and giant congenital nevi, disfiguring scars, or tumor resection remain major clinical problems to patients and physicians. Skin flaps and grafts represent the current standard of care (SOC), but often present limitations associated with surgical morbidity and donor site availability. The investigators will enroll 64 patients who have their skin cancer surgically removed and require reconstructive procedure such as a skin flap/graft.

To objective of this study is to assess the efficacy and safety of a nanofat-seeded biological scaffold versus the SOC in healing larger surgical defects (\>1.5cm) involving the lower limb that cannot be closed by direct suture and thus need a reconstructive procedure such as a skin flap/graft.

Detailed description: Large full-thickness skin defects, such as those resulting from trauma, large and giant congenital nevi, disfiguring scars, or tumor resection remain major clinical problems to patients and physicians. Skin flaps and grafts represent the current standard of care (SOC), but often present limitations associated with surgical morbidity and donor site availability. To overcome these limitations, cultured epidermal autografts consisting of keratinocytes were developed to provide enough autologous skin. However, the routine use of these cultured epidermal autografts was hampered by its high risk of recurrent wound opening, long-term fragility, and increased rates of scar contractures.

Tissue-engineered dermal skin substitutes containing complex dermal layers have also been developed to produce large, near-natural skin substitutes. They promote healing and avoid scar contracture; however, the healing times are long as they lack the active cellular and paracrine components of healing, and they often need a second delayed surgical procedure, a split-thickness skin graft, to obtain complete epithelization.

The term "nanofat grafting" was first used by Tonnard et al. and constitutes a rich reservoir of regenerative precursor cells (including stromal vascular fraction cells, among which adipose-derived stem cells) with pro-angiogenic capabilities. The many proprieties of nanofat and the stromal vascular fraction in regenerative and aesthetic surgery are just being discovered. In particular, numerous in vitro and in vivo studies have demonstrated the ability of these cells to differentiate into various skin cell lineages. Moreover, they are recognized as a powerful source for tissue regeneration because of their capability to secrete paracrine factors, initiating tissue repair and accelerating wound closure by skin regeneration instead of fibrotic scar formation.

Few anecdotal reports have documented the efficacy of the stromal vascular fraction in acute as well as chronic wounds. However, no observation has explored the efficacy of nanofat in healing surgical defects. Of note, nanofat is substantially easier, faster, and remarkably less expensive to obtain when compared to the mechanically- or enzymatically-isolated stromal vascular fraction. At present, there is a noticeable lack of randomized-controlled evidence in the international literature. Thus, this would represent the most comprehensive and the first randomized, controlled experience documenting the use of nanofat for wound healing.

Eligibility criteria: Inclusion Criteria:

* Subjects who need to undergo a surgical intervention resulting in complex lower limb surgical defects that cannot be closed primarily, and thus need a reconstructive phase
* Willing to undertake all study procedures, including nanofat harvesting from stomach site
* Willing to sign an informed consent form

Exclusion Criteria:

* Age less than 18 years of age
* Pregnant women
* Any contraindications to use of nanofat or collagen scaffold

Primary outcomes:
measure: Change in healing response to treatment (>95% healed in surface by physician assessment)
timeFrame: 7 days post-surgery, 15 days post-surgery, 30 days post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery
Secondary outcomes:
measure: Change in histogram planimetry for surgical site
timeFrame: 7 days' post-surgery, 15 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery, 12 months' post-surgery
measure: Cosmetic outcomes of surgical site by blinded physician Vancouver Scar Scale assessment
timeFrame: 3 months' post-surgery, 6 months' post-surgery
measure: Study subject completes the Patient Scar Assessment Scale
timeFrame: 3 months' post-surgery, 6 months' post-surgery
Other outcomes:
Locations:
city: Boston
country: United States
facility: Mohs and Dermatologic Surgery Center, Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Chrysalyne D Schmults, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
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