Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects

February 10, 2020 updated by: Abigail Waldman,M.D., Brigham and Women's Hospital

Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects: A Randomized, Controlled Study

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • Mohs and Dermatologic Surgery Center, Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nanofat-seeded biological scaffold on surgical defect
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 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.
Other: Nanofat-seeded biological scaffold on surgical defect
Nanofat-seeded biological scaffold in healing larger surgical defects (>1.5cm) involving the lower limbs
No Intervention: Standard of Care dressings
Immediately after surgical resection, each patient will be treated following the SOC, therefore with a local skin flap, rather than with a skin graft, based on surgeon assessment. Sutures, and moulage, if present, will be removed at 7 days and patient instructed to apply a daily silicone cream and sunscreen for 2 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in healing response to treatment (>95% healed in surface by physician assessment)
Time Frame: 7 days post-surgery, 15 days post-surgery, 30 days post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery
A blinded study physician will assess the healing surface area at each visit. A wound is considered "healed" when the wound has healed >95% in surface by the physician assessment. Wounds in the intervention group are expected to have faster healing compared to the standard of care group.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in histogram planimetry for surgical site
Time Frame: 7 days' post-surgery, 15 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery, 12 months' post-surgery
Histogram planimetry is a way to objectively assess wound area changes over time. It is based on the pixel count of a selected irregular area which is divided by the pixel count of 1cm^2 to find a result in terms of cm^2 or mm^2
7 days' post-surgery, 15 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery, 12 months' post-surgery
Cosmetic outcomes of surgical site by blinded physician Vancouver Scar Scale assessment
Time Frame: 3 months' post-surgery, 6 months' post-surgery
A physician blinded to the treatment group the subject is in will self-administer the Vancouver Scar Scale (VSS) which documents change in scar appearance over time. The VSS ranges from 0 (most desirable outcome) to 13 (least desirable outcome), thus, a lower score is considered to have a better outcome and a higher score is considered a worse outcome. The VSS consists of four sub-scales, with each sub-scale reporting a value. The "pigmentation sub-scale" ranges from 0 (normal pigmentation) to 2 (hyperpigmentation); the "vascularity sub-scale" ranges from 0 (normal appearance) to 3 (purple appearance); the "pliability sub-scale" ranges from 0 (normal pliability) to 5 (contracture); and the "height sub-scale" ranges from 0 (normal [flat]) to 3 (>5mm). Sub-scale scores are totaled to give an overall VSS assessment score.
3 months' post-surgery, 6 months' post-surgery
Study subject completes the Patient Scar Assessment Scale
Time Frame: 3 months' post-surgery, 6 months' post-surgery
Subjects will be asked to complete a Visual Analogue Scale (Patient Scar Assessment Scale, PSAS) for scar assessment to rate how they think their wound site appears cosmetically compared to normal skin, and any complaints about how painful the site is, and how itchy it feels. Each question ranges from 1 (no complaints with itch or pain/as normal skin) to 10 (worst imaginable itch or pain/very different from normal skin). The PSAS ranges from 6 (best outcome score) to 66 (worst outcome score), thus a lower score is considered to have a better outcome and a higher score is considered a worse outcome.
3 months' post-surgery, 6 months' post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: Chrysalyne D Schmults, MD, MSCE, Brigham And Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2019

Primary Completion (Anticipated)

March 31, 2021

Study Completion (Anticipated)

July 31, 2021

Study Registration Dates

First Submitted

May 17, 2018

First Submitted That Met QC Criteria

May 29, 2018

First Posted (Actual)

June 7, 2018

Study Record Updates

Last Update Posted (Actual)

February 11, 2020

Last Update Submitted That Met QC Criteria

February 10, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P001086

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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