Acellular Adipose Tissue (AAT) for Soft Tissue Reconstruction

Soft tissue volume loss acquired through trauma, congenital malformation or comorbid
conditions (i.e., HIV/AIDS) is a common and sometimes devastating problem. Traditional
therapies include local tissue transfer, allograft placement, and complex scar revision
techniques. Recently, autologous fat transfer has become one of the most commonly employed
techniques for improving soft tissue contour deformity particularly for the correction of
breast and body defects. While the results from this procedure continue to improve, it
requires an additional procedure to harvest fat tissue from the abdomen, thigh or flank
leading to donor site morbidity. Clinically, volume loss following autologous fat transfer
has been reported to be between 40-60% and usually occurs within the first 4-6 months.
Regrafting is often needed and implanted adipose tissue frequently leads to post-operative
calcifications. For these reasons, a predictable, "off-the-shelf" material that retains the
mechanical and biological properties of adipose tissue would be ideal for the reconstruction
of smaller soft tissue defects and soft tissue augmentation.

Investigators in the Elisseeff Laboratory (Johns Hopkins University Department of Biomedical
Engineering) generated a novel tissue-derived material to create instructive matrices for
soft tissue reconstruction [Acellular Adipose Tissue (AAT)]. In 2016, investigators conducted
a Phase 1, open-label, clinical trial of AAT in healthy volunteers who planned to have
elective surgery for the removal of redundant tissue (n=8). Overall, AAT demonstrated
satisfactory safety results. No participants experienced serious adverse events (SAEs) or
unanticipated adverse events (AEs) related to the study, or exited the study due to AEs. All
AEs noted were expected and mild, including redness, bruising, textural changes,
hyperpigmentation and tenderness at the injection site. Many other adverse events commonly
associated with injections were not observed in any participant throughout the study (i.e.,
scarring, ulceration, scabbing, purpura, oozing, crusting, blanching, blistering, edema or
abrasions). These data indicate that conducting a phase II, dose-escalation, safety and
efficacy study in humans is warranted. Based on investigators' experience, investigators
hypothesize that AAT will be safe and maintain its volume up to 6 months when injected
subcutaneously to restore 5-20cc defects in human soft tissue.

Inclusion Criteria:

Men and women aged 18-65 years with at least one modest (5-30cc) soft tissue defect on the
trunk and

- Willingness to wait up to 6 months to participate in the study (depending on defect
size and enrollment-to-date).

- Consent to photography for research purposes.

- Willingness to follow study requirements.

- Ability to give informed consent.

- Willingness to perform follow up visits for 12 months (+/- 30 days).

- Willingness to undergo complete blood count (CBC) with Differential and Serum
Chemistry.

For Men and Women of reproductive potential: Willingness to use approved methods of birth
control or abstain from sexual intercourse from screening until 6 months post-AAT
injection.

- Definition of non-childbearing potential for Women: amenorrhea (previous 12 months) or
surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy).

- Definition of non-reproductive potential for Men: confirmed surgically sterile
(vasectomy >3 months prior to screening).

Exclusion Criteria:

Use of AAT in patients exhibiting autoimmune connective tissue disease is not recommended.
When applied properly, AAT has been shown to support the migration of host cells from the
surrounding tissue. Therefore, this study will exclude patients with conditions that could
inhibit migration of host cells including, but not limited to, the following:

- Fever (oral temperature >99º F at time of screening)

- Insulin dependent diabetes

- Low vascularity of the tissue intended for elective excision

- Local or Systemic Infection

- Mechanical Trauma

- Poor nutrition or general medical condition

- Dehiscence and/or necrosis due to poor revascularization

- Specific or nonspecific immune response to some component of the AAT material

- Infected or nonvascular surgical sites

- Known cancer or receiving treatment for cancer

Also:

- Pregnant or Lactating females

- Inability to cooperate with and/or comprehend post-operative instructions

- Inability to speak or read English

- Known allergy or sensitivity to Streptomycin or Amphotericin B

- Any other reason the study physicians judge would be a contraindication for receiving
AAT injections