Effect of Concentrating Endogenous Stromal Cells in the Fat Graft

Craniofacial injuries have serious psychosocial sequele and affect quality of life. Many
individuals who suffer significant facial disfigurement from injury experience psychological
distress and impairment in functioning not limited to the acute phase of injury, but over a
longer term period of treatment, recovery, and adjustment. Until recently, treatment of
disfiguring craniofacial injuries has been mostly limited to surgical flap procedures,
microsurgical tissue transfer, and implantable prostheses. However, these methods can leave
conspicuous scars on the face and the donor site, and in the case of implants can lead to
complications associated with foreign materials. Autologous fat grafting with minimally
invasive cannulas is a procedure that has been used for decades in common plastic surgery
practice for facial aesthetic procedures. This technique is also a promising treatment for
soft tissue reconstruction after craniofacial trauma because the graft harvest and injection
are minimally invasive. The treatment is performed by using a small liposuction cannula to
aspirate fat tissue from the donor site, and then re-injecting the fat into the recipient
site with specialized injection cannulas. After harvest, and prior to injection, the fat
graft is subjected to a mechanical processing step to separate the aqueous layer and
concentrate the adipocytes. This often takes the form of centrifugation or filtering.

The main problem with autologous fat grafting is a variable resorption of the graft volume
over time. As much as 30-60% of the graft volume can diminish over time. Many variables may
influence the behavior of clinical fat grafts, including harvest site, harvest technique,
graft preparation, and injection technique. In our current IRB approved study on fat
grafting (IRB # PRO09060101), we are seeking to accurately quantify the fat graft resorption
over time following a highly standardized surgical technique. Evaluation methods include a
3D surface imaging, high resolution CT scanning, and quality of life measures. This study
has enrolled and treated patients without adverse event, and the evaluation methods have
been performed successfully.

In this proposed study, we plan to use essentially the same surgical procedure and
evaluation methods, but with modified preparation of the fat graft. This modified
preparation involves concentrating the endogenous stromal cells in the graft material in an
effort to increase graft retention over time. The aspirated fat material used for fat
grafting consists of mature adipocytes, a small amount of fibrous tissue, and immature
adipose stromal cells. These adipose stromal cells (ASCs) are a mixed population of
non-lipid laden cells that serve to turn over mature adipocytes and vascular elements.
"Preadipocytes," as well as endothelial precursor cells and multilineage progenitor cells,
are found. Of note, ASCs have been shown to stimulate angiogenesis when stressed under
hypoxic conditions and these cells may be instrumental in healing and volume retention of
fat grafts. Yoshimura, et. al. (1) found that fat aspirated with a liposuction cannula (i.e.
the method of fat harvest for fat grafting) is deficient in ASCs compared to whole fat. This
is due to the fact that a major portion of ASCs are located around larger blood vessels that
are left intact in the donor site after liposuction with a blunt cannula.

Inclusion Criteria:

1. Aged 18 years or older and able to provide informed consent

2. Have suffered injury resulting in craniofacial volume defects which could be treated
with a graft volume of between 3 and 100 cc of lipoaspirate

3. Be at least 3 months post-injury or post-surgery (from trauma procedures) so that
acute edema is resolved

4. Volume defects are covered by intact skin and do not communicate with oral cavity or
sinuses

5. The three dimensional geometry of the volume defects would allow for treatment with
lipoaspirate injection so that at least two distinct treated areas could be discerned
on gross examination and radiographically (e.g. treated regions are on opposite sides
of the face, on lower face versus upper face, or separated by a bony landmark such as
zygoma. This would include the ability to treat an uninjured regions with fat grafts
in order to obtain symmetry or balance.

6. Willing and able to comply with follow up examinations, including radiographic
studies

Exclusion Criteria:

1. Age less than 18 years

2. Inability to provide informed consent

3. Craniofacial defects intended for treatment have open wounds or communicate with oral
cavity or sinus (note: presence of such a defect in the setting of another defect(s)
that meets treatment criteria will not exclude the patient from participating).

4. Active infection anywhere in the body

5. Diagnosed with cancer within the last 12 months and /or presently receiving
chemotherapy or radiation treatment

6. Known coagulopathy

7. Systemic disease that would render the fat harvest and injection procedure, along
with associated anesthesia, unsafe to the patient.

8. Pregnancy

9. Diagnosis of Schizophrenia or Bipolar Disorder