Biocellular-Cellular Regenerative Treatment Scaring Alopecia and Alopecia Areata

The aesthetic surgical & cosmetic discipline of hair restoration is rooted in numerous
landmark studies and progressive medical science in the medical literature. With the advent
of advanced theories and science using cellular and platelet-derived growth factors within
the scope of regenerative medicine, have been well established in a number of peer-reviewed
publications, The use of biological modalities, e.g., HD-PRP concentrates (defined as > 4-6
times patient circulating baselines), have become recognized in a number of disciplines,
including value of stimulation of scalp tissues and hair follicles in androgenetic alopecia
(AGA). (See Clinical Trial Study STRAAND). A "retrograde" filling technique creating a
potential space and subsequently injecting into this space will insure uniformity of
placement and spread of the delivered treatment modality.

This study design is intended to be a prospective, randomized, multi-center trial with
blinding of outcomes for independent observers, clinical provider, and patient
observation/satisfaction study comparatives. The study proposes adipose-derived cellular and
stromal components when mixed with platelet high density concentrates (HD-PRP) offers an
advantage to produce a markedly more effective therapeutic profile in in treating patients
with scaring alopecia's (SA) and alopecia areata (AA), tissue age related senescence, and
encourage vascular capabilities by stimulation of vasculoneogenesis. The benefits of using
autologous adipose-derived stem & stromal cell (ADSC) populations are cell proliferation and
vasculogenesis that is intrinsically linked with native inflammatory modulation and
immunomodulatory capacities. Reports describing the safety and efficacy of this biocellular
combination have been reported in peer reviewed literature.

In the second and third arms of this study, use of regenerative protocols currently being
extensively been utilized in the treatment of degenerative musculoskeletal conditions and
plastic surgical procedures have been safely and effectively employed. These protocols
feature the use of an emulsified AD-tSVF + HD PRP (ARM 2) compared to use of emulsified
AD-tSVF + AD-cSVF (cell enrichment) + HD PRP (ARM 3) containing the full heterogeneous
stem/stromal cell population and its native bioactive matrix. Addressing regions of scalp
dermis containing the microenvironment (niche) of the hair follicle, progenitor tissues
("bulge").

In ARM 3, addition of cellular enrichment of the emulsified AD-tSVF is accomplished via a
semi-automated, closed sterile system (Healeon CentriCyte 1000 system) which effectively
isolates and concentrate the cellular elements. The AD-cSVF is then mixed with high-density
platelet rich plasma (HD-PRP) concentrates with emulsified AD-tSVF tissues prior to targeted
scalp injections. This injected cell-enriched product contains the bioactive native adipose
tissue scaffolding, autologous HD-PRP, and cell-enriched adipose stem/stromal cellular
concentrations of stromal/stem cells.

In ARM 4 of this study, the addition of intravenous cellular deployment of isolated cSVF is
performed following without direct injection to scalp sites. Observations in other trials
have suggested that increased hair growth in shaft size, coloration and speed is noted in the
majority of parenterally treated patients as an observed effect of infusions. In the future,
clinical trial extension of this study will combine both the components shown in ARM 3 and
add a concomitant ARM 4 to evaluate potential of stimulation of proliferative and
regenerative potentials in the form of combined therapy.

It has been noted by several investigators that parenteral us of AD-cSVF has had an
unexpected outcome of improve hair growth and color change. All of the study ARMs (with
exception of comparative control ARM 1) are tested by flow cytometry for viabilities and
numbers, which will be statistically compared to outcomes following the study completion to
examine whether a statistically significant difference in results follows with each ARM can
be shown.

The goal of this study is to demonstrate the safety and efficacy of each ARM. Biocellular
injections into the scalp of men and women with a diagnosis of scaring alopecias and alopecia
areata, with full reporting of AE and SAE (adverse events). In the intradermal injection
portions of the study, the biocellular material is injected 3-5 mm in depth within the
mid-reticular dermis to upper subcutaneous fat layer of the scalp. Placement of the
biocellular and cell-enriched biocelluar is intended to examine changes associated with
changes of the miniaturized hair follicle. It is hypothesized that delivery a milieu of
stroma and stem/stromal cells will facilitate regenerative changes of the treatment sites. In
addition to providing native bioactive tissue scaffolding, and a greater number of
stromal/stem cells to the tissues surrounding the follicular niche will result in a positive
effect.

Use of small needles for delivery is made possible with incorporating the novel use of
emulsification of adipose tissue complex (lipoaspirates) This emulsified AD-tSVF and HD PRP
methodology reduces surgeon injection pressure requirements resulting with use of smaller
gauge needles. When clinically compared to the use of much larger needles required to inject
non-emulsified AD-tSVF, it is an improvement on current techniques. A "retrograde" filling
technique creating a potential space and subsequently injecting into this space the
biocellular material as the needle is withdrawn is advanced in this study.

Successful stem/stromal cell-enrichment of AD-tSVF and HD PRP biocellular mixture has been
reported in numerous peer-reviewed and published clinical experiences of injections for
structural tissue augmentation in plastic surgery, chronic wound therapies, and ultrasound
guided musculoskeletal treatments in orthopedic & sports medicine.

Standard venipuncture for obtaining circulating whole blood is concentrating platelet
components to create a low hematocrit HD-PRP using FDA approved E USA) Emcyte II following
manufacturer's guidelines. Small volume closed syringe microcannula lipoaspiration is used to
acquire AD-tSVF tissues(Tulip Medical GEMS, San Diego, CA,, followed by emulsification via
the Healeon ACM System (Newbury Beach, CA, USA. Cellular testing of samples in Arm 2-4 will
be performed by flow cytometry (ORFLO, MoxiFlow, Ketchum, ID, USA) for viability and cell
concentrations.

A detailed patient medical history, study informed consent, and screening evaluations will
determine eligibility and candidacy for the study and complying with the inclusion/exclusion
criteria.

Recording of the platelet pre-operative measured baselines and achieved HD PRP concentrates,
flow cytometric examination of cell viability, and cell counts of AD-cSVF should be completed
on each patient. Biocellular injections and treatment will be given on two (2) separate
procedures three (3) months apart. Follow up clinical examinations are to be performed at 6
months and 1 year period with completion of outcomes analyses including independent observer,
clinician, and subject satisfaction. The volume of the therapueutic mix will be the
standardized in volume for all trial ARMs.

Immediate reporting to the study group for all AR and SAR will be documented and recorded for
the safety records directly to Ken Williams, DO, as Co-Principal Investigator. This Clinical
Trial will have a sample size of 60 patients at up to six (6) centers utilizing this
protocol.

Inclusion Criteria:

1. Males with a biopsy proven diagnosis of a Scaring alopecia (SA) or Alopecia Areata
(AA)

2. Females with a biopsy proven diagnosis of Scaring alopecia (SA) or Alopecia Areata
(AA)

3. Demonstrated ability to legally provide written informed consent and comply with the
study requirements

4. For women of childbearing potential with screening negative pregnancy test and subject
agrees to avoid pregnancy with two forms of contraception for the duration of study

5. Subject is willing to maintain existing and consistent hair length and color.

6. Ability to complete study procedures, patient surveys, and photodocumentation.

7. Subject is ≥ 18 years of age.

8. Five (5) year cancer free period without treatment and no evidence of recurrence

Exclusion Criteria:

1. Subjects who have used oral spironolactone, finasteride, dutasteride, minoxidil, or
any oral or topical medication including over the counter and herbal medications for
the treatment of hair loss within 12 months of study screening.

2. Simultaneous treatment with an investigational product or procedure within 30 days, or
planned future participation in another clinical study

3. Subject has previously failed or has been deemed non-responsive to a previous
experimental hair loss treatment.

4. Subject must have no recent PRP, biocellular treatments, micro needling, cold laser
therapies, or any other scalp or hair loss treatment.

5. Subject with previously diagnosed or suspected unspecified dermatologic condition, or
disorders that will make hair growth difficult (such as systemic burns, etc.).

6. History of or active diagnosis of systemic autoimmune disease or organ transplantation
or immunosuppressive medication(s).

7. Receiving active cancer treatment or have present or previous malignancies except a
history of squamous or basal skin cell carcinoma with excision for cure.

8. Active systemic infection at the time of enrollment. If acquired afterwards, exclusion
based on clinical judgment of investigator.

9. Use of chronic antibiotics and/or systemic corticosteroids.

10. Use of systemic agents that increase bleeding or clotting, or disorders associated
with these effects, including patients receiving GIIB/IIIa inhibitors in the 2 weeks
prior to the study procedure through to 1 week after the study procedure.

11. Clinically significant or current medical or psychiatric illness.

12. Prior surgery in the treatment area.

13. Any disease or condition (medical or surgical) that, in the opinion of the
investigator, might compromise dermatologic, hematologic, cardiovascular, pulmonary,
renal, gastrointestinal, hepatic, or central nervous system function; or any condition
that would place the subject at increased risk of increased morbidity or mortality.

14. Pregnant or lactating female, or women trying to become pregnant.

15. Known allergic reaction to components of study treatment and/or study injection
procedure

16. Subject has any disorder or any reason that may prevent compliance to study procedures
and visits.

17. Employees or family members of the study staff.

18. Untreated or uncontrolled thyroid disorder (abnormal TSH/free T4) or diabetes mellitus
(HgbA1C > 8.0).

19. Subject who has a sensitive, irritated, or abraded scalp area.

20. Clinically significant abnormal findings on laboratory screening panels:

- Hemoglobin > or = 10 g/dL

- Hepatic dysfunction, as defined as aspartate aminotransferase (AST), alanine
aminotransferase (ALT), or bilirubin levels > 1.5 times the upper limit of normal
range prior to randomization.

- Chronic renal insufficiency as defined as a serum creatinine > 1.2 mg/dL for
women and > 1.5 mg/dL for men.

- Elevated PT/PTT, INR,

- Platelet count < 100 x 109/L