Bone Tissue Engineering Using Autologous Bone Repair Cell (BRC) Therapy for Sinus Floor Bone Augmentation

The overall aim is to promote bone regeneration, using Aastrom's proprietary Adult Stem Cell
Therapy (AST) developed collaboratively with the University of Michigan, to enable placement
of dental implants in patients who lack adequate alveolar bone. This project addresses
specifically the placement of dental implants following bone regenerative sinus floor
augmentation. This novel therapy mitigates the risks of other therapies, providing
additional benefits of adequate cell numbers for high quality bone regeneration, and has the
potential to become the new standard of care. In Aastrom's patented manufacturing
technology, iliac bone marrow aspirates are expanded ex-vivo to enrich for adult multipotent
cells (Bone Repair Cells- BRC) capable of regenerating bone and blood vessels. BRC will then
be mixed with bone matrix graft extender, beta-tricalcium phosphate (β-TCP), before their
implantation into the regenerative site.

Inclusion Criteria:

- Age range: 20-70 yrs

- Gender: Male and female

- Systemically healthy: Physical status according to the American Society of
Anesthesiologists (ASA) I or II

- Requiring sinus augmentation to allow dental implant placement

- Missing teeth: Maxillary second premolar, maxillary first molar and/or maxillary
second molar

- Remaining alveolar bone height: 2 to 6 mm

- Must be able and willing to follow study procedures and instructions

- Must have read, understood and signed an informed consent form

Exclusion Criteria:

- Allergies or hypersensitivities to study related medications: dexamethasone,
chlorhexidine, ibuprofen. For patients allergic to amoxicillin a comparable
substitute antibiotic will be used

- Hematologic disorders/ blood dyscrasias

- Active infectious disease

- Liver or kidney dysfunction/failure- Patients will have blood drawn for serum
laboratory tests, including creatinine, blood urea nitrogen, AST, ALT, and bilirubin.
All of these must be within normal limits for a patient to be included in the study

- Laboratory values that will define normal renal and hepatic function, as well as
criteria for exclusion of metabolic bone disease are consistent with those
established by the University of Michigan Health System (UMHS). Normal clinical
values will be used to help assure the health of all subjects in this trial.
Potential subjects whose laboratory values fall outside the UMHS normal ranges and
are considered clinically significant will be required to have medical clearance from
their primary care provider prior to participation. Potential subjects presenting
with clinically insignificant laboratory abnormalities will not require medical
clearance and will be considered for inclusion in the study

- Endocrine disorders/dysfunctions (i.e. Type I and II diabetes)

- Cancer - The explicit definition of cancer used to exclude patients is consistent
with that described by the National Cancer Institute (NCI), National Institutes of
Health. According to NCI, cancer is any disease in which abnormal cells divide
without control and invade nearby tissues (invasive disease). These include
carcinomas, sarcomas, leukemias, and lymphomas. Any patient with a history of these
invasive diseases will be excluded from the study.

- Patients who currently use bisphosphonates or have a history of bisphosphonate use
will be excluded from the trial

- HIV+

- Metabolic Bone Diseases- Patients with metabolic bone diseases such as Paget's
disease, hypercalcemia, moderate to severe vitamin D3 abnormalities or any other
metabolic bone disease including osteoporosis and osteoporotic fractures will be
excluded

- Pregnant women- Female patients who are of childbearing potential are excluded except
those who are using hormonal or barrier methods of birth control (oral or parenteral
contraceptives, diaphragm plus spermicide, or condoms). Pregnancy status will be
determined with a urine test and patients who are pregnant will be excluded

- Patients with acute sinusitis, or presenting any sinus pathology that would
contraindicate sinus augmentation

- Patients with congenital or metabolic bone disorders

- Current smokers (have smoked within 6 mos. of study onset)

- Subjects with congenital, or co-morbid conditions that would affect the study outcome
or interpretation of study results will be excluded

- Individuals who have a BMI outside normal limits that deems them overweight (BMI >25)
will be excluded due to potential difficulties in locating appropriate surgical entry
of the iliac crest during the bone marrow aspiration procedure

- Long term (>2 weeks) use of antibiotics in the past 3 months

- Periodontally unstable subjects

- Subjects having any extractions in the possible treatment area in the past 3 months

- Subjects that are edentulous