Table 2.

Clinical study methods. Patient selection criteria and study endpoints

Inclusion criteria	1. Male or female patient 18 up to 80 years 2. Patient requiring at least one implant placement following mandibular pre-molar or molar tooth extraction 3. Alveolar mandibular ridge (empty socket):   - Height: not less than 10 mm, from the gingival margin to the mandibular nerve canal—as seen in the screening CT scan   - Width: not less than 5 mm, from buccal to lingual cortical plates—as seen in the screening CT scan 4. Ability to give informed consent for the study by a patient or legal guardian 5. Willingness to undergo 7 follow-up visits: 1 week; 1, 4, 6, and 10 months; 2.5 years; and 5 years following dental graft implantation, as well as unscheduled sick visits
Exclusion criteria	1. Pregnancy (all women of childbearing age would be questioned and told by the consenting physician regarding that criteria) 2. Known or suspected hypersensitivity to the constituents of the bone graft material (for example, porcine collagen) 3. Pathologies or conditions contraindicating surgery or presenting with active acute or chronic infections excluding periapical granuloma (for example, osteomyelitis, sinusitis), uncontrolled diabetes 4. Immunologic disorders or auto-immune pathologies, in particular, elderly subjects 5. Serious bone diseases of endocrine etiology 6. Serious disturbances of bone metabolism 7. Ongoing treatment with gluco- or mineralo-corticoids or with agents affecting calcium metabolism (e.g., calcitonin, bisphosphonates) 8. Irradiation therapy, chemotherapy, or immunosuppressive therapy in the last 5 years 9. Malignancies 10. Severe parafunction (bruxism and clenching) 11. Poor oral hygiene or active periodontitis 12. Heavy tobacco smoking habit (> 10 cigarettes per day)
Primary efficacy endpoints	1. Amount of new bone formation (mean area of mineralized and non-mineralized tissue) in alveolar bone core biopsies—“woven bone” (ratio 0–100%) at 4 months after grafting 2. Bone–graft material integration to host bone score in alveolar bone core biopsies at 4 months after grafting:   - 1 — Poor: no signs of new bone-to-graft interface visible   - 2 — Intermediate: minimal and focal signs of new bone-to-graft interface visible   - 3 — Good: abundant new bone-to-graft interface visible
Secondary efficacy endpoints	1. Alveolar bone strength (torque measurement) at 4 months after grafting 2. Alveolar bone radiodensity (Hounsfield scale) calculated by volumetric CT imaging at 4 months after bone grafting 3. Success of dental implant placement in a rigid post-bone grafting site, defined by immediate dental implant stability after 4 months from bone grafting (visit 5) 4. Changes from baseline in alveolar bone height (depth reduction) at 4 months, measured at mesial and distal root surface [in millimeters] on Posterior to Anterior (PA) radiographs or by CT 5. Changes from baseline in alveolar bone width (horizontal bone gain or loss) (in millimeters) at 4 months on posterior to anterior (PA) radiographs or by CT
Safety endpoints	1. Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 through study completion (short-term and long-term) 2. Number of participants requiring unscheduled hospital visit related to the study procedure through study completion (short-term and long-term) 3. Safety and tolerability following grafting (graft site infection, insufficient healing of graft site, excessive bleeding, and wound dehiscence) over both short-term and long-term
Usability endpoints	1. Physician assessment of the ease of graft placement using a 10-point satisfaction scale 2. Physician assessment of the ease of implant placement using a 10-point satisfaction scale