Guided bone regeneration

Primary Objective:  To evaluate the safety profile of autologous-derived Small Blood Stem Cells to enhance osseointegration of GBR in patients undergoing dental implant surgery. Secondary Objectives:  To determine the maximum tolerated dose (MTD) of autologous-derived Small Blood Stem Cells to enhance osseointegration of GBR in patients undergoing dental implant surgery.  To determine the biologically active range or optimal effective doses of autologous-derived Small Blood Stem Cells to enhance osseointegration of GBR in patients undergoing dental implant surgery.

SB stem cells

CD61- Lin - cell

injection

1×105 CD61-Lincells /0.25mL DPBS

Primary safety endpoint
• Bone mineral density (BMD) change from baseline to week 24 after GBR.
Safety evaluations
 Adverse events (AEs): weeks 1, 2, 4, 8, 12, 13, 16, 18, 20, and 24 after GBR.
 Vital signs: Day 0, weeks 12 and 24 after GBR.
 Laboratory tests: it includes biochemistry laboratory tests, complete blood count (CBC), and urinalysis
(weeks 8, 12, 16 and 24 after GBR)
 Immunology test: weeks 8, 12, 16 and 24 after GBR.

Secondary efficacy endpoints:
Hard Tissue Evaluation (weeks 1, 2, 8, 12, 16, 18, 20 and 24 after GBR)
 Dental periapical detection: changes from baseline.
 Osseous-integration region of interest (ROI) parameters: CT detection changes from baseline
 BMD: CT detection changes from baseline
 Bone volume index (BVI): CT detection changes from baseline
 Structure model index (SMI): CT detection changes from baseline
Dental implant stability detection
 Implant Stability Quotient (ISQ): changes from baseline using resonance frequency analysis (RFA)
(weeks 12, 16, 20 and 24 after GBR)
 Determine whether the implant can withstand 30 N / cm2 torque: Subject’s feedback (weeks 12 and 24
after GBR)
Soft Tissue Evaluation
 Soft tissue evaluation (weeks 1, 2, 4, 8, 12, 13, 16, 18, 20, and 24 after GBR).
Maximum tolerated dose (MTD)
• MTD is the previous concentration when DLT occurred; The MTD is determined at which no more than
one out of six patients experience a DLT.

1. Subjects 20 years old and over;
2. Sign of informed consent form;
3. Patients with one missing tooth with D2, D3 bone density;
4. Gums environment defined as alveolar bone height of 10 mm and above, bone width 8 mm and above;
5. Have only one missing maxillary or mandibular posterior tooth (No. 4, 5, 6 or 7) who require a GBR prior to a dental implant.
6. Bone defect(s) must be present with at least two walls missing.
7. The opposing dentition must be nature teeth or fixed crowns or bridges on natural teeth or implants. Removable prostheses or dentures opposing the study implants are not allowed;
8. Subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

1. Patients who have inadequate organ function described as below:
a. ANC < 1.5 x 109/L
b. Platelets < 100 x 109/L
c. Hb < 9 g/dL
d. Serum bilirubin > 1.5 x the upper limit of normal (ULN)
e. Aspartate aminotransferase (AST [SGOT]) > 2.5 × the ULN
f. Alanine aminotransferase (ALT [SGPT]) > 2.5 × the ULN
g. Serum creatinine > 1.5 mg/dL or a measured creatinine clearance < 60 mL/min;
2. History of neoplastic disease and had been treated with chemotherapy;
3. Uncontrolled Diabetes Mellitus;
4. Dialysis patients;
5. Patients with cardiovascular disease;
6. Osteoporosis patients and patients taking bisphosphonates;
7. History of radiation therapy to the head and neck;
8. Patients with temporomandibular disorder;
9. Pregnant or nursing women;
10. Presence of conditions requiring chronic routine prophylactic use of antibiotics (history of rheumatic heart disease, bacterial endocarditis, cardiac valvular anomalies, prosthetic joint replacements);
11. Medical conditions requiring prolonged use of steroids;
12. Physical handicaps that would interfere with the ability to perform adequate oral hygiene;
13. Use of any investigational drug or device within the 30-day period immediately prior to implant surgery on study day 0;
14. Alcoholism or drug abuse;
15. Patients infected with HIV;
16. Current smokers;
17. Local inflammation, including untreated periodontitis;
18. Mucosal diseases such as erosive lichen planus;
19. History of local radiation therapy;
20. Presence of osseous lesions;
21. Unhealed extraction sites;
22. Persistent intraoral infection;
23. Patients with inadequate oral hygiene or unmotivated for adequate home care;
24. Conditions or circumstances, in the opinion of the investigator, which would prevent completion of study participation or interfere with analysis of study results, such as history of non-compliance, or unreliability.
25. Patient with a pathology present near the site of dental implantation.