Study Year of
publication 		Sample size for this outcome/measure Defect location/defect type Measuring method
(clinical, histological, radiography) 		Test groups Surgical protocol Results Outcome
Kim et al. [45] 2014 69 patients
(69 extraction sockets) 		Single rooted teeth CBCT immediately and 3 months thereafter 1. DBM + rhBMP-2 (0.05 mg/mL; rhBMP-2/DBM)
2. DBM 		Teeth were extracted atraumatically with full flap elevation and primary closure was performed. Ridge width change:
1. -1.06 (SD 1.26) mm;
2. -1.21 (SD 1.31) mm; P > 0.05 		The addition of rhBMP-2 did not induce significant differences in the radiographic changes of alveolar bone remodelling after tooth extraction
Ridge high change:
1. -1.17 (SD 0.82) mm;
2. -1.5 (SD 1.07) mm; P > 0.05
Commes et al. [46] 2014 39 patients
(39 extraction sockets) 		Sockets with ≥ 50% buccal dehiscence CBCT immediately and 5 months thereafter 1. rhBMP‐2 + absorbable collagen sponge;
2. Collagen sponge 		Atraumatic extraction without flap elevation and primary closure. Ridge width change:
1. -2.07 (SD 1.17) mm;
2. -3.4 (SD 1.73) mm; P < 0.05 		The inclusion of rhBMP‐2 in the collagen sponge applied in extraction socket with a buccal dehiscence improves the regeneration of the lost buccal plate
Huh et al. [47] 2011 72 patients
(72 extraction sockets, molars/premolars) 		< 50% of localized alveolar vertical bone loss CBCT scans were took before and 3 months after treatment 1. Escherichia coli-derived rhBMP-2, coated β-TCP and hydroxyapatite;
2. β-tricalcium phosphate and hydroxyapatite 		Teeth were extracted atraumatically without flap elevation and no primary wound closure was performed. Ridge width change at 25%
extraction socket length:
1. 1.279 (SD 1.387) mm;
2. 0.006 (SD 1.149) mm; P < 0.01 		β-TCP and hydroxyapatite bone grafts coated with Escherichia coli-derived rhBMP-2 were found to be useful in preserving alveolar bone and more effective than conventional β-TCP and hydroxyapatite alloplastic bone grafts
Ridge height change:
1. -0.059 (SD 0.96) mm;
2. -1.087 (SD 1.413) mm; P < 0.01
Jain et al. [48] 2016 10 bilateral symmetrical extraction sockets Premolars Radiography immediately, 3 and 6 months after extraction (CBCT). Widths (mesiodistal; buccolingual) measures at: 2, 5 and 8 mm below CEJ. 1. Collagen membrane;
2. MSCs seeded on collagen membrane 		Teeth were extracted atraumatically. Extracted socket sides were closed primarily with nonresorbable sutures. Mean difference (P < 0.05) Using MSCs and collagen membrane was successful in maintaining the dimensions of the post extraction socket
After 3 months:
2 mm below CEJ: buccolingual -0.64 mm; mesiodistal -1.42 mm.
5 mm below CEJ: buccolingual -1.44 mm; mesiodistal -1.2 mm.
8 mm below CEJ: buccolingual -1.03 mm; mesiodistal -1.02 mm
After 6 months:
2 mm below CEJ: buccolingual -1.26 mm; mesiodistal -1.07 mm.
5 mm below CEJ: buccolingual -1.13 mm; mesiodistal -0.69 mm.
8 mm below CEJ: buccolingual -0.81 mm; mesiodistal -1.21 mm
Saulacic et al. [49] 2018 5 male Beagle dogs
(20 premolars sockets) 		Buccal bone of the sockets was removed After 8 weeks of healing:
micro-CT;
histological analysis 		All extraction sockets were filled with deproteinized bovine bone mineral and covered with collagen membrane loaded with:
1. sterile saline as a control;
2. 20 μg of rhBMP-9;
3. 4 μg of rhBMP-9;
4. rhBMP9 		Premolars were hemi sected, and the distal roots were extracted. The canal of the mesial roots was then reamed and filled with gutta‐percha. Full thickness flap was elevated, and the buccal bone was removed. rhBMP-9 defects showed higher values of bone (P = 0.024), bone marrow (P = 0.044), and total augmentation volume (P = 0.033) than the rhBMP2 (20 μg) or control sites. Highest bone area was found in rhBMP-9 defects (P = 0.895) rhBMP-9 demonstrated the highest density of bone substitute and lowest level of soft/connective tissue density
Pelegrine et al. [50] 2010 13 patients
(30 extraction sockets) 		Upper anterior teeth After 6 months:
clinical (CEVM; CIVM; CHM);
histological analysis (mineralized bone) 		1. Test group - sockets grafted with an autologous bone marrow;
2. Control group - blood clot 		Teeth were extracted and full thickness flap with two vertical incisions were elevated.
Sutured using nonresorbable nylon 5-0 sutures. 		CEVM:
1. -0.62 (SD 0.51) mm;
2. -1.17 (SD 0.26) mm 		According to the results, the autologous bone marrow graft could contribute to alveolar bone regeneration after tooth extraction
CIVM:
1. -10.06 (SD 1.1) mm;
2. -10.44 (SD 0.84) mm
CHM:
1. -1.14 (SD 0.87) mm;
2. -2.46 (SD 0.4) mm
Mineralized bone:
1. 45.47 (SD 7.21)%;
2. 42.87 (SD 11.33)%
Geurs et al. [51] 2014 41 extraction sockets Premolars (n = 26), anterior teeth (n = 10)
or canines
(n = 5) 		Histological analysis after 8 weeks:
bone graft;
new bone;
organic matrix;
artefact/air 		1. Collagen plug (control);
2. FDBA/β-TCP/collagen plug;
3. FDBA/β-TCP/platelet-rich plasma/collagen plug;
4. FDBA/β-TCP/PDGF-BB/collagen plug 		Teeth were extracted atraumatically and without flap elevation.
Sutured with 4.0 resorbable crossing mattress sutures. 		1. Bone graft: 0 (SD 0)%a;
new bone: 43 (SD 24)%;
organic matrix: 45 (SD 23)%a;
artefact/air: 10 (SD 10)%a		 Inclusion PDGF-BB produced less residual bone graft material, indicating more rapid turnover of bone graft during early healing (8 weeks)
2. Bone graft: 35 (SD 13)%a;
new bone: 27% (SD 7)%;
organic matrix: 24% (SD 10)%a;
artefact/air: 12% (SD 8)%a
3. Bone graft: 27 (SD 13)%a;
new bone: 28 (SD 9)%;
organic matrix: 28 (SD 12)%a;
artefact/air: 25 (SD 12)%a
4. Bone graft: 17 (SD 10)%a;
new bone: 28 (SD 9)%;
organic matrix: 28 (SD 12)%a;
artefact/air 25 (SD 12)%a
Wallace et al. [52] 2014 7 patients
(10 extraction sockets) 		Single rooted teeth with 4 intact walls and a minimum of 5 mm crestal bone height Every 2 weeks - clinically;
4 weeks post extraction - CBCT;
CBCT and histological analysis after 4 months of healing 		rhBMP-2 + collagen membrane. Teeth were extracted atraumatically and full-thickness flaps were released, advanced to achieve primary closure and sutured with polypropylene sutures Bone: 49.6%;
Marrow/fibrous tissue: 50.4%;
Bone density: 562 Hounsfield units 		rhBMP-2/absorbable collagen sponge could be used as substitute of the combination of barrier membranes over allografts, xenografts, and alloplasts
Mayer et al. [53] 2018 24 Sprague-Dawley rats Two connected maxillae molars sockets Histological analysis after 8 weeks of healing 1. BB-PLCL;
2. Bio-Oss®;
3. Unassisted healing 		Maxillae molars were extracted, and the sockets were connected using a diamond bur.
Flaps were coronally positioned and sutured using resorbable vicryl 5-0 sutures. 		New bone formation:
1. Bovine bone: 39.1 (SD 14.3)%;
2. Bio-Oss®: 23.7 (SD 10.8)%; P = 0.096 		Higher percentage of new bone and lower connective tissue portion were found in the BB-PLCL compared with Bio-Oss®
Connective tissue:
1. Bovine bone: 49.6 (SD 13.7)%;
2. Bio-Oss®: 73.7 (SD 11.1)%;
P = 0.018
Residual grafting martial:
1. Bovine bone: 11.34 (SD 4.18)%;
2. Bio-Oss®: 2.62 (SD 1.23)%;
P = 0.011
Heberer et al. [54] 2012 25 patients
(47 extraction sockets) 		All kind of teeth Histological (immunohistochemical) analysis after 6 weeks 1. MSCs embedded in Bio-Oss collagen;
2. Unassisted healing 		Teeth were extracted atraumatically without flap elevation and no primary wound closure was performed 1. Grafted sockets:
Cbfa1/Runx2 73.3%; osteonectin 61.4%; osteocalcin 20.1% 		The quantity of osteogenic cells in the post extraction socket was not influenced by grafting procedure
2. Non-grafted sockets:
Cbfa1/Runx2 72.3%; osteonectin 66.9%; osteocalcin 23.4%
Kaigler et al. [55] 2013 24 patients
(24 extraction sockets) 		All kind of nonrestorable teeth was performed 6 or 12 weeks postsurgery micro-CT and histological analysis
(bone mineral density [mg/cc];
bone volume fraction;
bone area/tissue area) 		1. Tissue repair cells
(or ixmyelocel-T) suspension + absorbable gelatin sponge;
2. Guided bone regeneration-only absorbable gelatin sponge 		Teeth were extracted with full flap elevation.
In both groups, a bioabsorbable collagen barrier membrane was placed over the sponge and the tissues were closed. 		Bone mineral density (6/12 weeks):
1. 195a/186.8;
2. 85.5a/146.6 		Cell therapy applied in post extraction sockets showed accelerated bone healing, demonstrated both by clinical and laboratory analyses
Bone volume fraction (6 /12 weeks):
1. 0.28/0.3;
2. 0.13/0.24
Bone area/tissue area (6 /12 weeks):
1. 0.335/0.352;
2. 0.196/0.351

aIndicates statistical significance.
CBCT = cone-beam computed tomography; CT = computed tomography; CEJ = cementoenamel junction; DBM = demineralized bone matrix; CEVM = clinical external vertical measurement; CIVM = clinical internal vertical measurement; CHM = clinical horizontal measurement; Cbfa1/Runx2 = core-binding factor a 1/runx-related protein 2; MSC = mesenchymal stem cells; β-TCP = β–tricalcium phosphate; platelet-derived growth factor-BB homodimers (PDGF-BB).