Microbiological Effects of Sodium Hypochlorite/-Amino Acids and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment.

PURPOSE: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. MATERIALS AND METHODS: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). RESULTS: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). CONCLUSIONS: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis.

Histological evaluation of nonsurgical periodontal treatment with and without the use of sodium hypochlorite / amino acids and cross-linked hyaluronic acid gels in dogs.

OBJECTIVES: To evaluate periodontal wound healing following scaling and root planing (SRP) in conjunction with the application of sodium hypochlorite/amino acids and cross-linked hyaluronic acid (xHyA) gels in dogs. MATERIALS AND METHODS: In four beagle dogs, 2-wall intrabony defects were created and metal strips were placed around the teeth. Clinical parameters were measured 4 weeks after plaque accumulation. The experimental root surfaces were subjected to SRP with either the subgingival application of a sodium hypochlorite/amino acid gel and a xHyA gel (test group) or SRP alone (control group) using a split-mouth design. Clinical parameters were re-evaluated at 6 weeks. The animals were sacrificed at 8 weeks for histological analysis. RESULTS: The test group showed significant improvements in all clinical parameters compared to the control group. Histologically, the test group exhibited statistically significantly greater new bone formation [i.e., length of newly formed bone, new bone area] compared with the control group (p < 0.05). Furthermore, statistically significantly greater formation of new attachment [i.e., linear length of new cementum adjacently to newly formed bone with inserting collagen fibers] and new cementum was detected in the test group compared with the control group at 8 weeks (p < 0.05 and p < 0.01, respectively). CONCLUSION: The adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA gels to SRP offers an innovative novel approach to enhance periodontal wound healing/regeneration. CLINICAL RELEVANCE: The present findings have for the first-time shown histologic evidence for periodontal regeneration in support of this novel treatment modality.

The development of non-resorbable bone allografts: Biological background and clinical perspectives.

Bone grafts are typically categorized into four categories: autografts, allografts, xenografts, and synthetic alloplasts. While it was originally thought that all bone grafts should be slowly resorbed and replaced with native bone over time, accumulating evidence has in fact suggested that the use of nonresorbable xenografts is favored for certain clinical indications. Thus, many clinicians take advantage of the nonresorbable properties/features of xenografts for various clinical indications, such as contour augmentation, sinus grafting, and guided bone regeneration, which are often combined with allografts (e.g., human freeze-dried bone allografts [FDBAs] and human demineralized freeze-dried bone allografts [DFDBAs]). Thus, many clinicians have advocated different 50/50 or 70/30 ratios of allograft/xenograft combination approaches for various grafting procedures. Interestingly, many clinicians believe that one of the main reasons for the nonresorbability or low substitution rates of xenografts has to do with their foreign animal origin. Recent research has indicated that the sintering technique and heating conducted during their processing changes the dissolution rate of hydroxyapatite, leading to a state in which osteoclasts are no longer able to resorb (dissolve) the sintered bone. While many clinicians often combine nonresorbable xenografts with the bone-inducing properties of allografts for a variety of bone augmentation procedures, clinicians are forced to use two separate products owing to their origins (the FDA/CE does not allow the mixture of allografts with xenografts within the same dish/bottle). This has led to significant progress in understanding the dissolution rates of xenografts at various sintering temperature changes, which has since led to the breakthrough development of nonresorbable bone allografts sintered at similar temperatures to nonresorbable xenografts. The advantage of the nonresorbable bone allograft is that they can now be combined with standard allografts to create a single mixture combining the advantages of both allografts and xenografts while allowing the purchase and use of a single product. This review article presents the concept with evidence derived from a 52-week monkey study that demonstrated little to no resorption along with in vitro data supporting this novel technology as a "next-generation" biomaterial with optimized bone grafting material properties.

Clinical evaluation of sodium hypochlorite/amino acids and cross-linked hyaluronic acid adjunctive to non-surgical periodontal treatment: a randomized controlled clinical trial.

OBJECTIVES: To compare the clinical outcomes obtained with either mechanical subgingival debridement in conjunction with a sodium hypochlorite and amino acids containing gel followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with mechanical debridement alone. MATERIALS AND METHODS: Fourty-eight patients diagnosed with stages II-III (Grades A/B) generalised periodontitis were randomly treated with either scaling and root planing (SRP) (control) or SRP plus adjunctive sodium hypochlorite/amino acid and xHyA gels (test). The primary outcome variable was reduction of probing depth (PD), while changes in clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were secondary outcomes. The outcomes were assessed at baseline, at 3 and 6 months following therapy. RESULTS: All patients completed the 6 months evaluation. At 6 months, the test group showed statistically significantly better results in terms of mean PD reduction (2.9 ± 0.4 vs 1.8 ± 0.6 mm, p < 0.001). Similarly, mean CAL gain was statistically higher in the test group compared to the control one (test: 2.6 ± 0.5 vs control: 1.6 ± 0.6 mm, p < 0.001). Mean BOP decreased from 81.8 ± 16.2% to 48.9 ± 14.5% in control (p < 0.001) and from 83.2 ± 15.5% to 17.6 ± 11.5% in test (p < 0.001) groups with a statistically significant difference favouring the test group (p < 0.001). Mean PI scores were reduced statistically significantly in both groups (from 38.8 ± 26% to 26.5 ± 20.5% in control (p = 0.039) and from 60.6 ± 10.9% to 12.7 ± 8.9% in test group (p < 0.001)), with a statistically significant difference between the groups (p < 0.001). The number of moderate pockets (4-6 mm) were reduced from 1518 (41.2%) to 803 (22.6%) in the control and from 1803 (48.6%) to 234 (7.7%) in the test group with a statistically significant difference between the groups (p < 0.001), while the number of deep pockets (≥ 7 mm) changed from 277 (7.6%) to 35 (1.0%) in the control and from 298 (8.7%) to 4 (0.1%) in test group (p = 0.003). CONCLUSION: Within their limits the present data indicate that: a) both treatments resulted in statistically significant improvements in all evaluated clinical parameters, and b) the adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA to SRP yielded statistically significantly higher improvements compared to SRP alone. CLINICAL RELEVANCE: The combination of sodium hypochlorite/amino acid and xHyA gels to subgingival mechanical debridement appears to represent a valuable approach to additionally improve the outcomes of non-surgical periodontal treatment. Clinical Trial Registration Number NCT04662216 (ClinicalTrials.gov).

Multidisciplinary approach involving strategic implant placement before orthodontic (SIMBO) treatment for generalized stage IV grade C periodontitis: A case report with 10-year follow-up.

OBJECTIVE: The aim of this case report was to demonstrate the long-term effects of a multidisciplinary approach involving periodontal reconstructive surgery and strategic implant placement before orthodontic (SIMBO) treatment in a patient with severe periodontitis (e.g., stage IV/grade C). CLINICAL CONSIDERATIONS: The patient presented with severe periodontitis and pathologic tooth migration (PTM) without stable occlusion or occlusal support. After performing cause-related therapy, periodontal regenerative surgery, pre-orthodontic posterior implant placement, and orthodontic treatment involving anterior implant placement with papilla reconstruction, the patient achieved full-mouth rehabilitation and improvement of dental and smile esthetics. The clinical and radiographic results obtained were maintained over a 10-year period. CONCLUSION: Within the limits of this as a single case, multidisciplinary treatment involving the SIMBO approach appeared to allow long-term improvement of periodontal condition, stability of the dental arches and occlusion, and esthetics in a patient with severe periodontitis, PTM and posterior bite collapse. Future studies with more subjects are needed to evaluate and validate this approach. CLINICAL SIGNIFICANCE: When addressing periodontal disease, SIMBO approach-based multidisciplinary treatment appears safe and effective as a clinical protocol for establishing esthetic and functional rehabilitation in generalized stage IV/grade C periodontitis.

Cross-linked hyaluronic acid gel with or without a collagen matrix in the treatment of class III furcation defects: A histologic and histomorphometric study in dogs.

AIM: To histologically evaluate the effects of cross-linked hyaluronic acid (xHyA) with or without a collagen matrix (CM) on periodontal wound healing/regeneration in class III furcation defects in dogs. MATERIALS AND METHODS: Class III furcation defects were surgically created in the mandibular premolars in six beagle dogs. The defects were randomly treated as follows: open flap debridement (OFD) + CM (CM), OFD + xHyA (xHyA), OFD + xHyA + CM (xHyA/CM) and OFD alone (OFD). At 10 weeks, the animals were euthanized for histological evaluation. RESULTS: The newly formed bone areas in the xHyA (4.04 ± 1.51 mm2 ) and xHyA/CM (4.32 ± 1.14 mm2 ) groups were larger than those in the OFD (3.25 ± 0.81 mm2 ) and CM (3.31 ± 2.26 mm2 ) groups. The xHyA (6.25 ± 1.45 mm) and xHyA/CM (6.40 ± 1.35 mm) groups yielded statistically significantly (p < .05) greater formation of new connective tissue attachment (i.e., new cementum, with inserting connective tissue fibres) compared with the OFD (1.47 ± 0.85 mm) group. No significant differences were observed in any of the histomorphometric parameters between the xHyA and xHyA/CM groups. Complete furcation closure was not observed in any of the four treatment modalities. CONCLUSIONS: Within their limits, the present results suggest that the use of xHyA with or without CM positively influences periodontal wound healing in surgically created, acute-type class III furcation defects.

Comparison of periodontal wound healing/regeneration by recombinant human fibroblast growth factor-2 combined with ß-tricalcium phosphate, carbonate apatite, or deproteinized bovine bone mineral in a canine one-wall intra-bony defect model.

AIM: To evaluate periodontal wound healing/regeneration of one-wall intra-bony defects treated with recombinant human fibroblast growth factor-2 (rhFGF-2) and beta-tricalcium phosphate (ß-TCP), carbonate apatite (CO3 Ap), or deproteinized bovine bone mineral (DBBM) in dogs. MATERIALS AND METHODS: The stability of rhFGF-2 adsorbed onto the bone substitutes was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). One-wall intra-bony defects (5 × 5 × 5 mm) created in five adult male beagle dogs were treated with rhFGF-2 alone (rhFGF-2), rhFGF-2 with ß-TCP (rhFGF-2/ß-TCP), rhFGF-2 with CO3 Ap (rhFGF-2/CO3 Ap), or rhFGF-2 with DBBM (rhFGF-2/DBBM). Histological outcomes (e.g., linear length of new cementum adjacent to the newly formed bone with inserting collagen fibres [NA] as the primary outcome) were evaluated at 10 weeks post surgery. RESULTS: Significantly higher amount of rhFGF-2 was adsorbed onto CO3 Ap compared with ß-TCP. Among the treatment groups, the rhFGF-2/DBBM group showed the highest amount of periodontal tissue regeneration. The rhFGF-2/DBBM group showed significantly greater formation of NA (3.22 ± 0.40 mm) compared with rhFGF-2 (1.17 ± 1.00 mm, p < .01) group. Additionally, new bone area in the rhFGF-2/DBBM group (9.78 ± 2.30 mm2 ) was significantly higher than that in the rhFGF-2 (5.08 ± 1.26 mm2 , p < .01), rhFGF-2/ß-TCP (5.91 ± 1.27 mm2 , p < .05), and rhFGF-2/CO3 Ap (6.51 ± 1.49 mm2 , p < .05) groups. Slight ankylosis was found in the rhFGF-2/ß-TCP (1/9 sites), rhFGF-2/CO3 Ap (3/10 sites), and rhFGF-2/DBBM (1/9 sites) groups. CONCLUSIONS: Within their limitations, the present data indicate that DBBM seems to be a suitable carrier for rhFGF-2 and that rhFGF-2/DBBM treatment promotes favourable periodontal regeneration compared with rhFGF-2, rhFGF-2/ß-TCP, and rhFGF-2/CO3 Ap treatments in one-wall intra-bony defects.

Histological Evaluation of Gingival and Intrabony Periodontal Defects Treated with Platelet-rich Fibrin Using Different Protocols: A Canine Study.

PURPOSE: To histologically compare the effects of platelet-rich fibrin (PRF) produced using different protocols on periodontal wound healing/regeneration in periodontal defects in dogs. MATERIALS AND METHODS: Dehiscence-type gingival recession and two-wall intrabony defects were created bilaterally in the maxillary canines and mandibular premolars, respectively, in four beagle dogs. The recession defects were randomly treated with coronally advanced flap (CAF) alone, CAF and PRF produced via fixed-angle centrifugation (F-PRF; Leukocyte and PRF (L-PRF) protocol) or CAF and PRF produced via horizontal centrifugation (H-PRF). After 2 weeks, the two-wall intrabony defects were randomly treated as follows: open flap debridement (OFD), OFD + F-PRF, OFD + H-PRF and OFD + heated albumin with PRF using bio-heat technologies (Alb-PRF). Eight weeks after the 2nd reconstructive surgery, the animals were euthanised for histological evaluation. RESULTS: In the PRF-applied defects, new bone and new cementum formation occurred to varying degrees regardless of the protocols used to produce PRF. Particularly in the two-wall intrabony defects, new bone formation extended from the host bone toward the coronal region of the defects in the H-PRF applied sites compared with those in the OFD, F-PRF and Alb-PRF groups, and the H-PRF group showed the greatest amount of newly formed cementum. CONCLUSION: PRF induced periodontal regeneration in gingival recession and two-wall intrabony defects in dogs. Further studies are needed to determine the optimal protocol for obtaining predictable periodontal regeneration in periodontal defects in humans.

Enhanced bone formation of calvarial bone defects by low-intensity pulsed ultrasound and recombinant human bone morphogenetic protein-9: a preliminary experimental study in rats.

OBJECTIVES: The aim of this study was to evaluate the combined effects of recombinant human bone morphogenetic protein - 9 (rhBMP-9) loaded onto absorbable collagen sponges (ACS) and low-intensity pulsed ultrasound (LIPUS) on bone formation in rat calvarial defects. MATERIALS AND METHODS: Circular calvarial defects were surgically created in 18 Wistar rats, which were divided into LIPUS-applied (+) and LIPUS-non-applied (-) groups. The 36 defects in each group received ACS implantation (ACS group), ACS with rhBMP-9 (rhBMP-9/ACS group), or surgical control (control group), yielding the following six groups: ACS (+/-), rhBMP-9/ACS (+/-), and control (+/-). The LIPUS-applied groups received daily LIPUS exposure starting immediately after surgery. At 4 weeks, animals were sacrificed and their defects were investigated histologically and by microcomputed tomography. RESULTS: Postoperative clinical healing was uneventful at all sites. More new bone was observed in the LIPUS-applied groups compared with the LIPUS-non-applied groups. Newly formed bone area (NBA)/total defect area (TA) in the ACS (+) group (46.49 ± 7.56%) was significantly greater than that observed in the ACS (-) (34.31 ± 5.68%) and control (-) (31.13 ± 6.74%) groups (p < 0.05). The rhBMP-9/ACS (+) group exhibited significantly greater bone volume, NBA, and NBA/TA than the rhBMP-9/ACS (-) group (2.46 ± 0.65 mm3 vs. 1.76 ± 0.44 mm3, 1.25 ± 0.31 mm2 vs. 0.88 ± 0.22 mm2, and 62.80 ± 11.87% vs. 42.66 ± 7.03%, respectively) (p < 0.05). Furthermore, the rhBMP-9/ ACS (+) group showed the highest level of bone formation among all groups. CONCLUSION: Within their limits, it can be concluded that LIPUS had osteopromotive potential and enhanced rhBMP-9-induced bone formation in calvarial defects of rats. CLINICAL RELEVANCE: The use of rhBMP-9 with LIPUS stimulation can be a potential bone regenerative therapy for craniofacial/peri-implant bone defects.

Periodontal wound healing/regeneration of two-wall intrabony defects following reconstructive surgery with cross-linked hyaluronic acid-gel with or without a collagen matrix: a preclinical study in dogs.

OBJECTIVES: In-vitro data have shown that cross-linked hyaluronic acid (HA) enhances the proliferative and migratory properties of cells involved in periodontal wound healing/regeneration, stabilizes the blood clot, reduces the inflammatory response, and facilitates angiogenesis. The aim of this study was to histologically evaluate the effects of cross-linked HA alone or combined with a collagen matrix (CM) on the periodontal wound healing/regeneration in intrabony defects. METHOD AND MATERIALS: Two-wall intrabony defects (5 mm wide, 5 mm deep) were surgically created at the distal and mesial aspects of mandibular premolars in six beagle dogs. The 24 defects were randomly treated as follows: open flap debridement (OFD) + HA, OFD + CM, OFD + HA + CM (HA/CM), and OFD alone (control). At 2 months, the animals were euthanized for histologic evaluation. RESULTS: The HA (2.43 ±â€¯1.25 mm) and HA/CM (2.60 ±â€¯0.99 mm) groups yielded statistically significantly (P < .05) greater formation of new attachment (ie, linear length of new cementum adjacent to newly formed bone, with inserting collagen fibers) compared with the OFD (0.55 ± 0.99 mm) group. Among the four treatment groups, the HA/CM group demonstrated the highest amount of regenerated tissues, although no statistically significant differences in any of the histometric parameters were observed between the HA and HA/CM groups. CONCLUSION: Within their limits, it can be concluded that cross-linked HA alone or combined with CM promotes periodontal wound healing/regeneration in two-wall intrabony defects in dogs.

Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis.

OBJECTIVES: This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF). RESULTS: From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF. CONCLUSIONS: The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed. CLINICAL RELEVANCE: The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.

Healing of intrabony defects following regenerative surgery by means of single-flap approach in conjunction with either hyaluronic acid or an enamel matrix derivative: a 24-month randomized controlled clinical trial.

OBJECTIVES: The aim of this randomized controlled clinical trial was to compare the clinical outcomes obtained in intrabony defects following regenerative periodontal surgery using the single-flap approach (SFA) in conjunction with either hyaluronic acid (HA) or enamel matrix derivative (EMD). MATERIALS AND METHODS: Thirty-two intrabony defects in 32 healthy subjects were randomly assigned: HA (test group) or EMD (control group). Clinical attachment level (CAL), probing depth (PD), gingival recession (REC), and bleeding on probing (BOP) were recorded at baseline,12, 18, and 24 months after surgery. RESULTS: At 24 months, both treatments resulted in statistically significant clinical improvements evidenced by PD-reduction and CAL-gain (p<0.001). The mean CAL-gain was 2.19±1.11 mm in the test and 2.94±1.12 mm in the control sites (p=0.067). PD-reduction was statistically significantly higher for the control group (4.5±0.97 mm) than the test group (3.31±0.70 mm), (p=0.001). CAL-gain ≤ 3 mm was observed in 87.5% and in 62.5% of the test and control sites, respectively. Test sites showed slightly lower REC values than the control sites. No statistically significant differences were found for BOP between treatments. CONCLUSIONS: The present findings indicate that both treatments led to statistically significant clinical improvements compared to baseline, although the application of EMD resulted in statistically significantly higher PD-reduction compared to the use of HA. CLINICAL RELEVANCE: The use of HA in conjunction with a SFA resulted in significant PD-reduction and CAL-gain, pointing to the potential clinical relevance of this material in regenerative periodontal surgery.

Healing of buccal gingival recessions following treatment with coronally advanced flap alone or combined with a cross-linked hyaluronic acid gel. An experimental study in dogs.

AIM: To clinically and histologically evaluate in dogs the healing of gingival recessions treated with coronally advanced flap (CAF) with or without cross-linked hyaluronic acid (HA). MATERIALS AND METHODS: Gingival recession defects were surgically created on the vestibular side of both maxillary canines in 8 dogs. After 8 weeks of plaque accumulation, the 16 chronic defects were randomly treated with either CAF alone or CAF and HA-gel (CAF/HA). Clinical and histological outcomes were evaluated at 10 weeks post-surgically. RESULTS: Compared to baseline, the clinical measurements at 10 weeks revealed a statistically significant decrease in gingival recession for both CAF (p < 0.01) and CAF/HA (p < 0.001) groups. Statistically significant differences were found in clinical attachment level (p < 0.05) and width of gingival recession (p < 0.01) favouring the CAF/HA group. Bone formation was statistically significantly greater in the CAF/HA group than in the CAF group (1.84 ± 1.16 mm vs., 0.72 ± 0.62 mm, respectively, p < 0.05). Formation of cementum and connective tissue attachment were statistically significantly higher in the CAF/HA group compared with the CAF group (i.e. 4.31 ± 1.78 mm versus 2.40 ± 1.35 mm and 1.69 ± 0.98 mm versus 0.74 ± 0.68 mm, respectively (p < 0.05)). CONCLUSIONS: The present data have for the first time provided histologic evidence for periodontal regeneration of gingival recession defects following treatment with CAF and HA. CLINICAL RELEVANCE: The use of HA in conjunction with CAF may represent a novel modality for treating gingival recession defects.

Use of platelet-rich fibrin for the treatment of gingival recessions: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to compare the use of platelet-rich fibrin (PRF) with other commonly utilized treatment modalities for root coverage procedures. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the performance of PRF with that of other modalities in the treatment of Miller class I or II (Cairo RT I) gingival recessions. Studies were classified into 5 categories as follows: (1) coronally advanced flap (CAF) alone vs CAF/PRF, (2) CAF/connective tissue graft (CAF/CTG) vs CAF/PRF, (3) CAF/enamel matrix derivative (CAF/EMD) vs CAF/PRF, (4) CAF/amnion membrane (CAF/AM) vs CAF/PRF, and (5) CAF/CTG vs CAF/CTG/PRF. Studies were evaluated for percentage of relative root coverage (rRC; primary outcome), clinical attachment level (CAL), keratinized mucosa width (KMW), and probing depth (PD) (secondary outcomes). RESULTS: From 976 articles identified, 17 RCTs were included. The use of PRF statistically significantly increased rRC and CAL compared with CAF alone. No change in KMW or reduction in PD was reported. Compared with PRF, CTG resulted in statistically significantly better KMW and RC. No statistically significant differences were reported between the CAF/PRF and CAF/EMD groups or between the CAF/PRF and CAF/AM groups for any of the investigated parameters. CONCLUSIONS: The use of CAF/PRF improved rRC and CAL compared with the use of CAF alone. While similar outcomes were observed between CAF/PRF and CAF/CTG for CAL and PD change, the latter group led to statistically significantly better outcomes in terms of rRC and KTW. In summary, the use of PRF in conjunction with CAF may represent a valid treatment modality for gingival recessions exhibiting adequate baseline KMW. CLINICAL RELEVANCE: The data indicate that the use of PRF in conjunction with CAF statistically significantly improves rRC when compared with CAF alone but did not improve KMW. Therefore, in cases with limited baseline KMW, the use of CTG may be preferred over PRF.

Periodontal tissue regeneration after low-intensity pulsed ultrasound stimulation with or without intra-marrow perforation in two-wall intra-bony defects-A pilot study in dogs.

AIM: To evaluate the effects of low-intensity pulsed ultrasound (LIPUS) with/without intra-marrow perforation (IMP) on periodontal healing in two-wall intra-bony defects in dogs. MATERIALS AND METHODS: Two-wall intra-bony defects (5 mm wide, 5 mm deep) were created at the distal and mesial aspects of mandibular premolars in four beagle dogs (four defects per dog). The 16 defects were divided into four treatment groups: IMP, LIPUS, IMP + LIPUS (IMP/LIPUS) and control (open flap debridement). The LIPUS and IMP/LIPUS sites received daily LIPUS exposure for 3 weeks starting 1 week after surgery. The animals were euthanized 4 weeks after surgery for histologic evaluation. RESULTS: There was significantly greater new bone formation at LIPUS (2.93 ± 0.74 mm) and IMP/LIPUS (3.18 ± 0.52 mm) sites than at control sites (1.65 ± 0.46 mm). New bone area at LIPUS (6.36 ± 2.28 mm2 ) and IMP/LIPUS (6.13 ± 1.25 mm2 ) sites was significantly greater than that at control sites (2.15 ± 1.75 mm2 ). New cementum length at LIPUS sites (4.09 ± 0.75 mm) was significantly greater than that at control (2.29 ± 1.02 mm) and IMP (2.41 ± 0.41 mm) sites. No significant difference was observed between LIPUS and IMP/LIPUS sites in any histomorphometric parameter. CONCLUSIONS: These findings suggest that LIPUS effectively promotes periodontal regeneration in two-wall intra-bony defects in dogs.

Efficacy of flapless intentional replantation with enamel matrix derivative in the treatment of hopeless teeth associated with endodontic-periodontal lesions: A 2-year prospective case series.

OBJECTIVE: In this prospective case series, the effects of flapless intentional replantation (IR) with root surface conditioning with enamel matrix derivative (EMD) was evaluated for the treatment of periodontally-endodontally involved hopeless teeth. METHOD AND MATERIALS: A total of 17 teeth (17 patients, aged 40 to 73) with ≥ 10 mm attachment loss and radiographic bone loss to the apex were included in the study. The affected teeth were atraumatically extracted using a flapless approach, then granulation tissues, calculus, and necrotic cementum on the root surfaces were removed. EMD was applied for 5 minutes to the root surfaces. The teeth were reinserted to the socket without any bone grafts and splinted. RESULTS: After 2 years, clinical healing was uneventful in 16 cases and the radiographs revealed no root resorption or ankylosis. IR with EMD treatment provided statistically significant reduction in probing depth (6.4 ± 2.6 mm), gain in clinical attachment level (5.9 ± 2.5 mm), and gain in radiographic bone level (48.2 ± 26.1%) compared to baseline values (P < .01). CONCLUSION: Within the limitations of the study, flapless IR with EMD treatment appeared to act as an alternative strategy to extraction of severely compromised teeth with endodontic-periodontal lesions beyond the root apex.

Healing of two-wall intra-bony defects treated with a novel EMD-liquid-A pre-clinical study in monkeys.

AIM: To investigate the effect of a novel enamel matrix derivative formulation (EMD-liquid or Osteogain) combined with an absorbable collagen sponge (ACS) on periodontal wound healing in intra-bony defects in monkeys. MATERIALS AND METHODS: Chronic two-wall intra-bony defects were created at the distal aspect of eight teeth in three monkeys (Macaca fascicularis). The 24 defects were randomly assigned to one of the following treatments: (i) open flap debridement (OFD) + ACS alone, (ii) OFD + Emdogain + ACS (Emdogain/ACS), (iii) OFD + Osteogain + ACS (Osteogain/ACS) or (iv) OFD alone. At 4 months, the animals were euthanized for histologic evaluation. RESULTS: Osteogain/ACS resulted in more consistent formation of cementum, periodontal ligament and bone with limited epithelial proliferation compared to OFD alone, Emdogain/ACS and OFD + ACS. Among the four treatment groups, the Osteogain/ACS group demonstrated the highest amount of regenerated tissues. However, complete periodontal regeneration was not observed in any of the defects in the four groups. CONCLUSIONS: The present findings indicate that in two-wall intra-bony defects, reconstructive surgery with Osteogain/ACS appears to be a promising novel approach for facilitating periodontal wound healing/regeneration, thus warranting further clinical testing.

Comparison of Two Porcine Collagen Membranes Combined with rhBMP-2 and rhBMP-9 on Osteoblast Behavior In Vitro.

PURPOSE: To investigate the bone-inducing properties of two types of collagen membranes in combination with recombinant human bone morphogenetic protein (rhBMP)-2 and rhBMP-9 on osteoblast behavior. MATERIALS AND METHODS: Porcine pericardium collagen membranes (PPCM) and porcine dermis-derived collagen membranes (PDCM) were coated with either rhBMP-2 or rhBMP-9. The adsorption and release abilities were first investigated via enzyme-linked immunosorbent assay up to 10 days. Moreover, murine bone stromal ST2 cell adhesion, proliferation, and osteoblast differentiation were assessed by MTS assay; real-time polymerase chain reaction for genes encoding runt-related transcription factor 2 (Runx2); alkaline phosphatase (ALP); and osteocalcin, ALP assay, and alizarin red staining. RESULTS: Both rhBMP-2 and rhBMP-9 adsorbed to collagen membranes and were gradually released over time up to 10 days. PPCM showed significantly less cell attachment, whereas PDCM demonstrated comparable cell attachment with the control tissue culture plastic at 8 hours. While both rhBMPs were shown not to affect cell proliferation, collagen membranes combined with rhBMP-9 significantly increased ALP activity at 7 days and ALP mRNA levels at either 3 or 14 days compared with the control tissue culture plastic. Furthermore, rhBMP-9 increased osteocalcin mRNA levels and alizarin red staining at 14 days compared with the control tissue culture plastic. CONCLUSION: The results from this study suggest that both porcine-derived collagen membranes combined with rhBMP-9 accelerated the osteopromotive potential of ST2 cells. Interestingly, rhBMP-9 demonstrated additional osteogenic differentiation compared with rhBMP-2 and may serve as a suitable growth factor for future clinical use.

Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects.

OBJECTIVES: Among bone morphogenetic protein (BMP) family members, BMP-2 and BMP-9 have demonstrated potent osteoinductive potential. However, in vivo differences in their potential for bone regeneration remain unclear. The present study aimed to compare the effects of recombinant human (rh) BMP-2 and rhBMP-9 on bone formation in rat calvarial critical-size defects (CSD). MATERIALS AND METHODS: Twenty-eight Wistar rats surgically received two calvarial defects bilaterally in each parietal bone. Defects (n = 56) were allocated into four groups: absorbable collagen sponge (ACS) alone, rhBMP-2 with ACS (rhBMP-2/ACS), rhBMP-9/ACS, or sham surgery (control), on the condition that the treatments of rhBMP-2/ACS and rhBMP-9/ACS, or the same treatments were not included in the same animal. Animals were sacrificed at 2 and 8 weeks post-surgery. The calvarial defects were analyzed for bone volume (BV) by micro-computed tomography and for percentages of defect closure (DC/DL), newly formed bone area (NBA/TA), bone marrow area (BMA/NBA), adipose tissue area (ATA/NBA), central bone height (CBH), and marginal bone height (MBH) by histomorphometric analysis. RESULTS: The BV in the rhBMP-2/ACS group (5.44 ± 3.65 mm3, n = 7) was greater than the other groups at 2 weeks post-surgery, and the rhBMP-2/ACS and rhBMP-9/ACS groups (18.17 ± 2.51 and 16.30 ± 2.46 mm3, n = 7, respectively) demonstrated significantly greater amounts of BV compared with the control and ACS groups (6.02 ± 2.90 and 9.30 ± 2.75 mm3, n = 7, respectively) at 8 weeks post-surgery. The rhBMP-2/ACS and rhBMP-9/ACS groups significantly induced new bone formation compared to the control and ACS groups at 8 weeks post-surgery. However, there were no statistically significant differences found between the rhBMP-2/ACS and rhBMP-9/ACS groups in any of the histomorphometric parameters. The ATA/NBA in the rhBMP-2/ACS group (9.24 ± 3.72%, n = 7) was the highest among the treatment groups at 8 weeks post-surgery. CONCLUSIONS: Within the limits of this study, it can be concluded that rhBMP-2/ACS induced a slight early increase in new bone formation at 2 weeks and that rhBMP-9/ACS provided comparable new bone formation to rhBMP-2/ACS with less adipose tissues after a healing period of 8 weeks in rat CSD. CLINICAL RELEVANCE: RhBMP-9/ACS treatment provided new bone formation with less adipose tissues compared with rhBMP-2/ACS.

Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine-derived natural bone mineral.

BACKGROUND: The use of enamel matrix derivative (EMD) has been shown to facilitate periodontal regeneration by histologically resulting in formation of cementum, periodontal ligament and bone. Recently, a new liquid carrier system for EMD has been introduced with better physicochemical properties specifically designed for bone graft mixing (Osteogain). The aim of this study was to investigate the combination of Osteogain with a bovine-derived natural bone mineral (NBM) on osteoblast migration, adhesion, proliferation and differentiation. MATERIALS AND METHODS: Undifferentiated mouse ST2 stromal bone marrow cells were seeded onto 1)NBM particles alone or 2)NBM + Osteogain. Samples were compared for cell migration at 8 h, cell adhesion at 4 h, cell proliferation at 1, 3 and 5 days and real-time PCR at 3 and 14 days for genes encoding runt-related transcription factor 2 (Runx2), collagen1alpha2 (COL1a2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, alizarin red staining was utilized to investigate the mineralization at 14 days. RESULTS: Osteogain significantly upregulated cell adhesion over twofold onto NBM particles and promoted cell proliferation at 3 and 5 days after seeding. Furthermore, the combination of NBM with Osteogain significantly upregulated genes encoding Runx2, ALP, COL1a2 and OCN (from 1.5- to 3-fold) and increased alizarin red staining over 3 fold at 14 days when compared to NBM particles alone. CONCLUSION: Pre-coating Osteogain onto NBM bone grafting particles significantly increased cell adhesion, proliferation and differentiation of osteoblasts in vitro. Future animal studies are now necessary to further investigate the regenerative potential of Osteogain in combination with a bone grafting material prior to clinical use for bone regeneration.