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.

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.

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.

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.

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.

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 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.

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.

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.