Ossification and Bone Regeneration in a Canine GBR Model, Part 2: Glycated Cross-Linked Collagenated Alloplastic Hydroxyapatite Scaffold vs Non-Cross-Linked Collagenated Xenographic Bone Hydroxyapatite.

PURPOSE: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). MATERIALS AND METHODS: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. RESULTS: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. CONCLUSION: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration.

Ossification and Bone Regeneration in a Canine GBR Model, Part 1: Thick vs Thin Glycated Cross-Linked Collagen Devices.

Purpose: To compare glycated multilayered membranes (OV) to a commercially available thin-layer membrane (OP) in a lateral ridge augmentation model in dogs. Materials and Methods: This was designed as a three-arm study, where one negative control (empty defect) was compared to two test arms: alveolar bone defects grafted with a mixture of 90% deproteinized bovine bone mineral and 10% porcine collagen, then covered with either a thick- (OV) or thin-layered (OP) membrane. Animals were randomly divided into three groups corresponding to the final sacrifice times of 4 weeks, 12 weeks, and 24 weeks. Sections underwent microCT, histology, histopathology, and histomorphometry. Results: No statistical differences were observed for OV compared to OP regarding the percentage of mineral volume and mean mineral density, amount of bone maturation, percentage of bone graft and membrane remaining in the grafted area, alveolar ridge width measurements, membrane mineralization, or ossification. Test groups presented significantly higher values compared to the empty control for all the endpoints. Conclusions: Within its limitations, this in vivo study highlighted that multilayered thick glycated membranes can serve as effective occlusive barriers for up to 6 months.

Use of a Sugar Cross-Linked Collagen Membrane Offers Cell Exclusion and Ossification.

Resorbable barrier membranes are advantageous for use in guided bone regeneration for treatment of peri-implant defects, eliminating the need for surgical re-entry. Ribose, a natural sugar-based material that has been used to cross-link collagen, is able to be utilized in high concentrations to extend barrier function for long periods without eliciting inflammation or foreign body reactions in situ. A unique finding with a ribose cross-linked collagen membrane is the in situ ossification of the material upon re-entry. This article presents two cases that clinically demonstrate the efficacy of a sugar cross-linked collagen membrane in peri-implant and site development type defects and suggest its ability to ossify and achieve bone regeneration.

In vivo degradation of collagen barrier membranes exposed to the oral cavity.

OBJECTIVES: The purpose of this human clinical trial was to compare the degradation profiles of three different collagen membranes under conditions mimicking exposure to the oral cavity. MATERIALS AND METHODS: Three collagen membranes, ribose cross-linked (RCL), glutaraldehyde cross-linked (GCL), and non-cross-linked (NCL) were tested. The membranes were placed over the buccal mucosa of 20 human volunteers, apical to the gingival margins in the maxillary premolar and molar region. A periodontal dressing was placed over the membranes and secured in the interproximal spaces. The dressing was removed after 10 days, and membrane integrity was evaluated by two examiners using a Likert-like grading scale (grades 1-5). RESULTS: Eight subjects withdrew from the study due to discomfort, pain, or dislodging of the pack. Of the three membranes tested, RCL appeared to be the most resistant to degradation (median grade 5), compared with GCL (2.25) and NCL (1.75). CONCLUSIONS: Marked differences in membrane integrity were found between the three tested membranes after 10 days in the oral cavity. These differences may be part of the important factors determining the outcome of the regenerative treatment modality in cases of premature membrane exposure.

Ossification of a collagen membrane cross-linked by sugar: a human case series.

BACKGROUND: Collagen membranes cross-linked by glycation (GLYM) for guided bone regeneration (GBR) and guided tissue regeneration (GTR) are used extensively with proven safety and efficacy. Complete GLYM ossification, when placed in contact with bone, was described in a canine jaw model, suggesting that GLYM may serve as an ossification substrate. The purpose of this case series was to histologically evaluate GLYM in GBR procedures in humans. METHODS: We retrospectively selected seven consecutive patients with implant-related bony defects who underwent GBR with GLYM. Six defects had bone grafts, and one had a barrier alone. Selection criteria were primary closure upon post-surgical examination and tissue that was 2- to 3-mm thick over the implant's cover screw. Tissue was removed when the implants were uncovered after 20 to 29 weeks. Decalcified sections were stained and analyzed under light microscopy. RESULTS: In five of seven specimens, GLYM was identified and preserved its barrier effect. The mean membrane thickness was 0.17 +/- 0.054 mm. In two cases, the bone grafts under the membrane were embedded in new bone, whereas in five cases, they were embedded in fibrous connective tissue. Formation of new dense bone was observed along the side of the membrane facing the original bone, and various degrees of membrane ossification were evident in all five cases. CONCLUSIONS: GLYM maintained its barrier effect in five of seven cases for 25 weeks and induced dense new bone along its interface with underlying tissues. To the best of our knowledge, this is the first report on GLYM ossification in humans with direct mineral apposition on glycated collagen and suggests a new concept of tissue-integrated active barriers.

Ossification of a novel cross-linked porcine collagen barrier in guided bone regeneration in dogs.

BACKGROUND: Collagen membranes for guided bone regeneration (GBR) and guided tissue regeneration (GTR) are used extensively as bioabsorbable barriers. Cross-linking of collagen increases its biodurability and enables the control of its degradation kinetics and barrier function. A novel cross-linking technology was used to produce a porcine type I collagen membrane (GLYM). The purpose of this study was to evaluate the safety, efficacy, and degradation kinetics of GLYM compared to a non-cross-linked bilayer type I and III porcine collagen membrane (BCM) in surgically created defects in dogs. METHODS: After tooth extraction, two mandibular bilateral critical size defects were created in 12 beagle dogs that were randomly assigned to one of five groups: GLYM + bovine bone mineral (BBM), BCM + BBM, BBM alone, sham-operated, or GLYM alone. Dogs were euthanized after 8, 16, and 24 weeks, and sites were prepared for qualitative, semiquantitative, and quantitative light microscopy analyses. RESULTS: Membrane-protected sites displayed bone filling between the BBM particles with almost complete restoration of the original ridge morphology that increased with time up to 16 weeks and remained unchanged at 24 weeks. Both membranes showed marked degradation within 16 to 24 weeks, with BCM inconsistency that was undetectable in one of four sites at 8, 16, and 24 weeks. Membrane ossification was observed in all GLYM sites and in only one BCM site, which progressed with time to 24 weeks. Bone increased by approximately 1 mm on the lingual side, where the GLYM membrane was in direct contact with bone. CONCLUSIONS: Both membranes were safe and effective in supporting bone regeneration in critical size alveolar ridge defects in dogs and completely degraded within 24 weeks with marked BCM inconsistency. In areas of direct contact with bone, all GLYM sites were progressively ossified with time and augmented the original alveolar ridge. To the best of our knowledge, this is the first report of complete ossification of a collagen barrier membrane in GBR procedures.