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Experimental animal investigation of bone regeneration with collagen-apatite.

Multicentric osteoregeneration is a new principle of osteoinduction [31a] which can be realized with the combination of collagen and fine dispersed hydroxyapatite ceramic particles (Collapat). This was histomorphometrically proved in the present study involving 14 rabbits with 28 6-mm-wide bore holes in the distal femoral condyles. With Collapat, an average of 5 times more new bone was regenerated than in the control defects without implant. The Wilcoxon matched-pairs signed-ranks test proved the positive effect of the implant Collapat on osteoregeneration with a significance of P less than 0.0001. At sites of Collapat insertion bone regeneration begins in the 2nd week, reaches its climax in the 3rd week, and is completed after the 4th week. in the course of development the histological picture is typified by a lively bone remodeling. Bone formation can be recognized in direct contact to the apatite granules. Foreign body or allergic reactions are not observed. Remodeling of the bone is not hindered by the slowly resorbable apatite granules. About 250 human implantations have been performed in our hospital since 1979, with good results and no negative effects.

Animals↗

In vivo bone regeneration with injectable calcium phosphate biomaterial: a three-dimensional micro-computed tomographic, biomechanical and SEM study.

This in vivo study investigated the efficiency of an injectable calcium phosphate bone substitute (IBS) for bone regenerative procedures through non-destructive three-dimensional (3D) micro-tomographic (microCT) imaging, biomechanical testing with a non-destructive micro-indentation technique and 2D scanning electron microscopy (SEM) analysis. The injectable biomaterial was obtained by mixing a biphasic calcium phosphate (BCP) ceramic mineral phase and a cellulosic polymer. The BCP particles were 200-500 microm or 80-200 microm in diameter. The injectable material was implanted for 6 weeks into critical-sized bone defects at the distal end of rabbit femurs. Extensive new bone apposition was noted with both 2D and 3D techniques. Micro-CT showed that newly formed bone was in perfect continuity with the trabecular host bone structure and demonstrated the high interconnectivity of the restored bone network. For both IBS formulations, SEM and microCT gave very close measurements. The only detected significant difference concerned the amount of newly formed bone obtained with IBS 80-200 that appeared significantly higher with microCT analysis than with SEM (p=0.00007). Student t-tests did not show any significant difference in the amount of newly formed bone and remaining ceramic obtained from microCT analysis or SEM. Regression analysis showed satisfactory correlation between both the amount of newly formed bone and remaining ceramic obtained from microCT or SEM. For IBS 200-500, the newly formed bone rate inside the defect was 28.0+/-5.2% with SEM and yield strength of the samples was 18.8+/-5.4 MPa. For IBS 80-200, the newly formed bone rate inside the defect was 31.7+/-5.1% with SEM and yield strength of the samples was 26.8+/-4.5 MPa. Yield strength appeared well correlated with the amount of newly formed bone, specially observed with microCT. This study showed the ability of non-destructive techniques to investigate biological and mechanical aspects of bone replacement with injectable biomaterials.

Animals↗

Histology of human alveolar bone regeneration with a porous tricalcium phosphate. A report of two cases.

Porous beta-phase tricalcium phosphate particles (pTCP) (Cerasorb) were used in two patients to restore or augment alveolar bone prior to the placement of dental implants. In one patient, pTCP was used to fill a large alveolar defect in the posterior mandible after the removal of a residual cyst, and in another patient to augment the sinus floor. Biopsies were taken at the time of implant placement, 9.5 and 8 months after grafting, respectively, and processed for hard tissue histology. Goldner-stained histological sections showed considerable replacement of the bone substitute by bone and bone marrow. In the 9.5 months biopsy of the mandible, 34% of the biopsy consisted of mineralised bone tissue and 29% of remaining pTCP, while the biopsy at 8 months after sinus floor augmentation consisted of 20% mineralised bone and 44% remaining pTCP. Bone and osteoid were lying in close contact with the remaining pTCP and were also seen within the micropores of the grafted particles. Tartrate resistant-acid phosphatase (TRAP) multinuclear cells, presumably osteoclasts, were found surrounding, within and in close contact with the pTCP particles, suggesting active resorption of the bone substitute. Remodelling of immature woven bone into mature lamellar bone was also found. No histological signs of inflammation were detected. The limited data presented from these two cases suggest that this graft material, possibly by virtue of its porosity and chemical nature, may be a suitable bone substitute that can biodegrade and be replaced by new mineralising bone tissue.

Absorbable Implants↗

Bone graft substitutes in periodontal and peri-implant bone regeneration.

Regenerative medicine provides different therapy alternatives alongside gold standard autogenous grafts for the treatment of periodontal or peri-implant osseous defects. Continuing progress in the field of alloplastic bone substitutes has yielded promising solutions to the appropriate indications with the membrane technique either alone or in combination with enamel matrix derivatives. Their clinical outcomes, however, still require critical discussion.

Alveolar Bone Loss↗

Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

Animals↗

The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment.

A dome-shaped bioresorbable membrane was fixed to the wounded rabbit calvaria and filled with a bioresorbable fibre conglomerate. After 4 weeks, the histologic preparation revealed an intimate spatial and temporal correlation between newly formed blood vessels and de novo extraskeletal bone formation. These observations emphasize the significance of angiogenesis in guided bone generation.

Animals↗

Preprosthetic vertical distraction osteogenesis of the mandible using an L-shaped osteotomy and titanium membranes for guided bone regeneration.

PURPOSE: Vertical osteodistraction is a new alternative method for alveolar ridge augmentation of the mandible. The purpose of this article is describe a technique using an L-shaped osteotomy and titanium membranes for guided bone regeneration (GBR) in the distraction gap. PATIENTS AND METHODS: Ten patients with severe atrophy of the edentulous molar region of the mandible underwent vertical callus distraction in 13 sites using intraoral microplate distractors. An L-shaped osteotomy with a short vertical part mesially and a longer horizontal part ending in the retromolar region was made, and the osteotomized segment was fixed to the mandibular ramus at its distal edge by a microplate, which became the center of rotation when distraction began. In this way, more callus generation could be achieved mesially than in the distal molar region. Follow-up computed tomography (CT) scans reconstructed axially to the axis of the mandible revealed semilunar excavations of the generated bone buccally in the distraction gap in the first cases. Clinical inspection on removal of the distractors showed fibrous connective tissue in the gap. Therefore, to prevent this from happening, titanium membranes covering the distraction gap were applied in subsequent cases. RESULTS: Ten patients (13 sites) were treated by vertical callus distraction. In 4 cases, GBR was achieved using titanium membranes. In all cases, the increase in alveolar height was sufficient to make dental implantation possible. In 1 patient, a fracture of the distractor occurred, and dehiscence was observed in 2 cases. These complications did not change the plan of therapy nor did they influence the results. The CT scans showed a homogenous surface on the regenerated mandible in the cases of GBR application. CONCLUSION: Both an L-shaped osteotomy and the application of titanium membranes for GBR in the distraction gap are of great value for mandibular augmentation, producing a physiologically shaped alveolar ridge.

Adult↗

Receptor technology--cell binding to P-15: a new method of regenerating bone quickly and safely-preliminary histomorphometrical and mechanical results in sinus floor augmentations.

Modern implantology involves the application and optimization of bone engineering biomaterials and scaffolds to achieve predictability in quality and quantity of the regeneration result and to avoid the high morbidity factor of the present gold standard. In this respect, acceleration of (woven) bone formation and completeness of the regeneration result seems to be an reasonable attempt by multiplication of the whole cascades by duplicating all phases of cell binding, migration, proliferation and differentiation. Collagen I is an extracellular matrix protein with multiple main binding domains for osteogenic progenitor cells and therefore plays a crucial role in osteogenesis. PepGen P15 is the first man engineered collagen I binding domain for potential osteoblasts and is able to multiply the complete regeneration cascade. The article explains the principles of micromolecular receptor engineering and its application in sinus floor augmentations as a preliminary report. It presents the first clinical and histomorphometrical results of this new technology in sinus floor elevations. The future potential of individual bone regeneration will be discussed.

Adult↗

Bone regeneration by grafting of an autogenous cultured bone/ceramic construct.

The in vivo osteogenic potential of autogenous cultured bone/ceramic constructs in large animals or humans is unknown, and thus we performed a preliminary study of this issue prior to clinical application. All autogenous cultured-bone/ceramic constructs at 3 weeks after implantation in dogs showed obvious histological bone formation within the ceramic pores. In many pores, the HE staining of decalcified specimens revealed thick lamellar bone formation on the pore surface of ceramic. On the surface of bone tissue, numerous active cuboidal osteoblasts were evident. Biochemically, high alkaline phosphatase activity was detected in all dogs. Histological examination of the constructs at 8 weeks postimplantation showed lamellar bone formation with vascular system invasion into the pores, and regenerated hematopoietic bone marrow was often detected in association with the new bone in grafting of human cultured bone/ceramic constructs. Trilineage hematopoietic cells (i.e., granulocytic, erythroblastic, and megakaryocytic cells) were identified in the ceramic pores. Biochemically, high alkaline phosphatase activity and significant human osteocalcin content was detected in the constructs. Based on these findings, in the near future, this technique (grafting of patient-derived cultured bone/HA constructs) will be able to be applied to various bone reconstruction surgical treatments.

Alkaline Phosphatase↗

[Effect of opiod peptides on free radical oxidation in a bone regenerate after fracture].

Opioid peptides (DSLET and DAGO) stimulating bone tissue regeneration were studied for effects on content of free radical products in regenerate tissue from the region of leg fracture in mice at various terms of reparative osteogenesis. These opioids reduce concentration of malonic dialdehyde and dienic conjugastes in bone for 10 days after fracture.

Animals↗

The clinical use of deproteinized bovine bone mineral on bone regeneration in conjunction with immediate implant installation.

Twenty-one c.p. titanium screw-shaped implants were immediately installed after extraction and thorough curettage of the alveoli in 15 patients. Granules of deproteinized bovine bone of 0.25-1.0 mm diameter were used to fill the remaining defect when the distance of the defect wall to the implant surface was > 3 mm. Dimensional measurements of the defect height and width were made with a pocket probe. Fourteen sites in the upper jaw and 7 sites in the lower jaw were thus treated. The mean defect depth varied between 7 mm vestibularly and 10 mm mesially. The mucoperiosteal flaps were hermetically closed. At re-entry, the particles were packed and firmly attached but still distinguishable from the surrounding bone. Of the 21 sites treated, 5 sites had an exposure of the implant cover screw during the healing period. An exposure of the granular material occurred in 4 sites, but loss of granules in only 3. Even in these sites no signs of infection or inflammation of the soft tissues were observed. At re-entry after 6 months, 10 sites were completely and 9 partially filled. For the partial fills, the mean remaining defect height was 1.6 mm (range: 0.6-3.0 mm). Two sites showed an increased defect of respectively 2.4 and 4.8 mm. No fixtures were lost. The present results indicate that deproteinized bovine bone is a safe filling material to fill remaining defects around implants installed in fresh extraction sockets.

Adolescent↗