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Bioabsorbable scaffolds for guided bone regeneration and generation.

Several different bioabsorbable scaffolds designed and manufactured for guided bone regeneration and generation have been developed. In order to enhance the bioactivity and potential osteoconductivity of the scaffolds, different bioabsorbable polymers, composites of polymer and bioactive glass, and textured surface structures of the manufactured devices and composites were investigated in in vitro studies and experimental animal models. Solid, self-reinforced polyglycolide (SR-PGA) rods and self-reinforced poly L-lactide (SR-PLLA) rods were successfully used as scaffolds for bone formation in muscle by free tibial periosteal grafts in animal experiments. In an experimental maxillary cleft model, a bioabsorbable composite membrane of epsilon-caprolactone and L-lactic acid 50/50 copolymer (PCL/LLA) film and mesh and poly 96L,4D-lactide (PLA96) mesh were found to be suitable materials for guiding bone regeneration in the cleft defect area. The idea of solid layer and porous layer combined together was also transferred to stiff composite of poly 70L,30DL-lactide (PLA70) plate and PLA96 mesh which structure is introduced. The osteoconductivity of several different biodegradable composites of polymers and bioactive glass (BG) was shown by apatite formation in vitro. Three composites studied were self-reinforced composite of PLA70 and bioactive glass (SR-(PLA70 + BG)), SR-PLA70 plate coated with BG spheres, and Polyactive with BG.

Animals↗

Comparison between a conventional technique and two bone regeneration techniques in periradicular surgery.

AIM: The aim was to demonstrate the efficacy of two materials for bone regeneration during periradicular surgery and their effects on the healing of periapical tissues. METHODOLOGY: Twenty-eight patients (30 surgical sites) were selected and distributed into three groups:group A, conventional technique; group B, conventional technique plus nonbioabsorbable GoreTex R Augmentation membrane; and group C, conventional technique plus the same membrane placed over a synthetic bioactive resorbable graft of a hydroxylapatite (OsteoGen) product in the bony defect. Clinical and radiological evaluations were completed immediately prior to surgery, a week later and every 3 months after surgery up to 12 months. Two histological evaluations were performed (at the beginning and at 12 months). RESULTS: The results showed complete clinical and radiographic healing (eight cases) for group C, with histologic evidence of trabecular bone in all cases. For group B, six out of nine cases showed complete radiographic healing, incomplete in one case and uncertain in two cases, with histologic evidence of trabecular bone in five out of eight cases, scar tissue in one case and granuloma in two cases. For group A, there was complete radiographic healing in four out of nine cases, incomplete in four and unsuccessful in one case, with evidence of granuloma in four out of eight, scar tissue in two cases and trabecular bone in two cases. CONCLUSIONS: It was concluded that the conventional technique was less predictable in its healing response during the 12 months of this study. The use of bone regeneration materials, such as nonbioabsorbablemembranes and resorbable hydroxylapatite improved the predictability of clinical, radiographic and histological healing.

Absorbable Implants↗

Internal craniofacial distraction with biodegradable devices: early stabilization and protected bone regeneration.

Internal craniofacial distraction has several advantages over distraction with external devices. The scars may be less conspicuous; the devices are buried and therefore easier for patients to tolerate; and the devices are more rigidly secured to bone, preventing uncontrolled rotation of the advancing segments. There are several types of internal devices. The Modular Internal Distraction System developed by one of the authors (S.R.C.) and Stryker-Leibinger, Inc. has had widespread use for midface distraction, but requires a substantial surgical procedure for device removal. This is justified in selected children with syndromic craniosynostosis, who frequently need secondary orbitocranial reconstruction at the conclusion of distraction with any type of device. It would be preferable to develop a device that would retain the positive characteristics of the Modular Internal Distraction system, while allowing easy removability. Moreover, the entire distraction procedure would benefit from a technique that would assist in bone regeneration within the distraction gap. Such a biodegradable, stabilizing device may enable early explanation, accelerating the recovery period, while providing fixation of the distraction gap and protected bone regeneration. Accordingly, we have developed a new, biodegradable distraction device with Macropore, Inc. that may be used with the Modular Internal Distraction system to permit easy removability of the device without the need for a large operation for exposure. Second, we have developed a biodegradable stabilizer that permits earlier removal of the distraction device while providing simultaneous fixation and protected bone regeneration. Last, we have demonstrated the feasibility of midcourse correction of the distraction procedure, should this be necessary for whatever reason.

Absorbable Implants↗

[Osteoplasty of extensive jaw defects by protected bone regeneration using large pore resorbable implant].

This study was performed to demonstrate a protected bone regeneration method using macroporous resorbable sheets for the treatment of extended lower and upper jaw defects. By applying mechanical protection of bony defects with, e.g. membranes or titanium mesh, soft tissue prolapse as well as pressure on bone transplants which contributes to partial resorption can be avoided. The use of a pressure-resistant, resorbable, macroporous sheet combines the advantage of protected bone regeneration and complete resorption of the implanted sheet. The macroporous structure facilitates capillary ingrowth from the surrounding soft tissue. The sheet is made of 70:30 Poly(L-co-DL)-lactate with thermoplastic character and can be used as a container for autologous spongiosa or other osteoinductive and -conductive bone graft substitutes. In a pilot study, seven patients with lower jaw defects resulting from large cysts or tumor resections, some affecting the continuity of the mandible, were treated with this method. Following a protocol, X-rays were obtained to document the bony regeneration. The positive experience with this pilot study encouraged a multicenter project involving five university hospitals and 50 patients. The application of resorbable sheets in combination with transplantation of mersilized autologous spongiosa is currently being investigated. In future studies, fillings of sheets with osteoconductive and -inductive materials are planned.

Aged↗

Bone regeneration after removal of a mandibular cyst and following prosthetic rehabilitation with implants. Case report.

This study shows the spontaneous bone regeneration after a Partch II surgical operation without using filling materials. The following functional and esthetic rehabilitation was made with overdenture on implants even in the recovery zone. A male patient, 59 years old, with a cystic lesion of 3.5 mm diameter in the mandibular bone was submitted to surgical enucleation of this neoformation. Postoperative radiological examinations, orthopantomography and TC DentaScan were performed to value the bone regeneration. Four implants of 10 mm diameter and 4.1 mm length were subsequently fixed in the mandibular bone and also in the regeneration area. Then, the rehabilitation of the patient with an overdenture on implants was possible. Radiographic controls after cystic enucleation showed a good recovery of the region occupied by the neoformation. The implants fixed proved to be solid and it was possible to carry out an overdenture on them. The cystectomy alone, performed with conservative technique, without subsequent filling of the remaining cavity with biointegrative materials, permitted bone regeneration also in a large remaining cavity. This regeneration was sufficient to guarantee the success of the subsequent overdenture on implants, and very good functional and esthetic results in a patient totally edentulous in the mandibular bone.

Bone Regeneration↗

Effect of capacitive coupled electrical stimulation on regenerate bone.

An in vivo study was carried out to determine if capacitive coupled electrical stimulation increased the rate of recovery of strength of regenerate bone produced as a result of lengthening by the Ilizarov technique. Thirty-four adult male beagles underwent a right tibial mid-diaphyseal corticotomy, followed by a 5-day delay, and then 21 days of lengthening (1 mm/day). At the start of the post-distraction period (day 27), stimulation (3-6.3 V peak to peak, 5-10 mA root-mean-square at 60 kHz) was applied for 28 days to one group. The nonstimulated group (n = 17) underwent a 28-day period with no stimulation. From each group, four tibiae were prepared for histology; both ends of the remaining bones were embedded in polymethylmethacrylate and tested in torsion (internal rotation at 4.7 degrees/sec) until failure. Statistically significant changes included a 37% lower maximum torque capacity and a 40% decrease in strain energy to failure in the stimulated group compared with the nonstimulated group. The findings are supported by measured trends to a lower modulus of rigidity (37% decrease) and a smaller percentage of active osteoid perimeter (20% decrease) for the stimulated group. The experimental data suggest that when this dose of capacitive coupled electrical stimulation is applied to the regenerating bone created during distraction osteogenesis, it delays the recovery of bone strength compared with an untreated control.

Animals↗

Custom-shaping system for bone regeneration by seeding marrow stromal cells onto a web-like biodegradable hybrid sheet.

New bone for the repair or the restoration of the function of traumatized, damaged, or lost bone is a major clinical need, and bone tissue engineering has been heralded as an alternative strategy for regenerating bone. A novel web-like structured biodegradable hybrid sheet has been developed for bone tissue engineering by preparing knitted poly(DL-lactic-co-glycolic acid) sheets (PLGA sheets) with collagen microsponges in their openings. The PLGA skeleton facilitates the formation of the hybrid sheets into desired shapes, and the collagen microsponges in the pores of the PLGA sheet promote cell adhesion and uniform cell distribution throughout the sheet. A large number of osteoblasts established from marrow stroma adhere to the scaffolds and generate the desired-shaped bone in combination with these novel sheets. These results indicate that the web-like structured novel sheet shows promise for use as a tool for custom-shaped bone regeneration in basic research on osteogenesis and for the development of therapeutic applications.

Absorbable Implants↗

Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials.

The aim of the present clinical study was to test whether peri-implant bone defects can successfully be filled with bone by applying bioresorbable materials for guided bone regeneration (GBR) procedures in conjunction with implants in the transmucosal healing position. Three women and 7 men ranging in age from 32 to 68 years (median 54.5) needed tooth replacement with dental implants. Eight to 14 weeks following careful tooth extraction, implants of the ITI Dental Implant System were placed at the extraction sites. At this time, all implants presented dehiscence defects of the alveolar bone partly exposing the rough titanium plasma sprayed (TPS) surfaces. GBR procedures were performed using deproteinized bovine bone mineral (Bio-Oss) as a membrane-supporting material and a bioresorbable collagen membrane (Bio-Gide) as a barrier. The membranes and the flaps were adjusted to fit around the necks of the implants, thus leaving the implants extending transmucosally into the oral cavity. Clinical measurements were taken at 6 sites around each implant (mesio-buccal, buccal, disto-buccal, disto-lingual, lingual, mesio-lingual) using a calibrated periodontal probe. These included: i) defect depth measured from the shoulder of the implant to the first bone-to-implant contact, ii) infrabony defect component measured from the bone crest to the first bone-to-implant contact, iii) defect width measured from the crest to the implant body in a direction perpendicular to the long axis of the implant. The Wilcoxon Matched Pairs Signed Rank Test was applied to detect differences over time. At baseline, the mean defect depth per patient amounted to 3.6 mm (Standard Deviation 1.6 mm, range 1.8-6.8 mm). The deepest extensions of the defects were located at the buccal aspects (mean 7.8 mm, SD 1.9 mm). At re-entry, the mean defect had decreased to 2.5 mm (SD 0.6 mm). This difference was statistically significant (P < 0.01). Initially, in 62% of sites the depth ranged from 0-3 mm, in 23% it ranged from 2-4 mm, and in 15% it amounted to more than 6 mm. Six to 7 months later, at re-entry, 95% of sites were 3 mm and less in depth and 5% ranged from 4-6 mm. Defect resolution, as assessed by the amount of coverage of the initially exposed rough implant surface, reached a mean value of 86% (SD 33%). One hundred percent resolution was accomplished at 8 out of 10 implants, 60% at one and 0% at another implant. The tissue at the latter implant showed signs of infection and inflammation during the healing phase. It is concluded that bioresorbable materials in GBR procedures at transmucosal implants can lead to successful bone regeneration into peri-implant defects.

Absorbable Implants↗

Use of mesenchymal stem cells to facilitate bone regeneration in normal and chemotherapy-treated rats.

Reconstructing segmental bone defects after resection of malignant bone tumors is a long-standing clinical problem. Treatment of bone tumors such as osteosarcoma involves chemotherapy. These chemotherapeutic agents are potent inhibitors of cell division and these drugs may affect regeneration of bone from osteoprogenitor cells. It may be possible to reconstruct segmental bone defects by a tissue-engineering approach. The aim of this study was to investigate the use of mesenchymal stem cells (MSCs) in a fibrin glue carrier to enhance bone regeneration after chemotherapy. Bone marrow was harvested from young adult male rats of the Wistar strain; stem cells were isolated and expanded. Bone regeneration in normal and chemotherapy-treated rats was investigated in 1.5-mm rat femoral defects created by osteotomizing the femur and stabilizing the femoral fragments by external fixation. The osteotomy gap was left either unfilled, filled with fibrin glue alone, or filled with glue containing stem cells. Bone formation within the gap was determined by radiography, dual-energy X-ray absorptiometry, and histology. It was shown that MSCs encapsulated within fibrin glue could remain viable for up to 96 h in tissue culture. Chemotherapy significantly reduced bone formation in unfilled defects and defects filled only with fibrin glue. When MSCs were used in conjunction with fibrin glue, even in non-chemotherapy-treated rats bone formation in the gap was significantly increased. Using stem cells, the effects of chemotherapy on bone formation could be alleviated by bone formation in the gap similar to that seen in non-chemotherapy-treated animals with MSCs. These studies demonstrated that a tissue-engineering approach in patients undergoing chemotherapy may be beneficial for treating segmental bone defects after tumor resection.

Animals↗

Poly(ethylene glycol) hydrogels cross-linked by hydrolyzable polyrotaxane containing hydroxyapatite particles as scaffolds for bone regeneration.

Poly(ethylene glycol) (PEG) hydrogels cross-linked by a hydrolyzable polyrotaxane containing hydroxyapatite particles (PRX-HAp) were developed as scaffolds for bone regeneration. Five scaffolds with various composition of the polyrotaxane, PEG and HAp particles were prepared to examine cell adhesion in vitro using rat primary cultured osteoblast. Cells were observed to attach well on a PRX-HAp that have the same weight ratio of the polyrotaxane and HAp particles at 7 days after seeding. These results indicate that HAp particles are necessary for cell adhesion and survival, but a higher ratio of the particles is not suitable for cell adhesion. The composites of rat osteoblast and the PRX-HAp were implanted subcutaneously in syngeneic rats and harvested at 5 weeks after implantation. In histological analysis, osteoblast-like cells became arrayed along the surface of the PRX-HAp, and osteoid-like tissues were observed in the region between a queue of osteoblast-like cells and PRX-HAp. These images are similar to intramembranous ossification, and it is expected that bone regeneration occurs on the surface of the PRX-HAp. This study strongly suggests the great potential of the PRX-HAp as scaffolds for bone regeneration.

Animals↗

Fresh frozen bone in femoral impaction grafting: can developments in bone regeneration improve on this?

Major advances in the understanding of bone regeneration have led to revolutionary applications of bone conduction and induction. Revision hip surgery is on the increase with an active, ageing population demanding increased quality of life. The technically demanding instrumentation and materials necessary for revision prosthetic hip replacements have been rapidly incorporated into clinical practice. Unfortunately, advantage has not been taken of the basic and fundamental principles of bone induction and regeneration, available for many years now. In impaction grafting for revision hip replacements where fresh frozen bone is currently used as a standard, we argue and demonstrate from the literature why this technique is biologically inferior to the results which potentially can be gained by exploiting osteoinductive grafts such as demineralised bone matrix, hydroxyapetite, and inductive factors such as bone morphogenetic proteins.

Animals↗

Healing response to anorganic bone implantation in periodontal intrabony defects in dogs. Part I. Bone regeneration. A microradiographic study.

The purpose of the present study was to explore the regenerative potential of anorganic bone plus collagen (AB-C) in experimental intrabony defects. Eight healthy female beagle dogs, 3 to 4 years old and weighing 15 to 16 kilos, were used. After extraction of the mandibular third premolars (P3), surgical defects were created and inflammation induced by placement of cotton and steel braids. Eight weeks later, the braids were removed. The experimental lesions thus obtained were either treated by plain flap curettage (group 1: control) or were, in addition, implanted with AB-C (group 2: experimental). Blocks of AB-C alone were observed by scanning electron microscopy (SEM). The results show that the surface of the particles have the characteristics of a bone tissue. These particles are gathered together with a fibrillar network. Six, 18, and 36 weeks postoperative (PO), non-decalcified specimens from both groups were examined histologically by contact microradiography. In group 1, no significant bone regeneration was observed at 6, 18, or 36 weeks PO. In group 2, trabeculae undergoing mineralization and circumscribing dense particles above the reference notch were seen at 6 weeks PO; 18 and 36 week specimens showed significant bone regeneration with more or less dense remaining particles. The periodontal ligament space was always clear and the only signs of ankylosis noticed were deep in the notch on one 18 week group 2 specimen and on one 36 week group 1 specimen.

Alveolar Bone Loss↗

Bone grafting and guided bone regeneration for immediate dental implants in humans.

This study evaluated bone regeneration and osseointegration of hydroxyapatite (HA) coated and titanium plasma sprayed (TPS) implants placed in sockets immediately after extraction in 36 adults, mean age 55.2 years (range 26 to 81 years). Twelve TPS and 10 HA-coated implants in 20 patients were grafted with demineralized freeze-dried bone allograft (DFDBA), covered with a barrier material, and the facial flap coronally positioned to attain primary closure (experimental). The remaining 11 TPS and 10 HA-coated implants were placed similarly, except that no DFDBA was used (control). Osseous structures were measured at the initial placement and 6-month re-entry surgeries. At the 6-month re-entry, all implants placed were clinically osseointegrated. Bone resorption at the most coronal socket crest was -1.53 mm for the grafted group and -1.59 mm for the control group. Crestal bone apposition of 1.39 mm was noted at the most apical socket crest (ASC) for the grafted group, whereas crestal resorption of -0.11 mm was noted in the ungrafted control group (P < 0.02). Bone fill from the base of the deepest osseous defect was 5.68 mm for the grafted group and 3.18 mm for the control group (P < 0.04). Complete resolution of osseous defects occurred at 15 of 22 sites in the grafted group and at 9 of 21 sites in the control group. Clinical exposure of the barrier material and a subsequent inflammatory response at 27 of 43 sites, requires removal of the material prior to the 6-month re-entry and was associated with significantly more bone loss at the ASC sites (P < 0.01). There was no significant difference for any of the parameters when comparing the TPS with the HA-coated implants.

Adult↗

Comparison of resorbable and nonresorbable guided bone regeneration materials: a preliminary study.

The purpose of this study was to compare bone regeneration within a surgically created defect using three different resorbable membranes (polyglactin 910 knitted mesh/Vicryl, freeze-dried fascia lata, and crosslinked bovine type I collagen/BioMend) and two nonresorbable membranes (expanded polytetrafluoroethylene/Gore Tex, and polytetrafluoroethylene/Millipore). Each of three adult male dogs underwent surgical preparation of six bicortical defects of the calvarium, each 1.5 cm in diameter. The experimental barrier membranes were placed on both sides of the defects (inner and outer cranial tables). Five of the six defects were covered randomly by one of the five membrane materials, and one was left uncovered to serve as a negative control. The animals were sacrificed 10 weeks after membrane placement. Bone response was measured clinically, as well as radiographically, via densitometric examination. All surgical sites healed uneventfully. Variable degrees of new bone growth were present at all sites when evaluated by both clinical and radiographic examination. The general trend of observed osseous response indicates a greater, although not statistically significant, degree of bone growth using nonresorbable membranes. The animal model employed appears to be an efficient and reliable means of evaluating guided bone regeneration membranes.

Animals↗

Healing pattern of bone regeneration in membrane-protected defects: a histologic study in the canine mandible.

In this study, standard and prototype reinforced e-PTFE membranes were used to evaluate the pattern of bone regeneration in membrane-protected defects in the mandibles of four dogs. Following a healing period of 2 and 4 months, control sites without membranes exhibited incomplete osseous healing with a persisting defect. Test sites with membranes demonstrated significantly better bone healing, although bone regeneration was not yet completed at 4 months. The histologic evaluation showed that bone regeneration, once activated, progresses in a programmed sequence through a series of maturation steps, which closely resemble the pattern of bone development and growth.

Alveolar Process↗

Osseointegration of titanium implants in bone regenerated in membrane-protected defects: a histologic study in the canine mandible.

In the present histologic study of the mandibles of five foxhounds, 15 nonsubmerged titanium implants were placed in bone regenerated in extended membrane-protected defects during a 6-month healing period. The clinical and radiographic evaluation demonstrated that all 15 implants achieved functional ankylosis within 3 months following implant placement. Subsequently, eight implants were restored with fixed partial dentures and were functionally loaded for 6 months, and seven implants were left unrestored. At the completion of the study, the histologic analysis demonstrated osseointegration with direct bone-to-implant contact for all 15 implants. Therefore, it can be concluded that bone regenerated in membrane-protected defects responds to implant placement like nonregenerated bone, and that this bone is capable of bearing and sustaining functional load. The histologic comparison of restored and unrestored sites demonstrated no apparent differences concerning bone remodeling activities. Furthermore, control sites without implant placement demonstrated bone atrophy underneath the membranes with a thin cortical layer and sparse bone trabeculae. Thus, it can also be concluded that the placement of an implant into regenerated bone stimulated bone maturation and bone remodeling, whereas implant loading did not influence bone remodeling in the present study model.

Alveolar Bone Loss↗

Conditions for success in guided bone regeneration: retrospective study on 376 implant sites.

BACKGROUND: Used alone or in association with bone, guided bone regeneration is a clinically accepted method to increase the volume of bone during implant placement. Concerns about appropriate surgical techniques and the predictability of the results questions still exist. The aim of this study was to assess the conditions for success. METHODS: Three-hundred-seventy-six implants were placed in association with 214 non-resorbable membranes. In 109 implants, the membrane was secured on a blood clot; for 213 implants, membrane was placed with autogenous bone; and for 54 implants it was placed with allogenic bone. The surgical procedure, the primary closure, the timing of re-entry, and the density of regenerated tissue were studied. RESULTS: In 19 membranes, barrier exposure occurred before 3 months in these instances, the regenerated tissue was removed; another 7 membranes were exposed between 3 and 6 months. The 188 non-exposed membranes were removed between 6 and 12 months. In cases of exposure before 3 months, the regenerated tissue was soft and then removed. After closure for 6 months or more, the regenerated tissue was dense and resistant to probe pressure. The best results were obtained when the membranes were placed with autogenous bone. CONCLUSIONS: If all the clinical steps are appropriately followed, guided bone regeneration using an autogenous bone graft and implant placement is a predictable technique for increasing bone volume.

Adult↗

Comparison of calcium alginate film with collagen membrane for guided bone regeneration in mandibular defects in rabbits.

PURPOSE: We sought to compare calcium alginate film (CAF) with collagen membrane (CM) regarding their effects on guided bone regeneration. MATERIALS AND METHODS: Circular bone defects with 5-mm diameter were created in the region anterior to both mandibular angles in 34 rabbits. The defects on one side were covered with a CAF, and the contralateral side with CM. Healing condition was analyzed with gross, radiographic, electromicroscopic, histologic, and immunohistochemical studies and image pattern analysis system after 1, 2, 4, 6, and 8 weeks. RESULTS: CM absorbed more slowly but collected fewer osteoinductive factors (P <.05) in the early period. CAF induced dense bone formation, whereas CM produced less newly formed bone. CONCLUSION: CAF is more efficacious than CM in guided bone regeneration in this animal model.

Alginates↗