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PubMed2001

Temporal and local appearance of alkaline phosphatase activity in early stages of guided bone regeneration. A descriptive histochemical study in humans.

Alkaline phosphatase (ALP) catalyzes the hydrolysis of phosphate esters and it seems to be a prerequisite for normal skeletal mineralization. Also, ALP is the most widely recognized marker of osteoblast phenotypes. By a tissue regenerative technique called Guided Bone Regeneration (GBR), it is possible nowadays to regenerate small bony defects. The aim of the present study was to investigate early events in bone healing and neogenesis by studying histochemically the temporal and local appearance of the marker Alkaline Phosphatase (ALP) in a GBR model system. Nine healthy volunteers (5 males, 4 females, mean age 31.7 years) participated in the experiment. After raising a mucoperiosteal flap from the mandibular second molar to the retromolar area in each volunteer, a hollow titanium test cylinder was placed into a congruent bony bed and the coronal end of the cylinder was closed with an ePTFE-membrane. Then the flap was adapted and sutured to obtain primary wound closure. After 2, 7 and 12 weeks, the regenerated tissue within the cylinders was harvested. Histologically, ALP activity was observed associated with the osteoid seams in the very basal part of the regenerate where new bone trabeculae were in the process of being formed. More coronally, large round cells seemed to secrete an ALP-positive substance since in the center of such cell clusters strong ALP activity located extracellularly was detected. In the present experiment, ALP seemed to have been an early sign of osteoblast secretion of a matrix which subsequently was determined to become osteoid. ALP activity was never seen isolated within connective tissue and away from bone. This is an indication that its source is linked to existing bone. The present study has documented for the first time the appearance of ALP activity in guided bone regenerations in humans. It has revealed that: 1) Osteogenesis in guided bone regeneration is preceded by localized, marked expression of ALP in an organized connective tissue environment. 2) Bone neogenesis is an early event in this experimental setup and may be detected already 2 weeks after wounding. 3) Expression of ALP and subsequent bone neogenesis is originating from and topographically linked to pre-existing bone structures.

Adult↗
PubMed1994

Anorganic bovine bone and ceramic analogs of bone mineral as implants to facilitate bone regeneration.

A number of approaches have directed toward the development of a substance that can substitute for allogeneic bone for grafting procedures. Synthetic HA ceramic materials are limited in being able to serve as analogs of bone mineral for use as implants to facilitate bone regeneration. HA ceramics do not replicate the chemistry and crystalline structure of natural bone mineral. An alternative approach has been to deorganify bovine bone to produce bone mineral in forms that can be employed as implants.

Animals↗
PubMed1977

[Radiological interpretation of bone regeneration after cystectomy of odontogenic cysts].

38 patients who had undergone surgical intervention (Partsch II) for odontogenic cysts were examined radiographically as well as clinically. The extent of bone regeneration was estimated according to age, sex, location of the cyst in the jaw, cyst size, length of time elapsed after operation and function. To facilitate the interpretation of the results obtained, the patients were subdivided into five age groups. Bone regeneration was most frequent up to the age of 20 (85.7%). It occurred more often in women (in 11 of 16 patients = 68.75%) than in men (in 14 of 22 patients = 63.6%). Bone healing was most favourable in the anterior region of the mandible less, favourable in the posterior region of the maxillae and least favourable in the anterior region of the upper jaw. With increasing size of the cyst, the regenerative power of the bone decreased. An increase in regeneration was observed up to 3 years after surgical intervention.

Adolescent↗
PubMed2000

Mechanical properties of a biodegradable bone regeneration scaffold.

Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

Absorbable Implants↗
PubMed1985

Dose-response for bone regeneration after single doses of 60Co irradiation.

The Bone Growth Chamber (BGC) methodology was used to establish a dose-response relationship for regeneration of mature bone tissue after irradiation of 5, 8, 11, 15 and 25 Gy single dose 60Co. The BGC, which is a titanium implant, was inserted in the proximal tibial metaphyses, bilaterally, of a rabbit immediately following local irradiation to one tibia. Each animal thus served as its own control. During a healing period of 4 weeks, the two canals penetrating the implant became filled with more or less newly formed bone. At the end of the healing period, the implants were removed and taken apart and the newly formed bone was collected and its volume measured by microradiography and microdensitometry. It was found that in the dose range of 5 to 8 Gy bone regeneration was reduced by about 20% as compared to non-irradiated controls. Between 8 and 11 Gy, there was a critical range in that a small increase in dose resulted in a greatly reduced bone formation. At 11 Gy and above, the depression in bone formation, as compared to non-irradiated controls, was about 65 to 75%.

Animals↗
PubMed1998

Implants in regenerated bone: long-term survival.

This retrospective multicenter study analyzed 526 implants placed and loaded in regenerated bone. Both autogenous and allogeneic bone grafts were used in combination with a barrier membrane to reconstruct bone using either a simultaneous or staged approach. Implants were followed from 6 to more than 74 months postloading. Eight of the implants were lost, for a success rate of 97.5%. The type of graft material did not affect the clinical success of the implants, nor did the use of submerged versus nonsubmerged implants or a staged versus a simultaneous approach. In conclusion, regenerated bone reacted to implant placement in a manner that was clinically similar to native bone.

Adolescent↗
PubMed1994

Guided bone regeneration in mandibular defects in rats using a bioresorbable polymer.

The aim of this study was to explore the possibility of obtaining bone regeneration in jaw bone defects in rats after coverage of the defects with an occlusive bioresorbable membrane. The experiment was carried out in 31 rats. The mandibular ramus was exposed in both sides and a 2 x 3 mm defect was produced at its lower border. A gutta-percha point was placed to indicate the original level of the border. The defect on one side was covered with a polyhydroxybutyrate resorbable membrane, whereas the contralateral side received no membrane before closure of the wound. Macerated jaw specimens representing 3 and 6 months of healing demonstrated minimal bone fill in the control defects, whereas all test defects healed to or close to the gutta-percha point, indicating the original inferior border of the jaw. The histological analysis demonstrated increasing bone fill in the test specimens from 15-180 days, whereas only 35-40% of the defect area in the control sides was filled with bone after 3-6 months. Ingrowth of muscular, glandular and connective tissue was consistently occurring in the control defects during healing. It can be concluded that selective repopulation of bone defects with bone-forming cells can be ensured by excluding surrounding soft tissues from the wound area with an occlusive bioresorbable membrane.

Alveolar Bone Loss↗
PubMed2006

Mesenchymal stem cells and bone regeneration.

OBJECTIVE: To review the role of mesenchymal stem cells (MSC) in bone formation and regeneration, and outline the development of strategies that use MSC in bone healing and regeneration. STUDY DESIGN: Literature review. METHODS: Medline review, synopses of authors' published research. RESULTS: The MSC is the basic cellular unit of embryologic bone formation. Secondary bone healing mimics bone formation with proliferation of MSC then their differentiation into components of fracture callus. Bone regeneration, where large amounts of bone must form, mimics bone healing and can be achieved with MSC combined with strategies of osteogenesis, osteoinduction, osteoconduction, and osteopromotion. MSC based strategies first employed isolated and culture expanded stem cells in an osteoconductive carrier to successfully regenerate a critical segmental defect in the femur of dogs, which was as effective as autogenous cancellous bone. Because MSC appeared to be immunologically privileged, a study using mismatched allogeneic stem cells demonstrated that these cells would regenerate bone without inciting an immunologic response, documenting the possibility of banked allogeneic MSC for bone regeneration. A technique was developed for selectively retaining MSC from large bone marrow aspirates at surgery for bone regeneration. These techniques utilized osteoconductive and osteoinductive carriers and resulted in bone regeneration that was similar to autogenous cancellous bone. CONCLUSION: MSC can be manipulated and combined with carriers that will result in bone regeneration of critically sized bone defects. CLINICAL RELEVANCE: These techniques can be employed clinically to regenerate bone and serve as an alternative to autogenous cancellous bone.

Animals↗
PubMed1998

Bone regeneration in advanced periodontitis lesions after a single episode of root planing--case report with ten-years of follow-up.

This report describes a significant bone regeneration in a mandibular molar with advancing long-standing periodontal disease (defect extending to apex and into furcation) following a single episode of scaling and root planing. A 52-year-old female suffered from generalized moderate periodontitis for two years. An acute periodontal abscess with a 12 mm probing depth around the right mandibular first molar was noted. After incision and drainage, thorough scaling and root planing was performed under local anaesthesia. Three months later, radiographic examination showed complete bone regeneration with formation of a distinct lamina dura. It was concluded that favorable clinical and radiographic results could be obtained after a single episode of thorough subgingival root planing combined with excellent oral hygiene maintenance.

Bone Regeneration↗
PubMed2005

Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite.

PURPOSE: This animal study examined the de novo bone formation in bony defects following the insertion of autogenous bone alone versus an injectable nanoparticle hydroxyapatite alone and in combination with 25% autogenous bone. The regenerative potentials of the tested materials were compared with each other. MATERIALS AND METHODS: A model with biological similarity to humans with regard to bone regeneration was a prerequisite for the transferability of the results to clinical practice. Therefore, the adult domestic pig was the animal of choice. A total observation period of 6 months was selected. Microradiographic and histologic evaluation of the bone specimens was completed at 8 defined times. RESULTS: Microradiography indicated mineralization rates in the 2 bone substitute groups that were not significantly lower than those found in the autogenous bone group. Histologically, there was suitable osseointegration and osteoconduction of the used material. Complete resorption of the nanoparticle hydroxyapatite had taken place after 12 weeks. CONCLUSIONS: It can be concluded that the evaluated nanoparticular hydroxyapatite met the clinical requirements for a bone substitute material within the limits of this experimental setting. Due to its microstructure, complete resorption took place during the course of this study.

Absorbable Implants↗
PubMed1995

Biologic factors affecting spinal fusion and bone regeneration.

STUDY DESIGN: Literature review. OBJECTIVES: This article reviews the existing data on the multiplicity of local and systemic factors affecting lumbar spinal fusion and the general biology of bone regeneration. SUMMARY OF BACKGROUND DATA: Arthrodesis is one of the most commonly performed, yet incompletely understood, procedures in spinal surgery. There exists a paucity of knowledge about the basic biology involved in achieving a successful fusion. METHODS: Medline and manual search of all relevant articles were performed and summarized. RESULTS: The success or failure of spinal fusion may be influenced by a host of local and systemic factors. CONCLUSIONS: Future research should focus on expanding our existing knowledge pertaining to the basic biology of bone regeneration specific to spinal fusion.

Bone Regeneration↗
PubMed2006

Novel membrane for guided bone regeneration.

Membranes have been clinically used for guided tissue and bone regeneration for decades, but their use in every day clinical practice is rather limited. We developed a biodegradable membrane (InionGTR) composed of polylactide, polyglycolide and trimethylene carbonate aiming to improve the properties of membrane. Before application the membrane is treated with N-methyl-pyrrolidone (NMP) to achieve a rubber like consistency, to allow easy handling and manageability in the clinical setting. After placing the membrane NMP diffuses out from the polymer phase into the water phase. The loss of NMP in the polymer stiffens the membrane up and allows space maintenance in the defect area. In addition the influx and efflux of NMP creates a porous surface on the membrane leading to an improved integration of tissues into the porous surface layers of the InionGTR membrane. Therefore, the use of NMP improves the handling in the clinical setting, and allows tissue integration and space maintenance, both important for the outcome of the treatment.

Animals↗
PubMed2005

Long-term stability of autogenous bone grafts following combined application with guided bone regeneration.

The aim of the study was to compare the long-term stability of membranous and endochondral autogenous bone grafts with or without combined application of guided bone regeneration (GBR). Twenty-five, male, 6-month old, albino rats were used in the study. The animals were divided into four groups (A5, A11, B5 and B11). Group A5 (control): The inferior border of the mandible was exposed in both sides. At one side of the jaw, a calvarial bone graft (baseline -3 x 4 x 0.64 mm) was placed at the inferior border of the mandible and was fixed with a standardized screw-type titanium microimplant. At the contralateral side, an ischiac bone graft (baseline -3 x 4 x 0.87) was transplanted. The healing period was 5 months. Group A11 (control): The animals were treated in the same manner as in Group A5 with the difference that the healing period was 11 months. Group B5 (test): The animals were treated in the same manner as in Group A5 with the difference that an e-PTFE membrane was adapted over the bone graft on each side of the jaw. Group B11 (test): The animals were treated in the same manner as in Group B5 with the difference that 5 months following transplantation the animals were subjected to a second operation and the membranes were removed. The healing period was 11 months. The animals were killed at 5 (Groups A5 and B5) or at 11 months (Groups A11 and B11) following mandibular augmentation and the jaws were defleshed. The width, the length and the thickness/height of the bone graft were evaluated by means of a stereomicroscope. At 5 months, both types of the membrane-treated bone grafts presented increase in all dimensions compared with baseline. However at 11 months, both types of the membrane-treated bone grafts exhibited a decrease in their dimensions which were similar to the baseline measurements. In the control groups, both types of bone graft presented significant resorption both at 5 and at 11 months with the ischiac bone grafts presenting more resorption in width and length than the calvarial bone grafts. It can be concluded that the long-term volume stability of autogenous endochondral and membranous onlay bone grafts combined with GBR is superior to that of autogenous endochondral and membranous onlay bone grafts alone.

Animals↗
PubMed2005

Systemic regulation of angiogenesis and matrix degradation in bone regeneration--distraction osteogenesis compared to rigid fracture healing.

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing. Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1-3. In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.

Adult↗
PubMed1997

Bone regeneration with a calcium sulfate barrier.

OBJECTIVES: Bone defects are a challenge for the dental clinician. As widely accepted in guided tissue regeneration, physically halting soft connective tissue proliferation into bone allows for bone regeneration. This concept is the "osteopromotion principle." The aim of this study was to assess the osteopromoting effect of calcium sulfate as a barrier. STUDY DESIGN: Forty male Sprague-Dawley rats were used. Mucoperiosteal flaps were raised bilaterally at buccal and lingual aspects of the mandible to expose the angles. Next, 5 mm through-and-through bony defects were created bilaterally. On the test side, sterile medical grade prehardened calcium sulfate disks were applied both lingually and buccally to cover the defect. The control side defects were left uncovered. All flaps were sutured closed. Observation times were 3, 9, 18, and 22 weeks. RESULTS: Histologic analysis demonstrated that at 3 weeks all test sites showed partial or complete bone healing. Similar findings were reported for all observation times. The control group showed no bone growth at 3 and 9 weeks and partial bone healing at 18 and 22 weeks. CONCLUSIONS: This study indicates that calcium sulfate barriers can exclude connective tissues, allowing bone regeneration during healing.

Alveolar Process↗