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PubMed1999

[Polylactic acid combined with recombinant human bone morphogenetic protein and basic fibroblast growth factor to repair the mandibular defects in rabbits].

OBJECTIVE: To study the effect of basic fibroblast growth factor(bFGF) on bone formation induced by recombinant human bone morphogenetic protein-2(rhBMP-2) in repair of mandibular defects in rabbits. METHODS: 56 adult domestic rabbits were classified into five groups. The mandiblar three-wall defects(1.5 cm x 0.5 cm, full thick) were created in right sides. The defects were implanted with various grafts: PLA/rhBMP-2/bFGF, PLA/rhBMP-2, PLA/bFGF, PLA and no implant as control group. At 2, 4 and 8 weeks after operation, the effectivenesses of defect repaire were observed by histological and roentgenographic analysis. RESULTS: The composite consisting of three materials stimulated more bone formation than of two materials, and the latter was more than single PLA(at 4 weeks postoperation, P < 0.05). All experimental groups, which had one or two growth factors, were significantly higher compared with control group in every stage of postimplantation. CONCLUSION: PLA has good biocompatibility, absorbability and osteoconductibility, rhBMP-2 and bFGF are cooperated in bone healing process, and PLA/rhBMP-2/bFGF is a promising bone substitute in clinical uses.

Animals↗
PubMed2004

[Antibiotic-loaded bone cements: from laboratory studies clinical evaluation].

Antibiotic-loaded bone cements (ALBC) were initially used empirically, both for the treatment of infected prostheses and for antibioprophylaxis. We conducted in vitro and animal studies as a prerequisite for proper clinical evaluation. We measured gentamicin diffusion from methacrylate bone cement, and found that the concentration in surrounding fluid was significantly above the minimal inhibitory concentration (MIC). We then implanted ALBC in the proximal femora of 100 ewes, in conditions close to those of total hip replacement (THR). Antibiotic concentrations in bone were above 4 x MIC for more than 6 months. We subsequently measured antibiotic concentrations in drainage fluid, blood and urine samples from 50 patients undergoing THR. Concentrations were over 20 x MIC in periprosthetic fluid, but were below the detection limit in blood after 24 hours and in urine after one week. The blood concentration was less than 1 mg/l--far below the ototoxic and nephrotoxic threshold (8 mg/l). Having established antibiotic bioavailability, we then examined the clinical efficacy of ALBC. We participated in several studies, including a French multicentric review of 342 THR procedures (direct and two-stage exchanges). ALBC was beneficial in both settings, with an 85% infection control rate. This included patients with very severe infections (multiresistant strains, severe osteolysis) treated with two-stage exchanges; and moderate infections treated by direct exchange. (This latter procedure offers fewer complications, more durable functional results, a shorter hospital stay and lower treatment costs.) We also used ALBC for antibioprophylaxis in over 2000 THR procedures, and noted no complications. This method is now being assessed in more than 200 000 cases contained in the Swedish THR Register. The experimental methods that we developed (laboratory studies, animal implantation, clinical pharmacokinetics) set the groundwork for clinical studies of gentamicin ABLC, and also allowed us to develop other ALBC formats, containing vancomycin, for example (restricted to salvage therapy). We also used these methods to evaluate antibiotic-loaded bone substitutes (calcium and carbon phosphates), designed not only to control infectious osteitis but also to replace osteolytic bone.

Anti-Bacterial Agents↗
PubMed1991

When osteotomies should be considered.

Osteotomy at various levels of the facial skeleton is entirely justified in selected aesthetic surgical patients. By the very nature of aesthetic surgery, the morbidity potential associated with such osteotomies must be extremely low. Accordingly, osteotomy at the symphyseal level and the LeFort I level are the most commonly performed procedures in the aesthetic surgical patient. Aesthetic changes required in the vertical plane of space will require osteotomy, because these cannot be reliably and consistently achieved through changes in skeletal surface contour. Lastly, when the extent of change required is greater than what can be naturally achieved with surface augmentation, osteotomy must be considered. This last indication is frequently found in the aesthetic surgical patient presenting with a facial skeletal imbalance that has been previously treated with orthodontics to correct a skeletally based malocclusion. Recent technical advances have markedly reduced the associated morbidity of facial osteotomies and, therefore, have made this treatment option more acceptable to aesthetic surgical patients. Ceramic orthodontic brackets and surgical hooks and lingual orthodontic appliances have made presurgical orthodontic preparation more aesthetic and socially acceptable for LeFort I osteotomy patients. The use of rigid fixation, obviating the need for any postoperative intermaxillary fixation, has also made this treatment approach more appealing to aesthetic patients. Lastly, the efficacy of nonresorbable bone substitutes--in particular, porous, block hydroxyapatite--has, to a significant extent, obviated the need for harvesting autogenous bone grafts, further reducing surgical morbidity.

Face↗
PubMed1994

A new material with theoretical osteoinductive properties: experimental evaluation.

An intensive research for bone substitutes has been in progress for several decades in order to find a new ideal material for bone replacement. In the present study the Authors report some data on a new developed material in comparison with synthetic hydroxyapatite. The new material was characterised by means of a crystallographic spectroscopic and chemical study. An in vitro test was also performed using murine fibroblasts. The results of this preliminary study showed that the sintered material has an and beta-tricalcium-phosphate (TCP) lattice depending on thermal treatment in accordance with literature data. Moreover, it showed a high level of biocompatibility. Though it is still in an investigation stage, perhaps this biomaterial is a highly reactive and unstable compound that could interact with CO2 and H2O.

Animals↗
PubMed2001

Factors stimulating bone formation.

The aim of this review is to describe major approaches for stimulating bone healing and to review other factors affecting bone healing. Spinal bone fusion after surgery is a demanding process requiring optimal conditions for clinical success. Bone formation and healing can be enhanced through various methods. Experimental studies have revealed an array of stimulative measures. These include biochemical stimulation by use of hormones and growth factors, physical stimulation through mechanical and electromagnetic measures, and bone grafting by use of bone tissue or bone substitutes. Newer biological techniques such as stem cell transplantation and gene therapy can also be used to stimulate bone healing. Apart from bone transplantation, clinical experience with the many stimulation modalities is limited. Possible areas for clinical use of these novel methods are discussed.

Aging↗
PubMed1997

In vivo study of calcium phosphate cements: implantation of an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement paste.

alpha-Tricalcium phosphate (alpha-TCP)/dicalcium phosphate dibasic (DCPD)/tetracalcium phosphate monoxide (TeCP) cement was implanted in paste form into soft tissue (rate subcutaneous sockets) and bone tissue (defects in rabbit mandibles) to evaluate the setting behaviour of the cement and tissue responses to the cement. A histological study of the soft tissue implants revealed thin fibrous capsule formation, the appearance of multinucleated giant cells on and close to the cement surface, and small clusters of the cement near the main part of the set cement which were formed by the migration of the paste while setting. X-ray diffraction (XRD) analysis of the implanted cement showed peaks for hydroxyapatite (HA) which increased as the implant period increased. Histology and microradiography of the bone tissue implants showed well-set cement without migration, active bone formation around the cement and direct bone union to it. However, the cement disappeared from the implant site in 4 of 16 specimens where intense bleeding seemed to wash away the implants while setting. From the results of the present study, we concluded that the cement is well tolerated, especially by bone tissue. This may be related to the fact that the cement sets producing HA. The cement is a promising material as a bone substitute; however, there is a problem of migration while setting in soft tissue and of exclusion from the bone defects by intense bleeding.

Animals↗
PubMed1982

Bone models for use in radiotherapy dosimetry.

The development of completely artificial, realistic body phantoms for use in radiotherapy dosimetry is hampered by the lack of suitable, definitive elemental data for many skeletal materials. Using published and measured data, the proportions of the tissue components for the important human bones considered in radiotherapy treatments have been derived. Both the tissue proportions and the resulting elementary compositions are listed in tabular form. Simple models of the heads of the humerus and femur are also given. The data are presented in a form such that average bone substitutes can be readily formulated.

Adult↗
PubMed1991

Bone and biologically compatible materials in dentistry.

This review focuses on compatible materials that are either implanted in bone tissue to serve as prosthetic devices or used as bone substitutes. It attempts to evaluate the significance of studies of combined osteoconductive materials with osteoinductive factors, like demineralized bone or its purified components, and osteogenic cells. It is important to note that the term osseointegration, which is still widely used by clinicians to indicate the bioactivity of implants in bone healing, is not substantiated by any controlled basic study. Even pure titanium and hydroxyapatite can interfere with the normal healing of a surgical bone wound. This review emphasizes the three-dimensional structure of bone, intercellular communication, and the response of this system to bone damage and materials.

Animals↗
PubMed2004

The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant.

Currently available synthetic bone substitutes perform poorly compared to autograft. It is hoped that by adding osteogenic growth factors to the materials, new bone formation could be increased and the clinical outcome improved. In this study, IGF-1, bFGF and TGFbeta1, alone and in combination, were absorbed onto a carrier of beta-tricalcium phosphate (betaTCP) and implanted into a defect around a hydroxyapatite-coated, stainless steel implant in the proximal tibia of rat in a model of revision arthroplasty. Animals were sacrificed at 6 and 26 weeks for routine histology and histomorphometry and mechanical push out tests. The results show that only bFGF had a significant effect on ceramic resorption. The groups that received bFGF and bFGF in combination with TGFbeta1 had smaller and fewer betaTCP particles remaining in the defect at 6 and 26 weeks. No growth factor combination significantly enhanced new bone formation or the mechanical strength of the implant. These results indicate that, of the growth factors tested, only bFGF had any beneficial effect on the host response to the implant, perhaps by delaying osteoblast differentiation and thereby prolonging osteoclast access to the ceramic.

Animals↗
PubMed2005

Non-viral-mediated gene therapy approaches for bone repair.

OBJECTIVES: Bone repair strategies continue to be developed for alternatives to autografting, allogeneic implants of banked bone, and other bone substitutes. Efforts have included the delivery of potent growth and/or differentiation factors and the use of gene therapy. For bone regeneration, gene therapy is the delivery, uptake and expression of DNA that has been localized to a wound bed. The objective of the current study is to investigate methods to enhance non-viral-mediated means of gene uptake and expression for use in bone regeneration. METHODS: Several types of DNA-polymer complexes, either applied directly to baby hamster kidney (BHK) cells, or released from a porous, resorbable gene-activated matrix (GAM), were evaluated in vitro for their ability to transfect cells with a circular plasmid DNA construct expressing green fluorescent protein. Complexes included conjugates containing a lipophilic reagent, liposomes, poly-ethyl-oxazoline, and poly-ethyleneimine (PEI). Data were subjected to analysis of variance and Fisher's protected least significant difference for multiple comparisons with significance established at p < 0.05. RESULTS: Transfection efficiencies of the liposome and PEI complexes improved in vitro when released from resorbable GAMs. The lipophilic reagent FuGene 6 demonstrated abundant uptake and expression in the initial 1- and 2-day evaluation periods. In contrast, the DNA-liposome and PEI GAM complexes demonstrated a sustained release, uptake and expression by the BHK cells at the 2-, 4-, and 7-day, and 4- and 7-day evaluation intervals, respectively. CONCLUSION: GAM technology appears to improve the functional stability and release duration of incorporated DNA-polymer complexes in the present in vitro studies. The ongoing objective of our research is to develop a localized treatment to improve the uptake and expression of plasmid DNA by non-viral-mediated gene therapy.

Animals↗
PubMedDate not supplied

The clinical use of autologous marrow to improve osteogenic potential of bone grafts in pediatric orthopedics.

The high osteogenic potential of living autologous marrow cells can be combined with foreign bone to enhance new bone formation. Xenogeneic bone was combined with autologous red marrow and used in 23 patients aged 5-17 years. Kiel bone was impregnated with marrow aspirated from the iliac crest and, apart from one case of lesion recurrence, gave excellent results in all patients under conditions covering a wide range of indications for bone grafting. Unlimited supplies of xenograft bone and other bone substitutes can be rendered osteogenic by a simple procedure. Combining fresh autologous red marrow with other types of bank bone allograft or xenograft, or even with biological or synthetic biocompatible material that favors the induction of new bone, may provide even better results.

Adolescent↗
PubMed1998

Demineralized bone bandeau in a patient with kleeblattschädel skull deformity.

Management of complex craniofacial deformities in the neonatal setting can pose daunting reconstructive challenges due to the limited supply of autogenous bone. We present a patient who was born with idiopathic nonsyndromal pansynostosis and the associated kleeblattschädel skull deformity. In this setting the patient's initial evaluation was suggestive of raised intracranial pressure and, as such, an emergent decompression was required. The native bone was unsuitable for reconstruction. Therefore, an allogenic demineralized perforated cortical iliac bone graft was used as the cornerstone of the reconstruction. Subsequent 2-year follow-up utilizing both clinical and microscopic evaluation revealed excellent osseous integration of the demineralized bone implant with near-total transformation into living bone. This clinical success has encouraged us to increase our utilization of this bone substitute in the neonatal setting.

Bone Regeneration↗
PubMed2006

In vivo banking for vascularized autograft bone by intramuscular inoculation of recombinant human bone morphogenetic protein-2 and beta-tricalcium phosphate.

BACKGROUND: The gold standard of bone graft substitutes is vascularized autologous bone. Our strategy to acquire this bone substitute is using recombinant human bone morphogenetic protein (rhBMP)-2 with beta-tricalcium phosphate (TCP) as carrier to induce bone tissue in muscle and grafting as a muscle-pedicled bone flap. In our previous studies, morphologically controlled living bone was successfully induced in a rat muscular pedicle. Moreover, concurrent administration of bisphosphonate controlled the subsequent resorption of the induced bone. This study was conducted (1) to confirm that when the size of carrier is increased, the induced bone can form the same in the center as well as on the periphery of the carrier, and (2) to simulate in vivo banking for vascularized autograft bone. METHODS: In experiment 1200 microg rhBMP-2 and 10(-5) M bisphosphonate (Minodronate) were applied to a 1-cm-diameter sphere of beta-TCP. This sphere was then inoculated into rabbit quadriceps and harvested 5 weeks later (n = 3). In experiment 2, beta-TCP was generated as a one-third hollow cylinder with 4-mm outer radius, 2-mm inner radius, and 10-mm length. After 50 microg rhBMP-2 and 10(-5) M Minodronate were applied, this structure was then inoculated into rat quadriceps. Four weeks later, the induced bone was transplanted as a muscle-pedicled flap onto the adjacent femur and harvested after 4 and 8 weeks more (n = 3). RESULTS: In experiment 1, good bone formation was observed at the central as well as the peripheral region of the sphere. In experiment 2, good bone formation and bony union to the femur at both 4 and 8 weeks were detected on the X-ray film. The presence of new bone formation around the screw was observed. CONCLUSIONS: Transplantation of the beta-TCP carrier treated with rhBMP-2 and bisphosphonate into the muscular tissue may have clinical potential for in vivo banking for muscle-pedicled bone flaps.

Animals↗
PubMed1994

[Restoration of sound transmission in the middle ear by reconstruction of the ossicular chain in its physiologic position. Results of incus reconstruction with ionomer cement].

We report the use of an ionomeric based bone substitute to reconstruct the ossicles in their normal position. To reconstruct small defects of the incudo-stapedial joint, this bone replacement material is applied to the long process of the incus and the head of the stapes. After setting and hardening a stable contact to the adjacent bone is formed. The audiological results after reconstruction of small incus defects with ionomeric cement are discussed in comparison to stapedectomy and tympanoplasty.

Adult↗
PubMed1990

Maxillary sinus: anatomy, physiology, surgery, and bone grafting related to implantology--eleven years of surgical experience (1979-1990).

The sinus is a pneumatic cavity of the facial skeleton within maxillary bone. It is very closely linked to the alveolar crest, the resorption of which, especially when tooth loss occurs, could cause a serious obstacle to oral implantology. It is therefore of great importance for this obstacle to be removed by adequate surgical procedures aimed at reducing the expanded volume of this cavity either partially or totally. Several grafting techniques involving autogenous bone (either alone, mixed with a bone-substituting biomaterial, or with insertion of only a biomaterial) are now available. The biomaterials include an increasing variety of treated bone from a bone bank. This paper will endeavor to outline the basic scientific and clinical knowledge required for this important surgery and will also stress the grave dangers that lie behind complications that may result from the inadequate practice of surgery by untrained operators.

Bone Transplantation↗
PubMed1998

The use of bone grafts and substitutes in the craniomaxillofacial region.

Craniomaxillofacial defects arise from congenital abnormalities or are acquired following trauma or ablative surgery. Various bone grafting techniques have been developed for application in the facial skeleton to assist in the reconstruction of small alveolar deficiencies to more complex, extensive bony defects. Autogenous grafts from different sites vary in volume, stability and contour characteristics. The introduction of allogeneic grafts has further increased the possibilities for hard tissue replacement as have alloplastic substitutes which have been used successfully. Recent advances in bone regeneration in the maxillofacial region using distraction osteogenesis and the recent advent of cell culture techniques have introduced new therapeutic approaches that will provide the foundation for a significant shift in the approach to reconstructive surgery of the facial skeleton.

Biomedical Engineering↗
PubMed2005

The critical size bony defect in a small animal for bone healing studies (II): implant evolution and surgical technique on a rat's femur.

In the preclinical field of orthopaedic and trauma surgery critical size bony defects (CDS) were used to evaluate the biocompatibility and allow to investigate the osteoinductivity and -conductivity of bone substitutes. Concerning the anatomical size the laboratory rat indicates a lower limit in small animals which are appropriate for experiments on bone. The aim of this study was to define a CSD, to develop a suitable fixation system to stabilize bony fragments in CSD and to point out the specialities of the surgical technique. These informations should help for to design and practice studies concerning bone healing on rat's femur. Based on previously acquired anatomical data of rat's femur, the technical challenges and anatomical specialities of different osteosynthesis techniques in rat's femur surgery are demonstrated. Our experiences with different fixation systems and techniques lead to the development of an external fixator, which guarantees for a stable bone fragment fixation, prevents severe soft tissue damage, allows of a roentgenologic evaluation of the defect zone and prevents from undesired direct biomaterial-implant interactions. Neither the proximal nor the distal femoral nailing technique is appropriate for a stable fixation in CSD of rat's femur. To evaluate the reliability of an own developed external fixator 42 nude rats with a 4.0 mm CSD were investigated clinically and roentgenologically over 10 weeks. The external fixator showed only a small implant failure rate. A solid fusion of the bone fragments was not observed within the 10 weeks follow-up period.

Animals↗
PubMed1992

Induction of bone in composites of osteogenin and porous hydroxyapatite in baboons.

A major goal of the combined effort of basic scientists and plastic and reconstructive surgeons is the development of novel bone substitutes based on osteogenic growth and differentiation factors with optimal delivery systems for skeletal repair. Osteogenin is a protein initiator of bone differentiation. The present study examined the osteogenic potential of osteogenin in combination with porous hydroxyapatite replicas obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. Bovine osteogenin, with an apparent molecular weight of 28 to 42 kDa, purified by hydroxyapatite-Ultrogel adsorption chromatography, heparin-Sepharose affinity chromatography, and HR Sephacryl S-200 molecular sieve chromatography, was delivered into rods of nonresorbable and resorbable hydroxyapatite replicas with an average porosity of 600 microns. A total of 48 rods were bioassayed for osteogenic activity by intramuscular implantation into eight adult baboons (Papio ursinus) as a prerequisite for clinical trials in humans. Bovine osteogenin fractions reconstituted with baboon insoluble collagenous bone matrix were implanted in an additional four adult baboons. Specimens were harvested at 30 and 90 days after implantation and subjected to histomorphometry and alkaline phosphatase activity determination. Differentiation of bone occurred in nonresorbable hydroxyapatite rods, both osteogenin-treated and controls. However, no bone formation was observed in resorbable rods, even in the presence of osteogenin. These results demonstrate that the surface and chemical characteristics of the substratum, independent of the osteogenic stimulus, have a profound influence on the morphogenesis of bone. The demonstration of bone induction in nonhuman primates with porous nonresorbable hydroxyapatite replicas and baboon insoluble collagenous bone matrix reconstituted with bovine osteogenin establishes the therapeutic potential of the principle of bone induction in craniofacial, periodontal, and orthopedic reconstructive surgery.

Analysis of Variance↗