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PubMed2004

Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs.

BACKGROUND: The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. METHODS: Third and fourth mandibular premolars were extracted from three beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, titanium implants were immediately placed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and biphasic calcium phosphate ceramic granules. The right defects were left unfilled as controls. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. RESULTS: No post-surgical complications were observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (P<0.05) increase in terms of the number of threads in contact with bone, bone-to-implant contact, and peri-implant bone density of approximately 8.6%, 11.0%, and 14.7%, respectively. In addition, no significant difference was observed when number of threads, bone-to-implant contact, and bone density in the filled defects were compared to the no-defect sites. CONCLUSION: It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increases bone regeneration around immediately placed implants.

Alveolar Process↗
PubMed2000

Gene therapy approaches for modulating bone regeneration.

Following injury, bone has the ability to regenerate itself to a form and function nearly indistinguishable from the pre-injury state. However, if the injury is beyond a critical limit, recovery will not occur without therapeutic interventions. Autografts and implants with banked bone continue as the treatments of choice, although each exhibits limitations and liabilities. Alternatives have included the utilization of bone-graft substitutes that may incorporate bone derivatives and soluble signaling molecules such as mitogens and morphogens. In addition, an evolving treatment modality, gene therapy, offers an exciting avenue for bone regeneration. This review presents some of the current concepts for developing a rational gene therapy approach in bone regeneration.

Animals↗
PubMed2005

[Histological study of bone regeneration using vascular endothelial growth factor on rat mandibular bone defect].

PURPOSE: Local application of vascular endothelial growth factor (VEGF) was examined to determine whether it is effective in promoting bone regeneration. METHODS: We operated on live 6-week male SD rat mandibular bone tissue to prepare bone defects in order to attempt the guided bone regeneration (GBR) method. Laboratory animals were divided into 3 groups: the control group, the fibrin group, and the VEGF group. Both radiological observation using soft x-ray and histological observation were performed respectively on the 10th, 20th and 30th days after the operations. RESULTS: After 10 days, there was no apparent radio-photographic changes in the bone defects. However, after 20 days there were quite apparent changes, and after 30 days there were even more remarkable changes. The fibrin and VEGF groups changed more than the control group. In our histological observation, we observed rich capillary formation most notably in the VEGF group. This VEGF group also exhibited regeneration in the bone tissue. CONCLUSIONS: Histological and soft x-ray radiological observations indicated that VEGF was effective for blood vessel formation, and VEGF offers potential for bone regeneration.

Animals↗
PubMed2005

Biological approaches to bone regeneration by gene therapy.

Safe, effective approaches for bone regeneration are needed to reverse bone loss caused by trauma, disease, and tumor resection. Unfortunately, the science of bone regeneration is still in its infancy, with all current or emerging therapies having serious limitations. Unlike current regenerative therapies that use single regenerative factors, the natural processes of bone formation and repair require the coordinated expression of many molecules, including growth factors, bone morphogenetic proteins, and specific transcription factors. As will be developed in this article, future advances in bone regeneration will likely incorporate therapies that mimic critical aspects of these natural biological processes, using the tools of gene therapy and tissue engineering. This review will summarize current knowledge related to normal bone development and fracture repair, and will describe how gene therapy, in combination with tissue engineering, may mimic critical aspects of these natural processes. Current gene therapy approaches for bone regeneration will then be summarized, including recent work where combinatorial gene therapy was used to express groups of molecules that synergistically interacted to stimulate bone regeneration. Last, proposed future directions for this field will be discussed, where regulated gene expression systems will be combined with cells seeded in precise three-dimensional configurations on synthetic scaffolds to control both temporal and spatial distribution of regenerative factors. It is the premise of this article that such approaches will eventually allow us to achieve the ultimate goal of bone tissue engineering: to reconstruct entire bones with associated joints, ligaments, or sutures. Abbreviations used: BMP, bone morphogenetic protein; FGF, fibroblast growth factor; AER, apical ectodermal ridge; ZPA, zone of polarizing activity; PZ, progress zone; SHH, sonic hedgehog; OSX, osterix transcription factor; FGFR, fibroblast growth factor receptor; PMN, polymorphonuclear neutrophil; PDGF, platelet-derived growth factor; IGF, insulin-like growth factor; TGF-beta, tumor-derived growth factor beta; CAR, coxsackievirus and adenovirus receptor; MLV, murine leukemia virus; HIV, human immunodeficiency virus; AAV, adeno-associated virus; CAT, computer-aided tomography; CMV, cytomegalovirus; GAM, gene-activated matrix; MSC, marrow stromal cell; MDSC, muscle-derived stem cell; VEGF, vascular endothelial growth factor.

Biomimetics↗
PubMed1997

Macrophysiologic roles of a delivery system for vulnerary factors needed for bone regeneration.

Traditional histology identifies three components of bone: cells, an extracellular mineralized organic matrix, and a lymphatic-vascular component. Specialized bone cells known as osteoblasts promote bone regeneration. Clinically, this property has been exploited by surgeons with autografts and bank bone preparations to restore deficient form and function to almost every aspect of the skeleton. Unfortunately, these therapies can be inadequate for patients with panskeletal trauma. Therefore, a suitable alternative may be a laboratory-derived product consisting of a vulnerary factor and delivery system. The integration of a laboratory-engineered product in an osseous wound environment is a formidable challenge demanding a keen appreciation of the product's macrophysiologic roles in wound healing biology. Consequently, the purposes for this paper are 1) to define briefly macrophysiology relevant to a delivery system for vulnerary molecules and bone regeneration; 2) to review a key family of bone regenerating molecules, the bone morphogenetic proteins (BMPs); and 3) to relate delivery system engineering with bone regeneration.

Animals↗
PubMed2002

[Bone regeneration in oral surgery].

Bone regeneration is the technique of choice in order to repair small and medium sized bone defects in maxillary. It is used as an auxiliary medical treatment for dental implants. In this work, we show the different state of the art techniques used in bone lesions repair, and we also show experimental results obtained in our research group using bone morphogenetic protein BMP-2. This protein has been expressed in an E. Coli strain previously modified with the protein nucleotide sequence. We also show a carrier developed in our laboratory that is able to bind the rhBMP-2 and to liberate it in its active form. The mechanical properties of the carrier can be chemically modified. We have tested Ti implants covered with films of this material activated with rhBMP-2. The experimental in vivo results obtained with this kind of implants has been impressive.

Activin Receptors, Type I↗
PubMed2000

Histometric evaluation of bone regeneration around immediate implants partially in contact with bone: a pilot study in dogs.

Bone regeneration was evaluated around immediate implants partially in contact with bone, with or without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-1). Mandibular premolars were removed, and the implant osteotomies were prepared; a uniform circumferential gap was prepared 1.25 mm beyond the width of the implant bed in the coronal half. Twelve implants (8.5 x 3.75 mm) were inserted in six dogs. Before insertion, an implant received a single application of 5 micrograms/mL of PDGF and IGF-1 delivered in 0.10 mL of 4% methylcellulose gel or 0.10 mL of 4% methylcellulose gel only as a control. To label regenerated bone, a 2% calcein green solution was administered by intramuscular injection at 0, 7, 15, 30, and 45 days after implant insertion Three and 8 weeks after implant insertion undecalcified sections were obtained, and the degree of bone to implant contact, the bone area, and the intensity of bone labeling were measured into the limits of the eight most coronal threads of the implant (four threads on each side of each implant). The results showed a greater extension of bone-to-implant contact, a larger percentage of bone area, and greater intensity of bone labeling for test versus control implants (P < .01). Within the limits of the present study, it was concluded that the combination of PDGF/IGF-1 might be an alternative for enhancing bone healing around implants partially in contact with bone.

Animals↗
PubMed2004

Histologic analysis of alveolar bone following guided bone regeneration.

BACKGROUND: Questions on new bone quality following guided bone regeneration (GBR) with various graft materials and its importance in osseointegration have been raised. This study reports histologic analysis of bone sections from future implant sites at upper and lower jaws that were augmented with bovine porous bone mineral graft material plus a porcine collagen membrane. METHODS: Due to severe atrophy of the alveolar crest, GBR prior to implant placement was indicated in 11 patients (mean age 45.5 years). Following an average of 7 months of healing, implant placement surgery was performed. Bone sections from implant beds were fixed in formalin, decalcified in sodium citrate and formic acid, and placed in paraffin. Sections 5 to 7 microm thick were prepared, stained with hematoxylin and eosin, and analyzed under light microscopy. Results for 27 implant sites are presented. RESULTS: Compared to the lower jaw, segments from the upper jaw had a lower percentage of bone and higher percentage of residual material and vascularization. CONCLUSIONS: Within the limits of this study, we concluded that osteogenesis is completed and the rate of vascularization and osteoclastic activity was reduced by 7 months. Also, the upper jaw significantly differed from the lower jaw in bone formation, vascularization, and the amount of residual material. Thus, the anatomical location of the defect may be as important as the properties of the graft material used in obtaining successful osteogenesis using guided bone regeneration techniques.

Adult↗
PubMed2005

[Tissue engineered bone regeneration of periosteal cells using recombinant human bone morphogenetic protein 2 induce].

OBJECTIVE: To investigate bone regeneration of the cell-biomaterial complex using strategies of tissue engineering based on cells. METHODS: Hydroxyapatite/collagen (HAC) sandwich composite was produced to mimic the natural extracellular matrix of bone, with type I collagen serving as a template for apatite formation. A three-dimensional poly-porous scaffold was developed by mixing HAC with poly(L-lactic acid) (PLA) using a thermally induced phase separation technique (TIPS). The rabbit periosteal cells were treated with 500 ng/ml of recombinant human bone morphogenetic protein 2 (rhBMP-2), followed by seeded into pre-wet HAC-PLA scaffolds. Eighteen 3-month nude mice were implanted subcutaneously cell suspension (group A, n = 6), simple HAC-PLA scaffold (group B, n = 6) and cell-biomaterial complex (group C, n = 6) respectively. RESULTS: Using type I collagen to template mineralization of calcium and phosphate in solution, we get HAC sandwich composite, mimicking the natural bone both in composition and microstructure. The three dimensional HAC-PLA scaffold synthesized by TIPS had high porosity up to 90%, with pore size ranging from 50 microm to 300 microm. SEM examination proved that the scaffold supported the adhesion and proliferation of the periosteal cells. Histology results showed new bone formation 8 weeks after implantation in group C. The surface of group A was smooth without neoplasma. Fibrous tissue invasion occurred in group B and no bone and cartilage formations were observed. CONCLUSION: The constructed tissue engineering bone has emerged as another promising alternative for bone repair.

Animals↗
PubMedDate not supplied

[Mucopolysaccharides, collagen and calcium of bone regenerate in replacing a bone defect by a method of unilocular compression-distraction osteosynthesis].

Intensive synthesis of collagen, which constitutes the basis of organic matrix in bone tissue, was observed in the regenerate developed during compression-distractional osteoxynthesis. The organic matrix of the regenerate was quickly mineralized; after termination of the distraction it contained more than a half of calcium as compared with the mature bone of healthy animals. Relatively low accumulation of mucopolysaccharides in the regenerate appears to depend on development of favourable conditions of its blood supply together with suitable fixation of bone fragments.

Animals↗
PubMed2002

Gastrectomy has no effect on bone regeneration in rats despite a decrease in bone mass.

BACKGROUND: Gastrectomy, specifically the removal of the acid-producing part of the stomach (fundectomy), is known to cause osteopenia. This effect has been ascribed to the elimination of a hypothetical osteotropic peptide hormone, presumably produced in the oxyntic mucosa. Since osteopenia is due to a disturbed balance between bone formation and resorption, we assessed the effect of gastrectomy on osteogenesis, more specifically mandibular orthotopic bone regeneration. METHODS: Adult rats were either gastrectomized or sham-operated. Two weeks later, unilateral 5-mm transosseous defects were made in the mandibles and covered with microporous barrier membranes (GORE-TEX Membrane). After 6 weeks of healing. bone-bridging of the defects was analyzed by computerized light microscopic image analysis. Furthermore, bone mass was analyzed in the contralateral untreated mandibular side, in calvarial bone, and in femora by morphometry and dry/ash weights. RESULTS: While gastrectomy resulted in a clearly decreased bone mass, manifested as increased marrow spaces in all bones and as decreased dry and ash weights in femora, no difference in mandibular bone healing rate was found between the groups. CONCLUSIONS: Since secluding of the defect space by membrane barriers implies that osteogenic cells have to be recruited primarily from intra-osseous stem cells by their proliferation and differentiation into actively bone-forming osteoblasts, the results indicate that gastrectomy has no effect on these processes. The findings thus imply that the disturbed balance in bone remodeling caused by gastrectomy, resulting in osteopenia, may be due to stimulated bone resorption rather than to reduced bone formation.

Animals↗
PubMed2000

Guided bone regeneration around endosseous implants with anorganic bovine bone mineral. A randomized controlled trial comparing bioabsorbable versus non-resorbable barriers.

BACKGROUND: Guided bone regeneration (GBR) is a viable treatment for osseous defects surrounding dental implants. Controversy exists regarding the choice of barrier membrane used and the method of membrane fixation to achieve GBR. METHODS: This study compared the efficacy of a porcine-derived bioabsorbable collagen membrane and an expanded polytetrafluoroethylene (ePTFE) membrane (non-resorbable) for GBR using a bovine bone xenograft/autograft bone composite in defects surrounding dental implants. The study also examined the effect of primary barrier fixation on GBR. Defect size was recorded at Stage 1 and 2 surgeries (performed 6 months apart). Forty-eight subjects (41% males, 59% females) requiring GBR were treated with either collagen (23) or ePTFE (25) barriers, respectively. Implants were titanium self-tapping screw-type. In 34 GBR sites, barrier fixation was achieved with polylactic acid resorbable pins. The remaining barriers were secured with the implant cover screw and/or embedded beneath the flaps. RESULTS: At 6 months, a decrease in defect width (collagen barrier 1.95 +/- 0.60 mm, ePTFE barrier 2.65 +/- 0.56 mm), length (collagen barrier 2.65 +/- 0.61 mm, ePTFE barrier 2.26 +/- 0.66 mm), and circumference (degrees) (collagen barrier 57.7 +/- 18.7, ePTFE barrier 80.2 +/- 19.9) was observed for both membranes. A significant number (chi2, P = 0.041) of postoperative complications occurred when barrier fixation was lacking at initial surgery. Furthermore, a significant difference (P <0.05) in the success of GBR with respect to defect size was observed when barrier fixation was taken into account. CONCLUSIONS: In conclusion, both collagen and ePTFE barriers proved suitable for achieving GBR of osseous defects surrounding dental implants. The results of this study stress the importance of barrier fixation at the time of initial surgery.

Absorbable Implants↗
PubMed1993

Controlled release of TGF-beta 1 from a biodegradable matrix for bone regeneration.

Although bone has a remarkable capacity for regenerative growth, there are many clinical situations in which the bony repair process is impaired. TGF-beta 1 is a 25 kD homodimeric protein which modulates the growth and differentiation of many cell types. The ability of TGF-beta 1 to promote bone formation suggests that it may have potential as a therapeutic agent in disease of bone loss. However, there still exists a need for an effective method of delivering TGF-beta 1 to the site of an osseous defect for the promotion of bone healing. This paper describes a novel biodegradable controlled release system for TGF-beta 1 comprised of poly (DL-lactic-co-glycolic acid) (PLPG) and demineralized bone matrix (DBM). The amount and activity of TGF-beta 1 released was determined using several methods including 125I-labeled TGF-beta 1 as a tracer, an enzyme linked immunosorbent assay (ELISA) and a growth inhibitory assay (GIA). Protein was released from the devices for time periods of more than 600 h. The amount of TGF-beta 1 released was directly proportional to both the TGF-beta 1 loading and the weight percent of DBM in the device. The release kinetics could be further controlled by applying polymeric coatings of varying porosity to the devices. The GIA indicated that between 80 and 90% of the TGF-beta 1 released from the delivery system retained its bioactivity. The PLPG and DBM existed in phase separated domains within the device as determined by differential scanning calorimetry. Scanning electron microscopy suggested that the devices were sufficiently porous to allow bone ingrowth.

Animals↗
PubMed2000

Clinical and histological findings in guided bone regeneration (GBR) around titanium dental implants with autogeneous bone chips using a new resorbable membrane.

The aim of this study was to test the value of a polydioxanon-membrane (PDS(R), Ethicon, Norderstedt, Germany) in combination with autogenous bone as a spacer for guided bone regeneration of denuded implant surfaces in comparison to simple augmentation. Altogether, in 8 Beagle dogs of 12 months, the three mandibular premolars were extracted on both sides and, after an uneventful healing of the extraction sockets in each mandibular site, two seize defined bone defects were produced. The defects were 7 mm long, had a vertical extension of 7 mm, and were 7 mm deep. These also included, therefore, the resection of the lingual cortical bone wall. In the center of all these 32 bone defects, Brânemark fixtures with a diameter of 3 mm and a length of 10 mm were implanted. Every implant was primarily stable due to the fixation in the native bone under the created defects. In each mandible site, one bone defect was filled with autologous bone resulting from the previous defect preparation. Half of the defects were covered with a PDS membrane, and the other half were covered only by the relocation of the mucoperiosteal flap. During the observation period of 90-180 days, continuous clinical and radiological controls were executed. Aside from the observed clinical healing problems in the test sites, such as exposure of the membranes and serious inflammatory reactions, the histological and radiological results of the control group regarding bone regeneration were superior to these of the test group, which were valid also for the subgroups with or without autologous bone fillings.

Animals↗
PubMed2002

Effect of pore size of D, L-polylactic acid as bone repair material on bone regeneration.

OBJECTIVE: To study the bone regeneration behavior in porous D,L-polylactic acid (D,L-PLA) with different pore sizes. METHOD: A particulate-leaching method was employed to prepare porous biodegradable D,L-PLA with different pore sizes (75, 250, 400, 750 micrometer) and with porosity of 75% as the materials to repair bone defects in rabbits. The materials were then implanted at random into 40 rabbits with bilateral radius bone defect, leaving another 10 rabbits without implantation as blank control. Gross observation and X-ray and histomorphological examination as well as assessment of the biomechanics of the implants were performed in 2, 4, 8 and 12 weeks respectively after the operation. RESULTS: New bone tissue occurred around the implanted materials with pore sizes of 250, 400 or 750 micrometer 12 weeks after the operation. In the control group and in the rabbits with implants with pore size of 75 micrometer, the bone defect was filled with connective tissues. The implants with 250-micrometer pores had the strongest biomechanical strengths of all the materials (P<0.01) at 8 weeks and 12 weeks after the operation. CONCLUSION: The pore size of the porous implants decides the behavior of bone regeneration, and D, L-PLA polymer with 250-micrometer pores produces the most desired effects.

Animals↗
PubMed2001

Expression of vascular antigens by bone cells during bone regeneration in a membranous bone distraction system.

An in vivo system of membranous bone formation during distraction has been investigated in order to follow cells that express vascular markers with the objective of understanding the neovascularization process. Concomitantly, sustained proliferation of preskeletal cells was achieved through the application of mechanical force. New capillaries and leading edges that arose by angiogenesis from the periosteal and mucosal surfaces and invaded the central zone of the regenerating distraction tissue temporally preceded the growth of delicate woven bone trabeculae from both edges of the cut bone. Concentrically arranged 'onion-like' configurations were abundant in paracentral zones and in association with mesenchymal condensations, suggesting their de novo formation in situ. Vascular specific markers, the angiopoietin receptor Tie-2 and factor VIII-related antigen (FVIIIrAg), were localized immunohistochemically in order to follow cells of vascular origin. Endothelial cells of the new capillaries, centrally located cells of the concentric configurations, pericytes, and most of the adjacent polygonal mesenchymal cells stained positively with specific antibodies to both antigens. Moreover, preosteoblasts and osteoblasts that lie adjacent to or already embedded in the osteiod of the newly formed trabeculae were also FVIIIrAg and Tie-2 immunopositive. As the source of the bone-forming cells in regenerating tissue during distraction is not yet fully understood, this observation might support the possibility of their vascular origin.

Animals↗
PubMed1984

The influence of bis-dequalinium acetate on bone regeneration induced by grafts of combined inorganic heterologous bone and autologous marrow.

The present study was undertaken in order to determine the influence of BDA on bone regeneration and remodeling. Pieces of Kiel bone soaked with autologous bone marrow were implanted in the axial area of rats. The implantation sites were injected with 0.3 cc of 0.005% BDA 3 to 14 days after grafting; the control group was injected with Hartmann solution. Results indicated that BDA does not interfere with the bone-remodeling process. It does, however, have an inhibitory effect on the early stage of mesenchymal cell proliferation, that is, the development of osteoblasts from bone marrow stromal cells. Extrapolation of these findings to earlier evidence regarding the mode of action of this material is currently being investigated.

Animals↗
PubMed1998

[Guided bone regeneration for dental implantology].

Guided bone regeneration nowadays offers good possibilities to repair local bone defects. Membranes are used to cover the defects. There are many types available. The anatomy of the defect determines mainly which membrane type should be used or which surgical steps should be followed. Most difficult are the one-wall defects, less difficult are four-wall defects. Guided bone regeneration is predictable, but the procedure is technical sensitive and complications and contaminations will easy occur. All steps need to be done carefully, including patient selection and postoperative follow-up care. Implant insertion into the defect can be done simultaneously but will give a higher risk for complications. For this reason, care should be taken for regeneration procedures in aesthetic demanding areas.

Alveolar Process↗