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Expert Opinion on Drug Safety Nov 2006Demineralised bone matrix (DBM) acts as an osteoconductive, and possibly as an osteoinductive, material. It is widely used in orthopaedic, neurosurgical, plastic and... (Review)
Review
Demineralised bone matrix (DBM) acts as an osteoconductive, and possibly as an osteoinductive, material. It is widely used in orthopaedic, neurosurgical, plastic and dental areas. More than 500,000 bone grafting procedures with DBM are performed annually in the US. It does not offer structural support, but it is well suited for filling bone defects and cavities. The osteoinductive nature of DBM is presumably attributed to the presence of matrix-associated bone morphogenetic proteins (BMPs) and growth factors, which are made available to the host environment by the demineralisation process. Clinical results have not been uniformly favourable; however, a variable clinical response is attributed partly to nonuniform processing methods found among numerous bone banks and commercial suppliers. DBMs remain reasonably safe and effective products. The ultimate safe bone-graft substitute, one that is osteoconductive, osteoinductive, osteogenic and mechanically strong, remains elusive.
Topics: Animals; Bone Matrix; Bone Substitutes; Bone Transplantation; Humans; Wounds and Injuries
PubMed: 17044811
DOI: 10.1517/14740338.5.6.847 -
Macromolecular Bioscience Mar 2021Bone defects remains a challenge for surgeons. Bone graft scaffold can fill the defect and enhance the bone regeneration. Demineralized bone matrix (DBM) is an...
Bone defects remains a challenge for surgeons. Bone graft scaffold can fill the defect and enhance the bone regeneration. Demineralized bone matrix (DBM) is an allogeneic bone graft substitute, which can only be used as a filling material rather than a structural bone graft. Coating of the scaffolds with nanoscale DBM may enhance the osteoinductivity or osteoconductivity. Herein the lyophilization method is presented to coat the nano-DBM on surface of the porous polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffolds fabricated by 3D printing technology. The morphology, elastic modulus, in vitro cell biocompatibility, and in vivo performance are investigated. Scanning electron microscope (SEM) shows DBM particle clusters with size of 200-500 nm are observed on scaffolds fibers after coating. MC3T3-E1 cells on nano-DBM coated PCL/β-TCP scaffold show better activity than on PCL/β-TCP scaffold. In vivo tests show better infiltration of new bone tissue in nano-DBM coated PCL/β-TCP scaffold than PCL/β-TCP scaffold via the interface. These results show the presence of nano-DBM coating on PCL/β-TCP scaffold could enhance the attachment, proliferation, and viability of cells and benefit for the new bone formation surrounding and deep inside the scaffolds. Nano-DBM could potentially be used as a new kind of biomaterial for bone defect treatment.
Topics: Animals; Bone Matrix; Bone Regeneration; Calcium Phosphates; Cell Line; Mice; Nanoparticles; Organ Size; Polyesters; Prosthesis Implantation; Tissue Scaffolds; X-Ray Microtomography
PubMed: 33346401
DOI: 10.1002/mabi.202000336 -
The Journal of Cell Biology Jun 1976Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone...
Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation.
Topics: Alkaline Phosphatase; Animals; Bone Marrow; Bone Matrix; Calcium; Cartilage; Cell Differentiation; Collagen; Erythropoiesis; Hematopoiesis; Male; Neutrophils; Osteoblasts; Osteogenesis; Rats; Transplantation, Homologous
PubMed: 1270511
DOI: 10.1083/jcb.69.3.557 -
Matrix Biology : Journal of the... Jun 2012There is considerable interest in understanding prostate cancer metastasis to bone and the interaction of these cells with the bone microenvironment....
There is considerable interest in understanding prostate cancer metastasis to bone and the interaction of these cells with the bone microenvironment. Osteonectin/SPARC/BM-40 is a collagen binding matricellular protein that is enriched in bone. Its expression is increased in prostate cancer metastases, and it stimulates the migration of prostate carcinoma cells. However, the presence of osteonectin in cancer cells and the stroma may limit prostate tumor development and progression. To determine how bone matrix osteonectin affects the behavior of prostate cancer cells, we modeled prostate cancer cell-bone interactions using the human prostate cancer cell line PC-3, and mineralized matrices synthesized by wild type and osteonectin-null osteoblasts in vitro. We developed this in vitro system because the structural complexity of collagen matrices in vivo is not mimicked by reconstituted collagen scaffolds or by more complex substrates, like basement membrane extracts. Second harmonic generation imaging demonstrated that the wild type matrices had thick collagen fibers organized into longitudinal bundles, whereas osteonectin-null matrices had thinner fibers in random networks. Importantly, a mouse model of prostate cancer metastases to bone showed a collagen fiber phenotype similar to the wild type matrix synthesized in vitro. When PC-3 cells were grown on the wild type matrices, they displayed decreased cell proliferation, increased cell spreading, and decreased resistance to radiation-induced cell death, compared to cells grown on osteonectin-null matrix. Our data support the idea that osteonectin can suppress prostate cancer pathogenesis, expanding this concept to the microenvironment of skeletal metastases.
Topics: Animals; Blotting, Western; Bone Matrix; Cell Communication; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Shape; Cell Survival; Gamma Rays; Male; Mice; Osteoblasts; Osteonectin; Prostatic Neoplasms; Recombinant Proteins; Tumor Microenvironment
PubMed: 22525512
DOI: 10.1016/j.matbio.2012.03.002 -
Journal of Bone and Mineral Metabolism Jan 2016Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase...
Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.
Topics: Animals; Bone Matrix; Calcification, Physiologic; Durapatite; Male; Microscopy, Electron, Scanning; Rats; Skull; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 25773047
DOI: 10.1007/s00774-014-0647-x -
Current Osteoporosis Reports Jun 2004Fractal analysis is a quantitative method used to evaluate complex anatomic findings in their elementary component. Its application to biologic images, particularly to... (Comparative Study)
Comparative Study Review
Fractal analysis is a quantitative method used to evaluate complex anatomic findings in their elementary component. Its application to biologic images, particularly to cancellous bones, has been well practiced within the past few years. The aims of these applications are to assess changes in bone and the loss of spongious architecture, indicate bone fragility, and to show the increased risk for fracture in primary or secondary osteoporosis. The applications are very promising to help complete the studies that can define bone density (bone mineral density by dual energy x-ray absorptiometry or quantitative computed tomography), and also have the capacity to distinguish the patients with a high or low risk for fracture. Their extension to the clinical fields, to define a test for fracture risk, is still limited by difficult application to the medical quantitative imaging of bones, between correct application at superficial bones and unreliable application to deep bones. The future evolution and validity do not depend upon fractal methods but upon well-detailed imaging of the bones in clinical conditions.
Topics: Absorptiometry, Photon; Bone Density; Bone Matrix; Female; Fractals; Humans; Male; Microradiography; Osteoporosis; Sensitivity and Specificity; Severity of Illness Index
PubMed: 16036083
DOI: 10.1007/s11914-004-0004-4 -
Journal of Tissue Engineering and... Mar 2016Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic...
Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone matrix (DBM), alone or in combination with allograft or commercially available human cancellous bone (CB), may replace allografts, as they have the capability of inducing new bone and improving implant fixation through enhancing bone ongrowth. The purpose of this study was to investigate the effect of DBM alone, DBM with CB, or allograft on the fixation of porous-coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10 mm diameter, were inserted bilaterally into the femoral condyles of eight skeletally mature sheep. Thus, four implants with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: (a) DBM; (b) DBM:CB at a ratio of 1:3; (c) DBM:allograft at a ratio of 1:3; or (d) allograft (gold standard), respectively. A standardized surgical procedure was used. At sacrifice 6 weeks after implantation, both distal femurs were harvested. The implant fixation was evaluated by mechanical push-out testing to test shear mechanical properties between implant and the host bone and by histomorphometry. Non-parametric tests were applied; p < 0.05 was considered significant. Mechanical fixation showed that the strengths among the DBM/CB, DBM/allograft and allograft groups were not statistically different. The strength of the DBM group was 0.01 MPa, which was statistical significantly lower than the other three groups (p < 0.05). Histomorphometry results showed that the bone ongrowth in the DBM group was statistically significantly lower than the other three groups, while the volume fraction of new bone showed no significant difference among all the groups. Our data revealed that adding DBM to CB or to allograft resulted in comparable mechanical properties relative to the gold standard, allograft. We found inferior early effects of DBM alone on the fixation of porous-coated titanium implant in this animal model, while the long-term effects have to be investigated. The combination of DBM with CB, which can be used off the shelf, may represent an alternative to allograft. A cost-benefit analysis is necessary before application in clinical trial.
Topics: Animals; Bone Demineralization Technique; Bone Matrix; Cancellous Bone; Coated Materials, Biocompatible; Female; Humans; Materials Testing; Osteogenesis; Porosity; Prostheses and Implants; Sheep; Titanium
PubMed: 23349100
DOI: 10.1002/term.1685 -
Organogenesis Oct 2021Cells with osteogenic potential are believed to be an ideal source for bone tissue bioengineering. Large bone defects require temporary substitution of the damaged...
Cells with osteogenic potential are believed to be an ideal source for bone tissue bioengineering. Large bone defects require temporary substitution of the damaged parts. In this respect, the transplantation of bone cells cultured on osteogenic substrates has been investigated. To use the natural bone matrix, one approach is the so-called demineralized bone matrix (DBM). In this study, we evaluated the interaction of human fetal osteoblasts (hFOB 1.19 cells, a human fetal osteoblastic cell line) with DBM fragments. No additional bone differentiation inducer was used other than the DBM itself. The samples were processed, had adhesion pattern evaluated and analyzed by light microscopy (cytochemical and immunocytochemical analysis) and electron microscopy (scanning and transmission). The adhesion pattern of hFOB cells on DBM was similar to what was observed on the cell culture plate. Morphological analysis showed that the hFOB cells had emitted filopodia and cellular projections on both controls and DBM. On DBM, the adhered cells emitted prolongations and migrated into the matrix. The monolayer growth pattern was observed as well as the accumulation of filamentous and reticulate extracellular materials when hFOB cells were cultured on the DBM surface. EDS analysis revealed the deposition of calcium on DBM. Immunocytochemical data showed that the hFOB cells were able to secrete extracellular matrix molecules such as fibronectin and laminin on DBM. Our data indicate that DBM successfully stimulates the osteoblastic phenotype of osteoblast-like cells and corroborate with the fact that DBM is a considerable natural matrix that promotes fractured-bone healing.
Topics: Bone Matrix; Bone and Bones; Cell Differentiation; Humans; Osteoblasts; Osteogenesis
PubMed: 34845978
DOI: 10.1080/15476278.2021.2003134 -
Journal of the Mechanical Behavior of... Oct 2013In order to achieve successful clinical outcomes, biomaterials used for bone grafts must possess a number of traits including biocompatibility and osteoconductivity....
In order to achieve successful clinical outcomes, biomaterials used for bone grafts must possess a number of traits including biocompatibility and osteoconductivity. These materials must also demonstrate appropriate mechanical stability to withstand handling as well as support potentially significant stresses at the implant site. Synthetic and natural polymer scaffolds used for bone tissue engineering (BTE) often lack necessary mechanical properties. Our goal was to internally mineralize natural collagenous matrix, thereby increasing mechanical properties of the material to useful levels. Published methods for intrafibrillar collagen mineralization were applied to clinically relevant-sized constructs but did not successfully deposit mineral in the interior of the constructs. To address this limitation, we developed a new technique for the remineralization of demineralized bone matrix (DBM) based on alternating solution immersion, or ASI. Mineral was removed from equine bone specimens, leaving behind a demineralized bone matrix (DBM). This matrix provides a framework for the nucleation and growth of a replacement mineral phase. Plain film radiography and microcomputed tomography (microCT) indicated accumulation of mineral within the DBM, and mechanical testing (3 point bending and compression) revealed a significant increase in stiffness between the DBM and the remineralized bone matrix (RBM). We believe this remineralization process will be useful in the preparation of stiff and strong allografts for clinical application.
Topics: Animals; Bone Matrix; Bone Regeneration; Bone Transplantation; Calcification, Physiologic; Collagen; Compressive Strength; Fetuins; Horses; Immersion; Solutions; Tensile Strength; X-Ray Microtomography
PubMed: 23759125
DOI: 10.1016/j.jmbbm.2013.05.007 -
Biomaterials Nov 2012Decellularized bone has been widely used as a scaffold for bone formation, due to its similarity to the native bone matrix and excellent osteoinductive and biomechanical...
Decellularized bone has been widely used as a scaffold for bone formation, due to its similarity to the native bone matrix and excellent osteoinductive and biomechanical properties. We have previously shown that human mesenchymal and embryonic stem cells form functional bone matrix on such scaffolds, without the use of growth factors. In this study, we focused on differences in bone matrix that exist even among identical harvesting sites, and the effects of the matrix architecture and mineral content on bone formation by human embryonic stem cells (hESC). Mesenchymal progenitors derived from hESCs were cultured for 5 weeks in decellularized bone scaffolds with three different densities: low (0.281 ± 0.018 mg/mm(3)), medium (0.434 ± 0.015 mg/mm(3)) and high (0.618 ± 0.027 mg/mm(3)). The medium-density group yielded highest densities of cells and newly assembled bone matrix, presumably due to the best balance between the transport of nutrients and metabolites to and from the cells, space for cell infiltration, surface for cell attachment and the mechanical strength of the scaffolds, all of which depend on the scaffold density. Bone mineral was beneficial for the higher expression of bone markers in cultured cells and more robust accumulation of the new bone matrix.
Topics: Bone Matrix; Calcification, Physiologic; Cell Line; Embryonic Stem Cells; Humans; Immunohistochemistry; Tissue Engineering; Tissue Scaffolds; X-Ray Microtomography
PubMed: 22901965
DOI: 10.1016/j.biomaterials.2012.08.013