Enhanced Osteoinductivity of Demineralized Bone Matrix with Noggin Suppression in Polymer Matrix.
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ABSTRACT:
SUBMITTER: Chen C
PROVIDER: S-EPMC7877805 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDemineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken bisphosphonates to prevent osteoclast-mediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors.MethodsSex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken bisphosphonates and one who had not taken bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry.ResultsNine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without bisphosphonates and 1.9 ± 0.7 for those with bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity.ConclusionsDemineralized bone matrix samples from donors treated with bisphosphonates and donors not treated with bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling.
| S-EPMC3234347 | biostudies-literature
Project description:Demineralized dentin matrix (DDM) treated with gamma irradiation (GR) has shown promising results as an allograft without any adverse effects in in vivo and clinical studies. The purpose of this study was to evaluate the effects of 15 and 25 kGy GR on the osteoinductive properties of DDM at extra-skeletal sites. As a control group, non-irradiated DDM powder was implanted into the right subcutaneous tissues of the dorsal thigh muscles of 20 nude mice. DDM powder irradiated with 15 and 25 kGy was implanted into the left side. After two and four weeks, the bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. After confirming osteoblast- and osteoclast-specific activities by alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining, a histological analysis was performed to measure the new bone formation and the number of osteoblasts and osteoclast-like cells on the surface of the DDMs. Histomorphometry was used to calculate the new bone formation area on the surface of the DDM particles (DDMs). The BMD in all the groups increased from two and four weeks without statistically significant differences. The osteoblasts were dominantly activated on DDM without GR, and DDM treated with 25 kGy compared to DDM treated with 15 kGy. Among the groups, new bone formation was identified in all the groups at each time point. In conclusion, GR at doses of 15 and 25 kGy does not affect the osteoinductive properties of DDM powder.
| S-EPMC8883982 | biostudies-literature
Project description:Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.
| S-EPMC7103314 | biostudies-literature
Project description:The aim of this article is to describe the results of the use of demineralized bone matrix putty in alveolar cleft of patients with cleft lip and palate. We performed a prospective, descriptive case series study, in which we evaluated the results of the management of alveolar clefts with demineralized bone matrix. Surgery was performed in 10 patients aged between 7 and 26 years (mean 13 years), involving a total of 13 clefts in the 10 patients. A preoperative cone beam computed tomography (CBCT) was taken to the patients in whom the width of the cleft was measured from each edge of the cleft reporting values between 5.76 and 16.93 mm (average, 11.18 mm). The densities of the clefts were measured with a CBCT, 6 months postoperative to assess bone formation. The results showed a register of gray values of 1,148 to 1,396 (mean, 1,270). The follow-up was conducted for 15 to 33 months (mean, 28.2 months). The results did not show satisfactory bone formation in the cleft of patients with the use of demineralized bone matrix.
| S-EPMC4221138 | biostudies-other
Project description: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.
| S-EPMC3713112 | biostudies-literature
Project description:ObjectivesDentin, the bulk material of the tooth, resemble the bone's chemical composition and is considered a valuable bone substitute. In the current study, we assessed the cytotoxicity and osteogenic potential of demineralized dentin matrix (DDM) in comparison to HA nanoparticles (n-HA) on bone marrow mesenchymal stem cells (BMMSCs) using a hydrogel formulation.Materials and methodsHuman extracted teeth were minced into particles and treated via chemical demineralization using ethylene diamine tetra-acetic acid solution (EDTA) to produce DDM particles. DDM and n-HA particles were added to the sodium alginate then, the combination was dripped into a 5% (w/v) calcium chloride solution to obtain DDM hydrogel (DDMH) or nano-hydroxyapatite hydrogel (NHH). The particles were evaluated by dynamic light scattering (DLS) and the hydrogels were evaluated via scanning electron microscope (SEM). BMMSCs were treated with different hydrogel concentrations (25%, 50%, 75% and neat/100%) and cell viability was evaluated using MTT assay after 72 h of culture. Collagen-I (COL-I) gene expression was studied with real-time quantitative polymerase chain reaction (RT-qPCR) after 3 weeks of culture and alkaline phosphatase (ALP) activity was assessed using enzyme-linked immune sorbent assay (ELISA) over 7th, 10th, 14th and 21st days of culture. BMMSCs seeded in a complete culture medium were used as controls. One-way ANOVA was utilized to measure the significant differences in the tested groups.ResultsDLS measurements revealed that DDM and n-HA particles had negative values of zeta potential. SEM micrographs showed a porous microstructure of the tested hydrogels. The viability results revealed that 100% concentrations of either DDMH or NHH were cytotoxic to BMMSCs after 72 h of culture. However, the cytotoxicity of 25% and 50% concentrations of DDMH were not statistically significant compared to the control group. RT-qPCR showed that COL-I gene expression was significantly upregulated in BMMSCs cultured with 50% DDMH compared to all other treated or control groups (P < 0.01). ELISA analysis revealed that ALP level was significantly increased in the groups treated with 50% DDMH compared to 50% NHH after 21 days in culture (P < 0.001).ConclusionThe injectable hydrogel containing demineralized dentin matrix was successfully formulated. DDMH has a porous structure and has been shown to provide a supporting matrix for the viability and differentiation of BMMSCs. A 50% concentration of DDMH was revealed to be not cytotoxic to BMMSCs and may have a great potential to promote bone formation ability.
| S-EPMC10148431 | biostudies-literature
Project description:Demineralized bone matrix is a widely used allograft where not only the inorganic mineral but also embedded growth factors are removed by hydrochloric acid. The cellular response to the growth factors released during the preparation of demineralized bone matrix, however, has not been studied. Here we investigated the in vitro impact of acid bone lysates (ABL) prepared from porcine cortical bone chips on oral fibroblasts. Proteomic analysis of ABL revealed a large spectrum of bone-derived proteins including TGF-β1. Whole genome microarrays and RT-PCR together with the pharmacologic blocking of TGF-β receptor type I kinase with SB431542 showed that ABL activates the TGF-β target genes interleukin 11, proteoglycan 4, and NADPH oxidase 4. Interleukin 11 expression was confirmed at the protein level by ELISA. Immunofluorescence and Western blot showed the nuclear localization of Smad2/3 and increased phosphorylation of Smad3 with ABL, respectively. This effect was independent of whether ABL was prepared from mandible, calvaria or tibia. ABL prepared with 0.1 N HCL was most effective compared to lysates obtained with 0.01 N and also 1.0 N HCl. These results demonstrate that TGF-β is a major growth factor that is removed upon the preparation of demineralized bone matrix.
2018-11-04 | PXD010145 | Pride
Project description:The occurrence of bone-related disorders and diseases has dramatically increased in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision. In addition, these particles are susceptible to migration to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill a bone defect. The aim of this research was to develop a DBM carrier with such viscoelastic properties in order to obtain an injectable bone substitute (IBS). The developed DBM carrier consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO3 as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by an injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results showed that the developed material has great potential to be used in bone tissue regeneration.
| S-EPMC8395841 | biostudies-literature
Project description:Extracellular matrix (ECM) "raw materials" such as demineralized bone matrix (DBM) and cartilage matrix have emerged as leading scaffolding materials for osteochondral regeneration owing to their capacity to facilitate progenitor/resident cell recruitment, infiltration, and differentiation without adding growth factors. Scaffolds comprising synthetic polymers are sturdy yet generally lack cues for guiding cell differentiation. We hypothesized that opposing gradients of decellularized cartilage (DCC) and DBM in polymeric microsphere-based scaffolds would provide superior regeneration compared to polymer-only scaffolds in vivo. Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds were fabricated, either with opposing gradients of DCC and DBM encapsulated (GRADIENT) or without DCC and DBM (BLANK control), and implanted into rabbit osteochondral defects in medial femoral condyles. After 12 weeks, gross morphological evaluation showed that the repair tissue in about 30% of the implants was either slightly or significantly depressed, hinting toward rapid polymer degradation in scaffolds from both of the groups. Additionally, no differences were observed in gross morphology of the repair tissue between the BLANK and GRADIENT groups. Mechanical testing revealed no significant differences in model parameter values between the two groups. Histological observations demonstrated that the repair tissue in both of the groups was fibrous in nature with the cells demonstrating notable proliferation and matrix deposition activity. No adverse inflammatory response was observed in any of the implants from the two groups. Overall, the results emphasize the need to improve the technology in terms of altering the DBM and DCC concentrations, and tailoring the polymer degradation to these concentrations.
| S-EPMC7423242 | biostudies-literature
Project description:Demineralized bone matrix (DBM) is considered one of the most reliable bone tissue grafts for regular surgical use, as it provides a scaffold that is structurally like native bone, and that enhances bone regeneration. However, commercially available DBM products are not suited for surgical restitutions of large bones. Therefore, each Tissue Bank is urged to implement their own demineralization protocol, which usually does not meet the high demand for bone grafting. In this project, we developed an open source system for medium-scale manufacturing of DBM grafts from human cadaveric donors to automate the demineralization protocol and improve its reproducibility. The device consists in (1) unidirectional flow reaction chamber, where the demineralization protocol takes place; (2) automated syringe pump, which controls the reagent́s inlet and vacuum; and (3) reagent dispenser, for the management of the reagents need for the demineralization protocol. Validation of the device included histological analysis, DNA quantification temperature regulation, electrochemiluminescence and colorimetric protocols, followed by the optimization of physicochemical parameters based on Response Surface Methodology. The results showed values of residual lipids and calcium within standardized ranges, and the maintenance of the structural integrity of the DBM, demonstrating the capacity of the system to support the proposed demineralization protocol.
| S-EPMC9722481 | biostudies-literature