Functions and Metabolism of Amino Acids in Bones and Joints of Cats and Dogs.

The bone is a large and complex organ (12-15% of body weight) consisting of specialized connective tissues (bone matrix and bone marrow), whereas joints are composed of cartilage, tendons, ligaments, synovial joint capsules and membranes, and a synovial joint cavity filled with synovial fluid. Maintaining healthy bones and joints is a dynamic and complex process, as bone deposition (formation of new bone materials) and resorption (breakdown of the bone matrix to release calcium and phosphorus) are the continuous processes to determine bone balance. Bones are required for locomotion, protection of internal organs, and have endocrine functions to maintain mineral homeostasis. Joints are responsible for resisting mechanical stress/trauma, aiding in locomotion, and supporting the overall musculoskeletal system. Amino acids have multiple regulatory, compositional, metabolic, and functional roles in maintaining the health of bones and joints. Their disorders are prevalent in mammals and significantly reduce the quality of life. These abnormalities in companion animals, specifically cats and dogs, commonly lead to elective euthanasia due to the poor quality of life. Multiple disorders of bones and joints result from genetic predisposition and are heritable, but other factors such as nutrition, growth rate, trauma, and physical activity affect how the disorder manifests. Treatments for cats and dogs are primarily to slow the progression of these disorders and assist in pain management. Therapeutic supplements such as Cosequin and formulated diets rich in amino acids are used commonly as treatments for companion animals to reduce pain and slow the progression of those diseases. Also, amino acids (e.g., taurine, arginine, glycine, proline, and 4-hydroxyproline), and glucosamine reduce inflammation and pain in animals with bone and joint disorders. Gaining insight into how amino acids function in maintaining bone and joint health can aid in developing preventative diets and therapeutic supplementations of amino acids to improve the quality of life in companion animals.

Numerical calculation of streaming potential around osteocytes under human gait loading.

Streaming potential is a type of stress-generated potential in bone that affects the electrical environment of osteocytes and may play a role in bone remodeling. Because the electrical environment around osteocytes has been difficult to measure experimentally until now, a numerical solid-liquid-streaming potential coupling method was proposed to analyze the streaming potential generated by bone deformation in the lacunae and canaliculus network (LCN) of the bone. Using this method, the cellular shear stress caused by liquid flow on the osteocyte surface was first calculated, and the results were consistent with those reported in the literature. Subsequently, the streaming potentials in the LCN caused by bone matrix deformation under an external gait load were calculated numerically. The results showed that the streaming potential increased slowly in the lacuna and relatively rapidly in the canaliculus and that the streaming potential increased with a decrease in the radius or an increase in the length of the canaliculus. The results also showed that relatively large gaps between the lacunae and osteocytes could induce higher streaming potentials under the same loading.

Demineralized bone matrix for repair and regeneration of maxillofacial defects: A narrative review.

OBJECTIVES: Demineralized bone matrix (DBM) is a well-established bone graft material widely accepted by dentists and the public for its favorable osteoconductivity and osteoinductive potential. This article aimed to provide a narrative review of the current therapeutic applications and limitations of DBM in maxillofacial bone defects. STUDY SELECTION, DATA, AND SOURCES: Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic reviews. MEDLINE, PubMed, and Google Scholar were searched using keywords. CONCLUSIONS: Some evidence supported the therapeutic application of DBM in periodontal intrabony defects, maxillary sinus lifts, ridge preservation, ridge augmentation, alveolar cleft repair, orthognathic surgery, and other regional maxillofacial bone defects. However, the limitations of DBM should be considered when using it, including potential low immunogenicity, instability of osteoinductive potential, handling of the graft material, and patient acceptance. CLINICAL SIGNIFICANCE: With the increasing demand for the treatment of maxillofacial bone defects, DBM is likely to play a greater role as a promising bone graft material. Safe and effective combination treatment strategies and how to maintain a stable osteoinductive potential will be the future challenges of DBM research.

Influence of intramedullary pressure on Lacuno-Canalicular fluid flow: A systematic review.

While most of current models investigating bone remodelling are based on matrix deformation, intramedullary pressure also plays a role. Bone remodelling is orchestrated by the Lacuno-Canalicular Network (LCN) fluid-flow. The aim of this review was hence to assess the influence of intramedullary pressure on the fluid circulation within the LCN. Three databases (Science Direct, Web of Science, and PubMed) were used. The first phase of the search returned 731 articles, of which 9 respected the inclusion/exclusion criteria and were included. These studies confirm the association between intramedullary pressure and fluid dynamics in the LCN. Among the included studies, 7 experimental studies using animal models and 2 numerical models were found. The studies were then ranked according to the nature of the applied loading, either axial compression or direct cyclic intramedullary pressure. The current review revealed that there is an influence of intramedullary pressure on LCN fluid dynamics and that this influence depends on the magnitude and the frequency of the applied pressure. Two studies confirmed that the influence was effective even without bone matrix deformation. While intramedullary pressure is closely associated with LCN fluid, there is a severe lack of studies on this topic. STATEMENT OF SIGNIFICANCE: Since the 1990's, numerical models developed to investigate fluid flow in bone submicrometric porous network are based on the flow induced by matrix deformation. Bone fluid flow is known to be involved in cells stimulation and hence directly influences bone remodeling. Different studies have shown that intramedullary pressure is also associated with bone mechanosensitive adaptation. This pressure is developed in bone due to blood circulation and is increased during loading or muscle stimulation. The current article reviews the studies investigating the influence of this pressure on bone porous fluid flow. They show that fluid flow is involved by this pressure even without bone matrix deformation. The current review article highlights the severe lack of studies about this mechanism.

Preparation of black phosphorus@sodium alginate microspheres with bone matrix vesicle structure via electrospraying for bone regeneration.

Bone matrix vesicles are commonly acknowledged as the primary site of biomineralization in human skeletal tissue. Black phosphorus has exhibited favorable properties across various chemical and physical domains. In this investigation, a novel composite microsphere was synthesized through the amalgamation of sodium alginate (ALG) with black phosphorus nanosheets (BP) utilizing the electrospray (ES) technique. These microspheres were tailored to mimic the regulatory function of matrix vesicles (MV) upon exposure to a biomimetic mineralization fluid (SBF) during the biomineralization process. Results revealed that black phosphorus nanosheets facilitated the generation of hydroxyapatite (HA) on the microsphere surface. Live-dead assays and cell proliferation experiments showcased a cell survival rate exceeding 85 %. Moreover, wound healing assessments unveiled that M-ALG-BP microspheres exhibited superior migration capacity, with a migration rate surpassing 50 %. Furthermore, after 7 days of osteogenic induction, M-ALG-BP microspheres notably stimulated osteoblast differentiation. Particularly noteworthy, M-ALG-BP microspheres significantly enhanced osteogenic differentiation of osteoblasts and induced collagen production in vitro. Additionally, experiments involving microsphere implantation into mouse skeletal muscle demonstrated the potential for ectopic mineralization by ALG-BP microspheres. This investigation underscores the outstanding mineralization properties of ALG-BP microspheres and their promising clinical prospects in bone tissue engineering.

Static magnetic field enhances the bone remodelling capacity of human demineralized bone matrix in a rat animal model of cranial bone defects.

The regeneration of bone defects that exceed 2 cm is a challenge for the human body, necessitating interventional therapies. Demineralized bone matrices (DBM) derived from biological tissues have been employed for bone regeneration and possess notable osteoinductive and osteoconductive characteristics. Nevertheless, their efficiency in regenerating critically sized injuries is limited, and therefore additional signaling cues are required. Thanks to the piezoelectric properties of the bone, external physical stimulation is shown to accelerate tissue healing. We have implanted human DBM in critically sized cranial bone defects in rat animal models and exposed them to an external magnetic field (1 T) to enhance endogenous bone formation. Our in vitro experiments showed the superior cytocompatibility of DBM compared to cell culture plates. Furthermore, alkaline phosphatase activity after 14 days and Alizarin red staining at 28 days demonstrated differentiation of rat bone marrow mesenchymal stem cells into bone lineage on DBM. Computer tomography images together with histological analyses showed that implanting DBM in the injured rats significantly enhanced bone regeneration. Notably, combining DBM transplantation with a 2 h daily exposure to a 1 T magnetic field for 2 weeks (day 7 to 21 post-surgery) significantly improved bone regeneration compared to DBM transplantation alone. This research indicates that utilizing external magnetic stimulation significantly enhances the potential of bone allografts to regenerate critically sized bone defects.

The Effect of Structural Characteristics of Deproteinized Spongy Bone on Activity of Adipose Tissue Mesenchymal Stromal Cells.

We studied the effect of structural properties of deproteinized spongy bone (DSB) on functional activity of adipose tissue mesenchymal stromal cells of (MSC) for the potential use of these materials as components of a combined tissue-engineered construct. The porosity of the structure of DSB samples and the pore size promote MSC adhesion, migration, and proliferation on their surface and in the depth, revealing the architectonics of this bone matrix. The depth of cell penetration into the samples (from 273 to 702 µm) and an increase in the total number of cells (from 302 on day 1 to 1744 on day 7) demonstrated MSC adhesion, migration, and proliferation. The viability of cultured MSC was preserved for up to 7 days. The obtained results prove the possibility of using allogeneic DSB from femoral heads as a bone matrix in tissue-engineered constructs in combination with MSC. Such constructs can be used to efficiently restore the structural and functional integrity of the bone tissue in abnormal processes of various etiopathogenesis associated with the formation of bone defects or bone tissue deficiency.

Possible involvement of HtrA1 serine protease in the onset of osteoporotic bone extracellular matrix changes.

High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and osteoclasts. Recent and conflicting literature highlights HtrA1's role as a controller of bone remodeling, proposing it as a possible target for pathologies with unbalanced bone resorption, like Osteoporosis (OP). To add knowledge on this molecule function in bone physiopathology, here we compared HtrA1 distribution in the ECM of healthy (H) and OP bone tissue, also examining its localization in the sites of new bone formation. HtrA1 was homogeneously expressed in the mature bone ECM of H tissue showing a 55.6 ± 16.4% of the stained area, with a significant (p=0.0001) decrease in OP percentage stained area (21.1 ± 13.1). Moreover, HtrA1 was present in the endosteum and cells involved in osteogenesis, mainly in those "entrapped" in woven bone, whereas osteocytes in mature lamellar bone were negative. Based on our previous observation in OP tissue of a significantly increased expression of Decorin and Osteocalcin, both involved in bone mineralization and remodeling and equally substrates for HtrA1, we speculate that HtrA1 by controlling the proper amount of Decorin and Osteocalcin favors normal bone maturation and mineralization. Besides, we suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone. Overall, our data suggest HtrA1 as a positive regulator of bone matrix formation and maturation: its reduced expression in mature OP bone, affecting protein content and distribution, could hamper correct bone remodeling and mineralization.

Variables Influencing Bone Formation After Transcrestal Sinus Floor Elevation: Radiographic and Tomographic Evaluations.

PURPOSE: To evaluate the influence of initial implant protrusion within the subantral space on hard tissue gain for implants placed simultaneously with transcrestal sinus floor elevation (TSFE) with a biomaterial. MATERIALS AND METHODS: A total of 50 implants were placed after TSFE in 44 patients using either a human demineralized bone matrix or a deproteinized bone mineral matrix. Intraoral radiographs were obtained before and immediately after surgery. CBCT scans were obtained at the last follow-up (mean: 6.6 years). RESULTS: The initial bone crest height was 4.6 ± 1.4 mm, and the initial protrusion of the implants above the sinus floor was 3.5 ± 1.4 mm. At the follow-up assessments, the hard tissue mean gain was 2.5 ± 1.5 mm, resulting in a mean residual protrusion of 1.1 ± 1.3 mm. Only 10 implants did not protrude above the apical level of hard tissue. Positive correlations were found between hard tissue gain and initial protrusion (r = 0.55; 95% CI: 0.32 to 0.72; P = .0001), between the initial and final protrusions (r = 0.38; 95% CI: 0.10 to 0.60; P = .007), and between the follow-up period and final protrusion (r = 0.35; 95% CI: 0.07 to 0.58; P = .012). CONCLUSIONS: The higher the initial protrusion was, the higher were the hard tissue gain and the final protrusion of the implant above the apical level of the hard tissue.

Comparison of Fusion Rates among Various Demineralized Bone Matrices in Posterior Lumbar Interbody Fusion.

Background and Objectives: Posterior lumbar interbody fusion (PLIF) plays a crucial role in addressing various spinal disorders. The success of PLIF is contingent upon achieving bone fusion, as failure can lead to adverse clinical outcomes. Demineralized bone matrix (DBM) has emerged as a promising solution for promoting fusion due to its unique combination of osteoinductive and osteoconductive properties. This study aims to compare the effectiveness of three distinct DBMs (Exfuse®, Bongener®, and Bonfuse®) in achieving fusion rates in PLIF surgery. Materials and Methods: A retrospective review was conducted on 236 consecutive patients undergoing PLIF between September 2016 and February 2019. Patients over 50 years old with degenerative lumbar disease, receiving DBM, and following up for more than 12 months after surgery were included. Fusion was evaluated using the Bridwell grading system. Bridwell grades 1 and 2 were defined as 'fusion', while grades 3 and 4 were considered 'non-fusion.' Clinical outcomes were assessed using visual analog scale (VAS) scores for pain, the Oswestry disability index (ODI), and the European quality of life-5 (EQ-5D). Results: Fusion rates were 88.3% for Exfuse, 94.3% for Bongener, and 87.7% for Bonfuse, with no significant differences. All groups exhibited significant improvement in clinical outcomes at 12 months after surgery, but no significant differences were observed among the three groups. Conclusions: There were no significant differences in fusion rates and clinical outcomes among Exfuse, Bongener, and Bonfuse in PLIF surgery.

A physicochemical evaluation of ossein-hydroxyapatite within the bovine bone matrix revealed demineralization and making type I collagen available as a result of processing and solubilization by acids.

Bovine bone is an animal-origin matrix rich in type I collagen (COL I) and it necessitates prior demineralization and makes COL I available. This study investigated the ossein-hydroxyapatite physicochemical properties evaluation as a result of processing and solubilization by acids and revealed the bone matrix demineralization and making COL I available. The tibia residue from bovine sources was processed, ground, and transformed into bone matrix powder. The bone matrix was solubilized in acetic acid followed by lactic acid. The bone matrix was evaluated as a result of processing and solubilization by acids: ossein and hydroxyapatite percentages by nitrogen and ash content, mineral content, particle size distribution, Fourier-transformation infrared spectroscopy, x-ray diffraction, and scanning electron microscope. For the obtained residual extracts, pH and mineral content were evaluated. The solubilization by acids affected the ossein-hydroxyapatite physicochemical properties, and the bone matrix solubilized by acetic and lactic acid showed the preservation of the ossein alongside the loss of hydroxyapatite. The processing and the solubilization by acids were revealed to be a  alternative to bone matrix demineralization and enabling the accessibility of bone COL I. PRACTICAL APPLICATION: Bovine bone is an abundant type I collagen source, but processing maneuvers and demineralization effect present limitations due to the rigidity of the structural components. Exploring methodologies to process and demineralize will allow type I collagen to be obtained from the bone source, and direct and amplify the potentialities in the chemical and food industries. The research focused on bone sources and collagen availability holds paramount significance, and promotes repurposing agribusiness residues and development of protein-base products.

Self-Assembled Nanocomposite Hydrogels as Carriers for Demineralized Bone Matrix Particles and Enhanced Bone Repair.

Demineralized bone matrix (DBM) has been widely used as an allogeneic alternative to autologous bone graft for bone repair. However, more extensive use of DBM is limited due to its particulate nature after demineralization and rapid particle dispersion following irrigation, resulting in unpredictable osteoinductivity. Here, a new design of injectable hydrogel carriers for DBM that combine self-healing ability and osteogenic properties based on the self-assembly of guanidinylated hyaluronic acid and silica-rich nanoclays is reported. The nanoclays serve as reversible linkages to form a dynamic hydrogel network with the guanidine moieties on the polymer chains. Gelation kinetics and mechanical properties can be controlled by altering nanoclay content in the hydrogel. The resulting hydrogel exerts self-healing ability due to its dynamic crosslinks and well retains its overall performance with high DBM loading. The hydrogel exhibits great cytocompatibility and osteogenic effects mediated by the nanoclays. In vivo delivery of DBM using the nanocomposite hydrogel further demonstrates robust bone regeneration in a mouse calvarial defect model in comparison to DBM delivered with aqueous HA. This work suggests a promising hydrogel platform for many applications including therapeutic delivery and tissue engineering.

Augmented drug resistance of osteosarcoma cells within decalcified bone matrix scaffold: The role of glutamine metabolism.

Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl no. 5 cell lines as compared to two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance.

A bioartificial and vasculomorphic bone matrix-based organoid mimicking microanatomy of flat and short bones.

We engineered an in vitro model of bioartificial 3D bone organoid consistent with an anatomical and vascular microenvironment common to mammalian flat and short bones. To achieve this, we chose the decellularized-decalcified matrix of the adult male rat scapula, implemented with the reconstruction of its intrinsic vessels, obtained through an original intravascular perfusion with polylevolactic (PLLA), followed by coating of the PLLA-fabricated vascularization with rat tail collagen. As a result, the 3D bone and vascular geometry of the native bone cortical and cancellous compartments was reproduced, and the rat tail collagen-PLLA biomaterial could in vitro act as a surrogate of the perivascular extracellular matrix (ECM) around the wall of the biomaterial-reconstituted cancellous vessels. As a proof-of-concept of cell compatibility and site-dependent osteoinductive properties of this bioartificial 3D construct, we show that it in vitro leads to a time-dependent microtopographic positioning of rat mesenchymal stromal cells (MSCs), initiating an osteogenic fate in relation to the bone compartment. In addition, coating of PLLA-reconstructed vessels with rat tail collagen favored perivascular attachment and survival of MSC-like cells (mouse embryonic fibroblasts), confirming its potentiality as a perivascular stroma for triggering competence of seeded MSCs. Finally, in vivo radiographic topography of bone lesions in the human jaw and foot tarsus of subjects with primary osteoporosis revealed selective bone cortical versus cancellous involvement, suggesting usefulness of a human 3D bone organoid engineered with the same principles of our rat organoid, to in vitro investigate compartment-dependent activities of human MSC in flat and short bones under experimental osteoporotic challenge. We conclude that our 3D bioartificial construct offers a reliable replica of flat and short bones microanatomy, and promises to help in building a compartment-dependent mechanistic perspective of bone remodeling, including the microtopographic dysregulation of osteoporosis.

Histological and histomorphometric analysis of bone tissue using customized titanium meshes with or without resorbable membranes: A randomized clinical trial.

OBJECTIVES: To date, no clinical studies have investigated the effect of using resorbable collagen membrane in conjunction with customized titanium mesh to promote bone formation in guided bone regeneration. Therefore, a non-inferiority analysis (one-sided 95% CI approach) was designed to compare the augmented bone gained using meshes with and without collagen membranes, through histological and histomorphometric investigations. MATERIALS AND METHODS: Thirty patients undergoing bone augmentation procedures at both maxillary and mandible sites were randomly treated with customized titanium meshes alone (M-, n = 15) or covered with resorbable membrane (M+, n = 15), in both cases filled with autogenous bone and xenograft. After 6 months of healing, bone tissue biopsies were taken from the augmented region. The bone tissue (B.Ar), grafting material (G.Ar), and non-mineralized tissue (NMT.Ar) areas were quantified through histomorphometric analysis, as were the osteoid area (O.Ar) and its width. RESULTS: Collagen membrane did not appear to significantly influence the investigated parameters: B.Ar, G.Ar, NMT.Ar, and O.Ar were similar between Group M- (34.3%, 11.5%, 54.1%, 1.95 µm2 , respectively) and Group M+ (35.3%, 14.6%, 50.2%, and 1.75 µm2 , respectively). Considering the overall population, significantly higher rates of newly formed bone were obtained in mandibular sites, while non-mineralized and dense connective tissue rates were higher in the maxilla (p < .05). CONCLUSIONS: The application of collagen membrane over titanium mesh did not lead to significant results. Bone formation appeared significantly different in the maxilla compared with the mandible. Additional studies are required to further investigate the issues observed.

Subcutaneously Engineered Decalcified Bone Matrix Xenografts Promote Bone Repair by Regulating the Immune Microenvironment, Prevascularization, and Stem Cell Homing.

Immunoregulatory and vascularized microenvironments play an important role in bone regeneration; however, the precise regulation for vascularization and inflammatory reactions remains elusive during bone repair. In this study, by means of subcutaneous preimplantation, we successfully constructed demineralized bone matrix (DBM) grafts with immunoregulatory and vascularized microenvironments. According to the current results, at the early time points (days 1 and 3), subcutaneously implanted DBM grafts recruited a large number of pro-inflammatory M1 macrophages with positive expression of CD68 and iNOS, while at the later time points (days 7 and 14), these inflammatory cells gradually subsided, accompanying increased presence of anti-inflammatory M2 macrophages with positive expression of CD206 and Arg-1, indicating a gradually enhanced anti-inflammatory microenvironment. At the same time, the gradually increased angiogenesis was observed in the DBM grafts with implantation time. In addition, the positive cells of CD105, CD73, and CD90 were observed in the inner region of the DBM grafts, implying the homing of mesenchymal stem cells. The repair results of cranial bone defects in a rat model further confirmed that the subcutaneous DBM xenografts at 7 days significantly improved bone regeneration. In summary, we developed a simple and novel strategy for bone regeneration mediated by anti-inflammatory microenvironment, prevascularization, and endogenous stem cell homing.

Regenerative effect of microcarrier form of acellular dermal matrix versus bone matrix bio-scaffolds loaded with adipose stem cells on rat bone defect.

BACKGROUND: Bone defects lead to dramatic changes in the quality of life. Acellular dermal matrix (ADM) and decellularized bone matrix (DBM) are natural scaffolds for tissue regeneration. The microcarrier scaffolds enable better vascularization and cell proliferation. This study compared the effect of microcarrier forms of DBM and ADM-loaded with adipose stem cells (ASCs) in the repair of compact bone defect in-vivo. METHODS: Fifty-four male rats were divided into 4 groups; (i) Group (Gp) I: sham control; (ii) GpII: underwent femur bone defect induction and left to heal spontaneously; (iii) GpIII (ADM-Gp): included 2 subgroups; IIIa and IIIb: the bone defects were filled with non-loaded ADM and ADM-loaded with ASCs, respectively; (iv) GpIV (DBM-Gp): included 2 subgroups; IVa and IVb: the bone defects were filled with non-loaded DBM and DBM-loaded with ASCs, respectively. Animals were euthanized after 1, 2 and 3 months and their femur sections were stained with H&E, Masson's trichrome and immunohistochemistry for CD31, osteopontin and osteocalcin. RESULTS: Histological analysis illustrated limited bone regeneration in the cortical defect of GpII after 3 months. The histomorphometric analysis showed significant delayed mature collagen deposition as well as CD31, osteopontin and osteocalcin expression. Superior capacity of new bone regeneration was detected with bio-scaffold micro-carriers; loaded or non-loaded with ASCs. However, DBM-loaded with ASCs displayed enhanced regeneration properties confirmed by the apparently normal architecture of the new bone and accelerated expression of CD31, osteopontin and osteocalcin in the regenerated bone after 3 months. CONCLUSIONS: We concluded that decellularized scaffolds significantly improved compact bone regeneration with superiority of ASCs seeded-bone scaffolds.

Decellularized Bone Matrix/45S5 Bioactive Glass Biocomposite Hydrogel-Based Constructs with Angiogenic and Osteogenic Properties: Ex Ovo and Ex Vivo Evaluations.

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20 wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.

Recombinant bone matrix maintains the graft space, induces vascularized bone regeneration and preserves canine tooth extraction socket structure.

AIM: Recombinant bone matrix (RBM) is a newly conceived and engineered porous bone graft granule of average size 600 µm composed of purified recombinant collagen peptide. We sought to examine the behaviour with time of RBM that was grafted in the canine tooth extraction socket. MATERIALS AND METHODS: The canine tooth extraction socket of the hemisectioned mandibular third premolar distal root was grafted with RBM granules, whereas the opposite side extraction socket served as non-grafted control. The mandibular samples were harvested at 1, 3 and 6 months of healing and subjected to micro-CT imaging and decalcified paraffin-embedded histology. Separately, the effect of RBM was compared with that of deproteinized cancellous bovine bone (DCBB) and bovine atelocollagen plug (BACP) in the canine tooth extraction model at 3 months of healing. RESULTS: RBM maintained the grafted space in the socket and the gingival connective tissue until new bone was formed within its porous space. The regenerated bone was highly vascularized and continued to mature, while RBM was completely bioresorbed by 6 months. The buccal and lingual alveolar ridge heights of the RBM-grafted extraction socket was better preserved than those of non-grafted control sockets. The degree of socket preservation by RBM was equivalent to that by DCBB, although their healing mechanisms were different. CONCLUSIONS: This study demonstrated that RBM induced controlled active bone regeneration and preserved the extraction socket structure in a canine model. Bioresorbable RBM engineered without animal or human source materials presents a novel bone graft category with robust bone regenerative property.

Nano apatite growth on demineralized bone matrix capped with curcumin and silver nanoparticles: Dental implant mechanical stability and optimal cell growth analysis.

OBJECTIVES: The prevention of implant-associated infections is becoming increasingly clinically important in the field of dentistry. Extensive investigations into the development of innovative antibacterial materials that interact effectively to reinforce their functionality are currently being conducted in the biomedical sector. In the present study, a novel dental nano putty (D-nP) has been developed using demineralized bone matrix (DBM), calcium sulfate hemihydrate (CSH), curcumin nanoparticles (CU-NPs), and silver nanoparticles (AgNPs). METHODS: The produced D-nP was evaluated using physicochemical, mechanical, and in vitro analyses. Surface characterization, particularly the analysis of calcium and phosphorus content, was performed before and after immersion in the simulated body fluid (SBF). In addition, the impact of surface treatment on biological activity was studied. RESULTS: The results showed that the mechanical properties of the D-nP were outstanding and its performance is promising. D-nP exhibited excellent antibacterial activity against Actinomyces naeslundii (5.22 ± 0.07 mm) and Streptococcus oralis (5.41 ± 0.1 mm). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was conducted using MG-63 osteoblast cells, which exhibited 95 % viability in D-nP. CONCLUSIONS: Based on these characterization results, the D-nP developed in this study exhibited excellent performance for tooth tissue in bone repair.