Bone Research Articles

Recent Advances in Bone Grafts in Oral and Maxillofacial Surgery

Bone resorption, which is the loss of bone tissue, cannot be reversed after tooth loss. As a result, the affected area lacks sufficient bone volume for successful implant treatment. To address this issue, bone grafting is the only viable solution and is required in one out of every four dental implants. The ideal biomaterial substitute for bone repair should have osteogenic, osteoinductive, and osteoconductive properties, as well as the ability to stimulate the neo-angiogenesis process. It should also avoid any antigenic, teratogenic, or carcinogenic reactions, and prevent systemic toxicity complications. The purpose of this article is to provide an overview of the various materials used for bone grafts and biomaterial substitutes for bone repair, as well as to discuss current and future perspectives in this field.

Transcriptomic characteristics analysis of bone from chronic osteomyelitis

To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKβ), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKβ, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Production of Agarose-Hydroxyapatite Composites via Supercritical Gel Drying, for Bone Tissue Engineering.

Bone tissue engineering (BTE) is the most promising strategy to repair bones injuries and defects. It relies on the utilization of a temporary support to host the cells and promote nutrient exchange (i.e., the scaffold). Supercritical CO2 assisted drying can preserve scaffold nanostructure, crucial for cell attachment and proliferation. In this work, agarose aerogels, loaded with hydroxyapatite were produced in view of BTE applications. Different combinations of agarose concentration and hydroxyapatite loadings were tested. FESEM and EDX analyses showed that scaffold structure suffered from partial closure when increasing filler concentration; hydroxyapatite distribution was homogenous, and Young's modulus improved. Looking at BTE applications, the optimal combination of agarose and hydroxyapatite resulted to be 1% w/w and 10% w/v, respectively. Mechanical properties showed that the produced composites could be eligible as starting scaffold for BTE, with a Young's Modulus larger than 100 kPa for every blend.

Correlation between Ca Release and Osteoconduction by 3D-Printed Hydroxyapatite-Based Templates.

The application of hydroxyapatite (HA)-based templates is quite often seen in bone tissue engineering since that HA is an osteoconductive bioceramic material, which mimics the inorganic component of mineralized tissues. However, the reported osteoconductivity varies in vitro and in vivo, and the levels of calcium (Ca) release most favorable to osteoconduction have yet to be determined. In this study, HA-based templates were fabricated by melt-extrusion 3D-printing and characterized in order to determine a possible correlation between Ca release and osteoconduction. The HA-based templates were blended with poly(lactide-co-trimethylene carbonate) (PLATMC) at three different HA ratios: 10, 30, and 50%. The printability and physical properties of the HA templates were compared with those of pristine PLATMC. In vitro, osteoconductivity was assessed using seeded human bone marrow-derived mesenchymal stem cells. A mild rate of Ca release was observed for HA10 templates, which exhibited higher mineralized extracellular matrix (ECM) secretion than PLATMC at 14 and 21 days. In contrast, the high rate of Ca release exhibited by HA30 and HA50 templates was associated with reduced osteoconduction and impeded mineralized ECM secretion in vitro. Similar results were observed in vivo. In the calvarial defect model in rabbit, PLATMC and HA10 templates exhibited the highest amount of new bone formation, with obvious contact osteogenesis on their surfaces. In contrast, HA30 and HA50 exhibited distant osteogenesis and reduced amounts of new bone ingrowth. It is concluded that HA-based templates are osteoconductive only at low rates of Ca release.

Mechanical and modal analysis of different implant strategies for loss of three teeth with bone atrophy in the maxillary posterior region

Purpose: This study aimed to evaluate the stress distribution and secondary stability involved in five implant strategies, including implant-supported prostheses (ISP) and tooth-implant-supported prostheses (TISP), used for bone atrophy in the maxillary posterior region with teeth loss using finite element analysis, and to explore the more desirable implant methods. Methods: Five implant strategies were made to analyze and compare: M1, implant-supported prosthesis consisting of a short implant with a regular implant; M2, implant-supported prosthesis consisting of a tilted implant with a regular implant; M3, cantilever structure; M4, tooth-implant-supported prosthesis consisting of a short implant with a regular implant; M5, tooth-implant-supported prosthesis consisting of a regular implant, and M6, with only the natural teeth as a control group. Dynamic loading of the above models was performed in finite element analysis software to assess the stress distribution of the bone tissue and implants using the von Mise criterion. Finally, the secondary stability of different models was evaluated by modal analysis. Results: The maximum stress distribution in the cortical bone in M1(60 MPa) was smaller than that in M2(97 MPa) and M3(101 MPa), The first principal strain minimum was obtained in M2 (2271 μ ε ). M4 (33 MPa, 10085 Hz) with the best mechanical properties and highest resonance frequency. But increased the loading on the natural teeth. Conclusions: Short implants and tilted implants are both preferred implant strategies, if cantilever construction is necessary, a tooth-implant-supported prosthesis consisting of a short implant and a regular implant is recommended.

Freeze‐Casting of Arbitrary‐Shaped Porous Ceramics

Porous ceramics hold the great potential in the field such as bone tissue engineering, superinsulation material, and energy storage. However, it is quite challenging to fabricate them with arbitrary shape using conventional processes. Herein, a method to fabricate arbitrary‐shaped porous ceramic structure is presented by combining traditional freeze‐casting process and indirect three‐dimensional printing technology. Various polydimethylsiloxane (PDMS) soft molds are prepared for freeze‐casting, and diverse‐shaped porous ceramics are fabricated. It proves that PDMS molds are ideal choices for freeze‐casting of porous ceramics with complex geometries. The freeze‐casting process of a complex‐shaped model with PDMS is simulated by finite element analysis. The effect of the solid loading of the alumina suspension on the microstructure and compressive strength of the as‐fabricated porous ceramics are investigated. The present study provides a strategy to fabricate complex‐shaped porous ceramic structure that can be used in a wide variety of applications.

A bone remodeling approach encoding the effect of damage and a diffusive bio-mechanical stimulus

AbstractThe paper focuses on the effect of damage on the bone remodeling process. This is a crucial, although complex, aspect. A one-dimensional continuous deformable body is employed to model living bone tissue. The model incorporates the bone functional adaptation through an evolution law for an effective elastic modulus driven by mechanical feedback via a mechano-transduction diffusive signal. This type of information transduction, i.e., diffusion, is essential for the model to take into account remodeling in the case of minor injury or pathology-affected regions where there is no signal production. In addition, the model is able to also take into account potential tissue damage that may evolve over time according to a suitable evolution law. To illustrate the capability of the model to describe the mentioned complex coupled phenomena, numerical tests have been performed encompassing high external loads causing the onset of damage and cyclic loading for healing. The numerical simulations carried out via finite-element analyses yield insights into the mechanisms of bone remodeling, with the final goal of aiding clinical decisions and implant designs for bone health and repair. Overall, a key aspect of the paper is to highlight the feasibility of modeling the evolution in bone elasticity arising from the combined effect of damage and remodeling.

Enhancing tissue wet pressing performance and dry end material efficiency for cost savings

The steadily growing global tissue paper demand lays a foundation for new technologies targeting tissue production optimization, as well as improved material and time efficiency. Tissue making is an especially energy-intensive field of paper industry, creating unique demands for performance in wet pressing and drying processes to cut energy usage. Intelligent roll solutions offer new tools for tissue making to achieve these goals. These tools aim at improving press nip, moisture, and tension profiles; reeling nip and parent roll hardness profiles; rewinder runnability; and end product web handling characteristics in converting. Intelligent rolls can be utilized in all the main processes and positions on tissue production lines. With these tools, production cost reductions and energy savings can be obtained by optimizing the press nip-to-Yankee cylinder contact, avoiding moisture profile errors requiring overdrying with the Yankee hood and reducing reeling/winding broke under low nip load conditions typical to tissue windups. The intelligent roll system consists of a helically mounted force or temperature sensors, roll covers, measurement electronics, digital radio transmission, and a receiver system connected to a user interface or the mill automation system. What distinguishes these implementations is that no layout changes or added external measurement devices are required, helping to fit into compact tissue machine environments, regardless of the equipment type – traditional, hybrid, or through-air drying (TAD) concept. In tissue processing equipment, the optimal positions for these rolls are press nip rollers, reeling cylinders, rewinder or converting line paper lead rolls, or rewinder winding drums. In addition to these, temperature profile measurements are utilized, with the main application being the sheet temperature profile detection after Yankee drying for moisture profile and drying process optimization.

Enhancing Osteogenic Potential in Bone Tissue Engineering: Optimizing Pore Size in Alginate–Gelatin Composite Hydrogels

Bone tissue engineering relies on crucial scaffolds for tissue formation and stem cell differentiation. A composite scaffold of alginate‐gelatin effectively supports these processes. This study aims to design a porous alginate‐gelatin hydrogel and assess pore size effects on cell behavior, focusing on morphology, adhesion, and proliferation in distinct osteogenic environments. Hydrogels are prepared using various alginate‐gelatin concentrations: 4% alginate and 6% gelatin (4A6G) or 3% alginate and 5% gelatin (3A5G), cross‐linked with 2% CaCl2. Pore size optimization employs simple freezing and thawing cycles. Scanning electron microscopy reveals varying pore sizes: 340 µm ± 30 µm for 4A6G and 635 µm ± 25 µm for 3A5G. Stiffness measurements indicate significant differences: ≈26.3 kPa ± 0.6 KPa for 4A6G and 21.6 kPa ± 0.2 KPa for 3A5G. Cell interaction studies demonstrate higher adhesion and proliferation rates in larger‐pored hydrogels. Evaluation of bone tissue formation, including RT‐PCR, ALP activity, and ARS staining, reveal superior osteogenic potential in the 3A5G hydrogel compared to 4A6G. In conclusion, the 3A5G hydrogel (3% alginate and 5% gelatin) holds promise for bone tissue regeneration due to its biodegradability and favorable bone‐forming properties.

Hydroxyapatite/alginate/gellan gum inks with osteoconduction and osteogenic potential for bioprinting bone tissue analogues

There is a growing demand for engineered bone tissues custom-designed to match the patient-specific defect size and in vitro models for studying bone diseases and/or drug screening. Herein, we propose a bioprinted bone tissue construct using SaOs-2 cells within alginate/gellan gum/hydroxyapatite inks. Different ink formulations were developed with varying hydroxyapatite content and then evaluated for viscoelasticity, printability, biomineralization properties, post-printing viability, proliferation, metabolic activity, and osteogenic phenotype of SaOs-2-encapsulated cells. Results indicate that ink formulations exhibit non-Newtonian shear-thinning behaviour, maintaining shape integrity and structural stability post-printing. Ink mineralization rates increase with the hydroxyapatite content, rendering them suitable for bone defect strategies. Post-printed cells in the developed constructs remain live, spreading, and metabolically active but do not proliferate. Osteogenic gene and protein expression, both early and late, show upregulation at day 7 relative to day 1, followed by downregulation at day 14. Lower hydroxyapatite content inks demonstrate up to fourfold upregulation in genes and proteins at most time points. Additionally, these constructs release calcium and phosphate at levels conducive to mineralization. Overall, the tissue-engineered miniaturized constructs not only meet the criteria for early-stage bone defect/fracture regeneration but also serve as a promising platform for drug screening and evaluating potential therapeutic treatments.

Understanding morphological rib abnormalities in Atlantic salmon

Poor rib health in Atlantic salmon (Salmo salar L.) can lead to negative effects on welfare and fillet quality. The present research aimed to enhance the comprehension of long-term rib morphology within a broader musculoskeletal framework of harvest-sized salmon (3 kg), examining a population fed different smoltification diets. Generally, X-ray examinations revealed the highest concentration of abnormalities in the anterior-central area of the rib cage, and the mid-distal rib parts. The different diets, based on either marine (M-group) or vegetal (V-group) ingredients, modulated the morphology of the ribs in the central area of the rib cage. Compared to the V-group, the M-group had a lower prevalence of generalized radiolucency (GR) (19 vs. 26% of mid-distal rib parts), and axis deformations/malformations (12 vs. 17% of mid rib parts). Histological examination of GR, unrelated to near inflammatory processes, revealed potential degradation/transformation of central core chondrocytes to mesenchymal-like cells. The newly formed cavity progressed/expanded through osteolysis until it reached the periosteum. In parallel, there were progressive alterations of the concentric appositional growth pattern of the compact bone, with an increase of the external collagen layer under the cellular periosteum. Disorganized collagen-rich islands were also seen in the compact bone, as were signs of new osteoid deposition in the cavity. The degenerative process in GR was accompanied by an 18–20% increase in the cross-sectional diameter of the rib. The M-group presented numerically higher mechanical rib strength (p = 0.06), and phosphorus content (p = 0.07). The sensitivity of rib morphology to smoltification diet was higher than vertebrae in the long-term. This study enhances understanding of the etiology of the primary morphological rib abnormalities in Atlantic salmon, particularly in GR, by providing detailed histomorphology of pathological changes. The study associates these changes with altered rib development, degeneration, and possibly osteomalacia.

Mechanically suitable and osteoinductive 3D-printed composite scaffolds with hydroxyapatite nanoparticles having diverse morphologies for bone tissue engineering.

The challenge of integrating hydroxyapatite nanoparticles (nHAp) with polymers is hindered by the conflict between the hydrophilic and hygroscopic properties of nHAp and the hydrophobic properties of polymers. This conflict particularly affects the materials when calcium phosphates, including nHAp, are used as a filler in composites in thermal processing applications such as 3D printing with fused filament fabrication (FFF). To overcome this, we propose a one-step surface modification of nHAp with calcium stearate monolayer. Moreover, to build the scaffold with suitable mechanical strength, we tested the addition of nHAp with diverse morphology-spherical, plate- and rod-like nanoparticles. Our analysis showed that the composite of polycaprolactone (PCL) reinforced with nHAp with rod and plate morphologies modified with calcium stearate monolayer exhibited a significant increase in compressive strength. However, composites with spherical nHAp added to PCL showed a significant reduction in compressive modulus and compressive strength, but both parameters were within the applicability range of hard tissue scaffolds. None of the tested composite scaffolds showed cytotoxicity in L929 murine fibroblasts or MG-63 human osteoblast-like cells, supporting the proliferation of the latter. Additionally, PCL/nHAp scaffolds reinforced with spherical nHAp caused osteoactivation of bone marrow human mesenchymal stem cells, as indicated by alkaline phosphatase activity and COL1, RUNX2, and BGLAP expression. These results suggest that the calcium stearate monolayer on the surface of the nHAp particles allows the production of polymer/nHAp composites suitable for hard tissue engineering and personalized implant production in 3D printing using the FFF technique.

TPMS Microarchitectures for Vertical Bone Augmentation and Osteoconduction: An In Vivo Study.

Triply periodic minimal surface microarchitectures (TPMS) were developed by mathematicians and evolved in all kingdoms of living organisms. Renowned for their lightweight yet robust attributes, TPMS structures find application in diverse fields, such as the construction of satellites, aircrafts, and electric vehicles. Moreover, these microarchitectures, despite their intricate geometric patterns, demonstrate potential for application as bone substitutes, despite the inherent gothic style of natural bone microarchitecture. Here, we produced three TPMS microarchitectures, D-diamond, G-gyroid, and P-primitive, by 3D printing from hydroxyapatite. We explored their mechanical characterization and, further, implanted them to study their bone augmentation and osteoconduction potential. In terms of strength, the D-diamond and G-gyroid performed significantly better than the P-primitive. In a calvarial defect model and a calvarial bone augmentation model, where osteoconduction is determined as the extent of bony bridging of the defect and bone augmentation as the maximal vertical bone ingrowth, the G-gyroid performed significantly better than the P-primitive. No significant difference in performance was observed between the G-gyroid and D-diamond. Since, in real life, the treatment of bone deficiencies in patients comprises elements of defect bridging and bone augmentation, ceramic scaffolds with D-diamond and G-gyroid microarchitectures appear as the best choice for a TPMS-based scaffold in bone tissue engineering.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

A sono-responsive antibacterial nanosystem co-loaded with metformin and bone morphogenetic protein-2 for mitigation of inflammation and bone loss in experimental peri-implantitis

BackgroundDental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.MethodsIn this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.ResultsThe results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-α and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.ConclusionOur observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.

Biomechanical Investigation of the Osseointegration of Titanium Implants With Different Surfaces Placed With Allogeneic Bone Transfer.

Allogeneic grafts can be preferred to autogenous grafts in plastic and oral-maxillofacial surgery for vertical and horizontal bone deficiencies. Implant surface properties are an important factor in osseointegration. This study aims to evaluate the osseointegration levels of titanium implants with machined, sand-blasted, and acid-etched (SLA) and resorbable blast material (RBM) surfaces placed together with allogeneic bone tissue transplantations obtained from the tibia bone using biomechanical method. Twenty-five female Sprague-Dawley rats were included in the study. The rats were divided into groups in which machined (n=7), SLA (n=7), and RBM (n=7) surface implants were placed with the transplantation of bone taken from the tibia. Four rats (both left and right tibias) were used as donors. Grafts and implants were surgically placed in the corticocancellous part of the metaphyseal area of the tibia bones of rats. At the end of the 4-week experimental setup, all rats were killed, and the implants and surrounding bone tissue were subjected to biomechanical reverse torque analysis (N/cm). Sand-blasted acid-etched surface implants were observed to have higher biomechanical osseointegration levels than RBM and machined surface implants (P<0.05). No statistical difference could be detected between the RBM and machined surface implants (P>0.05). On the basis of the limited results of this study, it can be concluded that the osseointegration levels of SLA surface implants placed with allogeneic bone transplantation may be better than those of machined and RBM surface implants.

Sophoraflavanone G Inhibits RANKL-Induced Osteoclastogenesis via MAPK/NF-κB Signaling Pathway.

Osteoporosis is a common chronic bone metabolism disorder characterized by decreased bone mass and reduced bone density in the bone tissue. Osteoporosis can lead to increased fragility of the skeleton, making it prone to brittle fractures. Osteoclasts are macrophage-like cells derived from hematopoietic stem cells, and their excessive activity in bone resorption leads to lower bone formation than absorption during bone remodeling, which is one of the important factors inducing osteoporosis. Therefore, how to inhibit osteoclast formation and reducing bone loss is an important direction for treating osteoporosis. Sophoraflavanone G, derived from Sophora flavescens Alt and Rhizoma Drynariae, is a flavonoid compound with various biological activities. However, there have been few studies on osteoporosis and osteoclasts so far. Therefore, we hypothesize that genistein G can inhibit osteoclast differentiation, alleviate bone loss phenomenon, and conduct in vitro and in vivo experiments for research and verification purposes.

Oxford Spine Buddies: an acceptability and feasibility project for peer-to-peer support in a spine sarcoma service.

Primary bone and soft tissue sarcoma of the spine are rare and account for less than 0.2% of all neoplasm incidences. Following a patient and public involvement event, the need to explore patient support pathways was identified, which initiated this service evaluation project. To determine the acceptability and feasibility of a peer-to-peer support project among people using the spine sarcoma service. Users were paired and introduced via Microsoft Teams. Quantitative and qualitative data both pre- and post-introduction of a buddy were collected. Service users felt that, although they would have preferred having a buddy at the time of their diagnosis, being allocated a buddy made them feel reassured and better supported. The project was well received and preliminary data are encouraging. Therefore, due to early findings from the first participants, the service is continuing to roll out the buddy programme.

Editorial: New progress in the treatment of bone and soft tissue tumors

Editorial: New progress in the treatment of bone and soft tissue tumors

Practical Considerations in Computerized Surgical Planning for Frontofacial Surgery

AbstractThe field of frontofacial surgery has advanced considerably, building on the pioneering techniques of Paul Tessier, with computerized surgical planning (CSP) emerging as a critical component. CSP has enhanced the precision and efficiency of surgeries for craniofacial dysostoses and hypertelorism, resulting in improved outcomes. This review delves into the importance of understanding orbital anatomy and the crucial bony and soft tissue landmarks essential to the application of CSP in frontofacial procedures, encompassing Le Fort III and monobloc advancements, as well as the correction of hypertelorism.