Cancellous Bone Tissue Research Articles

Mimicking the Architecture and Dissolution Chemistry of Cancellous Bone Tissue to Optimize the Biocompatibility of Bioactive Scaffolds.

Synthesis of mechanically stable porous scaffolds with an architecture analogous to cancellous bone tissue poses significant challenges to bioactive glass (BG) based scaffolds. This is primarily due to densification and crystallization of the BG's during heat treatment. This study presents a modified BG series (42SiO2-xTiO2-24Na2O-21CaO-13P2O5, where x = 8 and 16 TiO2). TiO2 replaced the SiO2 concentration in the glass and was incorporated due to its biocompatibility and influence on glass structure. Material characterization determined that TiO2 did not induce crystallization within the glass but did increase the glass transition temperature (Tg) from 520°C to 600°C thereby indicating a more stable network connectivity. Scaffolds were synthesized using the foam replication method, resulting in scaffolds with a pore size of approximately 500 μm with the BG-4 composition (30SiO2-12TiO2-24Na2O-21CaO-13P2O5) retaining its amorphous character post-heat treatment. Scaffold ion release was monitored over 5-60 days in simulated body fluid (SBF). Si4+ release was found to decrease, while Ca2+ levels increased in SBF as TiO2 replaced SiO2 within the glass series. Cytocompatibility studies revealed that MC3T3 Osteoblast cells proliferated on the BG-4 scaffold surface and at its interface within culture media, and cell numbers were not significantly reduced.

Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment.

Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68-75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0-6 h), simulating a prophylactic situation, and the third dosing interval (12-18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.

3D-printed HA15-loaded β-Tricalcium Phosphate/Poly (Lactic-co-glycolic acid) Bone Tissue Scaffold Promotes Bone Regeneration in Rabbit Radial Defects.

In this study, a β-tricalcium phosphate (β-TCP)/poly (lactic-co-glycolic acid) (PLGA) bone tissue scaffold was loaded with osteogenesis-promoting drug HA15 and constructed by three-dimensional (3D) printing technology. This drug delivery system with favorable biomechanical properties, bone conduction function, and local release of osteogenic drugs could provide the basis for the treatment of bone defects. The biomechanical properties of the scaffold were investigated by compressive testing, showing comparable biomechanical properties with cancellous bone tissue. Furthermore, the microstructure, pore morphology, and condition were studied. Moreover, the drug release concentration, the effect of anti-tuberculosis drugs in vitro and in rabbit radial defects, and the ability of the scaffold to repair the defects were studied. The results show that the scaffold loaded with HA15 can promote cell differentiation into osteoblasts in vitro, targeting HSPA5. The micro-computed tomography scans showed that after 12 weeks of scaffold implantation, the defect of the rabbit radius was repaired and the peripheral blood vessels were regenerated. Thus, HA15 can target HSPA5 to inhibit endoplasmic reticulum stress which finally leads to promotion of osteogenesis, bone regeneration, and angiogenesis in the rabbit bone defect model. Overall, the 3D-printed β-TCP/PLGA-loaded HA15 bone tissue scaffold can be used as a substitute material for the treatment of bone defects because of its unique biomechanical properties and bone conductivity.

Histomorphological assessment of the germanium-doped calcium phosphate ceramics on reparative osteogenesis in rabbits with systemic osteoporosis

Bone fractures are mostly urgent in nature, complex in pathogenetic, diagnostic and therapeutic aspects, and reparative osteogenesis is multimodal and depends on the balanced and reciprocal interaction of many factors. The results of histological studies for osteoreplacement of bone defects in rabbits with systemic osteoporosis are presented. The purpose of the work is histomorphological evaluation of bone regenerates after osteoreplacement with germanium-doped hydroxyapatite ceramics in rabbits with secondary osteoporosis. Experimental osteoporosis in rabbits (n=18) was induced by administration of 0.4% dexamethasone solution. In animals of the experimental group, bone defects were replaced with granules of hydroxyapatite ceramics doped with germanium, and in animals of the control group, they healed under a blood clot. Histological sections were made on a rotary microtome with a thickness of 5 to 10 μm and stained with Weigert's iron hematoxylin and 1% alcohol-based eosin solution (manufactured by Diapath, Italy). On the 60th day of reparative osteogenesis in the animals of the experimental group, the site of the bone defect was flled with compact bone tissue with minor remnants of spongy bone tissue. Slightly expanded Haversian canals were noted. In the control group, the defect site was flled with coarse and spongy bone tissue. Bone beams of various thicknesses with a small number of osteoblasts and single walled osteocytes were visualized. A signifcant number of osteocyte lacunae were empty due to the process of osteocyte lysis. Haversian canals are signifcantly dilated with a small number of vessels. Also, lacunae of bone tissue resorption and acellular areas were observed on histological specimens. Histomorphological assessment of bone regenerates confrms the realization of osteoconductive, osteointegrative and osteoinductive properties of calcium-phosphate ceramics doped with germanium in conditions of osteoporotic fractures of tubular bones. Keywords: systemic osteoporosis, bone fractures, cancellous and compact bone tissue, histological sections, histomorphological changes, rabbits.

Vat photopolymerization of biomimetic bone scaffolds based on Mg, Sr, Zn-substituted hydroxyapatite: Effect of sintering temperature

In response to the urgent demand for innovative bone regeneration solutions, the focus of this study is to develop and characterize Mg, Sr, Zn-substituted calcium phosphate scaffolds that replicate the trabecular architecture of cancellous bone. Ion substitution represents a promising approach to improve the biological effectiveness of calcium phosphates and composite materials used in bone tissue engineering applications. Porous scaffolds mimicking the natural bone structure were additively manufactured from the photosensitive ceramic suspensions for vat photopolymerization using digital light processing. The impact of the selected trace elements (0, 1 and 5 mol.% substitution) and the sintering temperature (900, 1000, 1100, 1200, and 1300 °C) was investigated in relation to the obtained crystalline phase content, microstructure, elemental distribution, thermal stability, and mechanical properties. After sintering, in addition to hydroxyapatite, β-tricalcium phosphate was detected as a result of the added trace elements in the calcium-deficient hydroxyapatite used as a starting powder. The obtained scaffolds exhibited uniform distribution of the trace elements, and they feature 3D-designed porosity predominantly ranged from 10 to 900 μm in diameter, with an average pore size of 546.25 ± 10.95 μm. The total porosity of scaffolds was 76.24 ± 1.32 vol% and an average wall thickness of 217.03 ± 8.98 μm, closely resembling the morphology of cancellous bone tissue. The mechanical properties of the scaffolds sintered at 1100 °C, 1200 °C, and 1300 °C were in line with those typically observed in trabecular bone. The study demonstrates the feasibility of using custom made bioactive hydroxyapatite powders together with vat photopolymerization to design the porosity and properties of the bone scaffolds on demand, based on the requirements of individual bone defects.

Predicting the Fracture Toughness of Human Cancellous Bone in Fractured Neck of Femur Patients Using Bone Volume and Micro-Architecture.

The current protocol used to determine if an individual is osteoporotic relies on assessment of the individual's bone mineral density (BMD), which allows clinicians to judge the condition of a patient with respect to their peers. This, in essence, evaluates a person's fracture risk, because BMD is a good surrogate measure for strength and stiffness. In recent studies, the authors were the first to produce fracture toughness (FT) data from osteoporotic (OP) and osteoarthritic (OA) patients, by using a testing technique which basically analyzes the prerequisite stress conditions for the onset of growth of a major crack through cancellous bone tissue. FT depends mainly on bone quantity (BV/TV, bone volume/tissue volume), but also on bone micro-architecture (mArch), the inner trabecular design of the bone. The working research hypothesis of the present study is that mArch offers added prediction power to BV/TV in determining FT parameters. Consequently, our aim was to investigate the use of predictive models for fracture toughness and also to investigate if there are any significant differences between the models produced from samples loaded across (AC, transverse to) the main trabecular orientation and along (AL, in parallel) the trabeculae. In multilinear regression analysis, we found that the strength of the relationships varied for a crack growing in these two orthogonal directions. Adding mArch variables in the Ac direction helped to increase the R2 to 0.798. However, in the AL direction, adding the mArch parameters did not add any predictive power to using BV/TV alone; BV/TV on its own could produce R2 = 0.730. The present results also imply that the anisotropic layout of the trabeculae makes it more difficult for a major crack to grow transversely across them. Cancellous bone models and remodels itself in a certain way to resist fracture in a specific direction, and thus, we should be mindful that architectural quality as well as bone quantity are needed to understand the resistance to fracture.

Evaluation of Stress Distributions in All Ceramic Conometric Single Crown Restorations: 3-Dimensional Finite Element Analysis

Objective: The aim of the study is to compare the effect of monolithic translucent zirconia ceramic (TZI) and monolithic lithium disilicate glass ceramic (LDS) restorative materials on stress distributions in implant components and surrounding bone tissues in implant-supported conometric single crown restorations with a conical connection system by using 3D finite element analysis.
 Methods: Restorations produced with two different all-ceramic materials using a conometric abutment and a conometric cap on the implant with a conical connection system were placed in the maxillary right second premolar region. 3D finite element analysis was used to examine the amount and distribution of stresses in implant components, in cortical and cancellous bone tissues surrounding the implant and in crowns under vertical and oblique loading. For the statistical analysis one-way ANOVA and independent samples t-test were used (p

MINERAL COMPOSITION OF MANDIBULAR BONE TISSUE IN SIMULATED PERIODONTITIS DURING METABOLIC ACIDOSIS

Destructive changes in the mandibular cancellous bone tissue determine the severity of periodontal diseases and affect their treatment outcomes. The imbalance between macro- and microelements leads to structural and functional changes in the spongy bone tissue of the lower jaw, and when being combined with the inflammatory process in the soft tissues of the periodontium leads to the tooth loss. Mineral elements deposited in the bones are included in the body buffer systems and are able to influence the metabolic processes of the macroorganism by mobilizing them into the bloodstream.
 The aim of the study is to carry out a comparative analysis of mineral element concentrations in the bone tissue of the alveolar process of the lower jaw in rats with experimentally induced periodontitis under conditions of simulated metabolic disorders and following pharmacotherapeutic correction.
 Materials and methods. The reseach was conducted on 80 white outbred sexually mature male rats aged 2-4 months and weighing 120-200 g. The animals were divided into 5 groups (16 in each): two control groups representing NC (negative control) and PC (conditionally positive control) and three experimental groups: I Group, II Group, III Group. The NC group consisted of animals kept on a standard vivarium diet throughout the experiment. The animals of PC, I – III Groups were exposed to peridontitis simulation: the rats received 0.04% solution of ammonium chloride (NH4Cl) per os within 30 days. Animals in group III (experimental periodontitis) received intramuscular injections of 5% meldonium dihydrate solution in a dose of 0.2 mg/kg of body weight. The rats in group IV (periodontitis treatment) received "Calcium glycerophosphate" (a first-generation calcium supplement) in a dose of 133 mg/kg. Group V (combination treatment) received both the meldonium dihydrate solution and calcium glycerophosphate in the same respective doses. Tissue levels of zinc, magnesium, strontium, calcium, sodium, potassium, phosphorus, and iron were measured using atomic absorption (zinc, magnesium), atomic emission (strontium, calcium, sodium, potassium), and photometric (phosphorus, iron) methods.
 Results. The change in the amount of elements in the mandibular cancellous bone tissue reveals irregularity and different mechanisms over the course of the mineralization process, depending on the chosen means of correction. The findings obtained suggest that the corrective treatments (meldonium dihydrate, calcium glycerophosphate, or their combination) promoted gradual bone density improvement through the accumulation of studied elements in the rat mandible. This indicates potential reversibility of pathological changes at this experimental stage.
 Conclusions. The cancellous part of the mandible in rats appears to be a dynamic system, responding actively to both detrimental factors and corrective interventions by altering the content and proportions of macro- and microelements.

Cytocompatible and osteoconductive silicon oxycarbide glass scaffolds 3D printed by DLP: a potential material for bone tissue regeneration.

Bone lesions affect individuals of different age groups, compromising their daily activities and potentially leading to prolonged morbidity. Over the years, new compositions and manufacturing technologies were developed to offer customized solutions to replace injured tissue and stimulate tissue regeneration. This work used digital light processing (DPL) technology for three-dimensional (3D) printing of porous structures using pre-ceramic polymer, followed by pyrolysis to obtain SiOC vitreous scaffolds. The SiOC scaffolds produced had an amorphous structure (compatible with glass) with an average porosity of 72.69% ± 0.99, an average hardness of 935.1 ± 71.0HV, and an average maximum flexural stress of 7.8 ± 1.0MPa, similar to cancellous bone tissue. The scaffolds were not cytotoxic and allowed adult stem cell adhesion, growth, and expansion. After treatment with osteoinductive medium, adult stem cells in the SiOC scaffolds differentiated to osteoblasts, assuming a tissue-like structure, with organization in multiple layers and production of a dense fibrous matrix rich in hydroxyapatite. The in vitro analyses supported the hypothesis that the SiOC scaffolds produced in this work were suitable for use as a bone substitute for treating critically sized lesions, with the potential to stimulate the gradual process of regeneration of the native tissue. The data obtained stimulate the continuity of studies with the SiOC scaffolds developed in this work, paving the way for evaluating safety and biological activity in vivo.

Bioactive and biomimetic 3D scaffolds for bone tissue engineering using graphitic carbon nitride as a sustainable visible light photoinitiator

Graphitic carbon nitride (g-C3N4) is explored as a novel sustainable visible light photoinitiator for the preparation of biomimetic 3D hydrogel scaffolds comprising gelatin methacrylamide (GelMA) and dopamine methacrylamide for use in tissue engineering. The initiator efficiency was assessed by comparing the swelling behavior and the stability of photopolymerized hydrogels prepared with GelMA of different degrees of functionalization and different comonomer compositions. Bioactive composite hydrogels with a 50 wt% nanohydroxyapatite (nHAp) content, to closely mimic the actual bone composition, were successfully obtained by the introduction of nHAp in the prepolymer solutions followed by photopolymerization. The composite hydrogels demonstrated enhanced mechanical properties and excellent stability in PBS verifying the preparation of robust 3D scaffolds for use in cancellous or pre-calcified bone tissue engineering applications. The in vitro cell response of the composite scaffolds exhibited high cell viability and enhanced differentiation of pre-osteoblasts to mature osteoblasts, demonstrating their osteogenic potential. This work establishes, for the first time, the excellent properties of g-C3N4 as a sustainable, visible light initiator, fully satisfying the principles of green chemistry, for the preparation of robust and biologically relevant hydrogels, and proposes a new approach to overcome the main challenges of conventional photoinitiators in cell scaffold fabrication, such as photobleaching, high cost and non-scalable synthesis employing toxic organic precursors and solvents.

Bone defect management with tissue-engineered constructs based on deproteinized cancellous bone: an experimental study

Background Management of bone defects with autologous bone grafting has always been the "gold standard" but it is not always possible to use it for a number of reasons. Preprocessed materials of biological and non-biological origin were developed as an alternative. A new branch of these materials is tissue-engineered constructs that fully imitate autologous bone in required volume.Aim is to study in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs.Methods The study was carried out on 24 NZW line rabbits, since this line has a fully characterized stromal-vascular fraction formula (SVF). The study design included 3 groups. First group (control) had surgical modeling of bone defects in the diaphysis of the contralateral femur without reconstruction; Group 2 had bone defect reconstruction using fragments of a deproteinized cancellous bone graft; group 3 underwent bone defect reconstruction using fragments of deproteinized cancellous bone matrix along with the autologous adipose tissue SVF (obtained according to ACP SVF technology). Animals were sacrificed with ether anesthesia at 2, 4 and 6 weeks after the operation and subsequent histological study followed.Result During all periods of the study, the newly formed bone tissue volume density in the 3rd group (reconstruction with deproteinized human cancellous bone + stromal-vascular fraction) was 1.78 times higher (p < 0.001) than in the first group (bone defect without reconstruction), 1.21 times higher (p < 0.001) than in the 2nd group (reconstruction with deproteinized cancellous bone alone). The dynamics of changes in the mature bone tissue volume density was similar to those of the newly formed bone tissue.Discussion The comparative analysis of reparative processes using a tissue engeneered construst based on deproteinized cancellous human bone with adipose tissue stromal vascular fraction revealed that the use of these bone substitute materials contributes not only to the early activation of reparative regeneration of the main structural elements of bone tissue at the site of bone defect, but also their timely differentiation.Conclusion The use of deproteinized cancellous bone matrix combined with stromal-vascular fraction to create a tissue-engineered construct could unleash several regeneration mechanisms and accelerate the process of bone defect site repair, compared with 1st and 2nd group of study.

Restoration of X-ray bone density when replacing cortical plate defects with a tissue-engineered construct in the experiment

Over the past decade, in global practice, the frequency of using high-resolution multi-layer spiral computed tomography (MSCT) for assessing the state of cancellous and cortical bone tissue has significantly increased. Using high-resolution MSCT makes it possible to assess X-ray bone density at various times after replacement of cortical plate defects with osteoplastic materials. The aim of the research. To study the restoration of cortical bone density in the area of osteoplasty using tissue-engineered construct in the experiment. Materials and methods. In an in vivo experiment on New Zeland White (NZW) rabbits, perforation defects of cortical bone were formed in the femoral diaphysis. Three study groups were set up: group 1 – without bone defect replacement; group 2 – with bone defect replacement with deproteinized cancellous bone; group 3 – with bone defect replacement with tissue-engineered construct based on deproteinized cancellous bone with stromal vascular fraction of adipose tissue. Follow-up periods were 2, 4 and 6 weeks after the surgery. The X-ray density of cortical bone tissue was measured in Hounsfield units (HU). Fragments of deproteinized human cancellous bone were used alone and in combination with the stromal vascular fraction of NZW rabbit adipose tissue as a bone-replacing material for bone defect replacement. Results. Cortical plate density the in the area of the defect in the group 3 by the week 6 is on average 1.3 times lower than that of the intact cortical plate and corresponds to D1 according to Misch classification. Cortical plate density in the area of the defect on the side of medullary canal by the week 6 in the group 3 corresponds to D1 according to Misch classification and is equal to 1351.25 ± 221.18 HU (1052; 1805), which is 1.5 times higher than in group 2 (D2 according to Misch classification; p < 0.05). The obtained results indicate an earlier restoration of X-ray bone density when using a tissue-engineered construct (group 3) compared to the same indicators in groups 1 and 2.

GC-MS based comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis.

Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS). To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN. We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification. Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN. This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.

Ant-nest type porous scaffold with micro-struts consisting of carbonate apatite for promoting bone formation and scaffold resorption.

Scaffolds having appropriate mechanical strength and providing a proper microenvironment for osteogenesis are expected to be effective alternatives to autografts for bone regeneration. In this study, ant-nest type porous (ANP) scaffolds consisting of CO3 Ap were fabricated using calcium carbonate powder or slurry and two types of polyurethane foam through a dissolution-precipitation reaction. ANP-type, three-dimensional, interconnected porous CO3 Ap scaffolds were fabricated by burning out the struts of polyurethane foams embedded in CaCO3 , followed by compositional transformation from CaCO3 to CO3 Ap. The types of polyurethane foam and impregnation methods of CaCO3 into polyurethane form affected the geometry of the resulting ANP structures. Mechanical and in vivo biological performances of these scaffolds relied on the geometry of the ANP structures. The ANP structures displayed had a clear structural advantage in bone regeneration, owing to the promotion of cell and tissue migration throughout the scaffolds. In particular, ANP-structured scaffolds, which had highest porosity, interconnectivity, and smallest strut thickness, had a mechanical strength comparable to cancellous bone, formed more new bone, were highly resorbed, resulting in cancellous bone-like bone tissue regeneration at 12 weeks of healing. The results suggest that bone regeneration after the migration of cell and tissue into the entire scaffolds is affected by strut thickness preferentially over porosity and interconnectivity. ANP-structured CO3 Ap scaffolds are attractive for bone regeneration.

Structural Mechanical Properties of 3D Printing Biomimetic Bone Replacement Materials

One of the primary challenges in developing bone substitutes is to create scaffolds with mechanical properties that closely mimic those of regenerated tissue. Scaffolds that mimic the structure of natural cancellous bone are believed to have better environmental adaptability. In this study, we used the porosity and thickness of pig cancellous bone as biomimetic design parameters, and porosity and structural shape as differential indicators, to design a biomimetic bone beam scaffold. The mechanical properties of the designed bone beam model were tested using the finite element method (FEM). PCL/β-TCP porous scaffolds were prepared using the FDM method, and their mechanical properties were tested. The FEM simulation results were compared and validated, and the effects of porosity and pore shape on the mechanical properties were analyzed. The results of this study indicate that the PCL/β-TCP scaffold, prepared using FDM 3D printing technology for cancellous bone tissue engineering, has excellent integrity and stability. Predicting the structural stability using FEM is effective. The triangle pore structure has the most stability in both simulations and tests, followed by the rectangle and honeycomb shapes, and the diamond structure has the worst stability. Therefore, adjusting the porosity and pore shape can change the mechanical properties of the composite scaffold to meet the mechanical requirements of customized tissue engineering.

¿Son los fármacos biológicos antirreumáticos nuestros nuevos enemigos?.

Introduction: The aim of this paper is to review and update the information available to date on the influence of diseasemodifying antirheumatic drugs on increased risk of infections after prosthetic surgery or osteosynthesis, and the presentation of a clinical case of infection in a patient operated on for a tibia fracture, that was being treated with Secukinumab. Clinical Case: A 70-year-old patient with psoriatic arthritis treated with Secukinumab and low-dose methotrexate, who suffered a Schatzker type II fracture of the external tibial plateau, operated on by reduction and osteosynthesis with a screwed plate and contribution of cancellous bone tissue. The patient evolved towards deep infection, isolating Actinomyces Neuii. After an early approach with washing and local debridement, the infection was not resolved, so it was necessary to remove the material, clean it, and add Bioglass (Bonalife), given the clinical deterioration of the patient. Antibiotherapy was associated with Linezolid, Clindamycin, with favorable evolution in the resolution of the infection. Discussion and conclusions: Secukinumab is a monoclonal antibody that belongs to the group of drugs known as "interleukin inhibitors", which works by neutralizing the activity of a protein called IL-17A, present in high amounts in diseases such as psoriasis, psoriatic arthritis and axial spondyloarthritis. The current recommendations for the management of rheumatic patients under treatment with biological drugs, who are going to undergo hip or knee prosthetic surgery, is to perform it at the end of the half-life of each drug, but in the case of surgical intervention due to fracture, not there is no recommendation, so extreme precautions must be taken to avoid infection, assessing in each case whether greater antibiotic prophylaxis is necessary.

Deproteinized Bone Tissue as a Matrix for Tissue-Engineered Construction: Experimental Study

Background. At present, for a number of reasons the complete bone defect replacement with autogenous bone is not always possible. Bone substitute materials are used as an alternative to autogenous bone tissue and can be of either biological or non-biological origin. One of the ways of development of reconstructive technologies is the use of tissue-engineered constructs that fully imitate autogenous bone tissue in the required volume.
 Aim of study to define in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs.
 Methods. An in vivo study was carried out on NZW rabbits. To create a construct, we used the fragments of deproteinized cancellous bone tissue of the human femoral head and stromal vascular fraction of rabbit adipose tissue as a matrix. Bone defect modeling with its subsequent replacement was performed to evaluate the efficacy of reparative osteogenesis during bone defects reconstruction. Study groups were defined: group 1 (control) surgical modeling of a bone defect of the femur without its reconstruction; group 2 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix; group 3 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix in combination with stromal vascular fraction of adipose tissue (according to ACP SVF technology).
 Results. Comparative analysis of reparative processes in case of applying tissue-engineered constructs based on deproteinized human cancellous bone matrix in combination with adipose tissue-derived stromal vascular fraction on in vivo experimental model revealed that the use of these bone substitute materials contributes not only to an early activation of reparative regeneration of main structural elements of the bone tissue in the area of the bone defect replacement, but also to its well-timed differentiation. This determines the restoration of structural and functional viability of the bone tissue at the damage site without developing discernible reactive inflammation. Moreover, the effect of the selected tissue-engineered construct with the combined influence of several factors (ACP SVF) in its composition turned out to be more effective in stimulating bone tissue repair and differentiation.
 Conclusion. Combination of SVF and deproteinized bone matrix for creating tissue-engineered constructs enables to engage several regeneration mechanisms and accelerate the process of bone defect replacement in comparison with isolated deproteinized bone matrix without bone defect reconstruction.

Mechanical behaviour of cancellous bone tissues used for the manufacturing of heterologous bone grafts

In this work, the mechanical behaviour of cancellous bone tissues used for the manufacturing of commercial heterologous bone grafts was investigated both at small and at large strains. Three different tissues were examined. They were obtained from equine bones after a specific proprietary enzymatic-based treatment aimed at achieving perfect biocompatibility while preserving the collagenous part. Two tissues had the mineral content of the bones of origin (femur, humerus), whereas the third was markedly demineralized (femur). The response at small strains and at failure was studied by means of monotonic compression tests in quasi-static conditions. Stiffness and strength turned out to be governed by the apparent density of the tissue, with specimen size and geometry, and tissue macro-structural characteristics, only playing a secondary role. A ductile- and a brittle-like failure was exhibited by the demineralized tissue and the non-demineralized ones, respectively. The large deformation behaviour was studied by means of cyclic compression tests, which clearly highlighted the occurrence of plasticity (for strains higher than ≈1.9%), and allowed to study the strain accumulation processes, at the macromechanical level. More in-depth microstructural analyses were carried out on the demineralized tissue. Flexural tests were also performed.

369Fabrication of 3D gel-printed β-tricalcium phosphate/titanium dioxide porous scaffolds for cancellous bone tissue engineering.

Human bone is composed of cortical bone and cancellous bone. The interior portion of natural bone is cancellous with a porosity of 50%-90%, but the outer layer is made of dense cortical bone, of which porosity was not higher than 10%. Porous ceramics were expected to be research hotspot in bone tissue engineering by virtue of their similarity to the mineral constituent and physiological structure of human bone. However, it is challenging to utilize conventional manufacturing methods to fabricate porous structures with precise shapes and pore sizes. Three-dimensional (3D) printing of ceramics is currently the latest research trend because it has many advantages in the fabrication of porous scaffolds, which can meet the requirements of cancellous bone strength, arbitrarily complex shapes, and individualized design. In this study, β-tricalcium phosphate (β-TCP)/titanium dioxide (TiO2) porous ceramics scaffolds were fabricated by 3D gel-printing sintering for the first time. The chemical constituent, microstructure, and mechanical properties of the 3D-printed scaffolds were characterized. After sintering, a uniform porous structure with appropriate porosity and pore sizes was observed. Besides, biological mineralization activity and biocompatibility were evaluated by in vitro cell assay. The results demonstrated that the incorporation of TiO2 (5 wt%) significantly improved the compressive strength of the scaffolds, with an increase of 283%. Additionally, the in vitro results showed that the β-TCP/TiO2 scaffold had no toxicity. Meanwhile, the adhesion and proliferation of MC3T3-E1 cells on scaffolds were desirable, revealing that the β-TCP/TiO2 scaffolds can be used as a promising candidate for repair scaffolding in orthopedics and traumatology.

Design and manufacture of 3D-cylindrical scaffolds based on PLA/TPU/n-HA with the help of dual salt leaching technique suggested for use in cancellous bone tissue engineering

A series of 3-D scaffolds based on polylactic acid (PLA) and thermoplastic polyurethane (TPU) as major phase and hydroxyapatite nanoparticles (n-HA) were prepared by using the dual leaching technique. Fourier-transform infrared spectroscopy analysis showed that almost the interactions between the constituent materials can be identified based on their functional groups. The results of thermogravimetric analysis were used to obtain the best time to prepare the samples without residual of any progen additives. The scanning electron macroscopy images clearly proved that the dual leaching technique is an effective method to prepare the appropriate morphology and also a very good dispersion and distribution for n-HA can be obtained. Dynamic contact angles showed that the presence of TPU in the PLA matrix has a positive effect on the hydrophilicity of the scaffolds. The bulk modulus (κ) values of S-PLA70TPU30H5 in dry and wet conditions were 321 and 212 Pa, respectively and the compressibility coefficient (β) of pure samples was higher than that of other scaffolds, while among the nanocomposite samples, the compressibility coefficient of S-PLA70TPU30H5 and S-PLA50TPU50H5 samples in dry and wet conditions was higher than that of other samples. Biological tests such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay, cell adhesion, 4′,6-diamidino-2-phenylindole (DAPI) analysis and alizarin red were also performed, and the results obtained for 3D scaffolds were good. In the DAPI analysis test, sample 3D-S-PLA70TPU30H5 showed good behavior, and also in the alizarin red test, the amount of minerals created in 3D-S-PLA50TPU50H5 was significant.