Diseased Bone Tissue Research Articles

Review of Materials for the Fabrication of Microparticles in the Context of Bone Tissue Engineering

Bone tissue engineering (BTE) is a rapidly advancing field that seeks to repair or regenerate damaged or diseased bone tissue. Microparticles play an increasingly significant role in BTE by serving as drug delivery systems, cellular carriers, and scaffold components. This review aims to provide a comprehensive understanding of the variety of materials used in the fabrication of microparticles for bone tissue engineering applications. Natural polymers discussed include chitosan, collagen, gelatin, hydroxyapatite (HA), and silk fibroin, each offering unique biocompatibility and biochemical properties. Synthetic polymers such as ceramics, poly (lactic acid) (PLA), poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polycaprolactone (PCL) offer advantages in terms of mechanical stability and controlled degradation. The review also explores composite materials that combine the strengths of natural and synthetic polymers for enhanced biocompatibility, mechanical strength, and bioactivity. The functionalization and surface modification of these microparticles to meet specific requirements in bone tissue engineering are additionally covered. The objective is to guide researchers in selecting the most appropriate materials for specific applications within the realm of bone tissue engineering, considering factors such as biocompatibility, mechanical properties, and bioactivity.

Harnessing Engineered Extracellular Vesicles from Mesenchymal Stem Cells as Therapeutic Scaffolds for Bone‐Related Diseases

AbstractMesenchymal stem cells (MSCs) play a crucial role in maintaining bone homeostasis and are extensively explored for cell therapy in various bone‐related diseases. In addition to direct cell therapy, the secretion of extracellular vesicles (EVs) by MSCs has emerged as a promising alternative approach. MSC‐derived EVs (MSC‐EVs) offer equivalent therapeutic efficacy to MSCs while mitigating potential risks. These EVs possess unique properties that enable them to traverse biological barriers and deliver bioactive cargos to target cells. Furthermore, by employing modification and engineering strategies, the therapeutic effects and tissue targeting specificity of MSC‐EVs can be further enhanced to meet specific therapeutic needs. In this review, the mechanisms and advantages of MSC‐EV therapy in diseased bone tissues are highlighted. Through simple isolation and modification techniques, MSC‐EV‐based biomaterials have demonstrated great promise for bone regeneration. Finally, future perspectives on MSC‐EV therapy are presented, envisioning the development of next‐generation regenerative materials and bioactive agents for clinical translation in the field of bone regeneration.

Design of TPMS-based Uniform and Hybrid Graded Lattice Structures: A Fluid Flow Analysis

Each year, more than four million people around the world undergo bone grafts and prosthesis transplants to treat bone defects and injuries by repairing and/or replacing native bone. As a result, the scaffold holds great promise for the regeneration of damaged or diseased bone tissues. One of the key components is the design of scaffolds that can mimic the structure and function of natural bone. Based on unit cell design, triply periodic minimal surface (TPMS) has attracted the attention of researchers for designing porous scaffolds. In current study, uniform and multi-morphology hybrid graded structures were designed based on TPMS, namely, primitive and I-graph-wrapped package (IWP) minimal surfaces. Furthermore, a computational fluid dynamic (CFD) model was designed based on COMSOL Multiphysics to understand the fluidic characteristics (permeability and wall shear stress) of the structures. The results show that structures reported a permeability of 7.4 – 14.3 × 10 -8 m2, meeting the requirements of natural bone. Moreover, the average wall shear stress of 0.5 – 136 mPa was observed, suitable for osteoblast differentiation and proliferation.

DETERMINING THE POSSIBLE PERSPECTIVE OF USING CATTLE BONE ASH AS OBTAINABLE RAW MATERIAL FOR BIOACTIVE GLASS

Biominerals and bioceramics are widely used in medicine in replacement as well as in the process of regeneration of diseased bone tissue. Bioactive glass is known as one of the effective materials for restoring bone tissue. Dozens of bioenamel materials of different composition and purpose are known at present. Rilligate, borate and other base biomines are known, the main characteristics of which are the presence of two types of oxides, namely P2O5 and CaO in the composition of such class of glasses. At the same time, one important thing is noted - the amorphism of biotin, in contrast to ceramics of bioactive crystalline nature, provides the possibility of adjusting the ratio of CaO/P2O5 (Ca/P) present in them within wide limits. It creates prospects for the purposeful regulation of the already mentioned properties and the growth of the fields of application. Biomin materials that are practically usaed in medicine are obtained in compositions of religiate base, when they contain 4-9 wt. % P2O5 . Non-technological compounds such as volatile P2O5 or H3PO4, hygroscopic or refractory salts of phosphoric acids are mainly used as phosphorus-containing raw materials for obtaining such glasses. In order to expand the obtainable raw material base of bioactive enamel, a complex, containing CaO and P2O5 (total 90 wt. %) and presented in the form of bioactive hydroxyapatite, raw material - ash obtained from cattle bone (bone ash) was selected. 6-10 wt. % P2O5 containing glasses were obtained from the charges containing bone ash, quartz sand, chalk and calcined soda, and as well as crystallized materials by their further heat treatment. Their characteristic properties are: bending strength, 390-510 MPa (MPa). Chemical stability with weight losses of 1.1-1.6 wt. % and density 2660-2740 km/m3. By summarizing the research results it was concluded that it is possible to use of beef bone ash as a raw material containing P2O5 in the production of bioactive glass materials.

A Comprehensive Review of Biomaterials and Its Characteristic for Bone Tissue Engineering Scaffold

The engineering of bone tissue has emerged as a promising method for the restoration and regeneration of damaged or diseased bone tissue. Bone tissue engineering relies heavily on scaffold materials, which provide a three-dimensional structure that directs cell behaviour and promotes tissue growth. However, the success of bone scaffold applications is contingent on the selection of suitable biomaterials and testing methods to assure their safety and efficacy. This review provides an exhaustive summary of biomaterials and testing methodologies for bone tissue engineering scaffold applications. The review examines the characteristics of metal-based, polymer-based, ceramic-based, composite, as well as nanomaterials that are utilised in bone scaffold applications. In addition, it discusses the properties of the scaffold materials in term of mechanical and biocompatibility properties. The review also includes an examination of the biodegradability properties of scaffolds. This exhaustive review will provide researchers, engineers, and clinicians with valuable insights into the selection and testing of biomaterials for bone scaffold applications, thereby facilitating the development of safe and effective bone tissue engineering therapies.

The Effectiveness of Compartmentalized Bone Graft Sponges Made Using Complementary Bone Graft Materials and Succinylated Chitosan Hydrogels.

Bone defects can occur from many causes, including disease or trauma. Bone graft materials (BGMs) have been used to fill damaged areas for the reconstruction of diseased bone tissues since they are cost effective and readily available. However, BGMs quickly disperse around the tissue area, which ultimately leads to it migrating away from the defect after transplantation. We tested chitosan hydrogels as a useful carrier to hold BGMs in the transplantation area. In this study, we synthesized succinylated chitosan (SCS)-based hydrogels with a high decomposition rate and excellent biocompatibility. We confirmed that BGMs were well distributed inside the SCS hydrogel. The SCS-B hydrogel showed a decrease in mechanical properties, such as compressive strength and Young’s modulus, as the succinylation rate increased. SCS-B hydrogels also exhibited a high cell growth rate and bone differentiation rate. Moreover, the in vivo results showed that the SCS hydrogel resorbed into the surrounding tissues while maintaining the BGMs in the transplantation area for up to 6 weeks. These data support the idea that SCS hydrogel can be useful as a bioactive drug carrier for a broad range of biomedical applications.

Macrophage responses to selective laser-melted Ti-6Al-4V scaffolds of different pore geometries and the corresponding osteoimmunomodulatory effects toward osteogenesis.

Following recent advances in osteoimmunology, there is growing recognition of the vital role of immune cells in the osteogenesis process. The 3D-printed scaffold, as a substitute for injured and/or diseased bone tissues, has demonstrated satisfactory pro-osteogenetic performance. However, whether immune cells prompt the above pro-osteogenetic performance has not been elucidated in detail. In the present study, highly controllable Ti-6Al-4V scaffolds with different pore geometries were fabricated using a selective laser-melting technique, to reveal their osteoimmunological functions with macrophages. The results showed that macrophages displayed characteristics of M2 phenotype in response to scaffolds. As a result, an anti-inflammatory microenvironment was generated. When the pore geometry was considered, such observations were more apparent with the hexagonal pore scaffold than with the triangular one. In addition, inhibition of the toll-like receptor signaling pathway in macrophages has been proposed to cause the above phenomenon. Upon applying conditioned media derived from macrophages on pre-osteoblasts, the hexagonal pore scaffold group was found to significantly enhance osteoblastic differentiation, via macrophage-to-implant interactions. However, the effect of triangular pore scaffold was not statistically significant compared to that of hexagonal pore scaffolds or nonporous samples. In an attempt to quantify scaffold pore geometries, it was suggested that pores with higher circularity values tended to induce M2 polarization of macrophages, promote an anti-inflammatory milieu, and therefore, achieve better osteogenetic performance via immunomodulation.

Histopathological and immunohistochemical aspects of bone tissue in aseptic necrosis of the femoral head.

Femoral head osteonecrosis, also known as avascular necrosis, is a disease with a multifactorial etiology, characterized by a profound change of bone architecture, which leads to the diminishing of bone resistance and femoral head collapse. The main causes that lead to femoral head necrosis are represented by the decrease of local blood perfusion and increase of intraosseous pressure, because of an excessive development of adipose tissue in the areolas of the trabecular bone tissue in the femoral head. The histopathological and immunohistochemical (IHC) study performed by us showed that most of bone trabeculae were damaged by necrotic-involutive processes, their sizes being reduced, both regarding their length and their diameter; generally, the spans were thin, fragmented, distanced among them, which led to the occurrence of some large areolar cavities, full of conjunctive tissue, rich in adipocytes. Some of the residual bone spans even presented microfractures. In the structure of the trabecular bone tissue, numerous cavities showed lack of content, which indicates the death of osteocytes inside, while the endosteum appeared very thin, with few osteoprogenitor, flattened, difficult to highlight cells. The IHC study showed a low reaction of the bone reparatory processes and a reduced multiplication capacity of bone cells involved in the remodeling and remake of the diseased bone tissue. Nevertheless, there were identified numerous young conjunctive cells (fibroblasts, myofibroblasts), positive to proliferating cell nuclear antigen (PCNA), cells that have a high capacity of multiplication, participating in the formation of a fibrous conjunctive tissue (sclerous) instead of the damaged bone trabeculae. The formation of fibrous conjunctive tissue causes the reduction of mechanical resistance of the femoral head and its collapse. The IHC study of the microvascularization in the femoral head damaged by aseptic osteonecrosis showed the presence of a very low vascular system, both in the residual bone trabeculae and in the sclerous conjunctive tissue. Of the inflammatory cells present in the spongy bone tissue of the femoral head affected by osteonecrosis, the most numerous ones were the macrophages. Both macrophages and T- and B-lymphocytes had a heterogenous distribution.

Polymer-ceramic fiber nanocomposite coatings on titanium metal implant devices for diseased bone tissue regeneration

The osteoblast cell growth and cancer cell inhibition of titanium (Ti) metal implant coated with polyvinyl alcohol (PVA) reinforced hydroxyapatite (HAP) composite were investigated. The fibrous composite of PVA/HAP/folic acid (FA)/Methotrexate (MTX) was coated on the surface of a titanium plate and observed with microscopy. During the PVA/HAP/FA/MTX composite's preparation, the functional changes and crystalline phases were observed through Fourier-transform infrared spectroscopy and X-ray diffraction analysis, respectively. The fiber composite had an average diameter of 19 nm and a greater mechanical strength (9660 Pa) than that of pure HAP (4965 Pa), critical to the fibrous scaffold under load-bearing applications. Biocompatibility, cell growth, and proliferation capability of the PVA/HAP/FA/MTX composite were studied in human bone marrow-derived stem cells (hBMSCs). The fiber composite was found to have excellent biocompatibility with significant cell growth, while the MTX-loaded PVA/HAP/FA composite showed cytotoxicity against A459 cells. The prepared fibrous composites will serve as a superior biomaterial for osteosarcoma-diseased bone repair after evidencing of in-vivo and clinical trials.

Study on Gelatin/Hydroxyapatite/Chitosan Material Modified with Osteoblast for Bone Bioengineering

Designing of a suitable ‘cell-material’ construct has enabled the regeneration of bone. It was in accordance with the increasing demand for the repair of defective and/or diseased bone tissue. In this research, the relative behavior of the osteoblast-seeded materials was demonstrated. It enabled the selection of the cell-material system for rabbit bone bioengineering studies. Significant role of polypeptide-polymer-ceramic-cell material in bone tissue engineering was shown. The properties of natural polymer-based scaffold were attributed to their origin and chemical modifications. In this study, the lyophilized osteoblast-material conjugate was designed and characterized extensively. The same was done by physicochemical measurement, for surface and core morphology analysis. The atomic force microscopy (AFM) and transmission electron microscopy (TEM) data from these conjugates have shown surface parameters. The surface suitable for cell attachment and proliferation along with uniform interconnected porous morphology was selected. The calcium to phosphate proportion-based energy-dispersive X-ray was done. It defines the inorganic content in these composites. The crystal spots were found from the selected area electron diffraction pattern. It had supported the insights from the physicochemical measurements. AFM and TEM micrographs have shown surface and core morphology with median surface roughness of 14.96 nm and uniform porous architecture, respectively. Fourier transmission Infra-red spectroscopy and X-ray diffraction had confirmed the formation of mineral deposits within the scaffolds. The subsequent in vitro study has revealed that among the biomaterials, ‘gelatin in hydroxyapatite-coated chitosan matrix’ has prominence over ‘gelatin-hydroxyapatite.’ It was confirmed only after seeding them with the rabbit ‘iliac crest-derived’ osteoblast. Two types of rabbit osteoblast derivatives were used. They are the osteoblast from the bone tissue (rT) and osteoblast obtained after Mesenchymal stem cell (MSCs) differentiation. Bone marrow was the source of MSCs. This ‘rT-seeded’ biomaterial was found appropriate for bone bioengineering applications.

Animal models for studying metaphyseal bone fracture healing.

An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic burden for society. Osteoporotic fractures are frequently located in metaphyseal bone regions. They are often associated with healing complications, because of the reduced healing capacity of the diseased bone tissue, the poor primary stability of the fracture fixation in the fragile bone, and the high frequency of comorbidities in these patients. Therefore, osteoporotic fractures require optimised treatment strategies to ensure proper bone healing. Preclinical animal models can help understanding of the underlying mechanisms and development of new therapies. However, whereas diaphyseal fracture models are widely available, appropriate animal models for metaphyseal fracture healing are scarce, although essential for translational research. This review covers large and small animal models for metaphyseal fracture healing. General requirements for suitable animal models are presented, as well as advantages and disadvantages of the current models. Furthermore, differences and similarities between metaphyseal and diaphyseal bone fracture healing are discussed. Both large- and small-animal models are available for studying metaphyseal fracture healing, which mainly differ in fracture location and geometry as well as stabilisation techniques. Most common used fracture sites are distal femur and proximal tibia. Each model found in the literature has certain advantages and disadvantages; however, many lack standardisation resulting in a high variability or poor mimicking of the clinical situation. Therefore, further refinement ofanimal models is needed especially to study osteoporotic metaphyseal fracture healing.

Bone-on-a-chip: microfluidic technologies and microphysiologic models of bone tissue.

Bone is an active organ that continuously undergoes an orchestrated process of remodeling throughout life. Bone tissue is uniquely capable of adapting to loading, hormonal, and other changes happening in the body, as well as repairing bone that becomes damaged to maintain tissue integrity. On the other hand, diseases such as osteoporosis and metastatic cancers disrupt normal bone homeostasis leading to compromised function. Historically, our ability to investigate processes related to either physiologic or diseased bone tissue has been limited by traditional models that fail to emulate the complexity of native bone. Organ-on-a-chip models are based on technological advances in tissue engineering and microfluidics, enabling the reproduction of key features specific to tissue microenvironments within a microfabricated device. Compared to conventional in-vitro and in-vivo bone models, microfluidic models, and especially organs-on-a-chip platforms, provide more biomimetic tissue culture conditions, with increased predictive power for clinical assays. In this review, we will report microfluidic and organ-on-a-chip technologies designed for understanding the biology of bone as well as bone-related diseases and treatments. Finally, we discuss the limitations of the current models and point toward future directions for microfluidics and organ-on-a-chip technologies in bone research.

Fabrication of a Porous and Formable Ceramic Composite Bone Tissue Scaffold at Ambient Temperature

Broken or diseased bone tissue requires a multitude of repair strategies ranging from autografts, to allografts, to synthetic bone grafts. Herein we describe a fabrication approach to create all-ceramic resorbable porous scaffolds for bone tissue repair in the absence of traditional consolidation techniques for ceramics—a technique that has potential for in situ use in operating rooms, or in field hospitals. The room temperature and pressure process utilizes a reaction with a liquid ceramic precursor to form a silicate-glass binder phase to consolidate bioactive glass frit particles and make a formable paste. This formable paste is designed to be applied directly to a bone defect, hardening in situ to become a rigid scaffold and acting as a bone ‘spackling’ paste. Characterization of the composite scaffolds is evaluated with respect to design specifications required in biomedical implant materials, namely: formability, geometric stability, porosity, and load-bearing capacity. Of the fabricated scaffolds, the composite scaffold with 7.4 vol pct sodium silicate binder was found to have the most dispersed, well distributed, and largest amount of open porosity (44 pct), average compressive strength of 1.3 MPa (with the least amount of variability), surface area to volume ratio of 33 mm−1 (slightly greater than trabecular bone), and excellent geometric stability. Results of this study indicate that the developed fabrication method should be further explored for synthetic bone graft materials.

Microspheres containing biosynthesized silver nanoparticles with alginate-nano hydroxyapatite for biomedical applications

Scaffolding system plays an important role in the development of artificial bone for treatment of defective or diseased bone tissue. In the present work, we have developed microspheres (COS-Ag-Alg-HA) containing chitooligosaccharide (COS) coated silver nanoparticles (Ag NPs) with alginate (Alg) and hydroxyapatite (HA) as bone graft substitutes. The developed microspheres were characterized through various analytical techniques such as UV–visible spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, field emission scanning electron microscopy with EDX and evaluated the mechanical strength by using universal testing machine. In addition to this, antimicrobial activity and biocompatibility of the developed microspheres were evaluated with pathogenic microbes and osteoblast-like cells, respectively. Results suggest that microspheres are rigid, and strong chemical interactions were observed between the materials. The size of the microspheres was ranging from 1.5 ± 0.5 to 4.0 ± 0.5 mm. Significant microbial inhibition was observed against Staphylococcus aureus, and the developed microspheres are biocompatible with osteoblast-like cells. Based on the aforementioned finding results, the developed microsphere is proposed to be a potential candidate for bone tissue repair and regeneration.

Bone ‘spackling’ paste: Mechanical properties and in vitro response of a porous ceramic composite bone tissue scaffold

Bone defects are treated with bone grafts, replacing damaged or diseased bone tissue with either natural bone or bone substitutes. This study investigates the structure, mechanical properties, and in vitro response of an all-ceramic composite designed for use as a bone ‘spackling’ paste: a formable synthetic bone graft paste used to repair bone defects in place, reacting with CO2 gas in ambient conditions to become a void-filling, rigid scaffold. The composite is comprised of bioactive glass frit and a soluble liquid silicate precursor combined to form an air-setting, open porous scaffold with compressive strength within the low range for trabecular bone (1.3-4.4 MPa). Characterization of scaffolds, with varying amounts of binder, was executed in accordance with established design criteria of porosity, load-bearing capacity, and bioactivity. Bioactivity was assessed via morphological, structural, and chemical changes in surface mineralization that occurred during in vitro immersion in simulated body fluid. All phases of composite specimens were observed to form calcium phosphate minerals, indicating that a chemical change occurred between the bioactive glass and sodium silicate binder phase. Ion exchange between the two phases was likely, as sodium silicate (control) was not found to produce calcium phosphate in the absence of bioactive glass. Of the selected compositions, composites with 7.4 vol% sodium silicate binder were observed to possess the highest open porosity (44 vol%), highest rate of calcium phosphate mineralization, most uniform surface mineral distribution, and largest amount of hydroxycarbonate apatite formation. The structure, mechanical properties, and in vitro response of the composite scaffolds analyzed in this research signify their potential success as bone tissue scaffolds.

Dielectric characterization of diseased human trabecular bones at microwave frequency

The objective of this study is to determine whether in vitro dielectric properties of human trabecular bones, can distinguish between osteoporotic and osteoarthritis patients’ bone samples. Specifically this study enlightens intra-patient variation of trabecular bone microarchitecture and dielectric properties, inter-disease comparison of bone dielectric properties, and finally establishes the correlation to traditional bone histomorphometry parameter (bone volume fraction) for diseased bone tissue. Bone cores were obtained from osteoporotic and osteoarthritis patients (n = 12). These were scanned using microCT to examine bone volume fraction. An open-ended coaxial probe measurement technique was employed to measure dielectric properties over the 0.5 – 8.5 GHz frequency range. The dielectric properties of osteoarthritis patients are significantly higher than osteoporotic patients; with an increase of 41% and 45% for relative permittivity and conductivity respectively. The dielectric properties within each patient vary significantly, variation in relative permittivity and conductivity was found to be greater than 25% and 1.4% respectively. A weak correlation (r = 0.5) is observed between relative permittivity and bone volume fraction. Osteoporotic and osteoarthritis bones can be differentiated based on difference of dielectric properties. Although these do not correlate strongly to bone volume fraction, it should be noted that bone volume fraction is a poor predictor of fracture risk. The dielectric properties of bones are found to be influenced by mineralization levels of bones. Therefore, dielectric properties of bones may have potential as a diagnostic measure of osteoporosis.

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review.

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone‑related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration. Among the various external stimuli for targeted therapy, near infrared (NIR) light has attracted considerable interests due to its high tissue penetration capacity, minimal damage toward normal tissues, and easy remote control properties. The main objective of this systematic review was to reveal the current applications of NIR light-assisted phototherapy for bone-related disease treatment and bone tissue regeneration. Database collection was completed by June 1, 2020, and a total of 81 relevant studies were finally included. We outlined the various therapeutic applications of photothermal, photodynamic and photobiomodulation effects under NIR light irradiation for bone‑related disease treatment and bone regeneration, based on the retrieved literatures. In addition, the advantages and promising applications of NIR light-responsive drug delivery systems for spatiotemporal-controlled therapy were summarized. These findings have revealed that NIR light-assisted phototherapy plays an important role in bone-related disease treatment and bone tissue regeneration, with significant promise for further biomedical and clinical applications.

Penetration of linezolid into bone tissue 24 h after administration in patients with multidrug-resistant spinal tuberculosis.

BackgroundLinezolid has shown strong antimicrobial activity against multidrug-resistant (MDR)/rifampin-resistant strains of Mycobacterium tuberculosis. Linezolid achieves clinical efficacy mainly through area under the concentration time curve/minimum inhibitory concentration ratio in the infected lesion site. Previous studies mainly focused on the relationship between linezolid concentrations in the blood and infected bone tissue when the blood drug concentration reached the peak 2 h after administration. However, we do not know whether linezolid can maintain the same bone/plasma ratio in infected bone tissue when the blood concentration reaches the trough level. Therefore, this study aimed to evaluate the penetrability of linezolid into bone tissue 24 h after administration in patients with MDR spinal tuberculosis (TB).MethodsNine MDR spinal TB patients, who received a treatment regimen including linezolid and underwent surgery, were enrolled prospectively from April 2017 to March 2019. Blood and diseased bone tissue specimens were collected simultaneously during operations 24 h after taking 600 mg of linezolid orally. Linezolid concentrations in plasma and diseased bone tissue specimens were determined by high-performance liquid chromatography–tandem mass spectrometry.ResultsFollowing a 600 mg oral administration of linezolid 24 h before surgery, median concentrations of linezolid in plasma and diseased bone tissue for the 9 patients were 1.98 mg/L (range 0.30–3.44 mg/L) and 0.60 mg/L (range 0.18–2.13 mg/L), respectively, at resection time. The median diseased bone/plasma linezolid concentration ratio was 0.48 (range 0.30–0.67). Pearson’s correlation analysis showed that linezolid concentrations in the plasma were positively related to those in diseased bone tissue (r = 0.949, p < 0.001).ConclusionsAfter 24 h of medication, linezolid still had good penetrability into diseased bone tissue in patients with MDR spinal TB.

Clinical value analysis of limited debridement for the treatment of incomplete gangrenous diabetic foot osteomyelitis

Objective To investigate the clinical value of limited debridement in treating diabetic foot osteomyelitis with incomplete foot gangrene. Methods Retrospective analysis of traditional surgery (complete removal of diseased bone and soft tissue) and limited debridement (limited removal of diseased bone and soft tissue) in patients with incomplete foot gangrenuria foot osteomyelitis from February 2015 to March 2017, There were 38 cases in the traditional operation group and 76 cases in the limited debridement group. Between the two groups, the sex ratio (20/18 vs 41/35), age (64.90±8.40 vs 68.1±8.10), Wagner 3/4 grading ratio (12/26 vs 26/50), the ratio of nerve ulcers/ischemic neurotic ulcers (13/25 vs 24/52), the ulceration ratio of forefoot/middle foot+hind foot (33/5 vs 68/8) , arterial ABI (0.71±0.39 vs 0.67±0.33) , and lower extremity arterioplasty ratio (52.63% vs 59.21%), combined with hypertension (78.95% vs 77.63%), coronary heart disease (71.05% vs 69.74%), cardiac insufficiency (10.53% vs 9.21%), renal failure rate (21.05% vs 22.37%), incidence of hypoproteinemia (10.53% vs 10.53%), anaemia (15.79% vs 19.74%) and drug resistance of drug resistant bacteria (26.32 vs 23.68%) had no statistical difference. All the patients received antibiotic after surgery. The incidence of antibiotic related complications, the rate of amputation on the ankle, the average length of hospitalization, the average healing time of the ulcer/wound, the rate of readmission in one year, the rate of recurrent ulcer, the rate of new ulceration, the rate of ulceration and the death rate were collected to evaluate the clinical effects. Results The duration of antibiotic use in the traditional operation group (25.2±12.3 d) and the average hospitalization time (16.9±7.6 d). The average healing time of ulcer/wound (121.6 ±23.7 d) was shorter than that of limited debridement group (32.5±16.8 d, 24.7±12.5 d, 153.2±27.8 d). The amputation rate (1.32%), re-admission rate (1.32%), ulcer recurrence rate (2.63%) and ulcer recurrence rate (1.32%) in the limited debridement group were significantly lower than those in the traditional operation group (10.53%, 31.58%, 21.05%, 28.95%). There was no significant difference in the incidence of antibiotic-related complications and all-cause mortality between the two groups. Conclusion Conservative surgery for diabetic foot osteomyelitis of incomplete foot gangrene is scientific and reasonable, and the quality of life of patients can be improved. The clinical benefit is obvious. It is worth of clinical promotion. Key words: Diabetic foot; Debridement; Osteomyelitis

Generation of bioactive nano-composite scaffold of nanobioglass/silk fibroin/carboxymethyl cellulose for bone tissue engineering

The development of bone tissue construct through tissue engineering approach offers a great promise in meeting the increasing demand for repair and regeneration of damaged and/or diseased bone tissue. For the generation of bone tissue engineered construct, polymer-ceramic composite matrices with nanostructure architecture and mesenchymal stem cells (hMSCs) of human origin are of prime requirement. Keeping these in view, in the present work a novel electrospun nanofibrous silk fibroin (SF)/carboxymethyl cellulose (CMC)/nano-bioglass (nBG) composite scaffold that mimics native bone extracellular matrix with appropriate composition was designed and fabricated by free liquid surface electrospinning technique. The scaffold possesses desired morphological, structural, biodegradability, bioactivity, surface roughness and mechanical properties thereby exhibited an excellent platform to support the growth of cells. The in-vitro culture of hMSCs over the developed scaffold has shown adhesion, proliferation and viability of cells, thus facilitated cell-scaffold construct generation and further extracellular bone matrix formation through osteogenic differentiation as evident from alkaline phosphatase activity, biomineralization, immunostaining and Runx2/osteocalcin expression assessment. Thus, the developed hMSCs seeded scaffold construct might be suitable for bone tissue engineering applications.