3D-printing-assisted fabrication of chitosan scaffolds from different sources and cross-linkers for dental tissue engineering.

The aim of the present study was to fabricate and characterise chitosan scaffolds from animal and fungal sources, with or without gelatine as a co-polymer, and cross-linked to 3-glycidyloxyproply trimethoxysilane (GPTMS) or genipin for application in dental root tissue engineering. Chitosan-based scaffolds were prepared by the emulsion freeze-drying technique. Scanning electron microscopy (SEM) and nano-focus computed tomography (nano-CT) were used to characterise scaffold microstructure. Chemical composition and cross-linking were evaluated by Fourier transform infrared-attenuated total reflectance spectroscopy. Compression tests were performed to evaluate scaffold mechanical properties. Scaffold degradation was evaluated by gravimetric method and SEM. Scaffold bioactivity immersed in simulated body fluid was evaluated by SEM, with associated electron dispersive X-ray spectroscopy, and apatite formation was examined by X-ray diffraction. Finally, human dental pulp stem cells (hDPSCs) viability was evaluated. The fabrication method used was successful in producing scaffolds with organised porosity. Chitosan source (animal vs. fungal), co-polymerisation with gelatine and cross-linking using GPTMS or genipin had a significant effect on scaffold properties and hDPSCs response. Chitosan-genipin (CS-GEN) scaffolds had the largest pore diameter, while the chitosan-gelatine-GPTMS (CS-GEL-GPTMS) scaffolds had the smallest. Animal chitosan-gelatine co-polymerisation increased scaffold compressive strength, while fungal chitosan scaffolds (fCS-GEL-GPTMS) had the fastest degradation rate, losing 80 % of their weight by day 21. Gelatine co-polymerisation and GPTMS cross-linking enhanced chitosan scaffolds bioactivity through the formation of an apatite layer as well as improved hDPSCs attachment and viability. Tailored chitosan scaffolds with tuned properties and favourable hDPSCs response can be obtained for regenerative dentistry applications.

Formulation of a reactive oxygen producing calcium sulphate cement as an anti-bacterial hard tissue scaffold.

Prophylactic antibiotic bone cements are extensively used in orthopaedics. However, the development of antimicrobial resistance to antibiotics, demonstrates a need to find alternative treatments. Herein, an antimicrobial honey (SurgihoneyRO-SHRO) has been successfully incorporated into a calcium sulphate (CS) based cement to produce a hard tissue scaffold with the ability to inhibit bacterial growth. Antimicrobial properties elicited from SHRO are predominantly owed to the water-initiated production of reactive oxygen species (ROS). As an alternative to initially loading CS cement with SHRO, in order to prevent premature activation, SHRO was added into the already developing cement matrix, locking available water into the CS crystal structure before SHRO addition. Promisingly, this methodology produced > 2.5 times (715.0 ± 147.3 µM/mL/g) more ROS over 24 h and exhibited a compressive strength (32.2 ± 5.8 MPa) comparable to trabecular bone after 3 weeks of immersion. In-vitro the SHRO loaded CS scaffolds were shown to inhibit growth of clinically relevant organisms, Staphylococcus aureus and Pseudomonas aeruginosa, with comparable potency to equivalent doses of gentamicin. Encouragingly, formulations did not inhibit wound healing or induce an inflammatory response from osteoblasts. Overall this study highlights the prophylactic potential of CS-SHRO cements as an alternative to traditional antibiotics.

A Novel Resorbable Composite Material Containing Poly(ester-co-urethane) and Precipitated Calcium Carbonate Spherulites for Bone Augmentation-Development and Preclinical Pilot Trials.

Polyurethanes have the potential to impart cell-relevant properties like excellent biocompatibility, high and interconnecting porosity and controlled degradability into biomaterials in a relatively simple way. In this context, a biodegradable composite material made of an isocyanate-terminated co-oligoester prepolymer and precipitated calcium carbonated spherulites (up to 60% w/w) was synthesized and investigated with regard to an application as bone substitute in dental and orthodontic application. After foaming the composite material, a predominantly interconnecting porous structure is obtained, which can be easily machined. The compressive strength of the foamed composites increases with raising calcium carbonate content and decreasing calcium carbonate particle size. When stored in an aqueous medium, there is a decrease in pressure stability of the composite, but this decrease is smaller the higher the proportion of the calcium carbonate component is. In vitro cytocompatibility studies of the foamed composites on MC3T3-E1 pre-osteoblasts revealed an excellent cytocompatibility. The in vitro degradation behaviour of foamed composite is characterised by a continuous loss of mass, which is slower with higher calcium carbonate contents. In a first pre-clinical pilot trial the foamed composite bone substitute material (fcm) was successfully evaluated in a model of vertical augmentation in an established animal model on the calvaria and on the lateral mandible of pigs.

Effect of different preparation designs and all ceramic materials on fracture strength of molar endocrowns.

OBJECTIVE: The aim was to compare the fracture strength of Molar endocrowns fabricated from different all-ceramic materials and various preparation designs. MATERIALS AND METHODS: Ninety extracted human molar teeth were root canal treated and randomly divided into three groups according to the all ceramic materials used for fabrication of the endocrowns (n = 30): (1) Lithium disilicate (IPS e.max Press); (2) Polymer infiltrated ceramic (Vita Enamic); (3) High translucency zirconia (Ceramill Zolid HT). Each group was subdivided into 3 subgroups (n = 10) according to the preparation design as 2 mm occlusal reduction, 4.5 mm occlusal reduction, and 4.5 mm occlusal reduction with 2 mm radicular extension. The endocrowns from each material were fabricated and surface treated according to the manufacturer's recommendations. After cementation with self-adhesive resin luting cement, the specimens were stored in a humid environment for 72 hours and subsequently subjected to 5000 thermal cycles. After, a compressive, static-axial load was applied using a universal testing machine until failure. Load-to-failure was recorded (N) and the specimens were examined under a stereomicroscope to determine the failure type. The data was statistically analyzed using One-way ANOVA and Tukey HSD tests at p < 0.05. RESULTS: The Lithium Disilicate endocrowns recorded the higher mean fracture strength for 4.5 mm occlusal thickness and 2 mm radicular extension at 3770.28 N and 3877.40 correspondingly. The High translucency zirconia endocrowns at conventional 2 mm thickness showed the highest mean fracture load (3533.34 N). Even though polymer infiltrated ceramic endocrowns displayed comparatively lesser fracture load; they recorded the predominantly favorable fractures. CONCLUSIONS: Increased occlusal thickness showed a significant improvement in fracture strength of lithium disilicate and polymer infiltrated ceramic molar endocrowns. Although the 2 mm radicular extension had the substantial enhancement of fracture strength in high translucency zirconia, it resulted in more unfavorable failure types.

Biomechanical comparison of tigecycline loaded bone cement with vancomycin and daptomycin loaded bone cements.

OBJECTIVE: The objectives of this study were "1" to analyze the compressive and tensile mechanical strength characteristics of tigecycline loaded bone cement and "2" to compare them with those of vancomycin and daptomycin loaded bone cements which are used in prosthetic joint infections complicated with resistant microorganisms. METHODS: In this study, three experimental groups, which consisted of vancomycin (subgroups containing 1 g, 2 g, and 3 g vancomycin), daptomycin (subgroups containing 0.5 g, 1 g, and 1.5 g daptomycin), and tigecycline (subgroups containing 50 mg, 100 mg, and 150 mg tigecycline) and one control group without antibiotics were used. Using a standardized protocol, all antibiotic loaded bone cements were prepared. For each antibiotic group, including the control group, 10 samples were tested. All samples were biomechanically tested in terms of compressive strength and tensile strength. RESULTS: Compression tests showed that all determined antibiotic concentrations resulted in a significant decrease when compared with the control group (p<0.0011). Vancomycin and daptomycin study groups demonstrated lower tensile strength than the control group (p<0.0011). However, comparison of tensile values of tigecycline study groups with the control group revealed no significant difference (p>0.0011). In addition, all statistically significant results from between groups comparisons revealed higher tensile and compressive mechanical strength values for the tigecycline groups (p<0.0011). CONCLUSION: Evidence from this study has demonstrated that tigecycline loaded bone cement may have no mechanical disadvantage compared with vancomycin and daptomycin loaded bone cements in terms of mechanical strength when used at defined concentrations.

Evaluation of the antimicrobial activity and compressive strength of a dental cement modified using plant extract mixture.

Literature lacks sufficient data regarding addition of natural antibacterial agents to glass ionomer cement (GICs). Hence, the aim of the study was to increase the antimicrobial properties of GICs through its modification with mixture of plant extracts to be evaluated along with an 0.5% chlorohexidine-modified GIC (CHX-GIC) with regard to biological and compressive strength properties. Conventional GIC (freeze-dried version) and CHX were used. Alcoholic extract of Salvadora persica, Olea europaea, and Ficus carcia leaves were prepared using a Soxhlet extractor for 12 h. The plant extract mixture (PE) was added in three different proportions to the water used for preparation of the dental cement (Group 1:1 PE, 2:1 PE, and 1:2 PE). Specimens were then prepared and tested against the unmodified GIC (control) and the 0.5% CHX-GIC. Chemical analysis of the extract mixture was performed using Gas chromatography-mass spectrometry. Antimicrobial activity was evaluated using agar diffusion assay against Micrococcus luteus and Streptoccocus mutans. Compressive strength was evaluated according to ISO 9917-1:2007 using a Zwick testing machine at a crosshead speed of 0.5 mm/min. Antimicrobial activity against Streptoccocus mutans was significantly increased for all the extract-modified materials compared to the unmodified cement, and the highest concentration was comparable to the CHX-GIC mixture. The activity against Micrococcus luteus was also significantly increased, but only for the material with the highest extract concentration, and here the CHX-GIC group showed statistically the highest antimicrobial activity. Compressive strength results revealed that there was no statistically significant difference between the different mixtures and the control except for the highest tested concentration that showed the highest mean values. The plant extracts (PEs) enhanced the antimicrobial activity against S. mutans and also against M. luteus in the higher concentration while compressive strength was improved by addition of the PE at higher concentrations.

How Osmoviscoelastic Coupling Affects Recovery of Cyclically Compressed Intervertebral Disc.

STUDY DESIGN: Osmoviscoelastic behavior of cyclically loaded cervical intervertebral disc. OBJECTIVE: The aim of this study was to evaluate in vitro the effects of physiologic compressive cyclic loading on the viscoelastic properties of cervical intervertebral disc and, examine how the osmoviscoelastic coupling affects time-dependent recovery of these properties following a long period of unloading. SUMMARY OF BACKGROUND DATA: The human neck supports repetitive loadings during daily activities and recovery of disc mechanics is essential for normal mechanical function. However, the response of cervical intervertebral disc to cyclic loading is still not very well defined. Moreover, how loading history conditions could affect the time-dependent recovery is still unclear. METHODS: Ten thousand cycles of compressive loading, with different magnitudes and saline concentrations of the surrounding fluid bath, are applied to 8 motion segments (composed by 2 adjacent vertebrae and the intervening disc) extracted from the cervical spines of mature sheep. Subsequently, specimens are hydrated during 18 hours of unloading. The viscoelastic disc responses, after cyclic loading and recovery phase, are characterized by relaxation tests. RESULTS: Viscoelastic behaviors are significantly altered following large number of cyclic loads. Moreover, after 18-hour recovery period in saline solution at reference concentration (0.15 mol/L), relaxation behaviors were fully restored. Nonetheless, full recovery is not obtained whether the concentration of the surrounding fluid, that is, hypo-, iso-, or hyper-osmotic conditions. CONCLUSION: Cyclic loading effects and full recovery of viscoelastic behavior after hydration at iso-osmotic condition (0.15 mol/L) are governed by osmotic attraction of fluid content in the disc due to imbalance between the external load and the swelling pressure of the disc. After removal of the load, the disc recovers its viscoelastic properties following period of rest. Nevertheless, the viscoelastic recovery is a chemically activated process and its dependency on saline concentration is governed by fluid flow due to imbalance of ions between the disc tissues and the surrounding fluid. LEVEL OF EVIDENCE: 3.

Crosslinked porous three-dimensional cellulose nanofibers-gelatine biocomposite scaffolds for tissue regeneration.

Gelatine is a biocompatible and natural polymer with chemical properties similar to the extracellular matrix. However, it has poor mechanical properties and sensitive to enzymatic biodegradation that limits its application in 3D scaffold fabrication. Cellulose nanofibrous (CNF) offers biocompatibility, high surface area and excellent mechanical properties with slow in-vivo degradation. To fine tune their properties, CNF, and gelatine (CNF-GEL) were blended to form biocomposite aerogels. Epichlorohydrin (EPH) was incorporated into CNF-GEL as a chemical crosslinker to investigate its effect on the physiochemical, mechanical, and biological properties of the biocomposite aerogels both in-vitro and in-vivo. Regardless of the composition of the prepared aerogels, they possessed porosity of >90% with the pore size of 7-135 µm, which was confirmed in the morphological analysis. The presence of EPH improved the chemical interaction between CNF and gelatine, hence enhanced the compressive strength compared to uncrosslinked samples. The formulation of crosslinked CNF-GEL 90:10 offered the highest compressive strength of 61.35 kPa. The in-vitro and in-vivo studies showed adequate cytocompatibility, cell viability and cell attachment in the optimal crosslinked formulation with tuned enzymatic degradation. Antimicrobial property was also achieved in the optimal scaffold by incorporating curcumin as an antimicrobial agent.

Leprdb/+ Dams Protect Wild-type Male Offspring Bone Strength from the Detrimental Effects of a High-Fat Diet.

The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD). Here, we investigate the effect of maternal hyperleptinemia on offspring bone by using 2 independent maternal models. First, we compared wild-type (WT) offspring from severely hyperleptinemic Leprdb/+ (DB/+) dams with those from WT dams. In the second model, WT females were implanted with miniosmotic pumps that released either saline (group SAL) or leptin (group LEP; 650ng/hour) and the WT offspring were compared. At 23 weeks of age, a subset of offspring were challenged with a HFD for 8 weeks. When the offspring were 31 weeks of age, bone geometry, strength, and material properties were investigated. The HFD increased trabecular bone volume but decreased both total breaking strength and material strength of femora from the offspring of WT dams. However, male offspring of DB/+ dams were protected from the detrimental effects of a HFD, while offspring of LEP dams were not. Further material analysis revealed a modest decrease in advanced glycation end product accumulation coupled with increased collagen crosslinking in male offspring from DB/+ dams on a HFD. These data suggest that while maternal leptin may protect bone quality from the effects of a HFD, additional factors of the maternal environment controlled by leptin receptor signaling are likely also involved.

Effects of hydroxyapatite on PMMA-HAp cement for biomedical applications.

OBJECTIVE: The main goal of this study was to examine the influence of hydroxyapatite (HAp) macroaggreate concentrations on thermal and mechanical properties of radioactive bone cement and to study the relation of glass transition Tg with its mechanical properties. METHODS: The bone cement as (1-x)PMMA-xHAp binary system was prepared in six [x] distinct concentration parameters of 0.0 up to 0.5. The HAp was synthesized using a solgel procedure following calcination by thermal treatment. The composite was prepared in cold based (non-radioactive) mixing polymethyl methacrylate (PMMA) and HAp. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and mechanical compressive strength (CS) were used to measure the thermal and mechanical properties. RESULTS: The DSC and TGA thermal profiles in function to concentration parameter [x] were presented. The CS lies in a range of 3.71-7.37 MPa and the glass transition temperature Tg = 126.27 °C. There was a direct relationship between the PMMA-HAp thermoplastic properties with mechanical and thermal properties in function of HAp concentrations. CONCLUSION: The specific PMMA-HAp composite, with a concentration ratio of 1:1 and HAp thermal treatment at the Tg, provides a material with a compression strength of 7.37 MPa and a suitable amount of porous similar to a trabecular bone, possible to apply in bone cement implants, regardless of whether they are radioactive or not.

An injectable bioactive magnesium phosphate cement incorporating carboxymethyl chitosan for bone regeneration.

Magnesium phosphate cement (MPC) can be injected to form an in situ scaffold to repair bone defects. Here we synthesized novel injectable bioactive cements (CMPCs) by incorporating different ratios of carboxymethyl chitosan (CMC, 0-10%) into MPC. The physiochemical properties, compositions, and microstructures of CMPCs were evaluated. The in vitro cellular responses of pre-osteoblast MC3T3-E1 cells to CMPCs including adhesion, proliferation, and differentiation were quantified and the underlying cellular mechanisms investigated. CMPCs had longer setting times and lower setting temperatures. CMPC injectability was enhanced by the addition of CMC. The CMPC containing 5% CMC had the highest compressive strength and washout resistance. CMPCs had a more neutral pH compared to MPC at four weeks. Furthermore, CMPC samples showed similar degradability and Mg2+ release to MPC in Tris-HCl buffer. Osteoblasts (MC3T3-E1) showed significantly greater adherence, proliferation, and differentiation on CMPC specimens than on MPC. Finally, CMPCs effectively increased the adsorption of fibronectin and activated integrin signaling as indicated by enhanced FAK and ERK phosphorylation. Our novel CMPC composites have improved physicochemical properties and cellular responses and represent a promising material for bone regeneration.

Comparative study on biodegradation and biocompatibility of multichannel calcium phosphate based bone substitutes.

The objective of this study was to fabricate multichannel biphasic calcium phosphate (BCP) and ß-tricalcium phosphate (TCP) bone substitutes and compare their long-term biodegradation and bone regeneration potentials. Multi-channel BCP and TCP scaffolds were fabricated by multi-pass extrusion process. Both scaffolds were cylindrical with a diameter of 1-mm, a length of 1-mm, and seven interconnected channels. Morphology, chemical composition, phase, porosity, compressive strength, ion release behavior, and in-vitro biocompatibility of both scaffolds were studied. In-vivo biodegradation and bone regeneration efficacies of BCP and TCP were also evaluated using a rabbit model for 1 week, 1 month, and 6 months. BCP exhibited superior compressive strength compared to TCP scaffold. TCP showed higher release of both calcium ions and phosphorous ions than BCP in SBF solution. Both scaffolds showed excellent in-vitro biocompatibility and upregulated the expression of osteogenic markers of MC3T3-E1 cells. In-vivo studies revealed that both cylindrical TCP and BCP scaffolds were osteoconductive and supported new bone formation. Micro-CT data showed that the bone-regeneration efficacy of TCP was higher at one month and at six months after implantation. Histological examination confirmed that TCP degraded faster and had better bone regeneration than BCP after 6 months.

Physical, mechanical and biological performance of PHB-Chitosan/MWCNTs nanocomposite coating deposited on bioglass based scaffold: Potential application in bone tissue engineering.

Nowadays, using the nanocomposite coatings on bioceramic scaffolds is a great interest for many researchers to improve the properties of these scaffolds. In this study, the effect of poly (3-hydroxybutyrate) PHB-Chitosan (Cs)/multi-walled carbon nanotubes (MWCNTs) nanocomposite coating deposited on nano-bioglass (nBG)-titania (nTiO2) scaffolds fabricated by foam replication method was investigated. Structural analyses such as XRD and FT-IR confirmed the presence of PHB, Cs and MWCNTs in the coated scaffolds. The results of SEM and porosity measurement showed that even with 1 wt% MWCNTs, scaffolds have a high percentage of interconnected porosity. The compressive strength of the scaffolds coated with PHB-Cs/MWCNTs (1 wt%) was increased up to 30 folds compared to nBG/nTiO2 scaffold. The surface roughness of the coated scaffolds, which was determined by AFM, was increased. The nanocomposite coating caused a decrease in contact angle and retaining the negative zeta potential of the coated scaffolds. The increase in pH and degradation rate was observed in the coated scaffolds. Increasing the apatite-like formation by the presence of PHB-Cs/MWCNTs was confirmed by SEM, EDAX and XRD tests. PHB-Chitosan/MWCNTs nanocomposite coating lead to more proliferation and viability of MG-63 cells and higher secretion of alkaline phosphatase.

Importance of pressure plasticity during compression of probiotic tablet formulations.

The usefulness, the high production rate and the cost effectiveness make tablets the dosage form of choice for oral probiotics. Nevertheless, probiotic bacteria undergo a lot of mechanical stress during tableting which causes damage to their cell wall and membrane and other bio-active components. This can lead to an inactivation of the probiotic bacteria and therefore in a failure of the probiotic therapy. To obtain a tablet with a sufficient amount of viable cells, research on the influence of formulation and process parameters on bacterial survival is essential. This study aimed to decipher tableting properties of the probiotic powder blends that have a major impact on survival rates. The powder blends consisted of the prototype probiotic strain Lactobacillus rhamnosus GG, a filler-binder and a suitable amount of lubricant. They were manufactured by direct compression at different compression pressures and tableting speeds. The tableting properties were analysed in detail by a 3-D modelling technique, which characterized normalized time, pressure and displacement simultaneously. The results of the 3-D modelling demonstrated the significant effect of the pressure plasticity (e) and the angle of rotation (ω) on the viability of L. rhamnosus GG during direct compression.

Development of halloysite nanotube/carboxylated-cellulose nanocrystal-reinforced and ionically-crosslinked polysaccharide hydrogels.

We report the development of halloysite nanotubes (HNTs)/carboxylated-cellulose nanocrystals (cCNCs) - reinforced and ionically-crosslinked k-carrageenan (k-CG)/xanthan gum (XG) hydrogels. In this study, cCNCs were extracted from microcrystalline cellulose using ammonium persulfate and exhibit 'spindle-like' nanocrystals with approximate diameter of 15-30 nm and length of 30-120 nm. The freeze-dried hydrogels showed highly porous microstructure with good pore-interconnectivity. Further, tunable swelling ratio and in vitro degradation rate of hydrogels under physiological condition (pH 7.4 PBS, 37 °C) were observed. In wet or dry states, the dynamic mechanical analysis of kCXGHN20cCN20 hydrogel showed significantly improved compressive strengths (at 50% strain: 8.1 ±â€¯1.35 kPa or 81.33 ±â€¯1.66 kPa, whereas at 70% strain: 11.84 ±â€¯0.61 kPa or 120.7 ±â€¯1.16 kPa) when reinforced with HNTs (20 wt%)/cCNCs (20 wt%), respectively. The stiffness values are reported at different compressive strains. All hydrogels showed excellent attachment and proliferation of human skin fibroblasts (CCD-986Sk) cells on hydrogels for 7 and 14 days of culture periods. The results showed that these hydrogels may have potential application in soft tissue engineering.

Peptide-immobilized starch/PEG sponge with rapid shape recovery and dual-function for both uncontrolled and noncompressible hemorrhage.

It is challenging for traditional hemostatic sponges to meet the clinic demand for both uncontrolled and noncompressible hemorrhage. With the aim to develop a rapid shape recovery material with both active and passive hemostatic performance, a dual-functional hemostatic sponge (TRAP-Sp) with a macroporous structure and good mechanical properties for controlling massive and noncompressible hemorrhage was prepared by chemically immobilizing thrombin-receptor-agonist-peptide (TRAP) onto a starch/polyethylene glycol (PEG) sponge. The TRAP2-Sp1 showed the best hemostatic performance among all samples in both rat artery uncontrollable hemorrhage and liver defect noncompressible hemorrhage models. When analyzing the hemostatic mechanism of TRAP-Sp, the high water absorption capacity of the sponge contributed to absorbing plasma, concentrating blood cells, and enhancing blood coagulation. After absorbing water, the shape-fixed TRAP-Sp with sufficient mechanical strength and high resilience can rapidly expand and apply pressure to the wound. TRAP immobilized on the sponge could activate the adhered platelets in an active pathway. Additionally, evaluation of cytotoxicity, hemolysis, and histology further highlighted the adequate biocompatibility of TRAP-Sp. With excellent hemostatic performance and biosafety, this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage. STATEMENT OF SIGNIFICANCE: There is a need for innovative hemostatic materials for both uncontrolled and noncompressible hemorrhage. This manuscript describes a rapid shape recovery hemostatic sponge with both active and passive hemostatic performances synthesized by foaming technique, cross-linking reaction, and chemical immobilization of thrombin-receptor-agonist-peptide (TRAP). On contact with blood, the shape-fixed sponge can not only rapidly recover its original shape and concentrate platelets and RBCs but also activate the adhered platelets efficiently. The dual-functional sponge has excellent hemostatic efficacy in rat femoral artery hemorrhage and can control noncompressible hemorrhage in penetrating liver wound. Thus, we believe that this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage.

Three-dimensional Printed Mg-Doped ß-TCP Bone Tissue Engineering Scaffolds: Effects of Magnesium Ion Concentration on Osteogenesis and Angiogenesis In Vitro.

Background: Three-dimensional (3D) printed bone tissue engineering scaffolds have been widely used in research and clinical applications. ß-TCP is a biomaterial commonly used in bone tissue engineering to treat bone defects, and its multifunctionality can be achieved by co-doping different metal ions. Magnesium doping in biomaterials has been shown to alter physicochemical properties of cells and enhance osteogenesis. Methods: A series of Mg-doped TCP scaffolds were manufactured by using cryogenic 3D printing technology and sintering. The characteristics of the porous scaffolds, such as microstructure, chemical composition, mechanical properties, apparent porosity, etc., were examined. To further study the role of magnesium ions in simultaneously inducing osteogenesis and angiogenesis, human bone marrow mesenchymal stem cells (hBMSCs) and human umblical vein endothelial cells (HUVECs) were cultured in scaffold extracts to investigate cell proliferation, viability, and expression of osteogenic and angiogenic genes. Results: The results showed that Mg-doped TCP scaffolds have the advantages of precise design, interconnected porous structure, and similar compressive strength to natural cancellous bone. hBMSCs and HUVECs exhibit high proliferation rate, cell morphology and viability in a certain amount of Mg2+. In addition, this concentration of magnesium can also increase the expression levels of osteogenic and angiogenic biomarkers. Conclusion: A certain concentration of magnesium ions plays an important role in new bone regeneration and reconstruction. It can be used as a simple and effective method to enhance the osteogenesis and angiogenesis of bioceramic scaffolds, and support the development of biomaterials and bone tissue engineering scaffolds.

Grape seed extract supplement increases bone callus formation and mechanical strength: an animal study.

BACKGROUND: The positive effects of grape seed proanthocyanidin extract (GSPE) on bone health, which is a potent antioxidant, are known but its effects on fracture healing are not sufficiently covered in the literature. This study aims to investigate the effects of GSPE on fracture healing and biomechanics of healing bone. MATERIALS AND METHODS: Sixty-four adult Wistar-Albino male rats were divided into 8 groups of 8 animals in each group. Osteotomy was performed to the right femurs of all groups except the negative control (G1) and positive control (G2) groups, and intramedullary Kirchner wire was used for fixation. GSPE was given to half of the rats (G2-G4-G6-G8) 100 mg/kg/day by oral gavage. The rats were sacrificed on the tenth (G3-G4), twentieth (G5-G6), and thirtieth (G1-G2-G7-G8) days, respectively, and histopathological, radiological, and biomechanical examinations were performed. RESULTS: Histopathological examination of the specimens from the callus tissues revealed that bone healing was more prominent in the groups supplemented with GSPE (G4, G6, G8). There was a statistically significant improvement in radiological recovery scores and callus volumes in groups with GSPE. When biomechanical strengths were evaluated, it was found that GSPE increased bone strength not only in fracture groups but also in the positive control group (G2). CONCLUSIONS: As a result, this study showed that GSPE, a potent anti-oxidant, had a positive effect on bone healing and improved mechanical strength of the healing bone.

Development of Coprocessed Chitin-Calcium Carbonate as Multifunctional Tablet Excipient for Direct Compression, Part 2: Tableting Properties.

The use of multifunctional excipients is gaining interest as it simplifies formulations by replacing the need of multiple monofunctional excipients. In previous work, coprocessed chitin-calcium carbonate (CC) showed to have good potential as a multifunctional excipient for fast disintegrating tablets produced by direct compression. It allowed for good tablet strength, enhanced powder flowability, and higher true and bulk densities with fast disintegrating properties. The objective of this work is to gain insight on CC tableting properties under different tablet manufacturing conditions (different lubrication levels, compression speeds, and dwell times) and in formulations with drug models: ibuprofen and paracetamol. Results showed that CC exhibited good tabletability, compressibility, and compactibility profiles. CC does not require the addition of lubricant and can be used at high compression speeds and different dwell times. When included in formulations with ibuprofen and paracetamol at different percentages, CC enhanced tablets strength and promoted fast disintegration and drug dissolution. In conclusion, this study shows that CC can be used as a multifunctional excipient (filler-disintegrant-binder) for fast disintegrating tablets produced by direct compression.

The chitosan/tri-calcium phosphate bio-composite bone cement promotes better osteo-integration: an in vitro and in vivo study.

BACKGROUND: Polymethylmethacrylate bone cement has a variety of applications in orthopedic surgery, but it also has some shortcomings such as high heat generation during polymerization and poor integration with bone tissue. In this study, a bio-composite bone cement composed of tri-calcium phosphate and chitosan as additives to acrylic bone cement was developed. Our hypothesis is that this new bio-composite bone cement has a better osteo-integration than pure polymethyl methacrylate cement. METHODS: Physiological composition, i.e., 65 wt% inorganic and 35 wt% organic components, of tri-calcium phosphate and chitosan contents was selected as degradable additives to replace acrylic bone cement. A series of properties such as exothermic temperature changes, setting time, bio-mechanical characteristics, degradation behaviors, and in vitro cytotoxicity were examined. Preliminary in vivo animal study was also performed. RESULTS: The results showed that the bio-composite bone cement exhibited lower curing temperature, longer setting time, higher weight loss and porosity after degradation, lower compressive Young's modulus, and ultimate compressive strength as compared with those of pure polymethyl methacrylate cement. Cell proliferation tests demonstrated that the bio-composite bone cement was non-cytotoxic, and the in vivo tests revealed that was more osteo-conductive. CONCLUSIONS: The results indicated that the modified chitosan/tri-calcium phosphate/polymethyl methacrylate bio-composites bone cement could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth. This new bio-composite bone cement has potential in clinical application. Our future studies will focus on long-term implantation to investigate the stability of the bio-composite bone cement in long-term implantation.