In the present research, molecular modeling methods were used to study a novel bioadhesive composed of gelatin (protein) and alginate (polysaccharides), crosslinked with N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxysuccinimide (NHS). Three antibiotic drugs were added to the bioadhesive: Vancomycin, Ofloxacin, and Clindamycin. Computational tools were applied to estimate the crosslinking degree and compare the effect of the antibiotics on the physical properties of the gelatin‐alginate conjugate. The crosslinking degree was estimated by calculating the enthalpy of mixing of gelatin with alginate and their interaction with the crosslinking agents. The calculations revealed that gelatin mixes well with alginate, which enables their crosslinking. Various ratios between EDC and NHS were examined, and an optimal ratio was found. The interaction of alginate‐gelatin conjugate with the antibiotics was correlated to the experimental results of bonding strength. The most significant interaction of the conjugate is with clindamycin. The gelatin part is responsible for the strong interaction with clindamycin, and alginate forms strong interaction with ofloxacin. Thus, the interaction of alginate‐gelatin conjugate with the antibiotics is governed by the proportion between gelatin and alginate in the conjugate. The degradation rate of gelatin‐alginate was related to its interaction with water. It was found that the conjugate is highly hydrophilic. Gelatin is more soluble in water than both alginate and alginate‐gelatin and is probably the part in the conjugate that governs the solubility and degradation rate. Therefore, the degradation rate of the conjugate can be controlled by changing the proportion between gelatin and alginate. 相似文献
Nowadays, despite remarkable progress in developing bone tissue engineering products, the fabrication of an ideal scaffold that could meet the main criteria, such as providing mechanical properties and suitable biostability as well as mimicking the bone extracellular matrix, still seems challenging. In this regard, utilizing combinatorial approaches seems more beneficial. Here, we aim to reinforce the mechanical characteristics of gelatin hydrogel via a combination of Genipin‐based chemical cross‐linking and incorporation of the poly l ‐lactic acid (PLLA) nanocylinders for application as bone scaffolds. Amine‐functionalized nanocylinders are prepared via the aminolysis procedure and incorporated in gelatin hydrogel. The nanocylinder content (0, 1, 2, 3, and 4 wt%) and cross‐linking density (0.1, 0.5, and 1 wt/vol%) are optimized to achieve suitable morphology, swelling ratio, degradation rate, and mechanical behaviors. The results indicate that hydrogel scaffold cross‐linking by 0.5 wt% of Genipin shows optimized morphological feathers with a pore size of around 300 to 500 μm as well as an average degradation rate (40.09% ± 3.08%) during 32 days. Besides, the incorporation of 3 wt% PLLA nanocylinders into the cross‐linked gelatin scaffold provides an optimized mechanical reinforcement as compressive modulus, and compressive strength show a 4‐ and 2.6‐fold increase, respectively. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay indicates that the scaffold does not have any cytotoxicity effect. In conclusion, gelatin composite reinforced with 3 wt% PLLA nanocylinders cross‐linked via 0.5 wt/vol% Genipin is suggested as a potential scaffold for bone tissue engineering applications. 相似文献
Bacterial cellulose (BC)/GEL composites were prepared in situ by adding gelatin into BC-producing culture medium. The addition of gelatin interfered with the formation of the BC pellicle structure and thus made the BC yield and growth rate quite different from that of pure BC. Scanning electron microscope images showed that the width of cellulose ribbons became narrower than that of pure BC and the gelatin filled in the pores of BC to form a dense structure. The addition level of gelatin significantly influences the yield of BC/GEL composites. An optimum value of 0.5 wt/v% gelatin was attained, with which the highest yield of 0.0541 g/100 mL was achieved. Under this condition, the weight percentage of gelatin in BC/GEL composite was 65 wt%. BC/GEL composites were treated with glutaraldehyde to crosslink BC fibrils and gelatin. The crosslinking degree, determined by the concentration of glutaraldehyde and crosslinking time, could affect the swelling behavior, thermal stability and mechanical properties of composites. With increasing of the crosslinking degree, the crystallinity index and swelling behavior of the composites decreased. The increase in the crosslinking degree also descreased the composite’s strain at break in elongation but increased the compressive and tensile strength. Covalent bonding between BC and gelatin provides good strength retention to the glutaraldehyde-treated composites with a high crosslinking degree. Considering the cytocompatibility and properties of composites, the most appropriate concentration of glutaraldehyde and crosslinking time were 1.0 wt/v% and 24 h, respectively. 相似文献
A poly(l,l-lactide-co-glycolide) (70/30)/(tricalcium phosphate) (PLGA/TCP) composite scaffold was fabricated by low-temperature deposition (LDM) and its degradation performed in vitro for 22 weeks. Various changes during degradation in vitro, which included changes in acidity of the degradation medium, morphology, weight, composition, molecular weight of the PLGA component and mechanical properties of the scaffold, were investigated. It was found that the acidity of degradation medium of the PLGA(70/30)/TCP composite scaffolds reduced and became much lower than that of TCP-free scaffold. With degradation, the volume and porosity of the PLGA(70/30)/TCP composite scaffold reduced at first then increased slowly, while the surface morphology of the scaffold changed from smooth to rough. The weight loss of the scaffold increased by dissolution of the degraded products and TCP component, but mainly by dissolution of the glycyl-rich degraded products of the PLGA component. The molecular weight of the PLGA component reduced with time, but the molecular weight distribution increased at first and then reduced. The compressive strength and modulus of the scaffold increased at first and then reduced with further degradation. The effect of degradation on modulus was much bigger than that on compressive strength. Based on excellent cell affinity of the PLGA(70/30)/TCP composite scaffold, a potentially useful bone tissue engineering scaffold is proposed. 相似文献
Rate of polymer degradation is very important for implantable biomaterials since controlling the degradation rate may complement the biological response and affected mechanical property requirements. In spite of numerous publications on the potential use of combinations of poly lactic acid/bioactive glass fillers for degradable bone plate, little information exists on the controlling degradation rate and its effects on the other aspects such as biomechanical compatibility, bioactivity, etc. Our previous study revealed that a composite bone plate consist of poly l-lactic acid/braided bioactive glass fibers has the initial mechanical properties near to cortical bone. In this study, degradation rate and mechanical behavior of the composite bone plate were assessed, and also degradation rate was controlled by using proper manufacturing process and improving bonding between matrix and reinforcement. Moreover, bioactivity of the composite was considered before and after controlling degradation rate, because of the important role of bioactivity and ion release in healing acceleration. Results showed that degradation process of the composite could be controlled properly. Strength of the treated composite decreased only about 5% through 2 weeks and about 35% after 8 weeks while, the strength loss for the untreated composites was about 50 and 70 percent after 2 weeks and 8 weeks of degradation respectively. Although calcium-phosphate formation on the surface of the composite was postponed in the treated samples, the bioactivity of the composite remained unchanged and bone-like apatite was formed on the composite surface which is important for the application of the composite in bone tissue environment. 相似文献
Artificially fabricated hydroxyapatite (HAP) shows excellent biocompatibility with various kinds of cells and tissues which makes it an ideal candidate for a bone substitute material. In this study, hydroxyapatite nanoparticles have been prepared by using the wet chemical precipitation method using calcium nitrate tetra-hydrate [Ca(NO3)2.4H2O] and di-ammonium hydrogen phosphate [(NH4)2 HPO4] as precursors. The composite scaffolds have been prepared by a freeze-drying method with hydroxyapatite, chitosan, and gelatin which form a 3D network of interconnected pores. Glutaraldehyde solution has been used in the scaffolds to crosslink the amino groups (|NH2) of gelatin with the aldehyde groups (|CHO) of chitosan. The X-ray diffraction (XRD) performed on different scaffolds indicates that the incorporation of a certain amount of hydroxyapatite has no influence on the chitosan/gelatin network and at the same time, the organic matrix does not affect the crystallinity of hydroxyapatite. Transmission electron microscope (TEM) images show the needle-like crystal structure of hydroxyapatite nanoparticle. Scanning Electron Microscope (SEM) analysis shows an interconnected porous network in the scaffold where HAP nanoparticles are found to be dispersed in the biopolymer matrix. Fourier transforms infrared spectroscopy (FTIR) confirms the presence of hydroxyl group (OH-) , phosphate group (PO3-4) , carbonate group (CO2-3) , imine group (C=N), etc. TGA reveals the thermal stability of the scaffolds. The cytotoxicity of the scaffolds is examined qualitatively by VERO (animal cell) cell and quantitatively by MTTassay. The MTT-assay suggests keeping the weight percentage of glutaraldehyde solution lower than 0.2%. The result found from this study demonstrated that a proper bone replacing scaffold can be made up by controlling the amount of hydroxyapatite, gelatin, and chitosan which will be biocompatible, biodegradable, and biofriendly for any living organism. 相似文献
Aqueous gelatin (5%) is crosslinked in the presence of 0.040–0.020M peroxydisulfate at 70°C., but in 0.40M peroxydisulfate, gelatin initially is crosslinked and then redissolves to give a solution of reduced viscosity. The rate of crosslinking depends on the concentration of peroxydisulfate, the nature of peroxydisulfate's cation, and the pH range of the solution during crosslinking. Addition of silver ion to gelatin–peroxydisulfate solutions increases the rate of crosslinking, whereas addition of hydroquinone inhibits crosslinking. Further, induced decomposition of peroxydisulfate is observed in the presence of gelatin. Acetylated and esterified gelatins are crosslinked by aqueous peroxydisulfate, but the ability of deaminated gelatin to crosslink is greatly reduced. Crosslinking is believed to proceed via sulfate and hydroxyl free-radical attack of gelatin, with in situ generation of reactive intermediates that crosslink with other reactive sites in gelatin. Possible sites of crosslinking in gelatin have been suggested in light of viscosity data, chemical and amino acid analyses, and peroxydisulfate's known mode of decomposition. 相似文献
Uniform gelatin microspheres (GMS) of a wet size of 100 microm in diameter were fabricated by the electric field assisted precision particle fabrication (E-PPF) method and crosslinked with different glutaraldehyde (GA) concentrations to study the effect of the crosslinking density on drug release. The drug release profiles of the crosslinked GMS were studied along with the intraparticle drug distribution and the particle degradation characteristics. Due to the concentration gradient of GA along the diffusion path into the GMS, the crosslinking density is higher on the GMS surface, making it less susceptible to degradation. As a result, the GMS with higher GA concentrations (0.375-0.875%) exhibited a highly resistant surface toward enzymatic degradation. On the other hand, the amount of drug complexation at the surface decreases as the GA concentration increases, which can be attributed to the lowered basicity of gelatin caused by the increased crosslinking density. These factors collectively affect the drug release kinetics and give rise to similar release profiles for GMS above a GA concentration of 0.375%. 相似文献
Rational design and development of tailorable simple synthesis process remains a centerpiece of investigational efforts toward engineering advanced hydrogels. In this study, a green and scalable synthesis approach is developed to formulate a set of gelatin‐based macroporous hybrid hydrogels. This approach consists of four sequential steps starting from liquid‐phase pre‐crosslinking/grafting, unidirectional freezing, freeze‐drying, and finally post‐curing process. The chemical crosslinking mainly involves between epoxy groups of functionalized polyethylene glycol and functional groups of gelatin both in liquid and solid state. Importantly, this approach allows to accommodate different polymers, chitosan or hydroxyethyl cellulose, under identical benign condition. Structural and mechanical anisotropy can be tuned by the selection of polymer constituents. Overall, all hydrogels show suitable structural stability, good swellability, high porosity and pore interconnectivity, and maintenance of mechanical integrity during 3‐week‐long hydrolytic degradation. Under compression, hydrogels exhibit robust mechanical properties with nonlinear elasticity and stress‐relaxation behavior and show no sign of mechanical failure under repeated compression at 50% deformation. Biological experiment with human bone marrow mesenchymal stromal cells (hMSCs) reveals that hydrogels are biocompatible, and their physicomechanical properties are suitable to support cells growth, and osteogenic/chondrogenic differentiation, demonstrating their potential application for bone and cartilage regenerative medicine toward clinically relevant endpoints. 相似文献
Poly(propylene fumarate) (PPF) oligomers were synthesized by step polymerization using bis(2-hydroxypropyl fumarate) or propylene bis(hydrogen maleate) as starting materials. Oligomers possessing identical degrees of polymerization (DP), but varying in their end group character (either hydroxyl or carboxyl) were first prepared and characterized, then used as part of a bone cement preparation consisting of oligomer, tricalcium phosphate, calcium carbonate, and methyl methacrylate. Compressive strength of the resulting composite appeared to be dependent on both the degree of polymerization of the PPF, and the nature of the oligomers' end groups. 相似文献
Porous iron-substituted tricalcium phosphate (FeTCP) ceramics with a Fe content of 0.49 and 1.09% has been developed. The hydrostatically estimated ceramics porosity is 40–45%. The solubility of ceramics in an isotonic solution has been studied. The solubility rate of FeTCP ceramics is slightly higher as compared with iron-free ceramics. Based on the results of in vitro tests of FeTCP ceramics on cultured fibroblasts, these materials are believed to be biocompatible. The developed materials can be recommended for use in medicine in the treatment of diseases associated with bone lesions. 相似文献
The aim of this study was to evaluate the biodegradability and biocompatibility of gelatin matrices designed for drug-eluting stents (DESs). The matrices were prepared by crosslinking alkali-treated gelatin (AlGelatin) with a citric acid-based crosslinker, trisuccinimidyl citrate (TSC), to form AlGelatin-TSC. The biodegradation behavior of the matrices was evaluated in vitro and in vivo. An in vitro enzymatic degradation test showed that AlGelatin-TSC prepared at a TSC concentration of 20 mM is the most stable in collagenase solution compared to AlGelatin-TSC prepared at TSC concentrations higher or lower than 20 mM. Then, AlGelatin-TSC were implanted subcutaneously in rats to evaluate their biodegradability and tissue reaction in vivo. Similar to the in vitro degradation behavior, AlGelatin-TSC with TSC concentration of 20 mM exhibited the lowest biodegradable rate in vivo among all AlGelatin-TSC. In addition, strong inflammation and calcification were not observed for AlGelatin-TSC at any TSC concentration. From an analysis of the crosslinking density of the resulting AlGelatin-TSC, the lowest biodegradability of AlGelatin-TSC with TSC concentration of 20 mM was due to the highest crosslinking density of the matrix. These results suggest that AlGelatin-TSC is suitable for use as matrices in DESs because of its excellent biocompatibility and biodegradability. 相似文献
Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate material to introduce specific motifs for selective targeting to specific organs, but gelatin nanoparticles have not yet been modified to increase their affinity to mineralized tissue. By means of conjugating bone‐targeting alendronate to biocompatible gelatin nanoparticles, a simple method is developed for the preparation of gelatin nanoparticles which exhibit strong affinity to mineralized surfaces. It has been shown that the degree of alendronate functionalization can be tuned by controlling the glutaraldehyde crosslinking density, the molar ratio between alendronate and glutaraldehyde, as well as the pH of the conjugation reaction. Moreover, it has been shown that the affinity of gelatin nanoparticles to calcium phosphate increases considerably upon functionalization with alendronate. In summary, gelatin nanoparticles have been developed, which exhibit great potential for use in bone‐specific drug delivery and regenerative medicine.
Hydroxyapatite (HA) coatings have received considerable attention because they exhibit bone bonding capabilities. Unfortunately the common forms of coating production result in cracking and degradation of HA due to the thickness of the coatings and the elevated temperatures employed. This study demonstrates the production of sub-micron, crack-free calcium phosphate coatings on quartz glass substrates using a sol-gel dip-coating technique and firing temperatures below 1000°C.Coatings fired at 1000°C comprised a mixture of hydroxyapatite (HA) and tricalcium phosphate (TCP). XPS analysis of the coating surface showed that the Ca/P ratio lay in the range 1.5–1.67, and that there was a contribution from carbon in the form of carbonate.It is proposed that the sol-gel coatings comprising a resorbable (TCP) and an insoluble (HA) phase have potential benefits in certain implant applications. 相似文献