Biological Assessment of Composite Materials Based on Poly-L-lactide and Bovine Bone

Biodegradable polymers and bioactive fillers are being combined in a variety of composite materials for biomedical application. Biological properties in vivo of poly-L-lactide (PLLA) matrix containing bovine bone were investigated by using acute systemic toxicity in vivo, blood biocompatibility, sensitivity, pyrogen, and genetic toxicity testing methods. The results indicated that there were no toxic and death cases observed in the acute systemic toxicity test. The PLLA/bovine bone composite showed no genetic toxicity, pyrogen, or sensitizing response and the hemolytic index was 0.29%. The results from these studies demonstrated that PLLA/bovine bone has a good biocompatibility and good biological safety. Therefore, PLLA/bovine bone composite materials can be promising biomedical materials for bone tissue engineering.     

In vitro degradation behaviors of Poly-<Emphasis Type="SmallCaps">l</Emphasis>-lactide/bioactive glass composite materials in phosphate-buffered solution

In vitro degradation behaviors of composite materials composed of poly-l-lactide (PLLA) and bioactive glass (BG) were systematically investigated up to 20 weeks in phosphate-buffered solution (PBS) at 37 °C. The properties of PLLA/BG composites and PLLA materials, including weight loss, bending strength and modulus, shearing strength, polymer molecular weight and its distribution, and the morphologies, were investigated as a function of degradation time. The change of the pH value of the PBS media was also detected. The results showed that the presence of the bioactive glass modified the degradation of the matrix polymer. The degradation rate of the PLLA/BG composites was slower than the degradation rate of the sole PLLA materials.     

Microstructural,mechanical properties and strengthening mechanism of DLP produced β-tricalcium phosphate scaffolds by incorporation of MgO/ZnO/58S bioglass

The inherent brittleness of bioceramics restricts their applications in load-bearing implant, although they possess good biocompatibility and bioactivity. ZnO, MgO and 58S bioglass (BG) were incorporated as additives to further improve the mechanical properties and biocompatibility of β-TCP and ZnO/MgO/BG-β-TCP composite scaffolds were manufactured via digital light processing (DLP). The composite with the best comprehensive performance was selected for degradation behavior and biocompatibility evaluation. The effects of different proportions of ZnO/MgO/BG on mechanical strength were analyzed and ZnO0·5/MgO1/BG2-β-TCP (ZMBT) samples exhibited superior mechanical strength. The improvement by 272% and 99% respectively was achieved in fracture toughness and compressive strength with the optimal recipe. The enhancement effect is realized through phase transition, alterative sliding actions and transgranular fracture to effectively prevent the load transfer combining the functions of bioglass and metal oxide. ZMBT scaffolds exhibited a more desirable pH environment and an enhanced ability of apatite-mineralization formation, meanwhile Si⁴⁺, Mg²⁺ and Zn²⁺ were gradually released from scaffolds. Furthermore, in vitro evaluation indicated that ZMBT scaffolds presented not only excellent cell attachment, proliferation, alkaline phosphatase (ALP) activity, but they up-regulated osteogenic gene (ALP, OCN, Runx2). These results suggest that the addition of ZnO/MgO/BG to DLP-printed β-TCP scaffolds offer a smart strategy to fabricate porous scaffolds with conspicuously better biological and physicochemical properties including compressive strength, bioactivity, osteogenesis and osteogenesis-related gene expression. Metal-oxide and BG synergistically enhanced the mechanical and biological properties which make the ZMBT scaffolds a strong candidate for bone repair applications.     

Fabrication and cytotoxicity assessment of novel polysiloxane/bioactive glass films for biomedical applications

This work evaluates for the first time the cyto-compatibility of silicone (polysiloxane)/bioactive glass composite films produced by dip coating on stainless steel substrates using osteoblast-like (MG-63) cells. With the aim of creating corrosion resistant coatings for biomedical applications, bioactive glass (BG) of 45S5 composition was used as a filler in conjunction with commercial silicones (MK and H62C). Bioactive glass has the property of forming a direct bond to living bone, and polysiloxane is an attractive candidate for protective coatings due to its resistance to oxidation and corrosion. Suspensions based on polysiloxanes (MK/H62C) and micro-sized BG fillers were used for dip coating stainless steel substrates at room temperature, followed by curing in oxidative atmosphere at 260 °C and 500 °C. Fourier transform infrared spectroscopy (FTIR) analysis revealed the presence of Si–O–Si, Si–OR, Si–CH₃ and Si–OH groups on the substrate. Field emission scanning electron microscopy showed that the coatings were homogeneous with no obvious cracks or pinholes at relatively high concentrations of both polysiloxane and BG. The cell biology experiments confirmed that the expressed cell-morphology, analyzed on chosen surfaces, was pheno-typical for MG-63 cells after 48 h of incubation. On the film containing the lower amount of polysiloxane/BG the most dense cell layer was formed. Our results indicated that polysiloxane/BG composite films exhibited good cyto-compatibility at 260 °C and 500 °C and showed no toxicity toward MG-63 cells suggesting the potential of this composite for applications in medical implants.     

Influence of ceramic phosphate powders on the physicochemical and biological properties of poly(l-lactide)

In the present work, the attention is focused on cannulated, biodegradable olives made of poly(l-lactide) (PLLA) and PLLA with the addition of phosphate ceramics. The olive is an element expanding the intramedullary nail intended to be implantation the humerus bone. During degradation, the olive reduces the diameter of the nail, while ensuring the best conditions for the growth of bone tissue. The article examines the effect of the addition of tricalcium phosphate (β-TCP) and hydroxyapatite (HAp) on morphology, chemical structure, physicochemical and biological properties of PLLA during storage in a degradation medium imitating the natural environment of the human body. The introduction of β-TCP+HAp into PLLA led to significant changes in both surface morphology, chemical structure and physicochemical properties, which contributed to the faster course of the biodegradation of the orthopedic implant. Due to this process, it was found that the PLLA composite with phosphate ceramics can be successfully used in this application. Clinical studies have shown that the implantation of olive made of PLLA+β-TCP+HAp does not cause any negative systemic reactions. The orthopedic implant was biodegradable and significantly contributes to bone union.     

Evaluation of In-Vitro Cytotoxicity of Composite Materials Composed of Poly-L-lactic Acid and β-Tricalcium Phosphate

Composite material film composed of Poly-L-lactic acid (PLLA) and β-tricalcium phosphate (β-TCP) was prepared by a solvent evaporation technique. Cellular cultivation in vitro, Von Kossa staining and MTT assay were performed. The results of cytotoxicity test show that cells cultured in extracts of PLLA/β-TCP and on the surface of composite showed normal growth and proliferation, mineralization nodules were observed for fibroblasts cultured in PLLA/β-TCP extract at day 7. Compared with pure PLLA materials, β-TCP in the PLLA composite facilitate both adhesion and proliferation of rat fibroblasts on the PLLA/β-TCP composite film.     

Preparation and Properties of Bioactive Composite Based on Bioactive Glass and Poly-L-Lactide

Bioactive and bioresorbable composite was fabricated based on poly-L-lactide (PLLA) and bioactive glass (average particle size: 4.24 µm) by the combination of solvent evaporation technique and hot pressing. Bioactive glass granules are distributed homogeneously in the composite. With the increasing of the amount of bioactive glass, the bending strength and shearing strength of composite decrease while the bending modulus increases. PLLA/bioactive glass composites present a typical morphology of brittle failure with a smooth fracture surface. The biocompatibility test shows that the bioactive glass existing in the composite facilitates both adhesion and proliferation of rat fibroblast on the PLLA/bioactive glass composite film.     

Novel branched poly(l-lactide) with poly(glycerol-co-sebacate) core

A series of biodegradable poly (glycerol-sebacate-l-lactide) (PGSLA) copolymers, with variable PLLA length, were synthesized and characterized. The copolymers comprised PGS backbone chain with a nominal molecular weight of 2,800 g/mol. The length of each PLLA side chain covered the 800–14,000 range, while the length of the PLLA was easily controlled by the feed molar ratio of the l-lactide to the PGS. The structure of the copolymer was studied by nuclear magnetic resonance spectroscopy and gel permeation chromatography. Differential scanning calorimetric measurements and thermal gravimetric analysis had been performed to indicate the glass transition temperature (T _g), melting point (T _m), and the degree of crystallinity (χ _c). It was also found that the onset decomposition temperature (T _d) of the copolymers was lower than those of the linear polylactide (LPLLA). After solution casting and solvent evaporation, porous structures were found in the copolymer films by scanning electron microscope (SEM). Water contact angle results showed that the hydrophilicity of the copolymers was much higher than that of linear PLLA. In vivo, PGSLA copolymer demonstrated a favorable tissue response profile compared to PGS/LPLLA blend. There was also significantly less inflammation and fibrosis during degradation. PGSLA might therefore serve as an excellent candidate material for medical applications, given its minimal in vivo tissue response.     

Changes in the crystallinity and mechanical properties of poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid)/poly(butylene succinate-<Emphasis Type="Italic">co</Emphasis>-<Emphasis Type="SmallCaps">l</Emphasis>-lactate) blend with annealing process

Biodegradable polymer blends of poly(l-lactic acid) (PLLA) and poly(butylene succinate-co-l-lactate) (PBSL) at various blending ratios are prepared. The blending of PLLA with PBSL results in an increase in the ductility and thermal stability of the blend. However, flexural strength and modulus, as well as loss modulus, decrease with an increase in PBSL content. Annealing is employed to increase blend crystallinity and subsequently improve the mechanical properties of the PLLA/PBSL blend. The influences of annealing time on the crystal modification, thermal properties, and mechanical properties of the PLLA/PBSL blend are investigated by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and three-point bending test, respectively. Crystalline peaks are found in the XRD patterns of all annealed samples. DSC analysis reveals that the degree of crystallinity is enhanced with an increase in annealing time. The flexural modulus also increases with annealing time due to the change in crystalline phases. However, longer periods of annealing, especially over 20 h, result in thermal degradation and subsequently reduce the modulus value of the PLLA/PBSL blend.     

In vivo biocompatibility and bioactivity of in situ synthesized hydroxyapatite/polyetheretherketone composite materials

Hydroxyapatite/polyetheretherketone (HA/PEEK) composite materials were prepared via an in situ synthesis process in order to achieve strong bonding between PEEK matrix and hydroxyapatite fillers, and ultimately to improve the mechanical properties of the composites. In the study, the biocompatibility of the synthesized HA/PEEK materials was investigated by acute toxicity test, hemolytic test, sensitization test, pyrogen test, intradermal test, and toxicity assay test on animal tissue and cells for the purpose of examining the possible adverse effects of the residue organic chemicals from the in situ synthesis process. In vivo bioactivity of both lab‐synthesized PEEK and HA/PEEK composites with various HA content was also studied. It is found that the in situ synthesized composite materials possess good biocompability without toxicity. Although the bioactivity of the material increases with HA content, the composite material with 5.6 vol % HA exhibits satisfactory bioactivity without compromising its excellent mechanical performance, which hints to a potential use as load‐bearing orthopedic material. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Assessment of Cytocompatibility of Bulk Modified Poly-L-lactic Acid Biomaterials

The cytocompatibility and hydrophilicity tests were performed by culturing mouse fibroblastic cells on films of poly-L-lactic acid (PLLA), poly(L-lactic-co-glycolide) (PLGA) and poly(L-lactide-co-glycolide)/ bioactive glass (PLGA/BG) or in the presence of extracts from these polymeric materials. The solvent casting method was used to prepare these films. PLLA films were most hydrophobic and PLGA/BG was least hydrophobic. Compared to the other films, PLLA showed the worst results in cytocompatibility. PLGA also showed favorable results for fibroblastic cells viability. PLGA/BG films also demonstrated improved cell compatibility due to the good biocompatibility of the bioactive glass particles. The results of this study indicate the promising biocompatibility of PLGA/BG as biomaterials in medical field.     

抗感染重组合异种骨的生物相容性研究

目的 检测抗感染重组合异种骨（ARBX）产品的生物相容性,确保ARBX产品在临床上安全、有效。方法 根据卫生部制定的《生物材料和制品的生物学评价标准》及《相关生物材料和制品的企业标准 Q/JGY001-94》,进行了ARBX急性毒性试验、过敏性试验、熟原试验、骨内埋植试验、肌内埋植试验、溶血试验及细胞毒性试验。结果ARBX未引起小鼠急性毒性反应、豚鼠过敏反应及家兔热原反应。在兔骨内和小鼠肌内埋植,既未产生纤维包膜,也未引起淋巴细胞及炎性细胞浸润。对家兔红细胞溶血率为1.2％,无溶血现象。体外细胞毒性反应指标R=0.25/0,无细胞毒性。结论ARBX的生物相容性符合国家规定的生物材料和制品的生物学标准及企业标准,可试用于临床治疗相关疾病。     

Microstructure and flexural strength of the Y:TZP/BG composite

The addition of bioactive glasses to a Y:TZP matrix represents a feasible alternative to provide bioactivity to this material and optimize osseointegration. This work evaluated the effect of the BG concentration (0 and 10 wt%) and the sintering temperature (1200°C and 1300°C) on the microstructure, relative density, and flexural strength of the composite Y:TZP/BG. The Y:TZP and Y:TZP/BG powders were uniaxially pressed and sintered at 1200°C or 1300°C for 1 h. The microstructure was characterized by X-ray diffraction analysis, scanning electron microscopy, and energy-dispersive X-ray Spectroscopy. Relative density was calculated from density values obtained using the Archimedes’ principle. For the flexural strength, specimens (n = 6) were fractured in a biaxial flexural setup using a piston-on-three-balls fixture in a universal testing machine. Bioactivity test was performed in simulated body fluid solution. The results suggested that BG addition decreased the grain size of the composite, increased porosity and caused a significant decrease in the relative density and flexural strength. Crystalline phases of calcium stabilized cubic zirconia and sodium zirconium silicate were formed after the addition of BG. Finally, it was concluded that composite specimens sintered at 1300°C showed the highest density values and larger grains compared to those sintered at 1200°C.     

Bone Regeneration in rat using a gelatin/bioactive glass nanocomposite scaffold along with endothelial cells (HUVECs)

In our previous study, a three‐dimensional gelatin/bioactive glass nanocomposite scaffold with a total porosity of about 85% and pore sizes ranging from 200 to 500 μm was prepared through layer solvent casting combined with lamination technique. The aim of this study was to evaluate in vitro biocompatibility and in vivo bone regeneration potential of these scaffolds with and without endothelial cells when implanted into a critical‐sized rat calvarial defect. MTT assay, SEM observation, and DAPI staining were used to evaluate cell viability and adhesion in macroporous scaffolds and results demonstrated that the scaffolds were biocompatible enough to support cell attachment and proliferation. To investigate the in vivo osteogenesis of the scaffold, blank scaffolds and endothelial/scaffold constructs were implanted in critical‐sized defects, whereas in control group defects were left untreated. Bone regeneration and vascularization were evaluated at 1, 4, and 12 weeks postsurgery by histological, immunohistochemical, and histomorphometric analysis. It was shown that both groups facilitated bone growth into the defect area but improved bone regeneration was seen with the incorporation of endothelial cells. The data showed that the porous Gel/BaG nanocomposite scaffolds could well support new bone formation, indicating that the proposed strategy is a promising alternative for tissue‐engineered bone defects.     

Vitroceramic coatings deposited by laser ablation on Ti-Zr substrates for implantable medical applications with improved biocompatibility

The influence of vitroceramic coatings deposited onto Ti-Zr alloy plates on the biological properties of the final biomaterials was investigated. In this regard, two vitroceramic masses, different from compositional point of view, were synthesized by a sol-gel route, being subsequently converted into ceramic targets, suitable for ablation experiments. The film depositions were conducted in oxidative atmosphere, on substrates heated at 300 or 400 °C. The coated samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy coupled with selected area diffraction and energy-dispersive X-ray spectroscopy, contact angle measurements and in vitro biological analyses (MTT cell proliferation assay, GSH oxidative stress assay, optical and fluorescence microscopy). All results sustained the applicative potential of Ti-Zr alloy substrates covered with a thin vitroceramic layer for medical implant applications.     

Synthesis and Properties of Composite Biomaterials Based on Hydroxyapatite and Poly(L-Lactide)

Composite biomaterial composed of poly(L-lactide) (PLLA) and hydroxyapatite (HA) was obtained by using the combination of solvent evaporation technique and hot pressing. HA particles in the PLLA matrix were homogeneously dispersed. A typical morphology of brittle failure with a smooth fracture surface was observed. The addition of HA particles changed significantly the appearance of the impact fracture surface to a pattern of multiple cracks. With the increasing of the amount of the HA, the bending strength of composite decreases while the bending modulus increases. The PLLA/HA composite exhibits improved cell compatibility due to the good biocompatibility of the HA particles.     

The effect of bioactive glass nanoparticles on corrosion barrier performance and bioactivity of zinc oxide coatings electrodeposited on Ti6Al4V substrate

Zinc oxide coatings were electrodeposited on Ti6Al4V substrates from a nitrate bath with and without 1 wt% BG nanoparticles at ?1.2 and ?1.4 V_Ag/AgCl, where the former voltage created a spherical morphology, the latter developed a flower-like one. The spherical morphology was modified through the incorporation of BG nanoparticles, where surface roughness, wettability, and adhesion strength of the coating were enhanced. The coatings with spherical morphology also revealed complete barrier property after immersion in PBS solution. However, fully adverse effects were found for the coatings deposited at ?1.4 V_Ag/AgCl. This indicates that morphology is the most important factor determining the properties of ZnO and ZnO-BG coatings. The highest corrosion barrier performance was achieved for the ZnO-BG composite coating with spherical morphology. Although the composite coating with flower-like morphology did not provide complete barrier property at short immersion times, it earned that at longer times due to the plugging supported by the BG nanoparticles. The bioactivity tests in SBF at long times showed that the formation of Ca-P deposits on the surface of the composite coatings was noticeably improved.     

Biocompatibility of braided poly(L‐lactic acid) nanofiber wires applied as tissue sutures

Almost all sutures in current usage only play one role, i.e. to mechanically tie wound tissues together. Drug‐loaded composite nanofibers obtained through coaxial electrospinning can initiate the development of a new type of biodegradable sutures with drug release. In this work, electrospun poly(L ‐lactic acid) (PLLA) nanofibers with uniaxial alignment were made into braided wires and were coated with chitosan and applied as tissue sutures. Toxicity evaluation on cells for the chitosan‐coated PLLA braided wires was carried out using the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium) test, and an in vivo study was conducted by implanting the braided wires into muscle tissues of rats. The inflammation responses were examined at 3, 7, 14, 21 and 28 days after implanting. Experimental results indicated that the braided PLLA nanofiber wires coated with chitosan exhibited comparable tensile and knot strengths to those of a commercial suture, could tie wounded tissues for a complete healing without any breakage, had no cellular toxicity and could promote cell growth well. The chitosan‐coated PLLA sutures showed better histological compatibility than a silk suture in the in vivo study. Braided PLLA nanofiber wires fabricated using an electrospinning process followed by a braiding technique and coated with chitosan are applicable for uses within the body. Copyright © 2009 Society of Chemical Industry     

Effects of organic encapsulation on the properties of magnetic PLLA/Fe3O4 composites

Organic‐encapsulated Fe₃O₄ magnetic microspheres (MMS) were synthesized and used to prepare PLLA (poly (L ‐lactic acid))/MMS composites. The effects of organic encapsulation on the mechanical, thermal, and magnetic properties of the composites were investigated. When compared with the PLLA/Fe₃O₄ composite, the elongation ratio of the PLLA/MMS composite improved significantly (by nearly 300%). Scanning electron microscope (SEM) images of the fracture morphology revealed an interesting “silking” phenomenon within the PLLA/MMS composite, which explains the greatly improved toughness. The decreased crystallinity and increased thermal stability of the PLLA/MMS composite suggest the existence of strong interacting forces between the PLLA molecules and the organic layer of the MMS particles, thereby limiting the mobility of the macromolecular chains. A study of the composites' magnetic properties indicated that the saturation magnetization was determined by the relative Fe₃O₄ content in the matrix, but not the types of the filling particles. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers     

The electrical properties and crystallization of stereocomplex poly(lactic acid) filled with carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) filled poly(l-lactic acid) (PLLA) and PLLA/poly(d-lactic acid) (PDLA) composites were prepared through a directly melt mixing process. A special crystalline structure of stereocomplex was formed by PLLA and PDLA, which was easily found when mixing two polymers with identical chemical composition but different steric structures. The electrical conductivities were greatly improved by the formation of stereocomplex compared to that of PLLA/MWCNT composites at same MWCNT content. The percolation threshold of the PLLA/PDLA/MWCNT composite at a PLLA/PDLA weight ratio of 50/50 was 0.35 wt%, while being 1.43 wt% of PLLA/MWCNT composites. The X-ray diffraction, non-isothermal and isothermal crystallization results showed that the formation of stereocomplex greatly increased the crystallinity of the composites, meanwhile MWCNTs acted as heterogeneous nucleating agent, which significantly accelerated the nucleation and spherulite growth. Therefore, the PLLA/PDLA/MWCNT composites have a very low percolation threshold due to the volume exclusion effect.