Montmorillonite reduces crystallinity of poly‐l‐lactic acid scaffolds to accelerate degradation

Poly‐l‐lactic acid (PLLA) is considered as a potential bone scaffold material because of good biocompatibility and bioabsorbability, whereas too slow degradation rate limits its application. In this study, montmorillonite (MMT) was introduced into PLLA scaffolds fabricated via selective laser sintering to accelerate degradation by reducing crystallinity. To be specific, MMT was a layered silicate with large surface area and aspect ratio, which provided nucleation site for the crystallization of PLLA molecular chain along their surface during the sintering process. As the surface of MMT plate was randomly oriented in the matrix, the growth direction of crystallite was also random, which interrupted the orderly crystallization, thus decreasing the overall crystallinity of PLLA. As a result, the crystallinity of PLLA scaffolds was decreased from 32.3% to 27.4% when introducing 4.5% MMT. Accordingly, weight loss was increased from 0.83% to 7.25% after immersing for 4 weeks. Besides, the tensile strength and modulus of the scaffolds increased by 44.1% and 66.9% because of the change of fracture mode from brittle fracture to ductile fracture. In addition, the scaffolds also demonstrated good hydrophilic property and cell compatibility.     

Solvent Influences the Morphology and Mechanical Properties of Electrospun Poly(L-lactic acid) Scaffold for Tissue Engineering Applications

Electrospun micro- and nanofiber scaffolds have gained interest in biomedical applications, especially in tissue engineering, because they can be used to reproduce the structure of the extracellular matrix (ECM) of natural tissue. The selection of the solvent is an important factor which affects the diameter, the surface morphology and the crystallinity of the electrospun fibers, and, accordingly, their mechanical properties as well as their degradation kinetics. Furthermore, the surface morphology of the electrospun fibres can be controlled by solvent vapour pressure to produce porous structures which might be helpful for cell adhesion and proliferation. In the present work, poly (L-lactic acid) (PLLA) has been electrospun using solvents with different vapour pressures to investigate the influences of the solvent vapour pressure on morphology, diameter, crystallinity and mechanical properties of the electrospun fiber scaffolds. The results show that the vapour pressure of the solvents (or solvent mixtures) play an important role in the fiber diameter and crystallinity. Furthermore, the crystallinity of the fibers is increased by lowering the vapour pressure of the used solvent. In addition, the mechanical properties (e.g., tensile strength and Young's modulus) are strongly dependent on morphological features such average fibers diameter. The smaller the average diameter, the higher the tensile strength and Young's modulus.     

Microstructural and mechanical properties of porous biocomposite scaffolds based on polyvinyl alcohol,nano-hydroxyapatite and cellulose nanocrystals

In this study, in situ synthesis of polyvinyl alcohol (PVA)/nano-hydroxyapatite (n-HA)/cellulose nanocrystals (CNC) organic–inorganic biocomposite porous scaffolds is reported. The effect of the CNC content on the properties of the biocomposite scaffold was investigated and characterized using field-emission scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, porosity and compressive strength measurements, thermal studies, and in vitro biomineralization and degradation studies. The morphological study showed highly porous structures with good pore interconnectivity in which n-HA was homogeneously dispersed. XRD analysis showed a decrease in the crystalline fraction and crystallite size of nano-hydroxyapatite with introduction of PVA and with increasing content of CNC. It was observed that the porosity decreased to some extent with increasing CNC content, while increases in the compressive strength (from 0.85 to 2.09 MPa) and elastic modulus (from 4.68 to 16.01 MPa) were found as the CNC content was increased. In vitro biomineralization study revealed the formation of apatite on PVA/n-HA/CNC biocomposite scaffolds when soaked for 7 and 14 days in simulated body fluid (SBF) solution. The obtained porous scaffolds offering good mechanical performance may provide a promising alternative scaffolding matrix for use in the field of bone tissue engineering.     

Genipin‐crosslinked gelatin hydrogel incorporated with PLLA‐nanocylinders as a bone scaffold: Synthesis,characterization, and mechanical properties evaluation

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.     

Polyester scaffolds with bimodal pore size distribution for tissue engineering

This paper presents a method for the preparation of porous poly(L-lactide)/poly[(L-lactide)-co-glycolide] scaffolds for tissue engineering. Scaffolds were prepared by a mold pressing-salt leaching technique from structured microparticles. The total porosity was in the range 70-85%. The pore size distribution was bimodal. Large pores, susceptible for osteoblasts growth and proliferation had the dimensions 50-400 microm. Small pores, dedicated to the diffusion of nutrients or/and metabolites of bone forming cells, as well as the products of hydrolysis of polyesters from the walls of the scaffold, had sizes in the range 2 nm-5 microm. The scaffolds had good mechanical strength (compressive modulus equal to 41 MPa and a strength of 1.64 MPa for 74% porosity). Scaffolds were tested in vitro with human osteoblast-like cells (MG-63). It was found that the viability of cells seeded within the scaffolds obtained using the mold pressing-salt leaching technique from structured microparticles was better when compared to cells cultured in scaffolds obtained by traditional methods. After 34 d of culture, cells within the tested scaffolds were organized in a tissue-like structure. Photos of section of macro- and mesoporous PLLA/PLGA scaffold containing 50 wt.-% of PLGA microspheres after 34 d of culture. Dark spots mark MG-63 cells, white areas belong to the scaffold. The specimen was stained with haematoxylin/eosin. Bar = 100 microm.     

Preparation and characterization of new materials based on silk fibroin,chitosan and nanohydroxyapatite

Abstract

In this paper, a series of porous nanohydroxyapatite/silk fibroin/chitosan (nHA/SF/CTS) scaffolds were successfully prepared using the freeze-drying method. The biomaterials were characterized by attenuated total reflection Fourier transform infrared spectroscopy, and mechanical testing and thermogravimetric analysis. Moreover, studies of porosity, pore size, swelling properties and in vitro degradation test were performed. Research has proved that micro-structure, porosity, water adsorption and compressive strength were greatly affected by the components’ concentration, in particular the content of silk fibroin. SEM observations showed that the scaffolds of nHA/SF/CTS are highly porous, with pore size in wide range from 25 to 300?µm which is suitable for cell growth. nHA/SF/CTS scaffolds have sufficient mechanical integrity to resist handling during implantation and in vivo loading. Both, the compressive modulus and compressive strength of the scaffold, decrease with the increase in silk fibroin content.     

In vitro degradation and release behavior of porous poly(lactic acid) scaffolds containing chitosan microspheres as a carrier for BMP-2-derived synthetic peptide

To develop a novel tissue engineering scaffold with the capability of controlled releasing BMP-2-derived synthetic peptide, porous poly(lactic acid)/chitosan microspheres (PLA/CMs) composites containing different quantities of chitosan microspheres were prepared by a thermally induced phase separation method. FTIR analysis revealed that there were strong hydrogen bond interactions between the PLA and chitosan component. Introduction of less than 30% CMs (on PLA weight basis) did not remarkably affect the morphology and porosity of the PLA/CMs scaffolds. The compressive strength of the composite scaffolds increased from 0.48 to 0.66 MPa, while the compressive modulus increased from 7.29 to 8.23 MPa as the microspheres' contents increased from 0% to 50%. In vitro degradability investigation indicated that the dissolution of chitosan component was preferential than PLA matrix and the inclusion of CMs could neutralize the acidity of PLA degradation products. Compared with the rapid release from CMs, the synthetic peptide was released from PLA/CMs scaffolds in a temporally controlled manner, mainly depending on the degradation of PLA matrix. The promising microspheres based scaffold release system can be used to deliver bioactive factors for a variety of non-loaded bone regeneration and tissue engineering application.     

Characterization of biodegradable and cytocompatible nano-hydroxyapatite/polycaprolactone porous scaffolds in degradation in vitro

Porous nano-hydroxyapatite/polycaprolactone (nHA/PCL) scaffolds with different composition ratios of nHA/PCL were fabricated via a melt-molding/porogen leaching technique. All scaffolds were characterized before and after degradation in vitro for six months. The original scaffolds had high porosity at around 70% and showed decreasing compressive modulus (from 24.48 to 2.69 MPa for hydrated scaffolds) with the introduction of nHA. It was noted that the scaffolds could retain relatively stable architecture and mechanical properties for at least six months, although some slight changes happened with the nHA/PCL scaffolds in the mass, the nHA content, the PCL molecular weight and the crystallinity. Moreover, during the 7 days culture of bone marrow stromal cells (BMSCs) on scaffolds, the cell adhesion and proliferation of BMSCs were presented well on both the surface and the cross-section of the scaffolds. All of these results suggested the nHA/PCL scaffolds to be promising in bone tissue engineering.     

Poly(l,l-lactide-co-glycolide)/tricalcium phosphate composite scaffold and its various changes during degradation in vitro

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.     

Fabrication of open‐porous PCL/PLA tissue engineering scaffolds and the relationship of foaming process,morphology, and mechanical behavior

Tissue engineering scaffolds should provide a suitable porous structure and proper mechanical strength, which is beneficial for the delivery of growth factor and regulation of cells. In this study, the open‐porous polycaprolactone (PCL)/poly (lactic acid) (PLA) tissue engineering scaffolds with suitable porous scale were fabricated using different ratios of PCL/PLA blends. At the same time, the relationship of foaming process, morphology, and mechanical behavior in the optimized batch microcellular foaming process were studied based on the single‐factor experiment method. The porous structures and mechanical strength of the scaffolds were optimized by adjusting foaming parameters, including the temperature, pressure, and CO₂ dissolution time. The results indicated that the foaming parameters influence the cell morphology, further determine the mechanical behavior of PCL/PLA blends. When the PCL content is high, with the increase of temperature and time, the cell diameter and the elastic modulus increased, and the tensile strength and elastic modulus increased with the increase of the average cell size, and decreased as the increase of the cell density. While when the PLA content was high, the cell diameter showed the same trend, and the tensile strength and elastic modulus were higher, and the elongation at break was lower, and tensile strength and elastic modulus decreased with the increase of the average cell size and increased with the increase of cell density. This work successfully fabricated optimized porous PCL/PLA scaffolds with excellent suitable mechanical properties, pore sizes, and high interconnectivity, indicating the effectiveness of modulating the batch foaming process parameters.     

Synthesis and characterization of PLLA-PLCA-PEG multiblock copolymers and their applications in modifying PLLA porous scaffolds

Poly(l-lactic acid)-poly(l-lactic acid-co-citric acid)-poly(ethylene glycol) multiblock copolymers (PLLA-PLCA-PEG) were synthesized through polycondensation reaction and characterized by ¹H NMR and DSC. The three-dimensional ultrafine fibre microporous PLLA/PLLA-PLCA-PEG scaffolds were then fabricated by modifying PLLA with PLLA-PLCA-PEG through blending and characterized as well. Properties of scaffolds such as swelling and degradation behaviors, morphology and mechanical moduli were fully investigated. Tetrandrine-loaded PLLA/PLLA-PLCA-PEG scaffolds were also fabricated and their drug releasing behaviors were taken into consideration. Compressive testing research shows that the mechanical flexibility improves as the content of PLLA-PLCA-PEG copolymers in the scaffolds increases. The TED encapsulation efficiency of the scaffold is enhanced when the amount of PLLA-PLCA-PEG increases because of the acid-base interaction between carboxylic acid groups of the copolymer with TED. The releasing velocity of TED speeds up while the PLLA-PLCA-PEG blocks ratios in scaffolds increase. So modification of PLLA scaffold with PLLA-PLCA-PEG shall broaden its applications in tissue engineering.     

Polydopamine-Coated Poly-Lactic Acid Aerogels as Scaffolds for Tissue Engineering Applications

Poly-L-lactic acid (PLLA) aerogel-based scaffolds were obtained from physical PLLA gels containing cyclopentanone (CPO) or methyl benzoate (BzOMe) molecules. An innovative single step method of solvent extraction, using supercritical CO₂, was used to achieve cylindrical monolithic aerogels. The pore distribution and size, analyzed by SEM microscopy, were found to be related to the crystalline forms present in the physical nodes that hold the gels together, the stable α’-form and the metastable co-crystalline ε-form, detected in the PLLA/BzOMe and PLLA/CPO aerogels, respectively. A higher mechanical compressive strength was found for the PLLA/CPO aerogels, which exhibit a more homogenous porosity. In vitro biocompatibility tests also indicated that monolithic PLLA/CPO aerogels exhibited greater cell viability than PLLA/BzOMe aerogels. An improved biocompatibility of PLLA/CPO monolithic aerogels was finally observed by coating the surface of the aerogels with polydopamine (PDA) obtained by the in situ polymerization of dopamine (DA). The synergistic effect of biodegradable polyester (PLLA) and the biomimetic interface (PDA) makes this new 3D porous scaffold, with porosity and mechanical properties that are tunable based on the solvent used in the preparation process, attractive for tissue engineering applications.     

Effect of starch content on the biodegradation of polycaprolactone/starch composite for fabricating in situ pore-forming scaffolds

Bone tissue engineering is an efficient approach to regenerating bone-related defects. The optimal scaffold used for bone tissue engineering must possess adequate porosity and suitable mechanical properties. This work described the development of a biodegradable polymeric composite based on polycaprolactone (PCL) and starch that can form a porous structure in situ. The scaffold exhibited the required mechanical properties at the initial stage of implantation by controlling in situ degradation and subsequent pore formation. PCL/starch (SPCL) scaffolds with 100/0, 70/30, and 50/50 ratios were developed. Degradation studies were performed in phosphate buffer saline (PBS) containing α-amylase or lipase at 37 °C for 4 weeks. Fourier-transform infrared spectroscopy was used to analyze chemical bonds and their changes after degradation. Differential scanning calorimetry was applied to determine the crystallinity and recrystallization of samples before and after degradation. Mass loss and starch release were observed during degradation, and the porosity of samples was measured by the ethanol replacement method. Morphology was further determined using scanning electron microscopy. Finally, variations in compressive strength and modulus during degradation and pore formation were also measured. The porosity of samples reached 45% after 1 month of degradation, and mechanical properties were still appropriate for human bone tissue. Reduction in mechanical property after mass loss, starch release and pore formation was controlled by the hydrogen bonding and recrystallization effect of PCL after degradation. Results suggested that SPCL composite had potential to form porous scaffold with adequate mechanical properties in situ and is promising for bone tissue engineering applications.     

Microstructure and mechanical properties of bacterial cellulose/chitosan porous scaffold

A family of polysaccharide based scaffold materials, bacterial cellulose/chitosan (BC/CTS) porous scaffolds with various weight ratios (from 20/80 to 60/40 w/w%) were prepared by freezing (−30 and −80 °C) and lyophilization of a mixture of microfibrillated BC suspension and chitosan solution. The microfibrillated BC (MFC) was subjected to 2,2,6,6-tetramethylpyperidine-1-oxyl radical (TEMPO)-mediated oxidation to introduce surface carboxyl groups before mixing. The integration of MFC within chitosan matrix was performed by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC)-mediated cross-linking. The covalent amide bond formation was determined by ATR-FTIR. Because of this covalent coupling, the scaffolds retain their original shapes during autoclave sterilization. The composite scaffolds are three-dimensional open pore microstructure with pore size ranging from 120 to 280 μm. The freezing temperature and mean pore size take less effect on scaffold mechanical properties. The compressive modulus and strength increased with increase in MFC content. The results show that the scaffolds of higher MFC content contribute to overall better mechanical properties.     

Characterization of drawn and undrawn poly-L-lactide films by differential scanning calorimetry

Poly-L-lactic acid (PLLA) is an optically active, biocompatible and biodegradable polymer that has been widely investigated as an artificial cell scaffold material. In its most crystalline form, PLLA is highly anisotropic and is one of the most piezoelectric polymers known. Conversely, amorphous PLLA exhibits little, if any, piezoelectric behavior. Compression molded PLLA films can be endowed with varying amounts of crystalline character and piezoelectricity by uniaxially stretching the polymer in a hot air bath. Understanding the precise crystalline architecture of PLLA that results from tensile drawing is important for constructing cell scaffolds that have highly tailored biodegradation and cell guiding properties. In our work here, we investigate the changes in the thermal properties of PLLA at draw ratios between 1.0 and 5.5 using differential scanning calorimetry (DSC). The crystallinity of the compression molded undrawn starting material is characterized using X-ray diffraction. Our DSC results show an increase in percent crystallinity with increasing draw up to a draw ratio of 4.0. At greater draw ratios, there is a decrease in the crystalline character exhibited by PLLA.This revised version was published online in November 2005 with corrections to the Cover Date.     

Cell(MC3T3‐E1)‐Printed Poly(ϵ‐caprolactone)/Alginate Hybrid Scaffolds for Tissue Regeneration

A new cell‐printed scaffold consisting of poly(ϵ‐caprolactone) (PCL) and cell‐embedded alginate struts is designed. The PCL and alginate struts are stacked in an interdigitated pattern in successive layers to acquire a three‐dimensional (3D) shape. The hybrid scaffold exhibits a two‐phase structure consisting of cell (MC3T3‐E1)‐laden alginate struts able to support biological activity and PCL struts able to provide controllable mechanical support of the cell‐laden alginate struts. The hybrid scaffolds exhibit an impressive increase in tensile modulus and maximum strength compared to pure alginate scaffolds. Laden cells are homogeneously distributed throughout the alginate struts and the entire scaffold, resulting in cell viability of approximately 84%.     

聚丙交酯/聚乙二醇多嵌段共聚物的合成及其性能

聚丙交酯 (ＰＬＬＡ)由于具有良好的生物降解性和生物相容性 ,在医学领域已经得到了广泛的临床应用 ,近来又被制备成细胞支架大量应用于组织工程中[1,2 ] ,但由于其疏水性而造成细胞亲和性不好 .聚乙二醇 (ＰＥＧ)具有良好的亲水性 ,良好的生物相容性 ,但是ＰＥＧ是非降解性的 ,只有低分子量的ＰＥＧ可以被吞噬细胞所吞噬或透过肾滤膜而排出体外 ,因此 ,低分子量的ＰＥＧ常被用来与丙交酯 (Ｌ ＬＡ)共聚以改善ＰＬＬＡ支架的亲水性 .聚丙交酯 聚乙二醇共聚物 (ＰＬＥ)的三嵌段及两嵌段共聚物的合成及其性能的研究已被广泛报道[3～ 5] .研究…     

Preparation and mechanical properties of poly(chitosan‐g‐DL‐lactic acid) fibrous mesh scaffolds

DL ‐lactic acid was grafted onto chitosan to produce poly(chitosan‐g‐DL ‐lactic acid)(PCLA) without using a catalyst. These PCLAs were then spun into filaments and further fabricated into fibrous mesh scaffolds using an improved wet‐spinning technique. The diameter of filaments in different scaffolds could vary from a few micrometers to several tens of micrometers. The scaffolds exhibited various pore sizes ranging from about 20 µm to more than 200 µm and different porosities up to 80%. The several main processing conditions were optimized for obtaining the desired scaffolds with well‐controlled structures. The tensile and compressive mechanical properties of the mesh scaffolds in both dry and hydrated states were mainly examined. Significantly improved tensile strength and modulus, enhanced compressive modulus, and stress as well as the dimensional stability for these mesh scaffolds in their hydrated state were observed. Copyright © 2007 John Wiley & Sons, Ltd.     

聚L-乳酸/聚(天冬氨酸-co-乳酸)共混物的制备及其相容性研究

采用氯仿/乙醇共沸溶液浇铸法制备了混合均匀的聚L-乳酸/聚(天冬氨酸-co-乳酸)共混物(PLLA/PAL)体系.研究了PLLA/PAL共混体系的热性能、结晶行为、形态结构和力学性能,评价了PLLA和PAL之间的相容性.结果表明,PAL对PLLA的结晶行为和热性能产生了较大的影响,共混物的结晶度较低,共混体系中部分PAL会进入PLLA球晶的片晶而导致PLLA球晶结构不完善,熔点降低.PAL的含量小于20%的PLLA/PAL共混物的拉伸强度和断裂延伸率均高于纯PLLA.PLLA和PAL分子链相互缠结,产生的氢键使分子链间存在较强的相互作用,具有较好的相容性.     

Surface‐modified hydroxyapatite linked by L‐lactic acid oligomer in the absence of catalyst

A new surface modification method of hydroxyapatite nanoparticles (n‐HA) by surface grafting reaction of L ‐lactic acid oligomer with carboxyl terminal (LAc oligomer) in the absence of any catalyst was developed. The LAc oligomer with a certain molecular weight was directly synthesized by condensation of L ‐lactic acid. Surface‐modified HA nanoparticles (p‐HA) were attested by Fourier transformation infrared spectroscopy, ³¹P MAS‐NMR, and thermal gravimetric analysis (TGA). The results showed that LAc oligomer could be grafted onto the n‐HA surface by forming a Ca carboxylate bond. The grafting amount of LAc oligomer was about 13.3 wt %. The p‐HA/PLLA composites showed good mechanical properties and uniform microstructure. The tensile strength and modulus of the p‐HA/PLLA composite containing 15 wt % of p‐HA were 68.7 MPa and 2.1 GPa, respectively, while those of the n‐HA/PLLA composites were 43 MPa and 1.6 GPa, respectively. The p‐HA/PLLA composites had better thermal stability than n‐HA/PLLA composites and neat PLLA had, as determined by isothermal TGA. The hydrolytic degradation behavior of the composites in phosphate buffered saline (PBS, pH 7.4) was investigated. The p‐HA/PLLA composites lost their mechanical properties more slowly than did n‐HA/PLLA composites in PBS because of their reinforced adhesion between the HA filler and PLLA matrix. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5177–5185, 2005