Scaffolds for drug delivery,part I: electrospun porous poly(lactic acid) and poly(lactic acid)/poly(ethylene oxide) hybrid scaffolds

This is the first in a series of papers, focused on the development of a biodegradable, controlled, and potentially targeted drug delivery system. In this paper, we describe the production of highly porous biodegradable fibrous structures suitable for biomedical applications and as a matrix for drug delivery. Two structures are described below. The first structure is composed of electrospun poly(lactic acid) (PLA) fibers and is unique due to (1) the uniformity if its constitute fibers’ diameter, (2) consistent surface pore dimensions of each fiber, (3) the use of only a single solvent, (4) interior nano-size porosity throughout each individual fiber, and (5) the independency of surface pore dimensions on fiber diameter. The produced matrix will be further impregnated with cargo loaded nanoparticles—Red clover necrotic mosaic virus (RCNMV)—to achieve a controlled drug delivery system (described in Part III) for cancer treatments. Such a structure can also be used as tissue engineering scaffolds and filter media. The second electrospun structure has enhanced hydrophilicity compared to PLA matrix and is formed by blending poly(lactic acid)/poly(ethylene oxide) (PEO) polymers. The incorporation of PEO in the matrix introduces preferable sites for aqueous compounds to be attached to while retaining the overall structural integrity and porous morphology. It is hypothesized that the existence of alternative hydrophilic and hydrophobic segments in the structure may reduce post-implantation complications such as platelet adhesion.     

Parametric study of manufacturing poly(lactic) acid nanofibrous mat by electrospinning

Electrospinning is a versatile method for manufacturing polymer-based multi-functional and high-performance nanofibrillar network. Two important characteristics, namely minimum diameter variation and bead area, render the nanofibre mats acceptable for many membrane type applications, but the relationship between processing parameters and microstructures is still not well understood. This article outlines a systematic study via the design of experiments in the context of selecting process control parameters while electrospinning nonwoven mats of nanofibres from poly(l-lactic acid). The goals are to obtain a robust set of parameters to reduce the variation in product quality by performing the minimum number of experiments. A desirable combination has been found to be low concentration of polymer solution, low feed rate, comparatively high applied voltage and a large distance between the collector and the needle. However, a low concentration of polymer solution may result in some bead formation if other factors are not changed accordingly.     

In vitro degradation of porous poly(lactic acid)/quantum dots scaffolds

In this study, cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots (QDs) were introduced into poly(lactic acid) (PLA) for fabrication of photoluminescent PLA/QDs scaffolds. TEM images revealed that the QDs were uniformly dispersed in the PLA. Compressive modulus and thermal stability of the PLA/QDs scaffolds are higher than those of the unfilled PLA scaffold. Cytotoxicity test results confirmed the non-cytotoxicity of the PLA/QDs scaffolds. During the process of in vitro degradation, the degradation rate of the PLA was accelerated by the presence of the QDs, and the molecular weight distributions of the PLA/QDs scaffolds were much broader when compared with the unfilled PLA ones. During the first 84 weeks of the degradation process, the photoluminescence (PL) intensity of the PLA/QDs scaffolds decreased with almost the same degradation ratio. The results suggested that the CdSe/ZnS QDs have potential applications for monitoring in vivo degradation of tissue engineering scaffolds.     

浸没凝胶相分离法制备聚己内酯多孔支架

为了制备结构和性能满足骨组织工程支架要求的聚己内酯(PCL)多孔支架材料,采用浸没凝胶相分离法,以冰醋酸和丙酮为混合溶剂,水为凝固剂,壳聚糖(CS)颗粒为添加剂制得一系列PCL多孔支架。探讨了溶剂组成、PCL浓度、CS添加量对PCL多孔支架结构和性能的影响。结果表明:添加CS颗粒有利于形成多孔三维支架,随着CS含量的增加,孔隙率略微下降,抗压强度提高。随着PCL质量分数的增加,孔隙率明显下降,但抗压强度增大。当溶剂组成中丙酮含量为50 wt%~60 wt%,PCL质量分数不高于10 wt%时,通过改变CS用量,可制得孔隙率和力学性能满足骨组织工程要求的相互贯通的三维多孔支架材料。     

Fabrication of nanofibrous macroporous scaffolds of poly(lactic acid) incorporating bioactive glass nanoparticles by camphene-assisted phase separation

Here we produced macroporous and nanofibrous scaffolds with bioactive nanocomposite composition, poly(lactic acid) (PLA) incorporating bioactive glass nanoparticles (BGnp) up to 30 wt%, targeting bone regeneration. In particular, the nanofibrous structure in the scaffolds was generated by using a bicyclic monoterpene, camphene (C₁₀H₁₆), through a phase-separation process with PLA-BGnp phase in chloroform/1,4-dioxane co-solvent. Furthermore, macropores were produced by the impregnation of salt particles and their subsequent leaching out, followed by freezing and lyophilization processes. The produced PLA-BGnp scaffolds presented highly porous and nanofibrous structure with porosities of 90–95% and pore sizes of over hundreds of micrometers. BGnp with sizes of ∼90 nm were also evenly impregnated within the PLA matrix, featuring a nanocomposite structure. The nanofibrous scaffolds exhibited enhanced hydrophilicity and more rapid hydrolytic degradation as the incorporated BGnp content increased. The bone-bioactivity of the scaffolds was substantially improved with the incorporation of BGnp, exhibiting rapid formation of apatite throughout the scaffolds in a simulated body fluid. The developed macroporous and nanofibrous scaffolds with PLA-BGnp bioactive composition are considered as a novel 3D matrix potentially useful for bone tissue engineering.     

ZnMn2O4微/纳米纤维的制备及其性能的研究

以聚乙烯吡咯烷酮(PVP)为络合剂与醋酸锌〔Zn(CH3COO)2〕和乙酸锰(Mn(CH3COO)2)反应制得前驱体溶液,用静电纺丝法制备了PVP/Zn(CH3COO)2/Mn(CH3COO)2复合纳米纤维,经煅烧得到具有微孔结构的Mn掺杂ZnO微/纳米纤维。对所制备纤维分别采用差热-热重分析(TG-DTA)、红外光谱(IR)、X射线衍射(XRD)、扫描电镜(SEM)等手段进行了表征。结果表明:PVP/Zn(CH3COO)2/Mn(CH3COO)2纤维表面光滑,直径约300～700nm,经煅烧后,可得到Mn掺杂ZnO微/纳米纤维,XRD测试表明煅烧后的无机纳米纤维呈ZnMn2O4晶相。     

聚乙二醇增容纳米纤维素/聚乳酸共混体系的研究

采用溶液浇铸法制备纳米纤维素/聚乳酸/聚乙二醇三元复合材料,与纯聚乳酸相比,该复合材料的抗张强度和断裂伸长率分别提高了41.2%和38.4%.傅立叶红外(FT-IR)表明聚乙二醇的存在使纳米纤维素和聚乳酸之间形成了强烈的氢键作用,明显改善了纳米纤维素和聚乳酸之间的相容性,提高了界面黏结力.扫描电子显微镜(SEM)观察了...     

Fabrication of fibrous poly(butylene succinate)/wollastonite/apatite composite scaffolds by electrospinning and biomimetic process

In this paper, a novel kind of Poly(butylene succinate) (PBSU) /wollastonite/apatite composite scaffold was fabricated via electrospinning and biomimetic process. Pure PBSU scaffold and composite scaffolds with 12.5 wt% and 25 wt% wollastonite were firstly fabricated by electrospinning. SEM micrographs showed that all the electrospun scaffolds had homogeneous fibrous structures with interconnected pores and randomly oriented ultrafine fibers. The composite scaffolds were then surface modified using a biomimetic process. SEM and XRD results showed that apatite could deposit on the surfaces of the composite fibers after incubation in SBF and a novel fibrous structure with microspheres composed of worm-like apatite on composite fibers was formed. Incubation time and wollastonite content were found to influence the morphology of the scaffolds during the biomimetic process obviously. Both the amount and the size of the microspheres on the composite scaffolds increased with increased incubation time. After a certain incubation time, microspheres formed on the composite fibers with less wollastonite had a relatively larger size. Therefore, the microstructure of the composite scaffolds could be adjusted by controlling the wollastonite content and the incubation time. All of these results suggest that it is an effective approach to fabricate PBSU/wollastonite/apatite fibrous composite scaffolds with different material content and controllable microstructure for bone tissue engineering.     

Fabrication of poly(lactic acid)-poly(ethylene oxide) electrospun membranes with controlled micro to nanofiber sizes

Biodegradable poly(L-lactide acid) (PLLA) nanofiber membranes were prepared by electrospinning of PLLA and poly(ethylene oxide) (PEO). The selective removal of PEO by water allows to obtain smaller fiber diameters and to increase the porosity of the membranes in comparison to PLLA membranes obtained under the same electrospinning conditions. After removal of PEO membranes with fiber sizes of 260 nm and average porosity close to 80% are obtained. Thermal and infrared results confirm the poor miscibility of PLLA and PEO, with the PEO randomly distributed along the PLLA fibers. On the other, PLLA and PEO mixing strongly affect their respective degradation temperatures. The influence of the PEO in the electrospinning process is discussed and the results are correlated to the evolution of the PLLA fiber diameter.     

羟基磷灰石的表面改性及其对聚乳酸基多孔支架性能的影响

分别采用柠檬酸和硬脂酸对纳米羟基磷灰石（n-HA）进行表面处理,并利用TGA、FTIR、XPS等研究了不同改性剂的改性效果,发现柠檬酸和硬脂酸能够成功接枝在n-HA表面,但硬脂酸的接枝率更高。将柠檬酸改性的n-HA与聚乳酸（PLA）共混制备复合材料,通过SEM观察发现,制备的n-HA/PLA复合材料在n-HA粉体添加量不超过20wt%时,经处理后的n-HA粉体在基体中分散均匀,两相界面处结合紧密。同时研究了n-HA/PLA复合材料制备多孔骨支架的3D打印成型工艺,并测试了其力学性能,结果表明,采用熔融沉积3D打印技术制备的支架有良好的压缩模量,但达到10%形变时所承受的压缩强度与PLA相比仍然有一定差距。     

Highly porous fibers prepared by electrospinning a ternary system of nonsolvent/solvent/poly(l-lactic acid)

In this work, a facile method for fabricating fibers with micro- and nano-porous structure by electrospinning a ternary system of nonsolvent/solvent/poly(l-lactic acid) is presented. Poly(l-lactic acid) (PLLA) was dissolved in a mixture of dichloromethane (solvent) and butanol (nonsolvent) with a certain ratio. During the electrospinning, the evaporation of solvent and nonsolvent would take the composition of polymer fluid jet to enter the two phase region of the ternary phase diagram, since the solvent is more volatile than the nonsolvent. Thus the jet yielded to different phase separated structures, and further evaporation of the residual nonsolvent would lead to porous fibers.     

Novel porous scaffolds of poly(lactic acid) produced by phase-separation using room temperature ionic liquid and the assessments of biocompatibility

Here we prepared three-dimensional (3D) porous-structured biodegradable polymer scaffolds for tissue regeneration using room temperature ionic liquids (RTILs) as a novel porogen, and addressed their biological properties, including in vitro cell growth and differentiation and in vivo tissue compatibility. RTIL based on 1-butyl-3-methylimidazolium ([bmim]) bearing hydrophilic anion Cl was introduced within the polymer structure to provide a pore network. A mixture of poly(lactic acid) (PLA) with RTIL dissolved in an organic solvent formed a bi-continuous network during the drying process. Selective dissolution of the RTIL phase was facilitated in ethanol, which resulted in a porous network of the polymer phase with complete removal of the RTIL. The RTILs-assisted porous scaffolds showed a typical open-channeled network with pore sizes over 100 μm and porosities of about 86–94%. For the biocompatibility assessments of the scaffolds, mesenchymal stem cells (MSCs) derived from rat bone marrow were seeded onto the PLA scaffold, and the cell proliferation and osteoblastic differentiation behaviors were examined. Results showed a typical on-going increase in the cell population with a level comparable to that observed on the tissue culture plastic control, indicating good cell compatibility. When cultured in an osteogenic medium, the alkaline phosphatase (ALP) activity of the cells on the PLA scaffolds was stimulated to increase with time from 7 to 14 days, in a similar manner to that on the control. Moreover, the expression of genes related to osteoblasts, including collagen type I, osteocalcin and bone sialoprotein, was stimulated on the 3D PLA scaffold during culture for up to 14 days, with levels higher than those on the control, suggesting the developed scaffold provided a 3D matrix condition for osteogenesis. An in vivo pilot study conducted subcutaneously in rat for 4 weeks revealed good tissue compatibility of the scaffold, with the ingrowth of cells and formation of collageneous tissue around and deep within the pores of the scaffold and no significant inflammatory reaction. Taken together, this novel method of using RTILs as a pore generator is considered to be useful in the development of biocompatible porous polymer scaffolds for tissue regeneration.     

Fabrication of aligned poly (vinyl alcohol) nanofibers by electrospinning

Electrospinning has become a versatile tool for fabricating nanofibers from materials of diverse origins. Normally, mats of randomly-aligned fibers were obtained. A number of techniques have been proposed to arrive at uniaxially-aligned fibers. This work reports a new technique, i.e., dual vertical wire technique, for fabrication of uniaxially-aligned fibers. This technique utilized two stainless steel wires that were vertically set in a parallel manner between a charged needle and a grounded collector plate. This technique allowed simultaneous collection of aligned fibers (between the parallel vertical wires) and a randomly-aligned fiber mat (on the collector plate). Application of the technique on poly(vinyl alcohol) (PVA) to prepare uniaxially-aligned fibers was found to be successful at short collection times. Unexpected formation of a large fiber tow consisting of individual as-spun nanofibers that were bound into a bundle was observed at long collection times. Morphological appearance and size of the fiber tow was affected by the change in the distance between the two vertical wire electrodes, while the average diameter of the individual fibers was not (i.e., about 340 to 350 nm). Lastly, mechanical properties and thermal behavior of the fiber tow were also investigated.     

Biodegradable poly(lactic acid)/hydroxyl apatite 3D porous scaffolds using high-pressure molding and salt leaching

Scaffolds comprising poly(lactic acid) (PLA) and hydroxyl apatite (HA) were fabricated by combination of the high-pressure compression-molding plus salt-leaching techniques. The optimized HA content was determined in terms of the pore morphology, porosity, storage modulus, degradation behavior, hydrophilicity as well as the cell growth ability of the scaffolds. At HA content of 20 wt%, the scaffolds exhibited an interconnected open pore structure with the high porosity of 82.2 %. More importantly, the storage modulus of PLA/HA scaffolds (87.6 MPa) achieved almost three times higher compared with pure PLA scaffolds, while under low-pressure condition, the increase of modulus caused by HA does not reach 150 %. The obvious contrast indicated that HA and high pressure had a synergistic effect on enhancing mechanical properties of porous scaffolds. It was truly interesting that the hydrophilicity of PLA/HA scaffolds was significantly improved by alkaline hydrolysis treatment, which eventually led to the excellent cellular biocompatibility of the scaffolds, as revealed from the morphology and spreading of the cells cultured in our scaffolds. On the whole, the resultant PLA/HA scaffolds are well-suited candidates for the design of tailor-made matrices in tissue engineering.     

Investigation of a novel poly (lactic acid) porous material toughened by thermoplastic polyurethane

Journal of Materials Science - Poly (lactic acid)/thermoplastic polyurethane (PLA/TPU) ductile fibrous porous material was obtained by electrospinning, which has better mechanical properties than...     

Characterisation and modelling of the elastic properties of poly(lactic acid) nanofibre scaffolds

The aim of this study is to predict the elastic response of poly(lactic acid) (PLA) electrospun nanofibre scaffolds through mathematical models based on homogenisation and the differential replacement method (DRM). These models principally seek to determine and analyse the effects of the internal morphology of the nanofibres on the effective Young’s modulus of polymer nanofibre scaffolds. The microstructure of the nanofibres was first characterised by SEM, XRD, DSC, AFM, and TEM techniques. From this characterisation, strong evidence of a hierarchical core–shell structure was found. With the experimental data, it was possible to design and validate better models than those currently used. In addition, the effects of the electrospinning parameters, such as take-up velocity and thermal treatment, were analysed and correlated with the morphology and the elastic properties of the nanofibres and their scaffolds. To validate the models’ results, we conducted a series of uniaxial tensile tests on the PLA nanofibre scaffolds. Using the data from the nanofibre measurements, the homogenisation approximations and the model based on the DRM predicted an effective Young’s modulus of 667 and 835 MPa, respectively. The predicted data were in excellent agreement with the experimental results (685–880 MPa). These models will be useful in understanding and evaluating the structure–property relationships of oriented nanofibre scaffolds for medical or biological applications.     

Fabrication of novel poly(lactic acid)/amorphous magnesium phosphate bionanocomposite fibers for tissue engineering applications via electrospinning

Fibrous bionanocomposites consisting of amorphous magnesium phosphate (AMP) nanospheres and polylactic acid (PLA) were fabricated by electrospinning. There are two important signatures of this paper. First, AMP, as an alternative to well-known calcium phosphate (CaP) materials, is added to PLA as the second phase. To the best of our knowledge, it is the first attempt to fabricate magnesium phosphate (MgP)/biopolymer composite. This is made possible by our previously reported research on the successful synthesis of AMP nanospheres via microwave processing. Second, the sustained release of magnesium and phosphate ions from PLA matrix can stimulate a series of cell responses. The structure of the composites and their bone-like apatite-forming abilities in simulated body fluid (SBF) were examined. Additionally, the effects on the proliferation and differentiation of preosteoblast cells were evaluated by performing in vitro cell culture and monitoring markers such as Osteocalcin (OCN), Osteopontin (OPN), Alkaline phosphatase (ALP) and Collagen type-I (Col I) using real-time polymerase chain reaction (PCR). For better dispersion of AMP in the fibers, a surfactant, 12-hydroxysteric acid (HSA), as previously reported in the literature, was used. However, HSA significantly inhibited the proliferation and differentiation of preosteoblast cells, indicating the potential risk in using HSA in the combination of AMP or MgP in tissue engineering applications.     

Nanodiamond/poly (lactic acid) nanocomposites: Effect of nanodiamond on structure and properties of poly (lactic acid)

Nanodiamond (ND)/poly (lactic acid) (PLA) nanocomposites with potential for biological and biomedical applications were prepared by using melting compound methods. By means of transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Thermogravimetric analyses (TGA), Dynamic mechanical analyses (DMA), Differential scanning calorimetry (DSC) and Tensile test, the ND/PLA nanocomposites were investigated, and thus the effect of ND on the structural, thermal and mechanical properties of polymer matrix was demonstrated for the first time. Experimental results showed that the mechanical properties and thermal stability of PLA matrix were significantly improved, as ND was incorporated into the PLA matrix. For example, the storage modulus (E′) of 3 wt% ND/PLA nanocomposites was 0.7 GPa at 130 °C which was 75% higher than that of neat PLA, and the initial thermal decomposition was delayed 10.1 °C for 1 wt% ND/PLA nanocomposites compared with the neat PLA. These improvements could be ascribed to the outstanding physical properties of ND, homogeneous dispersion of ND nanoclusters, unique ND bridge morphology and good adhesion between PLA matrix and ND in the ND/PLA nanocomposites.     

Fabrication and characterization of fully biodegradable natural fiber-reinforced poly(lactic acid) composites

Polymer composites were fabricated with poly(lactic acid) (PLA) and cellulosic natural fibers combining the wet-laid fiber sheet forming method with the film stacking composite-making process. The natural fibers studied included hardwood high yield pulp, softwood high yield pulp, and bleached kraft softwood pulp fibers. Composite mechanical and thermal properties were characterized. The incorporation of pulp fibers significantly increased the composite storage moduli and elasticity, promoted the cold crystallization and recrystallization of PLA, and dramatically improved composite tensile moduli and strengths. The highest composite tensile strength achieved was 121 MPa, nearly one fold higher than that of the neat PLA. The overall fiber efficiency factors for composite tensile strengths derived from the micromechanics models were found to be much higher than that of conventional random short fiber-reinforced composites, suggesting the fiber–fiber bond also positively contributed to the composites’ strengths.