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.     

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.     

Production and in vitro characterization of 3D porous scaffolds made of magnesium carbonate apatite (MCA)/anionic collagen using a biomimetic approach

3D porous scaffolds are relevant biomaterials to bone engineering as they can be used as templates to tissue reconstruction. The aim of the present study was to produce and characterize in vitro 3D magnesium-carbonate apatite/collagen (MCA/col) scaffolds. They were prepared by using biomimetic approach, followed by cross-linking with 0.25% glutaraldehyde solution (GA) and liofilization. Results obtained with Fourier-transform infrared spectroscopy (FT-IR) confirmed the type-B carbonate substitution, while by X-ray diffraction (XRD), a crystallite size of ~ 10 nm was obtained. Optical and electron microscopy showed that the cylindrical samples exhibited an open-porous morphology, with apatite nanocrystals precipitated on collagen fibrils. The cross-linked 3D scaffolds showed integrity when immersed in culture medium up to 14 days. Also, the immersion of such samples into an acid buffer solution, to mimic the osteoclastic resorption environment, promotes the release of important ions for bone repair, such as calcium, phosphorus and magnesium. Bone cells (SaOs2) adhered, and proliferated on the 3D composite scaffolds, showing that synthesis and the cross-linking processes did not induce cytotoxicity.     

可降解聚乳酸/淀粉共混复合材料的研究进展

将聚乳酸与淀粉共混是一种简单易行的好方法,可以得到完全降解的复合材料.综述了聚乳酸/淀粉共混体系的研究进展,分析了淀粉种类、相成分接枝改性、增容剂等因素对共混体系的机械性能、热性能和微观形态的影响,展望了聚乳酸/淀粉共混复合材料今后的发展方向.     

Cotton wool-like poly(lactic acid)/vaterite composite scaffolds releasing soluble silica for bone tissue engineering

Cotton wool-like poly(l-lactic acid) and siloxane-doped vaterite (SiV) composite scaffolds were prepared with a modified electrospinning system for bone tissue engineering applications. The effects of changing the SiV content in the materials from 10 to 30 wt% on elasticity and the ability to release calcium ions and soluble silica were evaluated. The elasticity of the cotton wool-like composites was almost the same as that of the PLLA from the results of compressibility and recovery tests. The materials released calcium ions for more than 56 days and soluble silica for 28–56 days in a tris buffer solution (pH 7.4). Mouse osteoblast-like cells (MC3T3-E1 cells) were cultured on/in the cotton wool-like materials or the fibremats out of the same composite materials as that used for the cotton wool-like materials. The cells penetrated into and proliferated inside the cotton wool-like materials, although they mainly adhered on the fibremat surface.     

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.     

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。     

Low-temperature inductively coupled plasma as a method to promote biomineralization on 3D printed poly(lactic acid) scaffolds

Journal of Materials Science - For bone tissue engineering, additive manufacturing offers promise in the development of biomimetic scaffolds; however, common polymers used in typical 3D printing...     

聚乳酸/聚乙二醇/羟基磷灰石多孔骨支架的3D打印制备及其生物相容性

聚乳酸(PLA)是一种应用广泛的生物高分子材料,但在应用过程中存在韧性、亲水性、生物活性差等缺点。用聚乙二醇(PEG)和羟基磷灰石(HA)对PLA进行改性。通过熔融共混制备不同质量比的PLA/PEG/HA复合3D打印线材,并通过分析PLA/PEG/HA线材的力学性能、结晶性能、热性能、流变性能等,筛选更适合熔融沉积成型(FDM)的3D打印成型线材,进而利用3D打印制备精度高的力学性能试样及生物相容性好、细胞可增殖和分化的生物多孔支架。结果表明:PEG的添加提高了PLA的韧性,降低了PLA的熔点。HA的添加则提高PLA/PEG/HA复合材料的弹性模量和冷结晶温度,同时HA也可以改善复合材料的加工性能。SEM与荧光标记结果表明多孔支架与细胞具有良好的生物相容性。生物支架对体外细胞的成功培养,为进一步发掘生物多孔支架在动物体内、生物医学及定制化应用方面提供了潜在可能。     

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.     

Biodegradable poly(lactic acid) microspheres containing total alkaloids of Caulis sinomenii

The fabrication of biodegradable poly(lactic acid) (PLA) microspheres containing total alkaloids of Caulis sinomenii was investigated. The formation, diameter, morphology and properties of the microspheres were characterized using Fourier transform infrared spectroscopy (FT-IR), laser particle size analyser and scanning electron microscopy (SEM), etc. In vitro releasing behaviour was also investigated using UV-Vis spectrometer. As a result, the drug-loaded microspheres with a narrower distributive, rounder and smoother surface were prepared. Drug-releasing behaviour from microspheres was affected by the concentration of emulsifier and the stirring rate. The results demonstrated that a medicated system, which can be potentially applied within a drug delivery system, was designed. This system acts in a systematic manner for the treatment of rheumatoid arthritis.     

Structure and thermal properties of poly(lactic acid)/cellulose whiskers nanocomposite materials

The goal of this work was to produce nanocomposites based on poly(lactic acid) (PLA) and cellulose nanowhiskers (CNW). The CNW were treated with either tert-butanol or a surfactant in order to find a system that would show flow birefringence in chloroform. The nanocomposites were prepared by incorporating 5 wt% of the different CNW into a PLA matrix using solution casting. Field emission scanning electron microscopy showed that untreated whiskers formed flakes, while tert-butanol treated whiskers formed loose networks during freeze drying. The surfactant treated whiskers showed flow birefringence in chloroform and transmission electron microscopy showed that these whiskers produced a well dispersed nanocomposite. Thermogravimetric analysis indicated that both whiskers and composite materials were thermally stable in the region between 25 °C and 220 °C. The dynamic mechanical thermal analysis showed that both the untreated and the tert-butanol treated whiskers were able to improve the storage modulus of PLA at higher temperatures and a 20 °C shift in the tan δ peak was recorded for the tert-butanol treated whiskers.     

Preparation of porous biodegradable poly(lactide-co-glycolide)/ hyaluronic acid blend scaffolds: Characterization, in vitro cells culture and degradation behaviors

A series of poly(lactide-co-glycolide) (PLGA)/ hyaluronic acid (HA) blend with different HA composition were used to fabricate scaffolds successfully. The pores of the three dimensional scaffold were prepared by particle leaching and freeze drying. The pore size was about 50–200 μ m and the porosity was about 85%. The characterizations of the scaffold, such as mechanical properties, hydrophilicity and surface morphologies were determined. Mouse 3T3 fibroblast was directly seeded on the scaffolds. The cell adhesion efficiency, cell morphology observed by scanning electron microscopy (SEM) and the degradation behavior of the blend scaffold were evaluated. In summary, the results show that the adhesion efficiency of cells on the PLGA/HA blend scaffold is higher than that on the PLGA scaffold. Moreover, the incorporation of HA in PLGA not only helps to increase the cell affinity but also tends to lead the water and nutrient into the scaffold easily.     

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.     

Gas anti-solvent precipitation assisted salt leaching for generation of micro- and nano-porous wall in bio-polymeric 3D scaffolds

The mass transport through biocompatible and biodegradable polymeric 3D porous scaffolds may be depleted by non-porous impermeable internal walls. As consequence the concentration of metabolites and growth factors within the scaffold may be heterogeneous leading to different cell fate depending on spatial cell location, and in some cases it may compromise cell survival.In this work, we fabricated polymeric scaffolds with micro- and nano-scale porosity by developing a new technique that couples two conventional scaffold production methods: solvent casting-salt leaching and gas antisolvent precipitation. 10–15 w/w solutions of a hyaluronic benzyl esters (HYAFF11) and poly-(lactic acid) (PLA) were used to fill packed beds of 0.177–0.425 mm NaCl crystals. The polymer precipitation in micro and nano-porous structures between the salt crystals was induced by high-pressure gas, then its flushing extracted the residual solvent. The salt was removed by water-wash. Morphological analysis by scanning electron microscopy showed a uniform porosity (~ 70%) and a high interconnectivity between porous. The polymeric walls were porous themselves counting for 30% of the total porosity. This wall porosity did not lead to a remarkable change in compressive modulus, deformation, and rupture pressure. Scaffold biocompatibility was tested with murine muscle cell line C2C12 for 4 and 7 days. Viability analysis and histology showed that micro- and nano-porous scaffolds are biocompatible and suitable for 3D cell culture promoting cell adhesion on the polymeric wall and allowing their proliferation in layers. Micro- and nano-scale porosities enhance cell migration and growth in the inner part of the scaffold.     

Preparation of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds for bone tissue engineering

Poly(3-hydroxybutyrate)/nano-hydroxyapatite (PHB/nHA) composite scaffolds were fabricated via powder mixing, compression moulding, and particle leaching technique. The scaffolds had high porosity with interconnected porous architecture, a favorable structure for cell attachment and new bone tissue ingrowth. A homogeneous dispersion and a uniform distribution of HA nanoparticles in the polymer matrix were obtained. The scaffolds exhibited improved compressive modulus and compressive strength, which were all in the range of compressive modulus and compressive strength of cancellous bone. In addition, the use of toxic organic solvents was eliminated. Thus, the fabricated PHB/nHA composite scaffolds tend to be promising for application in bone tissue engineering.     

Physical structure behavior to wettability of electrospun poly(lactic acid)/polysaccharide composite nanofibers

Poly(lactic acid) has been electrospun into submicron fibers with embedded cassava starch matrix. The fibers had average fiber diameters between 140 and 680?nm. The starch content varied from 10 to 20% in total solids. Water contact angles were measured on sheets of these fiber materials and correlated with the fiber size and starch content. Water contact angles varied from 80 to 120° which shows that the fiber composition can control the mat properties from hydrophilic to hydrophobic. The results also showed variation in the average fiber diameters alone did not always affect sheet wettability. These results show the importance of the relationship between the electrospun fiber sheet topography and material composition to the wettability of polysaccharide electrospun nanofibers.     

聚乳酸/小麦秸秆纤维复合材料降解性能研究

以聚乳酸为基体,以小麦秸秆纤维为增强体制备聚乳酸/小麦秸秆纤维复合材料。通过测试该复合材料在不同pH值PBS缓冲液降解过程中的吸水率、质量损失率和拉伸性能,并用扫描电子显微镜(SEM)观察降解过程中复合材料的表面形貌变化,研究其随时间变化的降解性能。结果表明,在不同pH值的PBS缓冲液中,聚乳酸/小麦秸秆纤维复合材料的吸水率、质量损失率都随着降解时间的增加而增大,但后期增大比较缓慢;复合材料在弱碱性环境中降解最快,弱酸性环境次之,中性环境最慢;随着降解时间的增加,复合材料的拉伸强度和杨氏模量明显降低,表面由光滑变成凹凸不平,小麦秸秆纤维裸露在表面。