Rheology of a polymer-based hybrid suspension composed of concentrated poly[(D,L-lactide)-co-glycolide] solution and inorganic salt particles

Suspensions composed of a solution of a biodegradable polyester in a volatile organic solvent, and solid inorganic particles of size in the order of hundreds of microns have been very important in the fabrication of porous scaffolds in the field of tissue engineering. This article reports the basic rheological investigations of this complex fluid type. A Couette geometry covered by silicon oil was found to be an appropriate geometry to retain stability of the rheological measurements. Suspension viscosity increased with the particle volume fraction, and the extent of the increase was much larger than that predicted by the Einstein suspension equation. Both start-up dynamics at the inception of steady shear and relaxation after an abrupt change of oscillatory shear frequency in the suspension showed significantly different behaviors from those in the associated polymer solution. Particle reorganization upon change of rheological state was anticipated.     

Fabrication of biodegradable poly(trimethylene carbonate) networks for potential tissue engineering scaffold applications

Biodegradable poly(trimethylene carbonate) (PTMC) networks were prepared by photopolymerization of linear (L)‐ and star (S)‐shaped PTMC macromonomers for potential tissue engineering scaffold applications. The L‐ (M_n, 6400) and S‐shaped (M_n, 5880) PTMC macromonomers were synthesized using 1,4‐butane diol and 2‐ethyl‐ 2‐hydroxyl‐propane‐1,3‐diol co‐initiated ring‐opening polymerization of trimethylene carbonate (TMC) in the presence of stannous octoate and subsequent acrylation with acryloyl chloride. Chemical structures of the PTMC macromonomers and their corresponding networks were characterized by ¹H NMR and ¹³C NMR spectroscopy. The human endothelial cell line, EA.hy926 was used to test the biocompatibility, cell adhesion, and proliferation behavior of both PTMC networks. The PTMC networks made from the S‐shaped macromonomers exhibited superior cell adhesion and proliferation behavior than those made of the linear macromonomers. Copyright © 2008 John Wiley & Sons, Ltd.     

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%.     

组织工程三维多孔支架的制备方法和技术进展

组织工程的关键技术之一在于将具有良好生物相容性和生物降解吸收性能的生物材料制备成具有特定形状和相连孔结构的三维多孔细胞支架（细胞外基质替代物）。本文着眼于多孔支架制备方法分别与多孔支架孔结构和外形的内在联系，从致孔和外形成型两个层次对组织工程多孔支架的制备方法和技术新近的研究进展进行了综述。     

Sorption and Swelling of Poly(D,L-lactic acid) and Poly(lactic-co-glycolic acid) in Supercritical CO2

Summary: The equilibrium sorption and swelling behavior in supercritical CO₂ of poly(D,L-lactic acid) and poly(lactic-co-glycolic acid) has been studied at a temperature of 35 °C and at pressures up to 200 bar. Sorption was measured through a gravimetric technique and swelling by visualization. From these data, the behavior of the different polymers can be compared. In terms of partial molar volume of CO₂ in the polymer matrix, all the polymers exhibit a behavior typical of rubbery systems. The experimental results have been modeled using the Sanchez-Lacombe equation of state, which is able to represent the actual behavior of the polymer-CO₂ systems with reasonable accuracy.     

聚乳酸组织工程支架材料

综述了生物活性因子固定化的聚乳酸-聚氨基酸衍生物共聚物和通过亲-疏水性设计的众多聚乳酸-聚氧化乙烯（PLA-PEO）共聚物的研究进展。展现了其在组织工程材料,药物控释体系和其他生物医用材料中的广泛应用前景。     

Heparin Interacting Protein Mediated Assembly of Nano‐Fibrous Hydrogel Scaffolds for Guided Stem Cell Differentiation

A new methodology is developed to conjugate hyaluronic acid (HA) hydrogel with novel nano‐fibrous architectures via non‐covalent assembly that specifically allows for targeted adipose‐derived stem cells (ASCs) differentiation and soft tissue engineering. The assembly of non‐covalently associated hydrogel network produced via the interaction of a low molecular weight heparin (LMWH) modified HA derivative and heparin interacting protein (HIP). The multifunctional star poly(ethylene glycol) (PEG) and HIP copolymer has the capability to mediate the non‐covalent assembly of nano‐fibrous HA hydrogel networks via affinity interactions with LMWH. The effect of the HIP mediation on in vitro gelation, rheological characteristics, degradation, equilibrium swelling, adipose‐derived stem cells (ASCs) proliferation and differentiation of nano‐fibrous hydrogel is examined. The results suggest the potential utility of this unique design of the bioactive nano‐fibrous HA hydrogel in directing the differentiation of ASCs and adipogenesis in ECM‐mimetic scaffolds in vitro. These studies demonstrate that this nano‐fibrous HA hydrogel can render the formulation of a therapeutically effective platform for in vitro adipogenesis applications.

     

聚乳酸与聚乳酸-羟基乙酸多孔细胞支架的制备及孔隙的表征

应用溶液烧铸致孔剂浸出技术制备了不同致孔剂用量与不同致孔剂颗粒尺寸条件下的一系列聚乳酸及不同组成的聚乳酸－羟基乙酸多孔细胞支架;用一种改进的方法－重量法测定其孔隙率;在聚乳酸－羟基乙酸多孔支架上进行了软骨细胞培养。研究结果表明,随着制备过程中致孔剂用量的增加,多孔支架的孔隙逐渐增加,而与致孔剂的颗粒大小基本无关;致孔剂的颗粒大小只影响多孔支架的孔径;在致孔剂用量及致孔剂颗粒尺寸都相同的情况下,随着共聚物中乙交酯含量的增加,孔隙率逐渐下降;软骨细胞在支架上繁殖情况良好,三周后已开始分泌细胞外基质。     

Characterization of Poly(vinyl alcohol)/Chitosan Hydrogels as Vascular Tissue Engineering Scaffolds

In this study, PVA/Chitosan hydrogels were fabricated by freeze/thaw cycles and further crosslinking with a KOH/Na₂SO₄ coagulation bath and the effect of freeze/thaw cycle number on cell behaviour was evaluated. The surface of the hydrogels were further modified with Collagen type I adsorption and seeded with bovine aortic vascular smooth muscle and endothelial cells. Increasing the number of freeze/thaw cycles resulted in a marked change in surface morphology, hydrophilicity and protein adsorption. Collagen coating caused an increase in initial attachment and proliferation. We concluded that hydrogels that have undergone 3 freeze/thaw cycles were optimum for cell attachment both in the presence and the absence of coating.     

Degradable Poly(amidoamine) Hydrogels as Scaffolds for In Vitro Culturing of Peripheral Nervous System Cells

This paper reports on the synthesis and physico‐chemical, mechanical, and biological characterization of two sets of poly(amidoamine) (PAA) hydrogels with potential as scaffolds for in vivo peripheral nerve regeneration. They are obtained by polyaddition of piperazine with N,N′‐methylenebis(acrylamide) or 1,4‐bis(acryloyl)piperazine with 1,2‐diaminoethane as cross‐linking agent and exhibit a combination of relevant properties, such as mechanical strength, biocompatibility, biodegradability, ability to induce adhesion and proliferation of Schwann cells (SCs) preserving their viability. Moreover, the most promising hydrogels, that is those deriving from 1,4‐bis(acryloyl)piperazine, allow the in vitro growth of the sensitive neurons of the dorsal root ganglia, thus getting around a critical point in the design of conduits for nerve regeneration.

     

Glycosaminoglycan-Based Cryogels as Scaffolds for Cell Cultivation and Tissue Regeneration

Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in this way correspond to the native extracellular matrix (ECM) in terms of both composition and molecular structure. Due to their specific structural feature and in addition to an excellent biocompatibility, GAG-based cryogels have several advantages over traditional GAG-hydrogels. This includes macroporous, interconnective pore structure, robust, elastic, and shape-memory-like mechanical behavior, as well as injectability for many GAG-based cryogels. After addressing the cryogelation process, the fabrication of GAG-based cryogels and known principles of GAG monomer crosslinking are discussed. Finally, an overview of specific GAG-based cryogels in biomedicine, mainly as polymeric scaffold material in tissue regeneration and tissue engineering-related controlled release of bioactive molecules and cells, is provided.     

低热-高压法制备PLGA多孔支架及其体外降解研究

采用低热-高压法制备了聚(dl-丙交酯／乙交酯)75／25(PLGA75／25)组织工程多孔支架。该方法避免了使用有机溶剂，支架的孔隙率在90％以上，孔径大小分布均匀。多孔支架经过酒精处理后，支架表面产生许多微小的凹陷；用藻酸钙改性处理后，支架形态保持良好。两种处理都使支架的压缩强度有所增大，亲水性增强。虽然孔隙率高的支架降解速率稍慢，但其体外降解规律基本一致：特性粘数争力学强度衰减快，而质量损失较慢，降解6周后，支架的质量损失仅为3％左右；体外降解3周后，支架的形态保持良好，可望在细胞移植争组织修复的早期发挥支撑作用。     

Molar Mass and Structural Characteristics of Poly[(lactide-co-(aspartic acid)] Block Copolymers

Summary: We report on various synthetic procedures for the preparation of biodegradable and biocompatible poly(lactide-co-aspartic acid) block copolymers based on natural monomeric units – lactic acid and aspartic acid. Multiblock poly(lactide-co-aspartic acid) copolymers of different comonomer composition were synthesized by heating a mixture of L-aspartic acid and L,L-lactide in melt without the addition of any catalyst or solvent and with further alkaline hydrolysis of the cyclic succinimide rings to aspartic acid units. Diblock poly(lactide-co-aspartic acid) copolymers with different block lengths were prepared by copolymerization of amino terminated poly(β-benzyl-L-aspartate) homopolymer and L,L-lactide with subsequent deprotection of the benzyl protected carboxyl group by hydrogenolysis. The differences in the structure, composition, molar mass characteristics, and water-solubility of the synthesized multiblock and diblock poly(lactide-co-aspartic acid) copolymers are discussed.     

Novel biodegradable poly(1,8-octanediol malate) for annulus fibrosus regeneration

A novel elastic scaffold that simulates the deformability of annulus fibrosus (AF) and has good biocompatibility was developed. The scaffold was formed of a malic acid-based polyester poly(1,8-octanediol malate) (POM), which was synthesized by direct polycondensation. The tensile strength of POM gradually increased with the extension of the polymerization time, while the degradation rate decreased. Rat AF cells proliferated on the POM films and maintained their phenotype. The 3D scaffold also supported the growth of the AF cells, as confirmed by Safranin-O and type II collagen staining. POM also demonstrated a good biocompatibility in an in vivo foreign body response assay, an important prerequisite for tissue engineering applications. This study suggests that elastic POM scaffold may be an ideal candidate for AF tissue engineering.     

Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds

Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs’ properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO₃. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10⁻³ S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents.     

聚乳酸自支持膜的叠加及其作为药物控释阻隔层的研究

发展了一种将自支持膜层层叠加制备多层膜的新方法,并研究了该薄膜对药物释放的调控效果. 首先利用聚乙烯醇作为牺牲层制备出聚乳酸自支持膜,然后将聚乳酸自支持膜转移或层层叠加到载药薄膜表面,最后对覆盖有聚乳酸薄膜的载药膜进行药物释放研究. 实验结果表明,聚乳酸薄膜对药物的释放起到了明显的调节作用,并且转移的薄膜的控释效果优于原位制备的薄膜,多层叠加的薄膜控释效果强于同等厚度的单层薄膜. 这可能是由于转移和叠加的薄膜层与层之间的空隙对药物的释放起到了缓冲作用所致. 这种基于自支持膜叠加制备多层膜的方法为药物涂层的研究提供了新思路,在生物材料、医用植入器件等领域都有一定的发展前景.     

层层自组装聚烯丙胺盐酸盐/Pd纳米复合薄膜的制备及其电催化特性

利用层层静电自组装技术将聚烯丙胺盐酸盐(PAH)和四氯合钯酸根离子( )交替沉积在基底上, 然后用硼氢化钠还原, 构筑了含钯纳米粒子的PAH/Pd纳米复合薄膜. 通过紫外-可见吸收光谱(UV-Vis)、扫描电子显微镜(FESEM), X射线光电子能谱(XPS)和循环伏安(CV)等手段对复合膜的组装、成分、微结构、表面形貌和光学性能进行了测试分析. FESEM图形显示膜表面有一定的粗糙度, 膜上生成了粒径在50～100 nm 范围的钯纳米粒子; UV-Vis结果显示多层膜在特征吸收峰处的吸光度数值随膜双层数增加逐渐增大, 呈良好的线性关系, 表明多层膜是均匀组装的; XPS结果证实了复合膜上有Pd生成, CV结果说明复合薄膜对尿酸的氧化具有较好的电催化活性, 有望用于电化学传感器.     

Fabrication of Highly Anisotropic and Interconnected Porous Scaffolds to Promote Preosteoblast Proliferation for Bone Tissue Engineering

Mimicking the complex structure of natural bone remains a challenge for bone tissue scaffolds. In this study, a novel processing strategy was developed to prepare the bone-like scaffolds that are featured by highly oriented and fully interconnected pores. This type of biomimetic scaffolds was evolved from solid phase stretching of immiscible polycaprolactone(PCL)/poly(ethylene oxide)(PEO) blends with cocontinuous structure and the pore morphology was inherited from selective extraction of water ...