Molecular Design of Synthetic Biodegradable Polymers as Cell Scaffold Materials

Poly(lactic acid) and its copolymers are regarded as the most useful biomaterials. The good biocompatibility, biodegradability and mechanical properties of them make the synthetic biodegradable polymers have primary application to tissue engineering. The advantages and disadvantages of the synthetic biodegradable polymers as cell scaffold materials are evaluated, This article reviews the modification of polylactide-family aliphatic polymers to improve the cell affinity when the polymers are used as cell scaffolds. We have developed four main approaches: to modify polyester cell scaffolds in combination of plasma treating and collagencoating; to introduce hydrophilic segments into aliphatic polyester backbones; to introduce pendant functional groups into polyester chains ; to modify polyester with dextran. The results of the cell cultures prove that the approaches mentioned above have improved the cell affinity of the polyesters and have modulated cell function such as adhesion, proliferation and migration.     

Biodegradable polymer matrix nanocomposites for tissue engineering: A review

Nanocomposites have emerged in the last two decades as an efficient strategy to upgrade the structural and functional properties of synthetic polymers. Aliphatic polyesters as polylactide (PLA), poly(glycolides) (PGA), poly(?-caprolactone) (PCL) have attracted wide attention for their biodegradability and biocompatibility in the human body. A logic consequence has been the introduction of organic and inorganic nanofillers into biodegradable polymers to produce nanocomposites based on hydroxyapatite, metal nanoparticles or carbon nanotructures, in order to prepare new biomaterials with enhanced properties. Consequently, the improvement of interfacial adhesion between the polymer and the nanostructures has become the key technique in the nanocomposite process. In this review, different results on the fabrication of nanocomposites based on biodegradable polymers for specific field of tissue engineering are presented. The combination of bioresorbable polymers and nanostructures open new perspectives in the self-assembly of nanomaterials for biomedical applications with tuneable mechanical, thermal and electrical properties.     

高吸水性树脂

用热力学理论和相转变理论阐明了高吸水性树脂的吸水机理。解释了高分子链上的电荷密度、外界溶液离子强度以及交联度对吸水倍数的影响，并指出了影响吸水速率的因素。介绍了淀粉类、纤维素类、共聚合类、复合类以及可生物降解类高吸水性树脂近30年来的研究状况以及存在的问题，简要介绍了高吸水性树脂的应用。     

Poly(ε-caprolactone) modified by functional groups: Preparation and chemical–physical investigation

Functionalization of polymers is a particular relevant approach in the field of biodegradable polymers, where modifications are often required to allow these materials to replace more conventional, not biodegradable polymers in a wider range of applications. This article will report on functionalization of poly(ε-caprolactone) with unsaturated monomers bearing either anhydride groups (PCL-g-(MA-GMA)) or tertiary amines (PCL-g-DMAEA), obtained through radical grafting in a Brabender mixer. Crystallization kinetics parameters have been determined with several techniques (rheology, optical microscopy and differential scanning calorimetry) and the results obtained are in good agreement. It was observed that the crystallization rate significantly increases in the case of the modified polymers.     

Modern mass spectrometry in the characterization and degradation of biodegradable polymers

In the last decades, the solid-waste management related to the extensively growing production of plastic materials, in concert with their durability, have stimulated increasing interest in biodegradable polymers. At present, a variety of biodegradable polymers has already been introduced onto the market and can now be competitive with non biodegradable thermoplastics in different fields (packaging, biomedical, textile, etc.). However, a significant economical effort is still directed in tailoring structural properties in order to further broaden the range of applications without impairing biodegradation. Improving the performance of biodegradable materials requires a good characterization of both physico-chemical and mechanical parameters. Polymer analysis can involve many different features including detailed characterization of chemical structures and compositions as well as average molecular mass determination. It is of outstanding importance in troubleshooting of a polymer manufacturing process and for quality control, especially in biomedical applications. This review describes recent trends in the structural characterization of biodegradable materials by modern mass spectrometry (MS). It provides an overview of the analytical tools used to evaluate their degradation. Several successful applications of MALDI-TOF MS (matrix assisted laser desorption ionization time of flight) and ESI MS (electrospray mass spectrometry) for the determination of the structural architecture of biodegradable macromolecules, including their topology, composition, chemical structure of the end groups have been reported. However, MS methodologies have been recently applied to evaluate the biodegradation of polymeric materials. ESI MS represents the most useful technique for characterizing water-soluble polymers possessing different end group structures, with the advantage of being easily interfaced with solution-based separation techniques such as high-performance liquid chromatography (HPLC).     

聚乙醇酸类生物降解高分子

聚乙醇酸类生物降解高分子具有良好的生物相容性,在药物缓释材料、组织工程材料、手术缝合线等医用领域有广泛的应用。文章按聚乙醇酸类生物降解高分子的种类不同,介绍了它们的合成、性能与应用,尤其是乙醇酸-乳酸共聚物的研究进展。展望聚乙醇酸类生物降解高分子的未来,降低合成成本是广泛应用的关键,因此简单易行的、以乙醇酸等单体为原料的直接缩聚法合成值得关注。     

Biodegradable polymers for microencapsulation of drugs

Drug delivery has become increasingly important mainly due to the awareness of the difficulties associated with a variety of old and new drugs. Of the many polymeric drug delivery systems, biodegradable polymers have been used widely as drug delivery systems because of their biocompatibility and biodegradability. The majority of biodegradable polymers have been used in the form of microparticles, from which the incorporated drug is released to the environment in a controlled manner. The factors responsible for controlling the drug release rate are physicochemical properties of drugs, degradation rate of polymers, and the morphology and size of microparticles. This review discusses the conventional and recent technologies for microencapsulation of the drugs using biodegradable polymers. In addition, this review presents characteristics and degradation behaviors of biodegradable polymers which are currently used in drug delivery.     

21世纪的高分子化学展望

对于２１世纪高分子科学的展望大致如下：２１世纪的特征是能源、材料和环保与健康（或称绿色）。作为材料领域中极其重要的部分,２１世纪对高分子材料在质量方面都有要求,大致可分二个方面同是通过控制聚合而得均匀高分子,其分子量概念不再是各种长短不齐高分子链的平均分子量;二是绿色高分子与绿色反应,前者主要是指生物高分子,对环境稳定高分子则将进行回收与重复使用;所谓绿色反应指所有高分子与相应单体的合成方法都必须     

Technology Trends in Biodegradable Polymers: Evidence from Patent Analysis

The public and governmental awareness regarding more sustainable products have gained significant momentum in the last decade and are directing the future research of the next generation of materials and processes. In such a setting, biodegradable polymers are regarded as one of the technologies driving the innovation and current market growth because they provide an additional end of life option. Tracing the evolving trends of these emerging technologies will help researchers, investors, and policy makers to better evaluate the opportunities of the technology as well as to understand the technology's changing characteristics. Therefore, within this study, we perform bibliographic analyses based on patent information to delineate the current research landscape and to anticipate the future development trends by focusing on the cases of poly(lactic acid) (PLA), poly(hydroxyalkanoates) (PHAs), polycaprolactone (PCL), poly(butylene succinate) (PBS), and poly(butylene adipate-co-terephthalate) (PBAT). The following findings were made: First, PLA gets the highest attention from both academia and industry. Second, the overall international presence of biodegradable polymer patents is high, especially in the field of PHAs. Third, technology maturity and technology strength show that PLA is the most promising technology at present in technological terms, whereas PHAs, PCL, and PBS are uncertain technologies and PBAT has a rather low development potential.     

生物降解聚合物的研究和产业化进展及展望

结合作者等近十年来在生物降解聚合物领域的研究和产业化工作,本文概述了聚乳酸、聚氨基酸、聚对二氧六环酮及其它生物降解聚合物的合成进展,综述了可生物降解温度敏感水凝胶、形状记忆高分子材料的研究概况,阐述了可生物降解聚合物在生物活性大分子控释体系、超细纤维组织工程支架上的应用研究,介绍了可生物降解聚合物在食品包装、纺织和汽车电子等方面的应用,总结了可生物降解聚合物、医疗器械、药物制剂和组织工程等领域产业化近况.最后展望了生物降解聚合物的研究、应用和产业化前景.     

Functionalized Synthetic Biodegradable Polymer Scaffolds for Tissue Engineering

Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating tissues in 3D. Biodegradable synthetic polymers are the most widely used scaffolding materials. However, synthetic polymers usually lack the biological cues found in the natural extracellular matrix. Significant efforts have been made to synthesize biodegradable polymers with functional groups that are used to couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is the most efficient way to elicit desired cell/material interactions. This paper reviews recent advancements in the development of functionalized biodegradable polymer scaffolds for tissue engineering, emphasizing the syntheses of functional biodegradable polymers, and surface modification of polymeric scaffolds.

     

Encapsulation and sustained release of a model drug, indomethacin, using CO(2)-based microencapsulation

A carbon dioxide (CO(2))-based microencapsulation technique was used to impregnate indomethacin, a model drug, into biodegradable polymer nanoparticles. Compressed CO(2) was emulsified into aqueous suspensions of biodegradable particles. The CO(2) plasticizes the biodegradable polymers, increasing the drug diffusion rate in the particles so that drug loading is enhanced. Four types of biodegradable polymers were investigated, including poly(d,l-lactic acid) (PLA), poly(d,l-lactic acid-co-glycolic acid) (PLGA) with two different molar ratios of LA to GA, and a poly(d,l-lactic acid-b-ethylene glycol) (PLA-PEG) block copolymer. Biodegradable nanoparticles were prepared from polymer solutions through nonsolvent-induced precipitation in the presence of surfactants. Indomethacin was incorporated into biodegradable nanoparticles with no change of the particle size and morphology. The effects of a variety of experimental variables on the drug loadings were investigated. It was found that the drug loading was the highest for PLA homopolymer and decreased in PLGA copolymers as the fraction of glycolic acid increased. Indomethacin was predicted to have higher solubility in PLA than in PLGA based on the calculated solubility parameters. The drug loading in PLA increased markedly as the temperature for impregnation was increased from 35 to 45 degrees C. Drug release from the particles is a diffusion-controlled process, and sustained release can be maintained over 10 h. A simple Fickian diffusion model was used to estimate the diffusion coefficients of indomethacin in the biodegradable polymers. The diffusion coefficients are consistent with previous studies, suggesting that the polymer properties are unchanged by supercritical fluid processing. Supercritical CO(2) is nontoxic, easily separated from the polymers, can extract residual organic solvent, and can sterilize biodegradable polymers. The CO(2)-based microencapsulation technique is promising for the production of drug delivery devices without the use of harmful solvents.     

Phosphorus containing hydrogels

Since the discovery of poly(2‐hydroxyethyl methacrylate) by Wichterle and Lim in 1960, hydrogels have been of great interest to biomedical scientists. Hydrogels are three dimensional hydrophilic polymer networks capable of swelling in water or biological fluids and retaining a large amount of fluids in the swollen state. In the last decade, hydrogels containing organophosphorus moieties were synthesized and used for proton conducting membrane, drug carriers, and scaffold for tissue engineering, pharmaceutical formulation, cosmetics, and bioseparation. One of the most versatile and rapidly developing classes of biomedical polymers is a family of polymers with a nitrogen and phosphorus backbone—polyphosphazenes. The advantage of the phosphorus–nitrogen backbone is that it can be rendered hydrolytically unstable when combined with appropriate side groups. Because of the tremendous variety of substituents that can be introduced in their structure, phosphazene polymers exhibit a very broad and sophisticated spectrum of chemical and physical properties leading to almost unlimited possibilities in the preparation of biodegradable materials Copyright © 2009 John Wiley & Sons, Ltd.     

Side chain crosslinking of aromatic polyethers for high temperature polymer electrolyte membrane fuel cell applications

Novel aromatic polymers bearing polar pyridine units in the main chain and side chain crosslinkable hydroxyl and propargyl groups have been successfully synthesized. The polymers have been investigated in terms of their critical properties related to their application in high temperature polymer electrolyte membrane fuel cells, such as doping ability, mechanical properties, and thermal stability. Crosslinked membranes were prepared by direct crosslinking of hydroxyl side chain groups with decafluorobiphenyl used for the first time as a crosslinking agent. However, further functionalization of hydroxyl groups to the propargyl derivative has also led to crosslinked polymers after thermal curing. Both types of crosslinked membranes exhibited higher glass transition temperatures as well as lower doping levels when doped in phosphoric acid compared with the non crosslinked analogs, confirming the formation of a successfully crosslinked network. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Star-shaped polymers with a doubled fullerene (C60) branching center

Star-shaped regular homopolystyrenes with 22 arms and heteroarm polymers with 12 PS arms and 10 poly(2-vinypyridine) arms have been synthesized by consecutive coupling-functionalization-coupling reactions. The synthesis includes the following stages: the exhaustive grafting of fullerene C₆₀ by polystyryllithium chains (living hexaadducts); the coupling of hexaadducts with the use of dimethyldichlorosilane or 1,4-dibromobutane into twelve-arm macromolecules, where the branching center is composed of two covalently bonded fullerene C₆₀ molecules; functionalization of twelve-arm double-core PS stars during the action of excess dihalides (the replacement of lithium atoms with groups containing chlorine or bromine atoms); and the coupling of living chains of PS or poly(2-vinylpyridine) via reactions with halogen-containing groups at the branching center of double-core PS stars. Linear living polymers used as arms have been prepared by anionic polymerization. Exclusion chromatography has been used to control the individual stages of synthesis. The molecular characteristics of the PS precursor and of star-shaped polymers have been studied in terms of hydrodynamics and light scattering.     

Recent advances on electrospun scaffolds as matrices for tissue-engineered heart valves

Valvular heart diseases (VHDs) are a major health problem increasing morbidity and mortality worldwide. Currently, treatment of VHDs relies on valve replacement with mechanical or biological valves, which have major drawbacks in terms of durability and the ability to grow, repair and remodel. To this end, tissue-engineered heart valves (TEHVs) have emerged as ideal substitutes. TEHVs are composed of biodegradable, biocompatible and mechanically stable scaffolds that resemble the native valves. These scaffolds are seeded with autologous cells and conditioned in a bioreactor prior to implantation. Scaffolds that have been utilized so far for such application are (i) biological, (ii) synthetic and (iii) cell entrapment in polymerized extra-cellular matrix based scaffolds. Synthetic scaffolds are considered superior over the other two types in terms of controlled mechanical properties and degradation rate. They can be subdivided into porous, hydrogel and fibrous scaffolds. Among the three subcategories, fibrous scaffolds are preferred because they resemble the natural extra-cellular matrix for the native valve. Such scaffolds can be fabricated using phase separation, self-assembly and electrospinning. Electrospinning is a versatile technique for fabricating scaffolds for tissue engineering applications that possess many advantages. Electrospun scaffolds processed using a wide range of synthetic and natural polymers were proven to be promising in terms of mechanical properties comparable to the native valves, fiber diameter within the range of the natural extracellular matrix and good cellular response. However, further investigation in fabricating fibrous scaffolds for tissue-engineered heart valves is still needed. In this review, we discussed electrospun scaffolds as TEHVs matrices, how far they succeeded in meeting the criteria of ideal scaffolds for such application and what the shortage aspects and possible solutions are.     

Vinylcarbonates and vinylcarbamates: Biocompatible monomers for radical photopolymerization

The last decade has seen a remarkable interest in the use of biocompatible and biodegradable polymers as scaffolds for tissue engineering. The fabrication of 3D scaffolds by lithography‐based additive manufacturing technology (AMT) represents an appealing approach. As poly(lactic acid), the state of the art biocompatible and biodegradable material, cannot be processed by these photopolymerization‐based techniques, it has so far been necessary to use selected (meth)acrylates. By developing new photopolymers based on vinyl carbonates and vinyl carbamates as a reactive group we have been able to avoid most of the disadvantages of classical (meth)acrylate‐based photopolymers. The new generation of biocompatible monomers show low cytotoxicity, have good storage stability, and are sufficiently photoreactive to be structured by lithography based AMT. The mechanical properties and rates of degradation of the polymers can be easily tuned over a broad range. Degradation results in the formation of nonacidic and nontoxic degradation products of low molecular weight that can be easily transported within the human body. Initial in vivo tests showed significant osseointegration of the 3D cellular scaffolds and no signs of implant rejection. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011