BIODEGRADABLE POLYMERS WITH A PHOSPHORYL-CONTAINING BACKBONE:TISSUE ENGINEERING AND CONTROLLED DRUG DELIVERY APPLICATIONS

This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.

Stereoselective synthesis of biodegradable polymers by salen-type metal catalysts

Biodegradable polymers are a promising sustainable alternative to conventional petroleum-based polymers and have attracted recent extensive research interest due to their potential environmental friendliness and sustainability. Among them, aliphatic polyesters and polycarbonates are the most extensively studied ones. The metal-catalyzed ring-opening polymerization(ROP) of cyclic esters and ring-opening copolymerization(ROCOP) of epoxides with anhydrides or CO_(2) are often considered to be the classic and efficient methods to synthesize stereoregular polymers. Moreover, the versatile salen-type metal complexes have been used to prepare almost all types of biodegradable polymers with excellent stereoselectivity control. Hence, this review focuses on stereoselective synthesis of biodegradable polymers by salen-type metal catalysts developed in the last decade.Aliphatic polyesters from ROP of cyclic esters, ROCOP of epoxides with cyclic anhydrides, and carbonylative polymerization of epoxides, as well as aliphatic poly(thio)carbonate from ROCOP of epoxides with CO_(2) or COS are discussed in detail. This review highlights the polymerization mechanisms, catalyst characteristics, and factors controlling the stereoselectivity of each polymerization reaction, aiming to provide general rules for the future design of stereoselective catalysts.

Synthesis and Properties of Biodegradable Copolymers of 9-Phenyl-2, 4, 8, 10-tetraoxaspiro-[5, 5]undcane-3-one and Ethylene Ethyl Phosphate

Novel biodegradable copolymer poly（CC-co-EEP） was synthesized by ring-opening copolymerization of cyclic carbonate 9-phenyl-2, 4, 8, 10-tetraoxaspiro-[5, 5]undcane-3-one （CC） and ethylene ethyl phosphate （EEP）. The obtained poly （CC-co-EEP）s were characterized by FTIR, ^1H NMR, ^13C NMR and gel permeation chromatography （GPC）. In vitro hydrolytic degradation of the copolymers were investigated in phosphate buffer solution （pH=7.4）. Hydrophilic phosphate units apparently improved the degradability of poly（carbonate-phosphate）.

Special Topic on Bio-based and Biodegradable Polymers

In the past decades,bio-based and biodegradable polymers have attracted wide and increasing interests because of the shortage of fossil resource,concerns on environmental pollution,demands for some medical fields as well as support of government policies.Depending on the sustainable source of organic carbon,biodegradability and biocompatibility,these polymers have shown promising applications in industry,agriculture,biomedicine and daily life.To impart excellent physical properties and functions to them,scientists and engineers have exploited versatile methods to

Current research on electrospinning of silk fibroin and its blends with natural and synthetic biodegradable polymers

Silk fibroin （SF） is a kind of natural polymers with a great potential in biomedical application. Due to its good biocompatibility, biodegradability and minimal inflammatory reaction, SF is an excellent candidate for generating tissue engineering scaffolds. Electrospinning is a simple and effective method to fabricate nanofibers, which has several amazing characteristics such as very large surface area to volume ratio, flexibility in surface functionalities, and superior mechanical performance. The electro- spun nanofibers from SF and its blends have been used for varied tissue engineering. This paper will give a brief review about the structure, properties and applications of SF and blend nanofibers via electrospinning.

Study on the Properties of Esterified Corn Starch/Polylactide Biodegradable Blends

Fully bio-based and biodegradable starch/polylactic acid blends have received increasing attentions for their biodegradability and potential to offset the use of unsustainable fossil resources,specifically,their application in packaging.Herein,corn starch was first esterified with maleic anhydride and then compounded with polylactide(PLA)to prepare esterified corn starch/polylactic acid blends with starch content up to 35 wt%.The structures,morphologies,thermal and mechanical properties of starch or blends were investigated.The results showed that corn starch was successfully grafted with maleic anhydride,which showed increased crystallinity and particle size than native starch.Esterified corn starch/polylactic acid blends showed good surficial compatibility and good thermal stability with main decomposition temperature in the range of 300℃to 400℃.Additionally,incorporation of corn starch increased the hydrophilicity and water uptake of composites.However,the tensile and flexural strengths of blends decreased with increasing esterified starch amount.

Composition Dependence of the Thermal Behavior,Morphology and Properties of Biodegradable PBS/PTMO Segment Block Copolymer

A series of aliphatic biodegradable poly（ether-ester）s based on poly（butylene succinate）（PBS）as hard segment and poly（tetramethylene oxide）（PTMO,M_n=1 000 g/mol） as soft segment were synthesized.The composition dependence of thermal behavior,morphology and mechanical properties was investigated by differential scanning calorimetry（DSC）,atomic force microscopy（AFM）,and tensile testing.The crystallization temperature（T_c） and melting temperature（T_m） of the PBS block within poly（ether-ester）s decrease steadily at first,but decrease sharply with PTMO content above 50 wt%.Two crystallization peaks were detected for PTMO in PBSPTMO60 sample,suggesting the occurrence of fractionated crystallization.The crystallization enthalpies（△H_c） and melting enthalpies（△H_m） of PBS block decrease at first,then increase as PTMO content increases further.AFM has demonstrated that phase-separated morphology transforms from a phase of continuous hard matrix to one of continuous soft matrix containing isolated hard domain as PTMO content is increased.Finally,the results of tensile testing show that the poly（ether-ester）s present the behavior of plastics when PTMO content is below 40 wt%,and of thermoplastic elastomers with PTMO content above 50 wt%.By varying the composition of copolymer,the aliphatic poly（ether-ester）s plastics,or especially biodegradable aliphatic poly（ether-ester）s thermoplastic elastomers can be obtained.

Syntheses and Drug Delivery Property of Biodegradable Polyether-Anhydrides

Both polyanhydrides and polyethers are new types of biodegradble polymers, They are of particular interest as materials for controlled drug release system duo to their excellent surface erosion properties of polyanhydrides and excellent biocompatibility of polyethers. They hate been widly used in biomaterials. A series of polyether anhydrides elastomer were firstly synthesed through introducing PEG into the polyanhydrides chains. Their degradation and drug release property were also studied. These materials may be used in applications where materials are needed with properties more close to those of natural skin.

Preliminary Clinical Outcomes after Implantation of Newer-Generation Biodegradable Polymer-Coated Everolimus-Eluting Stent in “Real-World” Patients with Coronary Artery Disease

Background and Objective: In the contemporary practice, the use of drug-eluting stents is still associated with low mortality benefits, restenosis and stent thrombosis. To address these issues, newer generation, thin-strut, biodegradable polymer coated stents has been designed. Thus, the aim of the study is to assess the safety and clinical performance of the Everoflex (Sahajanand Medical Technologies Pvt. Ltd., Surat, India), a newer generation biodegradable polymer coated everolimus-eluting stent, in unselected “real-world” patients with coronary artery disease. Methods: It is a multicentre, retrospective, non-randomized, single-arm study enrolling all the consecutive patients who underwent implantation with the Everoflex for coronary artery disease from April 2014 to March 2016. The primary end-point of the study is 30-day major adverse cardiovascular events (MACE) rate, which consists of cardiac death, myocardial infarction, target lesion revascularization and target vessel revascularization. Stent thrombosis was also analyzed and reported. Results: A total of 340 patients were intervened successfully with 395 everolimus eluting stents (1.3 ± 0.6 stents per patient). Out of total patients (58.7 ± 10.5 years), 77.9% were male and comorbidities like diabetes and hypertension were observed in 31.2% and 35.3% patients, respectively. According to ACC/AHA classification, there were 34.4% type B lesions and 53.2% type C lesions, indicating a higher proportion of complexity involved. Moreover, 57.9% patients had multivessel disease and there were 15.4% total occlusions. At 30 days, follow-up was completed in 100% patients. The MACE was found to be 1.5%, which is a composite of 1.2% cardiac death and 0.3% target lesion revascularization. Stent thrombosis at 30 days was found to be 0.3%. Conclusion: The low incidence of MACE and stent thrombosis clearly depicts excellent safety and clinical performance of the Everoflex in unselected real world patients with coronary artery disease.

All-Comers Study of Percutaneous Coronary Interventions with Ultrathin Strut Biodegradable-Polymer Sirolimus-Eluting Stents—ORSHINE Registry

Current new generation stent technology has made remarkable progress in stent design, structure, and component material to improve its performance in reducing stent thrombosis, and restenosis compared to earlier DES and BMS. Orsiro-Sirolimus eluting stent is new generation ultra-thin strut stent with biodegradable abluminal coating that leaves a polymer free stent after drug release enhances coverage of stent struts and prevents excess neo intimal proliferation. A retrospective data analysis was done to see safety and efficacy of Orsiro in patients treated with ultra-thin DES with Orsiro stents at Sunshine Hospitals, Hyderabad. A total of 331 patients with 525 lesions were treated with 506 Orsiro stents and the major adverse cardiac events (MACE) rate and stent thrombosis (ST) at 2 years’ follow-up were analysed. MACE rate was 1.6% for an average follow-up at 2 years. Out of 2 patients who developed ST, one presented with definite acute stent thrombosis and one with possible, late stent thrombosis and 1.8% non-cardiac death reported during the follow-up. Despite many patients with complex PCI in the ACS subset, Orsiro reduced significant reduction in MACE rate in all spectrum of coronary artery disease patients with excellent acute and long-term results similar to other established FDA-approved current generations stents.

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

Employment of Waste from the Textile Industry for the Production of Nanocomposites Aiming at the Generation of Thermal Shrinkable Films and the Non-Formation of Microplastics

With the increase of incorrectly discarded materials in the environment, including clothes, the need for recycling and reusing them becomes one of the alternatives to work around this problem, following the law of the 3 Rs. However, these polymeric materials which are deposited in the marine environment and land generate microplastics, due to their degradation/fragmentation due to the action of the weather, in these regions, including being carried by the air and transported from various regions. With the aim of reducing the impact of this inappropriate disposal and obtaining a material that does not generate microplastics, this study used waste from the textile industry, which would be unusable, and a biodegradable polymer. The tissue residues were submitted to acid hydrolysis with sulfuric acid, in order to weaken the interactions between the cellulose fibrils and promote a better dispersion of the latter when processed with the polymer, during the extrusion process, generating biodegradable polymeric nanocomposites. The results showed that the samples submitted to acid hydrolysis presented a higher degree of crystallinity and a greater number of interactions and lower mobility of hydrogen atoms. In addition, the samples treated for a longer time showed a small release of fibrils, suggesting that this treatment can help in the production of nanocomposites during their extrusion.

Biodegradable Poly(butylene adipate-co-terephthalate)/Poly(glycolic acid) Films: Effect of Poly(glycolic acid) Crystal on Mechanical and Barrier Properties

Binary biodegradable polymers films, poly(butylene adipate-co-terephthalate)(PBAT) and poly(glycolic acid)(PGA), were prepared through batch melt mixing to obtain Film Ⅰ and Film Ⅱ under two different processing conditions. PGA crystals played a major role in enhancing the mechanical and barrier properties of the films. For Film Ⅰ, there were initial PGA crystals before the film blowing process, the PGA molecular chain further crystallized, forming the oriented crystallization of PGA. Moreover, the Xcand crystalline size in Film Ⅰ were higher than those in Film Ⅱ. Compared with the different processing methods, Film Ⅰ has excellent mechanical and oxygen barrier properties due to the crystallization and orientation. The tensile strength reached 45.0 MPa, and tear strength exceeded 138.2 kN/m, while the elongation at break was as high as 750% for PBAT/PGA 85/15 in Film Ⅰ. The WVTR, WVP coefficients, and OP coefficients of PBAT/PGA films were decreased obviously with increasing the PGA content both in Film Ⅰ and Film Ⅱ. Moreover, the barrier properties of oxygen in Film Ⅰ were better than that in Film Ⅱ. This work reveals a feasible processing technique by introducing of initial crystallization of PGA to blow PBAT/PGA films with excellent mechanical and barrier properties.

Morphological Evaluation of PLA/Soybean Oil Epoxidized Acrylate Three-Dimensional Scaffold in Bone Tissue Engineering

Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.

RING OPENING COPOLYMERIZATION OF SUCCINIC ANHYDRIDE-ETHYLENE OXIDE BY Al(Ⅲ) ORGANOMETALLIC CATALYSTS

Ring opening copolymerization of succinic anhydride (SA) with ethylene oxide (EO)was successfully carried out by using a series of aluminum-based catalyst in 1,4-dioxane at62±2℃. The results showed that in-situ AlR_3-H_2O (R=ethyl, iso-butyl) catalysts gavehigher molecular weight (M_w～10~4), while Al(OR)_3 catalysts gave the higher alternatingcopolymer structure with slightly lower molecular weight. The in-situ AlR_3-H_2O systemshave been evaluated in more detail for the reaction which showed the optimum H_2O/Almolar ratio to be 0.5. The copolymers with different composition (F_(SA)/F_(EO)= 36/64to 45/55 mol/mol) were synthesized by using different monomer feed ratio. The melt-ing point (T_m), glass transition temperature (T_g) and enthalpy of fusion (ΔH_f) of thesecopolymers are depended on the copolymer composition and in the range of 87～102℃,-12～-18℃, and 37～66J/g, respectively. The second heating scan of DSC also in-dicated that the higher alternating copolymer was more easily recrystallized. The onsetdecomposition temperature was more than 300℃ under nitrogen and influenced by thecopolymer composition.

The Degradation Rate of Polyanhydride (Poly(sebacic acid), diacetoxy terminated, PSADT)

The in vitro degradation rate of polyanhydride （poly（sebacic acid）, diacetoxy terminated）, also known as PSADT, was investigated. PSADT tablets with a circular cross-section were formed using a compression molding device, and then immersed into phosphate buffer saline （PBS） for in vitro degradation experiments. The mechanisms of degradation and the degradation rate were characterized by the change in molecular weight and reduction in specimen mass. In addition, the effects of processing temperature and the geometry of the formed PSADT tablets on the rate of degradation were studied. The surface morphology at different degradation times was observed by scanning electron microscopy （SEM）. The experimental results showed that PSADT exhibited sur^hce erosion due to the fact that near zero-order degradation kinetics was observed during its degradation process. Moreover, it is found that the geometry of tablets played an important role on the rate of degradation, while the processing temperature had no significant effect on the PSADT degradation rate.

CO_(2)-based Biodegradable Supramolecular Polymers with Well-tunable Adhesive Properties

Supramolecular adhesives that enable debonding on-demand are of significant research interest for the development of adaptive and smart materials,yet,biodegrable supramolecular adhesives have been rarely exploited.Herein,telechelic,three-armed and four-armed CO_(2)-based polyols with close molecular weights and various content(or carbonate unite content)have been synthesized via a zinc-cobalt double metal cyanide complex catalyzed ring-opening copolymerization of CO_(2) and propylene oxide,and further exploited as sustainable and biodegradable building blocks for supramolecular polymers(SMPs)with 2-ureido-4[1H]-pyrimidinone(UPy)motifs.Notably,the orthogonal modulation of the CO_(2) content and the topology of CO_(2)-based polyols provide a unique opportunity to fine-tune the surface energy as well as the cohesive strength of the resulting CO_(2)-based SMPs.Notably,a three-armed SMP with 44%CO_(2)(3UPy-CO_(2)-44%)can well balance the trade-off between surface energy and cohesive strength,therefore bestowing a high adhesive strength of 7.5 and 9.7 MPa towards stainless steel and wood substrates respectively by testing the corresponding single lap joints.Moreover,the light-responsive adhesion property of 3UPy-CO_(2)-44%has been demonstrated exemplarily by blending with a UV sensitizer.

Fabrication of Porous Scaffolds Using NaHCO_3 Particulates as the Porogen Material

A new method of fabricating porous polymer scaffolds was developed, using sodium hydrogen carbonate particulates as the porogen to foam. The pore structure of polymer scaffolds can easily be manipulated by controlling the size and weight fraction of sodium hydrogen carbonate particulates. The scaffolds are highly porous with a porosity greater than 90% and with a larger pore size ranging from 100-400μm, and are well distributed with the interconnected and open pore wall structure which is necessary for tissue engineering. We investigated the effect of the porosity of scaffolds, the pore size of scaffolds and material of polymer on the mechanical properties of scaffolds. The scaffolds fabricated by the method have more big pores than those by the convenient method of salt leaching.

Zinc Oxide Nano Particles Integrated Kenaf/Unsaturated Polyester BioComposite

Increasing need for materials with special features have brought various new inventions,one of the most promising hope for new material with special features and functionalities is composites materials.Thus,this study report an integration of zinc nanoparticles into kenaf/polyester polymer composite to introduce new behavior to the composite.The composite behaviors were compared for mechanical,thermal,moisture absorption and biodegradability properties.Prepared Zinc Oxide nanoparticles entrenched in the kenaf/polyestaer composites net structure through chemical bonds between kenaf/ZnO/polyester resin,existence of ZnO significantly influence the mechanical and thermals properties of composites.Thermal analysis based on(TGA)response revealed the integration of ZnO nanoparticles improved the thermal stability when thermal decomposition temperature beyond 3650 C.The thermal cracking decreased with present of ZnO and increase with kenaf content(layers).The modulus,Tensile strength,break at elongation,flexural modulus,flexural strength and impact strength of the composites with higher content kenaf/ZnO nanoparticle are 560 MPa,58MPa,1.8%,1300 PMa,68 MPa and 31 MPa,respectively.Thus,addition of kenaf layers and ZnO results in larger mechanical properties enhancement,the results of the contact angle show improvement in wetting of the fibres with addition of ZnO nanoparticles.

SYNTHESIS OF POLY(ETHYLENE TEREPHTHALATE)-POLYCAPROLACTONE BLOCK COPOLYMER BY DIRECT COPOLYMERIZATION

Po ly(ethylene terephthalate)-polycaprolactone block copolymer (PCL-b-PET) is a polyester with improved biodegradability. In the present paper, a new direct copolymerization method of epsilon-caprolactone (epsilon-CL) and bishydroxyethylene terephthalate (BHET) in the presence of Ti(OBu)(4) was proposed for the synthesis of PCL-b-PET. The PCL-b-PET copolymer was characterized by IR, GPC and H-1-NMR techniques, and the effects of synthesis conditions, such as temperature, reaction time and concentration of catalyst on the copolymerization were discussed.