Self-accelerated biodegradation of electrospun poly(ethylene glycol)-poly(l-lactide) membranes by loading proteinase K

Proteinase K was successfully loaded inside ultrafine fibers of poly(ethylene glycol)-poly(l-lactide) (PELA) by emulsion electrospinning. A core/shell fiber structure was formed and verified by a transmission electron microscope. In vitro biodegradation of electrospun PELA membranes containing proteinase K (PELA-P) was examined in Tris-HCl buffer solution at pH 8.6 and 37 °C in comparison with electrospun PELA membranes without proteinase K. During biodegradation, mass loss, water absorption, pH value of the incubated buffer, fibrous morphology and thermal properties were monitored. Results suggested that PELA-P membranes degraded significantly faster than PELA membranes. A significant drop in pH value of the buffer after incubation of PELA-P membranes for 1 d was observed, and after 7 d, PELA-P membranes lost their fibrous appearance and masses almost completely. In contrast, electrospun PELA membranes did not show any obvious changes. The obtained electrospun PELA-P membranes exhibited self-accelerated biodegradability and could benefit drug controlled release and tissue regeneration.     

Encapsulation of proteins in poly(l-lactide-co-caprolactone) fibers by emulsion electrospinning

This study was aimed at investigating emulsion electrospinning to prepare biodegradable fibrous mats with encapsulation of human-nerve growth factor (NGF). One of the best methods for fabricating a bio-functional tissue engineering scaffold is to load bioactive agent into the scaffold. In this work, the feasibility of incorporating NGF into poly(l-lactide-co-caprolactone) fibers by emulsion electrospinning has been studied. The release behavior of encapsulated bovine serum albumin (BSA) was investigated. The bioactivity of NGF released from fibrous mats was verified by testing the neurite outgrowth of rat pheochromocytoma cells (PC12). Furthermore, the process of fiber forming during emulsion electrospinning was discussed. The results demonstrate that emulsion electrospun fibers can successfully encapsulate proteins and release them in a sustained manner. The bioactivity of NGF released from emulsion electrospun fibers was confirmed by PC12 bioassays.     

Biodegradable ultrafine fibers with core–sheath structures for protein delivery and its optimization

This study was aimed to design core–sheath‐structured polymeric fibers for protein delivery through emulsion electrospinning to enhance the encapsulation efficiency (EE), structural integrity, and activity retention, and to achieve controllable protein release. Integral core–sheath structure was achieved for electrospun fibers with lysozyme loading efficiency of 93.3% and the specific activity retention (SAR) of 64.6%, while the surface protein content (SP) was as low as 4.2%. The emulsion components were optimized to minimize the burst release and extend the release period, and the release profiles were found to be closely related with the fiber characteristics such as the SPs. An initial burst release as low as 6.2% followed by gradual release for 33 days was indicated from poly(ethylene glycol)‐poly(DL ‐lactide) (PELA) fibers. The gradual protein release was determined by a competition of fiber collapse leading to accelerated release and fiber fusion leading to decelerated release. Dependent on the matrix polymer and protein encapsulated, the degradation behaviors of the fiber matrices were correlated with the release rate and the effective lifetime of the drug release. The core–sheath‐structured ultrafine fibers could protect the structural integrity and bioactivity of encapsulated lysozyme, and an increase in the protective effect was demonstrated for fibers prepared from PELA matrix. Copyright © 2010 John Wiley & Sons, Ltd.     

聚乙二醇-b-聚乳酸的合成及其电纺形成超细纤维研究

为了提高聚乳酸的亲水性,以辛酸亚锡为催化剂、聚乙二醇单甲醚(mPEG)为大分子引发剂进行丙交酯(LLA)开环聚合,合成聚乙二醇-b-聚乳酸两嵌段共聚物(PELA).以红外光谱1、H核磁共振谱、接触角测试、差热扫描量热分析等方法对PELA的结构及性能进行表征.结果表明,通过调控mPEG与LLA的投料比可以控制PELA的相对分子质量,而随着mPEG组分含量或链长增加,共聚物亲水性增强,但其Tg、Tcc、Tm有所降低.由普通电纺制备PELA超细纤维,并分别由乳液电纺和同轴电纺得到以水溶性聚氧化乙烯(PEO)为芯、PELA为壳的芯/壳结构复合超细纤维(E-PEO/PELA和C-PEO/PELA).扫描电镜和透射电镜结果表明,PELA、E-PEO/PELA和C-PEO/PELA超细纤维形貌良好.随着PELA中mPEG含量的增加,电纺PELA纤维膜的吸水率增强,而由乳液电纺和同轴电纺制备的PEO/PELA芯/壳结构超细纤维膜,亲水性均好于PELA超细纤维膜.     

Magnolol entrapped ultra-fine fibrous mats electrospun from poly(ethylene glycol)-<Emphasis Type="Italic">b</Emphasis>-poly(L-lactide) and <Emphasis Type="Italic">in vitro</Emphasis> release

Ultra-fine fibrous mats with magnolol entrapped have been prepared by electrospinning biodegradable copolymer poly(ethylene glycol) blocked poly(L-lactide). Drug entrapment was perfect which was confirmed by scanning electron microscopy and differential scanning calorimetry. According to in vitro drug release investigation by high performance liquid chromatography, it was found that fibers with 10%, 20% and 30% drug entrapped respect to polymer (mass ratio) presented dramatically different drug release behavior and degradation behavior under the effect of proteinase K. The reason may be that fibers with 10% drug entrapped was more easily affected by enzyme while, to some degree, magnolol in fibers with 20% and 30% entrapped prevented polymer from being degraded by enzyme.     

Bioactive glass sol as a dual function additive for chitosan-alginate hybrid scaffold

Bioactive glass-chitosan-alginate hybrid scaffolds were fabricated using BG sol as a dual function additive, which behaves as both bioactive inorganic phase to confer the bioactivity and cross-linker to improve the structural stability and mechanical properties.     

INVESTIGATION OF POLYDL-LACTIDE-b-POLY（ETHYLENE GLYCOL）-b-POLYDL-LACTIDE MICROSPHERES CONTAINING PLASMID DNA

PolyDL-lactide (PDLLA) and the block copolymer, polyDL-lactide-b-poly(ethylene glycol)-b-polyDL-lactide (PELA) were used as the microsphere matrix to encapsulate plasmid DNA. The PDLLA, PELA, pBR322-1oaded PDLLA and pBR322-1oaded PELA microspheres were prepared by solvent extraction method based on the formation of multiple w1/o/w2 emulsion. The microspheres were characterized by surface morphology, mean particle size, particle size distribution and loading efficiency. The integrity of DNA molecules after being extracted from microspheres was determined by agarose gel electrophoresis. The result suggested that plasmid DNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could prevent plasmid DNA from being digested by DNase. The in vitro degradation and release profiles of plasmid DNA-loaded microspheres were measured in pH - 7.4 buffer solution at 37℃. The in vitro degradation profiles of the microspheres were evaluated by the deterioration in microspheres surface morphology, the molecular weight reduction of polymer, the mass loss of microspheres, the changes of pH values of degradation medium, and the changes of particle size. The in vitro release profiles of the microspheres were assessed by measurement of the amount of DNA presented in the release medium at determined intervals. The release profiles were correlation with the degradation profiles. The release of plasmid DNA from PELA microspheres showed a similar biphasic trend, that is, an initial burst release was followed by a slow, but sustained release.     

Bioactive,Elastic, and Biodegradable Emulsion Electrospun DegraPol Tube Delivering PDGF‐BB for Tendon Rupture Repair

Healing of tendon ruptures represents a major challenge in musculoskeletal injuries and combinations of biomaterials with biological factors are suggested as viable option for improved healing. The standard approach of repair by conventional suture leads to incomplete healing or rerupture. Here, a new elastic type of DegraPol® (DP), a polyester urethane, is explored as a delivery device for platelet‐derived growth factor—BB (PDGF‐BB) to promote tendon healing. Using emulsion electrospinning as an easy method for incorporation of biomolecules within polymers, DegraPol® supports loading and release of PDGF‐BB. Morphological, mechanical and delivery device properties of the bioactive DP scaffolds, as well as differences arising due to different electrospinning parameters are studied. Emulsion electrospun DP scaffolds result in thinner fibers than pure DP scaffolds and experience decreased strain at break [%], but high enough for successful surgeon handling. PDGF‐BB is released in a sustained manner from emulsion electrospun DP, but not completely, with still large amount of it being inside the polymeric fibers after 30 d. In vitro studies show that the bioactive scaffolds promote tenocyte proliferation in serum free and serum⁺ conditions, demonstrating the potential of this surgeon‐friendly bioactive delivery device to be used for tendon repair.

     

Synthesis and biomimetic mineralization of l‐proline substituted polyphosphazenes as bulk and nanofiber

This work presents the synthesis of polyphosphazenes bearing L ‐proline methyl ester (ProOMe) and 4‐hydroxy‐l ‐proline methyl ester (HypOMe), aiming for new bioactive polymers for bone repair. The polymers were characterized by ¹H and ³¹P NMR, FTIR, DSC, and TGA. Electrospun fibers were prepared using poly[bis(l ‐proline methyl ester)phosphazene] (PProP), and their potential for biomimetic mineralization, as well as the bulk material, were tested in simulated body fluid (1×SBF). Samples were analyzed between 24 h and 3 weeks of incubation using SEM/EDS and FTIR. After 24 h, spherical and flower‐like shapes of calcium phosphates (CaP) were crystallized on the bulk samples. The nanofibers presented spherical CaP crystals attached to them after 48 h of incubation. The Ca/P molar ratio of the crystals varied from 1.5 to 1.6. According to this study, PProP presents bioactivity in vitro, and its fibers offer sites for CaP nucleation like the collagen fibers in bone. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1318–1327     

Degradation patterns and surface wettability of electrospun fibrous mats

Degradation profiles and surface wettability are critical for optimal application of electrospun fibrous mats as drug carriers, tissue growth scaffolds and wound dressing materials. The effect of surface morphologies and chemical groups on surface wettability, and the resulting matrix degradation profiles were firstly assessed for electrospun poly(d,l-lactide) (PDLLA) and poly(d,l-lactide)-poly(ethylene glycol) (PELA) fibers. The air entrapment between the fiber interfaces clarified the effects of various surface morphologies on the surface wettability. Chemical groups with lower binding energy were enriched on the fiber surface due to the high voltage of the electrospinning process, and a surface erosion pattern was detected in the degradation of electrospun PDLLA fibers, which was quite different from the bulk degradation pattern for other forms of PDLLA. Contributed by the hydrophilic poly(ethylene glycol) segments, the degradation of electrospun PELA fibers with hydrophobic surface followed a pattern different from surface erosion and typical bulk degradation.     

In vitro degradation and release profiles for electrospun polymeric fibers containing paracetanol

In the paper, the poly(D,L-lactide) (PDLLA) and poly(ethylene glycol)-co-poly(D,L-lactide) (PELA) fibers with and without paracetanol drug loading were prepared with an electrospinning method. The morphology of the fibers was observed by scanning electronic microscope (SEM). Their glass transition temperatures (T(g)) were measured with differential scanning calorimetry (DSC). The water contact angle (CA) measurement was also performed to characterize surface properties of fibers. At 37 degrees C in a PBS buffer solution (pH 7.4), in vitro matrix degradation profiles of these fibers were characterized by measuring their weight loss, the molecular weight decrease, and their morphology change. The result showed that the effects of fiber diameter and porosities on the degradation of the electrospun scaffolds might exceed the effects of the molecular weight and the PEG contents, which was different from the polymeric microspheres degradation. In vitro paracetanol release profiles were also investigated in the same condition. The result showed that the drug burst release behaviour was mainly related with the drug-polymer compatibility and the followed sustained release phase depended on polymer degradation.     

Electrospinning of ultrafine core/shell fibers for biomedical applications

Because of the inherent appearance similar to the natural extracellular matrix, ultrafine fibrous membranes prepared via electrospinning exhibit widespread applications, especially in the biomedical area. Extensional modifications of coaxial and emulsion electrospinning have drawn much attention in preparation of core/shell fibers for applications as tissue engineering scaffolds and controlled delivery systems for bioactive substances. Due to incorporation of multi-components in the electrospun core/shell fibers, the process of coaxial and emulsion electrospinning became more susceptible. The theories have not been fully understood. A series of investigations were carried out evaluating the systematic and processing parameters. This paper reviews advantages and potentials of electrospun core/shell fibers as well as factors influencing their formation on the basis of our research and new progress.     

Enzymatic degradation of poly(L-lactide) and poly(epsilon-caprolactone) electrospun fibers

Poly(L-lactide) (PLLA) and poly(epsilon-caprolactone) (PCL) ultrafine fibers were prepared by electrospinning. The influence of cationic and anionic surfactants on their enzymatic degradation behavior was investigated by measuring weight loss, molecular weight, crystallinity, and melting temperature of the fibers as a function of degradation time. Under the catalysis of proteinase K, the PLLA fibers containing the anionic surfactant sodium docecyl sulfate (SDS) exhibited a faster degradation rate than those containing cationic surfactant triethylbenzylammonium chloride (TEBAC), indicating that surface electric charge on the fibers is a critical factor for an enzymatic degradation. Similarly, TEBAC-containing PCL fibers exhibited a 47% weight loss within 8.5 h whereas SDS-containing PCL fibers showed little degradation in the presence of lipase PS. By analyzing the charge status of proteinase K and lipase PS under the experimental conditions, the importance of the surface charges of the fibers and their interactions with the charges on the enzymes were revealed. Consequently, a "two-step" degradation mechanism was proposed: (1) the enzyme approaches the fiber surface; (2) the enzyme initiates hydrolysis of the polymer. By means of differential scanning calorimetry and wide-angle X-ray diffraction, the crystallinity and orientation changes in the PLLA and PCL fibers during the enzymatic degradation were investigated, respectively.     

Using CLEM to investigate the distribution of nano-sized antimicrobial agents within an EVOH matrix

Efficient characterization of the distribution of antimicrobial agents within a polymer matrix is of vital importance. Two antimicrobial agents, chitin nanowhiskers (ChNWs) and chitosan-based silver nanoparticles (CTSAgNPs), were produced and incorporated separately as well as combined into a poly(ethylene-co-vinyl alcohol) (EVOH) matrix by way of electrospinning. Correlative light and electron microscopy (CLEM) and energy dispersive X-ray mapping provided a holistic approach to visualize the distribution of the combinations of AgNPs and ChNWs within EVOH fibers. CLEM analysis revealed the tendency of the ChNWs to align themselves on the surface of the fibers, while the silver nanoparticles were localized inside the polymer matrix.     

Magnetically responsive hydrophobic pockets for on–off drug release

The vast majority of drugs available on the market are hydrophobic compounds. As a result, their poor water solubility can critically compromise the overall absorption of these drugs by patients. Although numerous different strategies have been developed to improve their bioavailability, the controlled delivery of these drugs is still a challenge. In this sense, stimuli-responsive hydrogels could be a solution to improve administration and stable release. However, the strategies required to render hydrogels hydrophobic mostly rely on weak hydrophobic interactions, which can lead to disassembly of the system and undesired burst discharge. Accordingly, the on-demand release of poorly water-soluble drugs is still a major milestone in this field. To circumvent these setbacks, we present for the first time a hydrophobic, magnetically responsive hydrogel based on the diaminotriazine (DAT) skeleton. The versatility of DATs in terms of H-bond formation and metal complexation simultaneously endows the hydrogel with hydrophobicity and magnetic responsiveness, thus allowing both the efficient loading and on–off release of a model hydrophobic drug as well as of a hydrophobic bioactive substance. Theoretical calculations further suggested stable formation of DAT aggregates that operate as efficient hydrophobic cavities or ‘pockets’ for these compounds. Moreover, these materials were found to be suitable for enhancing the viability and growth of cell lines often used as in vitro models of neuronal function and differentiation. The present magnetic hydrogels hold interesting potential for tissue engineering as biocompatible scaffolds for the on-demand release of hydrophobic compounds, which remains the focus of current research efforts.     

Human serum albumin in electrospun PCL fibers: structure,release, and exposure on fiber surface

Human serum albumin (HSA) introduced to the fibers produced by electrospinning from HSA and polycaprolactone (PCL) solutions in hexafluoroisopropanol has been studied in terms of its structure, release from the fibers, stability of interaction with basic polymer, accessibility for protease attack, and cellular receptors, as well as dependence of the studied parameters on the protein concentration in fibers. A limited part of the protein leaves the fibers right after soaking with water, whereas the remaining protein stays tightly bound to fibers for a long time because protein nanoparticles are tightly integrated with PCL, as shown by small‐angle X‐ray scattering. As has been demonstrated, the proteins leave the fibers in complexes with PCL. X‐ray photoelectron spectroscopy demonstrates that the protein concentration on the fiber surface is higher than the concentration in electrospinning solution. The surface‐exposed protein is recognized by cell receptors and is partially hydrolyzed by proteinase K. The data on pulse protein release, presence of PCL in the protein released from matrixes, overrepresentation of the protein on the fiber surface, and tight interaction of protein with PCL may be useful for rational design of electrospun scaffolds intended for drug delivery and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.     

PLA and PBAT-Based Electrospun Fibers Functionalized with Antibacterial Bio-Based Polymers

Antimicrobial fibers based on biodegradable polymers, poly(lactic acid) (PLA), and poly(butylene adipate-co-terephthalate) (PBAT) are prepared by electrospinning. For this purpose, a biodegradable/bio-based polyitaconate containing azoles groups (PTTI) is incorporated at 10 wt.% into the electrospinning formulations. The resulting fibers functionalized with azole moieties are uniform and free of beads. Then, the accessible azole groups are subjected to N-alkylation, treatment that provides cationic azolium groups with antibacterial activity at the surface of fibers. The positive charge density, roughness, and wettability of the cationic fibers are evaluated and compared with flat films. It is confirmed that these parameters exert an important effect on the antimicrobial properties, as well as the length of the alkylating agent and the hydrophobicity of the matrix. The quaternized PLA/PTTI fibers exhibit the highest efficiency against the tested bacteria, yielding a 4-Log reduction against S. aureus and 1.7-Log against MRSA. Then, biocompatibility and bioactivity of the fibers are evaluated in terms of adhesion, morphology and viability of fibroblasts. The results show no cytotoxic effect of the samples, however, a cytostatic effect is appreciated, which is ascribed to the strong electrostatic interactions between the positive charge at the fiber surface and the negative charge of the cell membranes.     

Controlled release of dual drugs from emulsion electrospun nanofibrous mats

The purpose of this work is to develop a novel type of tissue engineering scaffold or drugs delivery carrier with the capability of encapsulation and controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin (BSA) were successfully incorporated into nanofibers by means of emulsion electrospinning. The morphology of composite nanofibers was studied by Scanning Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion electrospinning were characterized by water contact angle measurement and X-ray diffraction. In vitro dual drugs release behaviors from composite nanofibrous mats were investigated. The results indicated that the incorporated drug and/or proteins in composite fibrous mats made from electrospinning could be control released by adjusting the processes of emulsions preparation.     

Encapsulation and release of biomolecules from Ca-P/PHBV nanocomposite microspheres and three-dimensional scaffolds fabricated by selective laser sintering

This study focused on the fabrication of calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite scaffolds loaded with biomolecules using the selective laser sintering (SLS) technique and their evaluation. Ca-P/PHBV nanocomposite microspheres loaded with bovine serum albumin (BSA) as the model protein were fabricated using the double emulsion solvent evaporation method. The encapsulation efficiency of BSA in PHBV polymer microspheres and Ca-P/PHBV nanocomposite microspheres were 18.06 ± 0.86% and 24.51 ± 0.60%, respectively. The BSA loaded Ca-P/PHBV nanocomposite microspheres were successfully produced into three-dimensional porous scaffolds with good dimensional accuracy using the SLS technique. The nanocomposite microspheres served as protective carriers and maintained the bioactivity of BSA during SLS. The effects of SLS parameters such as laser power and scan spacing on the encapsulation efficiency of BSA in the scaffolds and in vitro BSA release were studied. An initial burst release was observed, which was followed by a slow release of BSA. After 28-day release, The PHBV matrix was slightly degraded after 28-day in vitro release study. It was shown that nanocomposite scaffolds with controlled architecture obtained via SLS could be incorporated with biomolecules, enhancing them with more functions for bone tissue engineering application or making them suitable for localized delivery of therapeutics.     

Waterborne RAFT polymers

A recently invented novel family of RAFT (Reversible Addition-Fragmentation chain Transfer) agents having a common formula Z-C(S)-S-CR₂COOR¹ where Z = -SR, -NR₂, or -OR, and R¹ represents H or a variety of functional groups allows for tailoring their hydrophilicity-hydrophobicity balance. A limited hydrophilicity of the RAFT agents can be achieved which is sufficient for their diffusion through water, yet the agents are hydrophobic enough to phase-separate out of water. Thus, the limited hydrophilicity of otherwise hydrophobic agents allows them to be at the loci of polymerization making them suitable for the emulsion polymerization mechanism. With several RAFT agents, good control over molecular weight was demonstrated for a broad variety of ab initio acrylic emulsion polymers. For methyl methacrylate, a portion of RAFT did not engage, resulting in less than the theoretical number of polymer chains. It was found, however, that as little as ∼10 wt% of an acrylic monomer slowed down polymerization enough to engage all RAFT agent molecules and yield predicted molecular weights. A broad variety of colorless and odorless telechelic acrylic and methacrylic emulsion polymers were synthesized.Microemulsion and solution-dispersion techniques produced clean colloidally stable RAFT dispersions. These two techniques did not require RAFT agents with tailored hydrophilicity-hydrophobicity.The UV spectra and photooxidative stability of the RAFT polymers were studied. The RAFT fragment in polymers appeared to have no impact on their photooxidative stability.