Poly L-lactic Acid Fibers Research Articles

Piezoelectric Biomedical Material, Poly-L-Lactic Acid (PLLA), in the Treatment of Spinal Epidural Compression: Diagnosis, Monitoring, and Postoperative Support

This study aims to design an intelligent biomedical piezoelectric material for monitoring the pressure in the spinal epidural space caused by postoperative hematoma compression (spinal epidural hematoma). Hematoma compression in the spinal epidural space is a clinically challenging condition that is difficult to diagnose, and failure to address it within forty-eight hours may lead to severe consequences. Given its urgency, prompt and accurate diagnosis and intervention are crucial. Due to its elusive diagnostic nature, patients often miss the opportune time for treatment. Therefore, this study utilizes poly L-lactic acid (PLLA), an FDA-approved highly biocompatible biomaterial. After undergoing high-pressure polarization, PLLA exhibits excellent piezoelectric properties, making it an ideal material for monitoring intracavitary pressure. Additionally, since postoperative hematoma formation is a primary cause of spinal epidural membrane compression, this study integrates urokinase, a potent thrombolytic protein, with PLLA electrospun fibers, enabling preliminary treatment upon pressure detection.This intelligent organic biomedical material not only enables real-time monitoring of postoperative spinal epidural space pressure but also passively utilizes ultrasound to release urokinase from PLLA fibers for initial treatment when pressure is detected. Furthermore, the application of electrospun PLLA biomedical material makes the material more easily moldable and simplifies the manufacturing process, expanding its potential applications. In summary, this technology combines expertise in organic materials science, electrochemistry, and clinical medicine, offering an innovative approach to addressing the crisis posed by hematoma compression in the spinal epidural space. In future clinical applications, this technology holds the promise of providing earlier and more effective treatment for patients, potentially becoming a significant breakthrough in the fields of medical electronics and biomedical engineering. Keywords: Piezoelectric Biomaterial, Pressure Monitoring Sensor, Drug Control Release, Postoperative Support, Diagnostic Innovation

Simultaneous Coating of Electrospun Nanofibers with Bioactive Molecules for Stem Cell Osteogenesis In Vitro.

Mesenchymal stem cells (MSCs) are widely recognized as a promising cell type for therapeutic applications due to their ability to secrete and regenerate bioactive molecules. For effective bone healing, it is crucial to select a scaffold that can support, induce, and restore biological function. Evaluating the scaffold should involve assessing MSC survival, proliferation, and differentiation. The principal aim of this investigation was to formulate composite nanofibrous scaffolds apt for applications in bone tissue engineering. In this experimental study, nanofibrous scaffolds were fabricated using Poly-L-lactic acid (PLLA) polymer. The PLLA fibers' surface was modified by integrating collagen and hydroxyapatite (HA) nanoparticles. The findings demonstrated that the collagen- and nanohydroxyapatite-modified electrospun PLLA scaffold positively influenced the attachment, growth, and osteogenic differentiation of MSCs. Coating the nanofiber scaffold with collagen and nanoparticle HA significantly enhanced the osteogenic differentiation of MSCs on electrospun PLLA scaffolds.

Evaluation of the anti-oxidative and ROS scavenging properties of biomaterials coated with epigallocatechin gallate for tissue engineering

In tissue engineering, excessively generated reactive oxygen species (ROS) during biomaterial implantation or cell transplantation is a one of major causes of diminishing therapeutic effects. In this study, we prepared biomaterial surfaces coated with antioxidant epigallocatechin gallate (EGCG) and metal ions, and evaluated their anti-oxidative and ROS scavenging properties. We revealed that EGCG-coating on polycaprolactone (PCL) film surface increased hydrophilicity and anti-oxidative properties as a function of total phenol content (TPC) potentially due to the increase in phenolic -OH and π-electrons from structural maintenance and directly removed the hydrogen peroxide (H2O2) by resonance-stabilization. Furthermore, EGCG-coated PCL film increased attachment, spreading area, and viability of human adipose-derived stem cells (hADSCs) against H2O2 treatment while stimulated the cellular signaling to reduce apoptotic gene and enhance anti-oxidative enzyme expression. Further, we applied EGCG coating on the surface of poly-L-lactic acid (PLLA) fibers. Spheroids incorporating EGCG-coated PLLA fibers were able to maintain their shape and showed improved viability and anti-oxidative activities in response to H2O2-induced oxidative stress than control spheroids. Therefore, metal-phenolic network (MPN) coating of EGCG is a suitable method to impart the anti-oxidative properties to biomaterials by evaluating the structural properties and biological effects.

Evaluation of the Anti-Oxidative and ROS Scavenging Properties of Epigallocatechin Gallate (EGCG)-Coated Biomaterials for Tissue Engineering

In tissue engineering, excessively generated reactive oxygen species (ROS) during biomaterial implantation or cell transplantation is a one of major causes of diminishing therapeutic effects. In this study, we prepared biomaterial surfaces coated with antioxidant epigallocatechin gallate (EGCG) and metal ions, and evaluated their anti-oxidative and ROS scavenging properties. We revealed that EGCG-coating on polycaprolactone (PCL) film surface increased hydrophilicity and anti-oxidative properties as a function of the coated amount of EGCG potentially due to the increase in phenolic -OH and π-electrons from structural maintenance and directly removed the hydrogen peroxide (H2O2) by resonance-stabilization. Furthermore, EGCG-coated PCL film increased attachment, spreading area, and viability of human adipose-derived stem cells (hADSCs) against H2O2 treatment while stimulated the cellular signaling to reduce apoptotic gene and enhance anti-oxidative enzyme expression. Further, we applied EGCG coating on the surface of poly-L-lactic acid (PLLA) fibers. Spheroids incorporating EGCG-coated PLLA fibers were able to maintain their shape and showed improved viability and anti-oxidative activities in response to H2O2-induced oxidative stress than control spheroids. Therefore, MPN coating of EGCG is a suitable method to impart the anti-oxidative properties to biomaterials by evaluating the structural properties and biological effects.

Macrophage polarization induced by sustained release of 7,8-DHF from aligned PLLA fibers potentially for neural stem cell neurogenesis.

Neural stem cells (NSCs)-based regenerative medicine provides unprecedented therapeutic potential in neural insults. However, NSC-based neurogenesis is strongly influenced by the inflammatory environment after injury, which is mainly modulated by macrophages' secretion effects. In this study, we adopted poly L-lactic acid (PLLA) aligned fibers to guide macrophages elongating along the fiber directions and polarizing phenotypically toward anti-inflammatory M2 type. 7,8-DHF was loaded within the fibers with a sustained and controlled release pattern to promote the polarization of the macrophages and secretion of various anti-inflammatory factors. NSCs showed enhanced neuronal differentiation in the presence of the conditioned medium (CM) from M2 macrophages cultured on the 7,8-DHF-loaded PLLA aligned fibers. Moreover, M2-CM promoted neurogenesis by enhancing neurite outgrowth of NSC-derived neurons. In summary, we provided a novel therapeutic strategy for NSC neurogenesis by manipulating macrophage classification into anti-inflammatory M2 phenotypes with the 7,8-DHF-loaded PLLA aligned fibers, existing potential applications in treating neural injuries.

Coating Topologically Complex Electrospun Fibers with Nanothin Silk Fibroin Enhances Neurite Outgrowth in Vitro.

Electrospun poly-l-lactic acid (PLLA) fibers are commonly used for tissue engineering applications because of their uniform morphology, and their efficacy can be further enhanced via surface modification. In this study, we aimed to increase neurite outgrowth along electrospun fibers by coating with silk fibroin (SF), a bioinert protein derived from Bombyx mori cocoon threads, shown to be neurocompatible. Aligned PLLA fibers were electrospun with smooth, pitted, and divoted surface nanotopographies and coated with SF by immersion in coating solution for either 12 or 24 h. Specifically, thin-film coatings of SF were generated by leveraging the controlled self-assembly of SF in aqueous conditions that promote β-sheet assembly. For both 12- and 24-h coatings, Congo Red staining for β-sheet structures confirmed the presence of SF coatings on PLLA fibers. Confocal imaging of fluorescein-labeled SF further demonstrated a homogeneous coating formation on PLLA fibers. No change in the water contact angle of the surfaces was observed after coating; however, an increase in the isoelectric point (pI) to values comparable with the theoretical pI of SF was seen. Notably, there was a significant trend of increased dorsal root ganglia (DRG) adhesion on scaffolds coated with SF, as well as greater neurite outgrowth on pitted and divoted fibers that had been coated with SF. Ultimately, this work demonstrated that thin-film SF coatings formed by self-assembly uniformly coat electrospun fibers, providing a new strategy to increase the neuroregenerative capacity of electrospun scaffolds. To our knowledge, this is the first instance of biomedical modification of topologically complex substrates using noncovalent methods.

Lactonic Sophorolipid Increases Surface Wettability of Poly-l-lactic Acid Electrospun Fibers.

The hydrophobicity of electrospun poly-l-lactic acid (PLLA) fibers hinders their integration with surrounding tissue for a variety of applications. In this study, we increased PLLA fiber hydrophilicity by incorporating the natural surfactant, lactonic sophorolipid (LSL). PLLA+LSL fibers had similar fiber morphology but significantly greater surface wettability, which suggested LSL accumulation on the fiber surface. Differential scanning calorimetry results also suggested that LSL was phase separated from PLLA. Despite the altered surface wettability of these fibers, there was no change in fibroblast adhesion. Future studies may explore the use of this natural surfactant to deliver bioactive factors to enhance fibroblast adhesion.

Vascular tissue engineering: Fabrication and characterization of acetylsalicylic acid-loaded electrospun scaffolds coated with amniotic membrane lysate.

As the incidence of small-diameter vascular graft (SDVG) occlusion is considerably high, a great amount of research is focused on constructing a more biocompatible graft. The absence of a biocompatible surface in the lumen of the engineered grafts that can support confluent lining with endothelial cells (ECs) can cause thrombosis and graft failure. Blood clot formation is mainly because of the lack of an integrated endothelium. The most effective approach to combat this problem would be using natural extracellular matrix constituents as a mimic of endothelial basement membrane along with applying anticoagulant agents to provide local antithrombotic effects. In this study, we fabricated aligned and random electrospun poly-L-lactic acid (PLLA) scaffolds containing acetylsalicylic acid (ASA) as the anticoagulation agent and surface coated them with amniotic membrane (AM) lysate. Vascular scaffolds were structurally and mechanically characterized and assessed for cyto- and hemocompatibility and their ability to support endothelial differentiation was examined. All the scaffolds showed appropriate tensile strength as expected for vascular grafts. Lack of cytotoxicity, cellular attachment, growth, and infiltration were proved using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scanning electron microscopy. The blood compatibilities of different scaffolds examined by in vitro hemolysis and blood coagulation assays elucidated the excellent hemocompatibility of our novel AM-coated ASA-loaded nanofibers. Drug-loaded scaffolds showed a sustained release profile of ASA in 7 days. AM-coated electrospun PLLA fibers showed enhanced cytocompatibility for human umbilical vein ECs, making a confluent endothelial-like lining. In addition, AM lysate-coated ASA-PLLA-aligned scaffold proved to support endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells. Our results together indicated that AM lysate-coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Poly-l-lactic acid-co-poly(pentadecalactone) Electrospun Fibers Result in Greater Neurite Outgrowth of Chick Dorsal Root Ganglia in Vitro Compared to Poly-l-lactic Acid Fibers.

Electrospun poly-l-lactic acid (PLLA) fiber scaffolds are used to direct axonal extension in neural engineering models. We aimed to improve the efficacy of these fibers in promoting neurite outgrowth by altering surface topography and reducing fiber elastic modulus through the incorporation of a compatibilized blend, poly-l-lactic acid-poly(pentadecalactone) (PLLA-PPDL) into the solution prior to electrospinning. PLLA+PLLA-PPDL fibers had a larger diameter, increased surface nanotopography, and lower glass transition temperature than PLLA fibers but had similar mechanical properties. Increases in neurite outgrowth on PLLA+PLLA-PPDL fibers were observed, potentially due to the significantly increased diameter and surface coverage with nanotopography. Ultimately, these results suggest that greater electrospun fiber diameter and surface topography may contribute to increases in neurite outgrowth.

DEVELOPMENT OF LARGE DIAMETER BIORESORBABLE STENTS FOR CONGENITAL HEART DISEASE

There is an unmet need for bioresorbable stents (BRS) in sizes for growing children with congenital heart disease (CHD). A poly-L-lactic acid (PLLA) coil based, double opposed helical (DH) BRS has been designed. Mechanical, degradation and thermal properties of PLLA fibers 0.25 mm and 0.30 mm

Release behavior under proteinase K and existing position of Domiphen® in its complexed poly-L-lactic acid micro-fibers electrospun from solution and W/O emulsion

To study the release behavior and the existing position of Domiphen® in its its complexed poly-L-lactic acid (PLLA) micro-fibers, two series of fibrous films were prepared by electrospinning solution and W/O emulsion, which was added to Domiphen® directly and emulsified by Domiphen®, respectively, by complexing methods. The mass ratio of Domiphen® to PLLA was 0.25%, 0.5%, 0.75%, and 1% for both methods. According to the scanning electron microscopic observation, W/O emulsion and fibers of narrow-distributed diameters were obtained by W/O emulsion electrospinning. Fluorescence microscopic observation suggested that Domiphen® was incorporated within fibers by W/O emulsion electrospinning. X-ray diffraction and differential thermal analysis characterization suggested that Domiphen® complexed well with PLLA according to noncrystalline Domiphen® existing within and on PLLA fibers prepared by both methods. Domiphen® release curves were prepared and fitted after the amount of Domiphen® released from the PLLA fibers was determined by high-performance liquid chromatography. It was discovered that, with regard to the fibrous films prepared by homogeneous solution electrospinning, Domiphen® released from fibers in accordence with the Freundlich’s equation suggesting that Domiphen® almost existed within the outermost border of the fiber cross section and its release behavior could be considered as the counter adsorption process, while with regard to the fibers prepared by W/O emulsion electrospinning, the release curves were S shape under the effect of proteinase K degradation and could be fitted to the corrosion-mechanism Peppas’ equation of n value >0.5, which suggested that Domiphen® existed both on the surfaces in small proportion and the inner border of the core-sheath fibers in big proportion.

Removal of retained electrospinning solvent prolongs drug release from electrospun PLLA fibers

A major challenge in developing drug-releasing electrospun nanofibers is obtaining long-term drug release over many weeks with no burst release of drug. Here, we present new methods capable of prolonging the diffusive release of small molecule drugs from electrospun poly-l-lactic acid (PLLA) nanofibers. The methods focus on removal of retained electrospinning solvent through fiber heating, maintaining fibers in a laboratory setting, or a combination of these methods. These post-fabrication methods altered the release characteristics of a model small molecule drug, 6-aminonicotinamide (6AN), from PLLA fibers. Specifically, untreated fibers released 6AN over 9 days, and fibers that underwent a combined treatment of maintenance in a laboratory setting and heating released 6AN over 44 days. The unique and simple method presented here prolongs diffusive release of a small molecule drug from electrospun fibers and has potential to assist in lengthening small molecule drug release from a variety of polymeric nanomaterials.

Poly-l-lactic acid: Pellets to fiber to fused filament fabricated scaffolds, and scaffold weight loss study

Poly-l-lactic acid (PLLA) is a bioresorbable polymer used in a variety of biomedical applications. Many 3D printers employ the fused filament fabrication (FFF) approach with the ubiquitous low-cost poly-lactic acid (PLA) fiber. However, use of the FFF approach to fabricate scaffolds with medical grade PLLA polymer remains largely unexplored. In this study, high molecular weight PL-32 pellets were extruded into ∼1.7mm diameter PLLA fiber. Melt rheometric data of the PLLA polymer was analyzed and demonstrated pseudo-plastic behavior with a flow index of n=0.465 (<1). Differential scanning calorimetry (DSC) was conducted using samples from the extruded fiber to obtain thermal properties. DSC of the 3D printed struts was also analyzed to assess changes in thermal properties due to FFF. The DSC and rheometric analysis results were subsequently used to define appropriate FFF process parameters. Constant porosity scaffolds were FFF 3D printed with 4 distinct laydown patterns; 0/90° rectilinear (control), 45/135° rectilinear, Archimedean chords, and honeycomb using the in-house developed custom multi-modality 3D bioprinter (CMMB). The effect of laydown pattern on scaffold bulk erosion (weight loss) was studied by immersion in phosphate-buffered saline (PBS) over a 6-month period and measured monthly. A repeated measures analysis of variance (ANOVA) was performed to identify statistically significant differences between mean percent weight loss of the four laydown patterns at each time point (1–6 months). The resulting data follows distinct temporal trends, but no statistically significant differences between means at individual time points were found. Cross-sectional scanning electron microscope (SEM) images of the 6-month degraded scaffolds showed noticeable structural deterioration. The study demonstrates successful processing of PLLA fiber from PL-32 pellets and FFF-based 3D printing of bioresorbable scaffolds with pre-defined laydown patterns using medical grade PLLA polymer which could prove beneficial in biomedical applications.

Morphological study of dynamic culture of thermosensitive collagen hydrogel in constructing tissue engineering complex

ABSTACTThe purpose of this study is to research the morphologies and functional characteristics of the cell-scaffold complex in vitro constructed under dynamic culture conditions. BMSCs were isolated from the long bones of Fischer344 rats, and performed in vitro amplification to the third generation as seed cells, together with thermosensitive collagen hydrogel (TCH) as cell adhesion matrix, and poly-L-lactic acid (PLLA) as scaffold, to construct cell-scaffold complex. The cell-scaffold complexes in the experiment group and the control group were then performed dynamic culture and static culture. After 7 d of in vitro culture, the complexes in the 2 groups were performed gross observation and SEM; meanwhile, the total DNA content in the complex was detected on D0,1,3, and 7 of culture. After cultured using these 2 ways, collagen could both wrap the PLLA scaffold, forming dense film-like structures on the PLLA surface. The total DNA contents in the cell-scaffold complex of the experiment group on D1,3, and 7 were significantly higher than the control group (P < 0.05). Compared with D0, the total DNA contents on D1,3, and 7 in both groups were gradually increased, but only the total DNA contents on D7 showed statistically significant difference than D0 (P < 0.05). TCH -PLLA fiber joint-constructed complex extracellular matrix had good biocompatibility, and dynamic culture could promote the distribution of BMSCs on the surface and inside the structure, thus promoting cell proliferation, so it could be used for the in vitro construction of tissue engineering complex.

Effect of hydroxyapatite concentration on high-modulus composite for biodegradable bone-fixation devices.

There are over 3 million bone fractures in the United States annually; over 30% of which require internal mechanical fixation devices to aid in the healing process. The current standard material used is a metal plate that is implanted onto the bone. However, metal fixation devices have many disadvantages, namely stress shielding and metal ion leaching. This study aims to fix these problems of metal implants by making a completely biodegradable material that will have a high modulus and exhibit great toughness. To accomplish this, long-fiber poly-l-lactic acid (PLLA) was utilized in combination with a matrix composed of polycaprolactone (PCL) and hydroxyapatite (HA) nano-rods. Through single fibril tensile tests, it was found that the PLLA fibers have a Young's modulus of 8.09 GPa. Synthesized HA nanorods have dimensions in the nanometer range with an aspect ratio over 6. By dip coating PLLA fibers in a suspension of PCL and HA and hot pressing the resulting coated fibers, dense fiber-reinforced samples were made having a flexural modulus up to 9.2 GPa and a flexural strength up to 187 MPa. The flexural modulus of cortical bone ranges from 7 to 25 GPa, so the modulus of the composite material falls into the range of bone. The typical flextural strength of bone is 130 MPa, and the samples here greatly exceed that with a strength of 187 MPa. After mechanical testing to failure the samples retained their shape, showing toughness with no catastrophic failure, indicating the possibility for use as a fixation material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1963-1971, 2017.

Degradation and inflammatory response of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) under physiological conditions

Event Abstract Back to Event Degradation and inflammatory response of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) under physiological conditions Satoshi Fujita1, Nana Marubuchi1, Tadashi Nakaji-Hirabayashi2, Yuka Kimura1, Saki Furukawa2, Hiromi Kitano2 and Shin-Ichiro Suye1 1 University of Fukui, Department of Frontier Fiber Technology and Science, Graduate School of Engineering, Japan 2 University of Toyama, Graduate School of Science and Engineering, Japan Introduction: Various bioresorbable materials are proposed for clinical use including medical devices and tissue engineering scaffolds. Especially, polylactic acid (PLA), polyglycolic acid (PGA) and their copolymer have been widely used for scaffolds in virtue of their good mechanical properties and controllable bioresorption. However, their applications are limited due to their brittleness and little flexibility. Therefore, more flexible bioabsorbable materials are highly desired for the applications to soft tissue. In this study, we focused on poly ((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBH), which is a biodegradable polymer produced by bacteria[1]) and should be applicable to agricultural use such as a mulch sheet. PHBH is expected to be a good candidate of scaffolds for soft tissue because it has flexibility at physiological temperature due to its lower glass transition temperature than PLA and PGA. Although reports on the availability of PHBH for scaffold use are increasing[2],[3]), the degradation and resulting inflammatory responses of PHBH in a body have been still poorly understood. Here, to investigate the potency of PHBH as a bioresorbable material, we have examined the biodegradability and biocompatibility of PHBH with two different forms such as fibers and films, by comparing changes in polymer chains after the degradation in vitro and in vivo with poly-L-lactic acid (PLLA). Experimental: Nonwoven fiber sheets of PHBH and PLLA were fabricated by the electrospinning method and thin films were prepared by a casting method. For the in vitro degradation study, the samples were incubated in PBS at 37 ⁰C in dialysis tubes and their molecular weight distributions and crystallinity after a 1- to 6-month immersion were measured by gel permeation chromatography (GPC) and wide angle X-ray diffraction (WAXD), respectively. For the in vivo degradation study, samples were implanted into a subcutaneous space on the back of rats. After a week, samples were excised for the analysis of GPC, WAXD and histological analysis. Result and Discussion: From the results of the in vitro degradation study, the molecular distribution of PHBH films and fibers were shifted into low in the early stage, although the top peak of molecular weight of PLLA films and fibers did not show a shift even after 6 months immersion under physiological conditions. (Fig. 1) In addition, PHBH kept approximately a 60% crystallinity in the WAXD analysis after 6 months immersion. These results imply the polymer chains of PHBH were cleaved in a middle (endo) at the amorphous region, which is considered to be caused by a different degradation mechanism from PLLA. In the implantation experiments, PHBH fibers and films also showed fast degradation by GPC analysis. As the result of immunohistochemical staining, initial inflammatory response were suppressed in a PHBH-implanted tissue after two weeks of surgery, but observed in a PLLA-implanted tissue. (Fig. 2) These results suggest that the degradation products of PHBH might be milder for tissue than PLLA because of weak acidity and have potency to alternative materials with flexibility for tissue engineering scaffolds. Fig.1 Molecular weight distribution of PLLA and PHBH after in vitro degradation test at different months. Fig.2 Immunostaining of PLLA and PHBH fibers at different period after transplantation. This work was supported in part by Kaneka Corporation.

Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system.

The Effect of Surface Modification of Aligned Poly-L-Lactic Acid Electrospun Fibers on Fiber Degradation and Neurite Extension.

The surface of aligned, electrospun poly-L-lactic acid (PLLA) fibers was chemically modified to determine if surface chemistry and hydrophilicity could improve neurite extension from chick dorsal root ganglia. Specifically, diethylenetriamine (DTA, for amine functionalization), 2-(2-aminoethoxy)ethanol (AEO, for alcohol functionalization), or GRGDS (cell adhesion peptide) were covalently attached to the surface of electrospun fibers. Water contact angle measurements revealed that surface modification of electrospun fibers significantly improved fiber hydrophilicity compared to unmodified fibers (p < 0.05). Scanning electron microscopy (SEM) of fibers revealed that surface modification changed fiber topography modestly, with DTA modified fibers displaying the roughest surface structure. Degradation of chemically modified fibers revealed no change in fiber diameter in any group over a period of seven days. Unexpectedly, neurites from chick DRG were longest on fibers without surface modification (1651 ± 488 μm) and fibers containing GRGDS (1560 ± 107 μm). Fibers modified with oxygen plasma (1240 ± 143 μm) or DTA (1118 ± 82 μm) produced shorter neurites than the GRGDS or unmodified fibers, but were not statistically shorter than unmodified and GRGDS modified fibers. Fibers modified with AEO (844 ± 151 μm) were significantly shorter than unmodified and GRGDS modified fibers (p<0.05). Based on these results, we conclude that fiber hydrophilic enhancement alone on electrospun PLLA fibers does not enhance neurite outgrowth. Further work must be conducted to better understand why neurite extension was not improved on more hydrophilic fibers, but the results presented here do not recommend hydrophilic surface modification for the purpose of improving neurite extension unless a bioactive ligand is used.

Nebulized solvent ablation of aligned PLLA fibers for the study of neurite response to anisotropic-to-isotropic fiber/film transition (AFFT) boundaries in astrocyte–neuron co-cultures

Developing robust in vitro models of in vivo environments has the potential to reduce costs and bring new therapies from the bench top to the clinic more efficiently. This study aimed to develop a biomaterial platform capable of modeling isotropic-to-anisotropic cellular transitions observed in vivo, specifically focusing on changes in cellular organization following spinal cord injury. In order to accomplish this goal, nebulized solvent patterning of aligned, electrospun poly-l-lactic acid (PLLA) fiber substrates was developed. This method produced a clear topographic transitional boundary between aligned PLLA fibers and an isotropic PLLA film region. Astrocytes were then seeded on these scaffolds, and a shift between oriented and non-oriented astrocytes was created at the anisotropic-to-isotropic fiber/film transition (AFFT) boundary. Orientation of chondroitin sulfate proteoglycans (CSPGs) and fibronectin produced by these astrocytes was analyzed, and it was found that astrocytes growing on the aligned fibers produced aligned arrays of CSPGs and fibronectin, while astrocytes growing on the isotropic film region produced randomly-oriented CSPG and fibronectin arrays. Neurite extension from rat dissociated dorsal root ganglia (DRG) was studied on astrocytes cultured on anisotropic, aligned fibers, isotropic films, or from fibers to films. It was found that neurite extension was oriented and longer on PLLA fibers compared to PLLA films. When dissociated DRG were cultured on the astrocytes near the AFFT boundary, neurites showed directed orientation that was lost upon growth into the isotropic film region. The AFFT boundary also restricted neurite extension, limiting the extension of neurites once they grew from the fibers and into the isotropic film region. This study reveals the importance of anisotropic-to-isotropic transitions restricting neurite outgrowth by itself. Furthermore, we present this scaffold as an alternative culture system to analyze neurite response to cellular boundaries created following spinal cord injury and suggest its usefulness to study cellular responses to any aligned-to-unorganized cellular boundaries seen in vivo.

Electrospinning 3D Scaffolds for use in Neural Tissue Engineering

ABSTRACTPolymer nanofiber scaffolds for use in neural tissue engineering have been fabricated via electrospinning of poly-L-lactic acid (PLLA) directly onto a 3D printed support. Previously, the investigators have shown success in promoting the directed growth of neural axons on highly aligned PLLA substrates both in vitro and in vivo. However, one criticism of the earlier in vitro studies is that by spinning fibers on a flat, two-dimensional surface, the growth of the axons is restricted to one plane. Thus the axon-to-fiber attachment may not be the sole mechanism for aligning the growth of the axons along the fibers, and the channels between the fibers and the substrate could contribute to the results. Using 3D-printing, elevated or “bridge” spinning stages were made with supports at varying heights, allowing the fibers to be suspended 2 to 5 mm above the substrate surface in different configurations. This 3D structure promotes better access of in vitro cell cultures on the fibers to the growth media during incubation, reduces substrate effects, allows more degrees of freedom for axonal growth, and more closely simulates the growth environment found in vivo. Using these 3D stages, we have electrospun free-standing, highly-aligned pure PLLA fiber scaffolds. We are exploring spinning coaxial fibers with a PLLA sheath and a second core polymer. These coaxial fiber scaffold structures offer additional opportunities for in situ delivery of growth agents and/or electrical stimulation for improved axonal growth results.