Controllable Aligned Nanofiber Hybrid Yarns with Enhanced Bioproperties for Tissue Engineering

Electrospun nanofibers have large surface area, high porosity, and controllable orientation while conventional microfibers have appropriate mechanical properties such as stiffness, strength, and elasticity. Therefore, the combination of nanofibers and microfibers can provide building elements to engineer biomimetic scaffolds for tissue engineering. In this study, a core–shell structured fibrous structure with controllable surface topography is created by electrospinning polycaprolactone (PCL) nanofibers onto polyglycolic acid (PGA) microfibers. The surface morphology, surface wettability, and mechanical properties of the resultant core–shell structure are characterized. FE‐SEM images reveal that the orientation of PCL nanofibers on the yarn surface can be tuned by a fiber collector and rotating disks. Benefiting from the introduction of a shell of aligned PCL nanofibers on the core of PGA yarn, the uniaxially aligned PCL nanofiber–covered yarns (A‐PCLs) exhibit higher hydrophilicity, porosity, and mechanical properties than the core PGA yarns. Moreover, A‐PCLs promote the adhesion and proliferation of BALB/3T3 (mouse embryonic fibroblast cell line), and guide cell growth along the biotopographic cues of the PCL nanofibers with controllable alignment. The developed core–shell yarn having both the desired surface topography of PCL nanofibers and mechanical properties of PGA microfibers demonstrates great potential in constructing various tissue scaffolds.     

Production, mechanical properties and in vitro biocompatibility of highly aligned porous poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) scaffolds

We produced highly aligned porous poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) scaffolds by unidirectionally freezing PCL/HA solutions with various HA contents (0, 5, 10 and 20 wt% in relation to the PCL polymer) and evaluated their mechanical properties and in vitro biocompatibility to examine their potential applications in bone tissue engineering. All the prepared scaffolds had a highly aligned porous structure, in which the HA particles were uniformly dispersed in the PCL walls. The elastic modulus of the PCL/HA scaffolds significantly increased from 0.12 ± 0.02 to 2.65 ± 0.05 MPa with increasing initial HA content from 0 to 20 wt%, whereas the pore size decreased from 9.2 ± 0.7 to 4.2 ± 0.8 μm. In addition, the PCL/HA scaffolds showed considerably enhanced in vitro cellular responses that were assessed in terms of cell attachment, proliferation and osteoblastic differentiation.     

Reinforcement of electrospun poly(ε‐caprolactone) scaffold using diopside nanopowder to promote biological and physical properties

Considerable efforts have been devoted toward the development of electrospun scaffolds based on poly(ε‐caprolactone) (PCL) for bone tissue engineering. However, most of previous scaffolds have lacked the structural and mechanical strength to engineer bone tissue constructs with suitable biological functions. Here, we developed bioactive and relatively robust hybrid scaffolds composed of diopside nanopowder embedded PCL electrospun nanofibers. Incorporation of various concentrations of diopside nanopowder from 0 to 3 wt % within the PCL scaffolds notably improved tensile strength (eight‐fold) and elastic modulus (two‐fold). Moreover, the addition of diopside nanopowder significantly improved bioactivity and degradation rate compared to pure PCL scaffold which might be due to their superior hydrophilicity. We investigated the proliferation and spreading of SAOS‐II cells on electrospun scaffolds. Notably, electrospun PCL‐diopside scaffolds induced significantly enhanced cell proliferation and spreading. Overall, we concluded that PCL‐diopside scaffold could potentially be used to develop clinically relevant constructs for bone tissue engineering. However, the extended in vivo studies are essential to evaluate the role of PCL‐diopside fibrous scaffolds on the new bone growth and regeneration. Therefore, in vivo studies will be the subject of our future work. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44433.     

Immobilization of silk fibroin on the surface of PCL nanofibrous scaffolds for tissue engineering applications

Poly(?‐caprolactone) (PCL) is explored in tissue engineering (TE) applications due to its biocompatibility, processability, and appropriate mechanical properties. However, its hydrophobic nature and lack of functional groups in its structure are major drawbacks of PCL‐based scaffolds limiting appropriate cell adhesion and proliferation. In this study, silk fibroin (SF) was immobilized on the surface of electrospun PCL nanofibers via covalent bonds in order to improve their hydrophilicity. To this end, the surface of PCL nanofibers was activated by ultraviolet (UV)–ozone irradiation followed by carboxylic functional groups immobilization on their surface by their immersion in acrylic acid under UV radiation and final immersion in SF solution. Furthermore, morphological, mechanical, contact angle, and Attenuated total reflection‐ Fourier transform infrared (ATR‐FTIR) were measured to assess the properties of the surface‐modified PCL nanofibers grafted with SF. ATR‐FTIR results confirmed the presence of SF on the surface of PCL nanofibers. Moreover, contact angle measurements of the PCL nanofibers grafted with SF showed the contact angle of zero indicating high hydrophilicity of modified nanofibers. In vitro cell culture studies using NIH 3T3 mouse fibroblasts confirmed enhanced cytocompatibility, cell adhesion, and proliferation of the SF‐treated PCL nanofibers. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46684.     

An applicable electrospinning process for fabricating a mechanically improved nanofiber mat

Engineered polymer scaffolds play an important role in tissue engineering. An ideal scaffold should have good mechanical properties and provide a biologically functional implant site. Considering their large surface area and high porosity, nanofibers have good potential as biomimetic scaffolds. However, the main shortcomings of scaffolds consisting of nanofibers are their mechanical inability to sustain a stress environment for neotissues and shape‐ability to form a variety of shapes and sizes. In this study, we produced design‐based poly (ε‐carprolactone) (PCL) nanofiber mats using an electrospinning method with various auxiliary electrodes and an x‐y moving system. To achieve stable initial solution at a nozzle tip of the electrospinning, various types of auxiliary electrodes were introduced. To characterize the effect of the electrodes in the electric‐field distribution near the nozzle tip, we calculated the electric field concentration factor and compared it with the experimental results. The nanofiber mat produced using the moving x‐y target system demonstrated orthotropic mechanical properties due to the fiber orientation, and human dermal fibroblasts seeded on the structure tended to grow according to nanofiber orientation. POLYM. ENG. SCI., 47:707–712, 2007. © 2007 Society of Plastics Engineers.     

Three​-dimensional porous poly(ε-caprolactone)/beta-tricalcium phosphate microsphere-aggregated scaffold for bone tissue engineering

In this study, porous scaffolds made of polycaprolactone (PCL)/β-tricalcium phosphate (BTCP) biocomposite were fabricated for bone tissue engineering (BTE) applications. The microsphere-aggregated scaffolds were prepared with various BTCP concentrations (10wt%, 20wt%, 50wt%) by the freeze-drying method. The porosity of obtained microsphere-aggregated scaffolds with various pore sizes was 80–85%, where this value was about 70% for the PCL/BTCP (50) sample with no microsphere formation. The results indicated that adding BTCP has enhanced mechanical strength, and the mineralization of PCL/BTCP composite scaffolds has been increased compared to the pure PCL scaffolds in simulated body fluid (SBF). The adhesion and proliferation of mouse bone marrow mesenchymal stem cells (mMSCs) seeded onto PCL/BTCP scaffolds were enhanced compared to the PCL. In addition, in terms of differentiation, the incorporation of BTCP led to increasing the mineral deposition and alkaline phosphatase activity of mMSCs. The synergistic effect of using microsphere-aggregated scaffolds along with BTCP as a reinforcing agent in PCL biocomposite showed that these porous biocomposite scaffolds have the potential application in BTE.     

Investigating the effect of PGA on physical and mechanical properties of electrospun PCL/PGA blend nanofibers

In the field of tissue engineering there is always a need for new engineered polymeric biomaterials which have ideal properties and functional customization. Unfortunately the demands for many biomedical applications need a set of properties that no polymers can fulfill. One method to satisfy these demands and providing desirable new biomaterials is by mixing two or more polymers. In this work, random nanofibrous blends of poly (ε‐caprolactone) (PCL) and polyglycolic acid (PGA) with various PCL/PGA compositions (100/0, 80/20, 65/35, 50/50, and 0/100) were fabricated by electrospinning method and characterized for soft‐tissue engineering applications. Physical, chemical, thermal, and mechanical properties of PCL/PGA blend nanofibers were measured by scanning electron microscopy (SEM), porosimetry, contact angle measurement, water uptake, attenuated total reflectance Fourier transform‐infrared spectroscopy (ATR‐FT‐IR), X‐ray diffraction (XRD), differential scanning calorimetric (DSC), dynamic mechanical thermal analysis (DMTA), and tensile measurements. Morphological characterization showed that the addition of PGA to PCL results in an increase in the average diameter of the nanofibers. According to these results, when the amount of PGA in the blend solution increased, the hydrophilicity and water uptake of the nanofibrous scaffolds increased concurrently, approaching those of PGA nanofibers. Differential scanning calorimetric studies showed that the PCL and PGA were miscible in the nanofibrous structure and the mechanical characterization under dry conditions showed that increasing PGA content results in a tremendous increase in the mechanical properties. In conclusion, the random nanofibrous PCL/PGA scaffold used in this study constitutes a promising material for soft‐tissue engineering. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Fabrication of a Nanofibrous Scaffold for the In Vitro Culture of Cardiac Progenitor Cells for Myocardial Regeneration

In this study, random Poly (?-caprolactone) (PCL):Poly glycolic acid (PGA) nanofibrous scaffold with various PCL:PGA compositions were fabricated by electrospinning method. The nanofibrous scaffolds were characterized by SEM, contact angle measurement, ATR-FTIR, and tensile measurements. The results showed that with the increase of the concentration of PGA in spinning blend solution, the average diameter of nanofibers, hydrophilicity, and mechanical properties of the nanofibrous scaffolds increased. An in vitro degradation study of PCL:PGA nanofibers were conducted in phosphate-buffered saline, pH 7.2. The experiments confirm that increasing of PGA provides faster degradation rate in blended nanofibers. To assay the biocompatibility and cell behavior on the nanofibrous scaffolds, cell attachment and spreading of cardiac progenitor cells seeded on the scaffolds were studied. The results indicate that among electrospun nanofibrous scaffolds, the most appropriate candidate for myocardial tissue engineering scaffolds is PCL:PGA (65:35).     

Biocompatible graphene-embedded PCL/PGS-based nanofibrous scaffolds: A potential application for cardiac tissue regeneration

Research in the field of tissue engineering, especially heart tissue engineering, is growing rapidly. Herein, the morphological, chemical, mechanical and biological properties of poly (caprolactone) (PCL)/poly (glycerol sebacate) (PGS) and PCL/PGS/graphene nanofibrous scaffolds are investigated. Initially, PGS pre-polymer is synthesized and characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopies. Then, in order to use the benefits of PGS, this polymer is mixed with PCL. Blending PGS with PCL resulted in the enhancement of ultimate elongation and reduction in the elastic modulus due to the intrinsic properties of PGS. The hydrophobicity of PCL nanofibers is reduced by adding PGS as hydrophilic polymer (105 ± 3° vs. 44 ± 2°). Also, the addition of graphene to the blend nanofibers is balanced the hydrophilicity. Degradation rate of pure PCL nanofibers is very slow but it is increased in the presence of PGS. All nanofibrous scaffolds are biocompatible and non-toxic. The highest cell adhesion (covered area = 0.916 ± 0.032) and biocompatibility (98.79 ± 1%) are related to PCL/PGS loaded with 1% wt of graphene (PCL/PGS/graphene ₁). Thus, this sample can be a good candidate for further examinations of cardiac tissue engineering.     

Fabrication of polycaprolactone/zirconia nanofiber scaffolds using electrospinning technique

In the present study we have investigated the effect of Zirconia (ZrO₂) nanoparticles on the fiber morphology, swelling, degradation activity and enhanced cell adhesion of the electrospun polycaprolactone (PCL) non-woven nanofiber scaffolds. The composite nanofibers scaffolds were obtained with ZrO₂ weight contents varying in the range 6% to 30%. The effect of the ZrO₂ nanoparticles concentration on the fiber morphology was investigated using a Field effect scanning electron microscopy (FE-SEM). We also investigated the degradation and swelling activities of the fabricated material. The results demonstrated better swelling with controlled degradation in comparison to the PCL scaffolds. Cell viability studies proved the non toxic nature of the nanocomposite scaffolds. Interestingly, the scaffolds with ZrO₂ nanoparticles showed enhanced fibroblast proliferation and improved bioactivity of the scaffolds. Further, this is the first report regarding the ability of a biomaterial containing ZrO₂ nanoparticles to enhance cell adhesion and proliferation.     

Aloe vera incorporated biomimetic nanofibrous scaffold: a regenerative approach for skin tissue engineering

Aloe vera (AV) is one of the medicinal herbs with a well-established spectrum of wound healing, antimicrobial and anti-inflammatory property. AV-mediated therapeutics present significant tissue regenerative activity by modulating the inflammatory and proliferative phases of wound healing. The purpose of the present work was to combine the biological properties of AV and the advantages of electrospun meshes to prepare a potent transdermal biomaterial. The polycaprolactone (PCL) containing 5 and 10 wt % of lyophilized powder of AV was studied for electrospinning into nanoscale fiber mats and compared with PCL/Collagen blend for dermal substitutes. SEM revealed the average diameters of PCL, PCL-AV 5 %, PCL-AV 10 % and PCL/Collagen nanofiber scaffolds in the range of 519 ± 28, 264 ± 46, 215 ± 63 and 249 ± 52 nm, respectively. PCL-AV 10 % nanofiber scaffolds showed finer fiber morphology with improved hydrophilic properties and higher tensile strength of 6.28 MPa with a Young’s modulus of 16.11 MPa desirable for skin tissue engineering. The nanofibers were then used to investigate differences in biological responses in terms of proliferation and cell morphology of mice dermal fibroblasts. It was found that PCL-AV 10 % nanofibrous matrix favored cell proliferation compared to other scaffolds which almost increased linearly by (p ≤ 0.01) 17.79 % and (p ≤ 0.01) 21.28 % compared to PCL on sixth and ninth day. CMFDA dye expression, secretion of collagen and F-actin expression were significantly increased in PCL-AV 10 % scaffolds compared to other nanofibrous scaffolds. The obtained results proved that the PCL-AV 10 % nanofibrous scaffold is a potential biomaterial for skin tissue regeneration.     

Fabrication of shish–kebab structured poly(ε-caprolactone) electrospun nanofibers that mimic collagen fibrils: Effect of solvents and matrigel functionalization

Surface properties of tissue engineering scaffolds such as topography, hydrophilicity, and functional groups play a vital role in cell adhesion, migration, proliferation, and apoptosis. In this study, poly(ε-caprolactone) (PCL) shish–kebab scaffolds (PCL-SK), which feature a three-dimensional structure comprised of electrospun PCL nanofibers covered by periodic, self-induced PCL crystal lamellae on the surface, was created to mimic the nanotopography of native collagen fibrils in the extracellular matrix (ECM). Two different kinds of solvents used in creating kebabs on the shish were investigated by real-time observation. It was found that the solvent solubility directly affects the formation of kebabs: the lower the solubility of the solvent, the easier the formation of the kebabs on the surface of the electrospun nanofibers. In addition, matrigel was covalently immobilized on the surface of alkaline hydrolyzed PCL and PCL-SK scaffolds to enhance their hydrophilicity. This combined approach not only mimics the nanotopography of native collagen fibrils, but also simulates the surface features of collagen fibrils for cell growth. To investigate the viability of such scaffolds, HEF1 fibroblast cell assays were conducted and the results revealed that the nanotopography of the PCL-SK scaffolds facilitated cell adhesion and proliferation. The matrigel functionalization on PCL-SK scaffolds further enhanced cellular response, which suggested elevated biocompatibility and greater potential for tissue engineering applications.     

Coating of polyelectrolyte multilayer thin films on nanofibrous scaffolds to improve cell adhesion

The adhesion of L929 cells to poly(?‐caprolactone) (PCL) nanofibers was successfully improved via coating with polyelectrolyte multilayer thin films (PEMs), which enhanced the potential of this material as a scaffold in tissue engineering applications. With the electrostatic self‐assembly technique, poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium 4‐styrene sulfonate) (PSS) were formed as four‐bilayer PEMs on electrospun PCL nanofiber mats. Because PDADMAC and PSS are strong polyelectrolytes, they provided stable films with good adhesion on the fibers within a wide pH range suitable for the subsequent processes and conditions. PDADMAC and gelatin were also constructed as four‐bilayer PEMs on top of the PDADMAC‐ and PSS‐coated nanofibers with the expectation that the gelatin would improve the cell adhesion. L929 cells from mouse fibroblasts were then seeded on both uncoated and coated scaffolds to study the cytocompatibility and in vitro cell behavior. It was revealed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay that both the uncoated and coated nanofiber mats were nontoxic as the cell viability was comparable to that of those cultured in the serum‐free medium that was used as a control. The MTT assay also demonstrated that cells proliferated more efficiently on the coated nanofibers than those on the uncoated ones during the 48‐h culture period. As observed by scanning electron microscopy, the cells spread well on the coated nanofibers, especially when gelatin was incorporated. The surface modification of PCL nanofiber mats described in this research is therefore an effective technique for improving cell adhesion. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Fabrication and characterization of hydrophilic poly(ε‐caprolactone)/pluronic P123 electrospun fibers

Poly(ε‐caprolactone) (PCL) has been widely investigated for tissue engineering applications because of its good biocompatibility, biodegradability, and mechanical properties; however hydrophobic nature of PCL has been a colossal obstacle toward achieving scaffolds which offer satisfactory cell attachment and proliferation. To produce highly hydrophilic electrospun fibers, PCL was blended with pluronic P123 (P123) and the resulted electrospun scaffolds physiochemical characteristics such as fiber morphology, thermal behavior, crystalline structure, mechanical properties, and wettability were investigated. Moreover molecular dynamic (MD) simulation was assigned to evaluate the blended and neat PCL/water interactions. Presence of P123 at the surface of electrospun blended fibers was detected using ATR‐FTIR analysis. P123 effectiveness in improving the hydrophilicity of the scaffolds was demonstrated by water contact angel which experienced a sharp decrease from 132° corresponding to the neat PCL to almost 0° for all blended samples. Also a steady increase in water uptake ratio was observed for blended fibers as P123 content increased. The 90/10 blend ratio had the maximum tensile strength, elongation at break and crystallinity percentage. Therefore 90/10 blend ratio of PCL/P123 can balance the mechanical properties and bulk hydrophilicity of the resulted electrospun scaffold and would be a promising candidate for tissue engineering application. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43345.     

Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves

Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young’s modulus and mean elongation at F_max of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of F_max (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix.     

Mechanical properties and biocompatibility of MgO / Ca3(PO4)2 composite ceramic scaffold with high MgO content based on digital light processing

Magnesium oxide-calcium phosphate (MgO/Ca3(PO4)2) composite ceramic materials are considered a promising class of bioactive materials, expected to be used in artificial bone scaffolds. However, there are few pieces of research on the content of magnesium oxide in composite ceramic scaffolds. To study the effect of magnesium oxide content on the biocompatibility and mechanical properties of magnesium oxide-calcium phosphate composite ceramic scaffolds, six groups of scaffolds with magnesium oxide content of 10 wt%, 20 wt%, 30 wt%, 40 wt%, 100 wt%, and 0 wt% were produced by digital light processing (DLP) printing technology. And scaffolds’ pores size and porosity percentage were 0.6–1 mm and 50%, respectively. The compressive strength of the scaffold increased with the magnesium oxide proportion, and the 40 wt% group was almost twice that of the 0 wt% magnesium oxide group. The 40 wt% and 0 wt% magnesium oxide groups performed better for biocompatibility. Comprehensive analysis of the biocompatibility and mechanical properties of the scaffold confirmed that the 40 wt% magnesium oxide group was the best. The results show that high magnesium oxide content enhanced the mechanical properties and achieved well biocompatibility of the composite scaffolds, broadening the scope of future experimental research.     

RGD functionalized poly(ε-caprolactone)/poly(m-anthranilic acid) electrospun nanofibers as high-performing scaffolds for bone tissue engineering RGD functionalized PCL/P3ANA nanofibers

RGD functionalized nanofibers of poly(ε-caprolactone)/poly(m-anthranilic acid) (PCL/P3ANA) were fabricated to address the mechanical, structural and functional requirements of bone tissue engineering. Nanofibers containing the highest amount of P3ANA with more carboxyl groups for functionalization have exhibited higher surface area and better mechanical properties. FTIR-ATR and UV-visible measurements evidenced the covalent RGD immobilization. After RGD peptide immobilization, the surface properties of nanofibers changed as evidenced by contact angle and electrochemical impedance spectroscopy (EIS). The effects of RGD functionalized nanofibers (PCL/P3ANA-RGD) on Saos-2 cell attachment, proliferation, and osteogenic activity were investigated. PCL/P3ANA-RGD nanofibers favored cell attachment, proliferation, and osteogenic activity.     

Morphology and Mechanical Properties of PLLA and PCL Scaffolds

Human tissue engineering, comprising methods and tools to create implants, is a promising although as yet a very underdeveloped field of research into the regeneration of specific damaged or necrotic tissue. Porous scaffolds play an important role in tissue engineering. The porous cell culture scaffolds in this study were produced through thermally induced phase separation (lyophilization). This technique yields considerable variations in scaffold microstructures (pore size and morphology) as a function of the polymer, solvent and thermal processing. PLLA and PCL were used with chloroform, 1,4-dioxane and water as solvent. We observed a decrease in mechanical properties with increasing pore size in the two polymers under study. However, we found that PLLA, which possesses larger pore sizes than PCL, showed superior mechanical properties, which we explain in terms of crystallinity.     

Fabrication of LaCl3‐containing nanofiber scaffolds and their application in skin wound healing

Poly(?‐caprolactone) (PCL)/gelatin (GE) nanofiber scaffolds with varying concentrations of lanthanum chloride (LaCl₃, from 0 to 25 mM) were fabricated by electrospinning. The scaffolds were characterized by scanning electron microscopy, contact angle and porosity measurements, mechanical strength tests, and in vitro degradation studies. In vitro cytotoxicity and cell adhesion and proliferation studies were performed to assess the biocompatibility of the scaffolds, and in vivo wound healing studies were conducted to assess scaffold applications in the clinic. All prepared scaffolds were noncytotoxic, and the growth of adipose tissue–derived stem cells on LaCl₃‐containing scaffolds was better than on the pure PCL/GE scaffold. Cell proliferation studies showed the greatest cell growth in the PCL/GE/LaCl₃ scaffolds. Further, in vivo studies proved that the PCL/GE/LaCl₃ scaffolds can promote wound healing. The results suggest that nanofiber scaffolds containing LaCl₃ promote cell proliferation and have good biocompatibility, and thus potential for application in the treatment of skin wounds. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46672.     

Cross-Linking Agents for Electrospinning-Based Bone Tissue Engineering

Electrospun nanofibers are promising bone tissue scaffolds that support bone healing due to the body’s structural similarity to the extracellular matrix (ECM). However, the insufficient mechanical properties often limit their potential in bone tissue regeneration. Cross-linking agents that chemically interconnect as-spun electrospun nanofibers are a simple but effective strategy for improving electrospun nanofibers’ mechanical, biological, and degradation properties. To improve the mechanical characteristic of the nanofibrous bone scaffolds, two of the most common types of cross-linking agents are used to chemically crosslink electrospun nanofibers: synthetic and natural. Glutaraldehyde (GTA) is a typical synthetic agent for electrospun nanofibers, while genipin (GP) is a natural cross-linking agent isolated from gardenia fruit extracts. GP has gradually gained attention since GP has superior biocompatibility to synthetic ones. In recent studies, much more progress has been made in utilizing crosslinking strategies, including citric acid (CA), a natural cross-linking agent. This review summarizes both cross-linking agents commonly used to improve electrospun-based scaffolds in bone tissue engineering, explains recent progress, and attempts to expand the potential of this straightforward method for electrospinning-based bone tissue engineering.