Electrospinning has been used for the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several decades. Electrospun fibrous scaffolds provide nanoscale/microscale fibrous ...structures with interconnecting pores, resembling natural ECM in tissues, and showing a high potential to facilitate the formation of artificial functional tissues. In this review, we summarize the fundamental principles of electrospinning processes for generating complex fibrous scaffold geometries that are similar in structural complexity to the ECM of living tissues. Moreover, several approaches for the formation of three-dimensional fibrous scaffolds arranged in hierarchical structures for tissue engineering are also presented.
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During the last decade, translational research on biodegradable metallic materials has shown the feasibility of these novel materials for use in the fields of cardiology and ...orthopedics. Implants prepared with biodegradable metals are significantly stronger than their polymer counterparts, and there is now convincing evidence demonstrating that these materials fully biodegrade in vivo, thus reducing the need for secondary surgery. Clinical trials of such novel materials show significant potential, with the prospect of a paradigm shift in the way musculoskeletal and cardiovascular conditions are treated. This work provides an overview of the rapidly advancing technology of biodegradable metals, as well as defining some challenges in the application of these new biodegradable materials in the medical field.
Abstract Myotubes assemble with bundles of myofibers to form the structural units in skeletal muscle. Therefore, myotube formation plays an important role in restoring muscular functions, and ...substrates to promote the differentiation of myoblasts to myotubes need to be developed for muscle tissue engineering. In this study, we developed electrically conductive composite fibers of poly( l -lactide-co-ε-caprolactone) (PLCL) blended with polyaniline (PANi) using an electrospinning method, and then investigated the effect of these composite fibers on the differentiation of myoblasts. The prepared PLCL/PANi fibers showed no significant difference in fiber diameter or contact angle, regardless of the incorporation of PANi. The fibers containing 30% PANi (PLCL/PANi-30) maintained elastic properties of maximum elongation at break (160 ± 14.4%). The composite fibers were cytocompatible, as the DNA content on each fiber was similar for up to 8 days of C2C12 myoblast culture. After 4 days of culture, the number of cells positive for sarcomeric myosin was 3.6-times greater on the electrically conductive fibers (21 ± 1 and 19 ± 2 for PLCL/PANi-15 and -30 fibers, respectively) than on the PLCL/PANi-0 fibers (6 ± 2). Furthermore, the level of myogenin expression detected on day 8 of culture on PLCL/PANi-15 was approximately 1.6-fold greater than the PLCL/PANi-0 fibers. Similar results were observed for the expression of other genes including troponin T (2-fold greater) and the myosin heavy chain gene (3-fold greater). These results indicate that electrically conductive substrates can modulate the induction of myoblasts into myotube formation without additional electrical stimulation, suggesting that these fibers may have potential as a temporary substrate for skeletal tissue engineering.
The native extracellular matrix (ECM) can exhibit heterogeneous nano‐sequences periodically displaying ligands to regulate complex cell–material interactions in vivo. Herein, an ECM‐emulating ...heterogeneous barcoding system, including ligand‐bearing Au and ligand‐free Fe nano‐segments, is developed to independently present tunable frequency and sequences in nano‐segments of cell‐adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano‐segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand‐free nano‐segments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano‐ligand frequency in the same sequences and terminally sequenced nano‐ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD‐Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano‐ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano‐sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.
A heterogeneous barcoding system including RGD‐bearing Au and RGD‐free Fe nano‐segments is developed to independently present tunable nano‐ligand frequency and sequences without modulating nanoscale and macroscale ligand density. The low‐frequency and terminally sequenced nano‐ligands are demonstrated as novel and independent parameters facilitating focal‐adhesion‐mediated mechanotransduction of stem cells, both in vitro and in vivo, which facilitate their subsequent differentiation.
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► We developed electrospun PLLA fibers modified by polydopamine coating. ► We characterized the surface morphology and surface chemical properties of polydopamine coated PLLA fibers ...(PD-PLLA). ► PD-PLLA fibers had only negligible effects on the roughness and hydrophobicity of the fibers. ► We evaluated the effect of polydopamine on the adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs). ► Cell responses of hMSCs on PD-PLLA fibers were significantly enhanced relative to those on PLLA.
Development of biomaterials to control the fate of stem cells is important for stem cell based regeneration of bone tissue. The objective of this study is to develop functionalized electrospun fibers using a mussel-inspired surface coating to regulate adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs). We prepared poly(
l-lactide) (PLLA) fibers coated with polydopamine (PD-PLLA). The morphology, chemical composition, and surface properties of fiber were characterized by SEM, AFM, XPS, Raman spectra and water contact angle measurements. Incubation of fibers in dopamine solution for 1
h resulted in formation of polydopamine with only negligible effects on the roughness and hydrophobicity of the fibers. However, PD-PLLA fibers modulated hMSC responses in several aspects. Firstly, adhesion and proliferation of hMSCs cultured on PD-PLLA were significantly enhanced relative to those on PLLA. In addition, the ALP activity of hMSCs cultured on PD-PLLA (1.74
±
0.14
nmole/DNA/30
min) was significantly higher than on PLLA (0.97
±
0.07
nmole/DNA/30
min). hMSCs cultured on PD-PLLA showed up-regulation of genes associated with osteogenic differentiation as well as angiogenesis. Furthermore, the calcium deposition from hMSCs cultured on PD-PLLA (41.60
±
1.74
μg) was significantly greater than that on PLLA (30.15
±
1.21
μg), which was double-confirmed by alizarin red S staining. Our results suggest that the bio-inspired coating synthetic degradable polymer can be used as a simple technique to render the surface of synthetic biodegradable fibers to be active for directing the specific responses of hMSCs.
The development of materials capable of varying macroscale ligand distributions can emulate an extracellular matrix (ECM) remodeling and regulate the adhesion and polarization of macrophages. In this ...report, negatively charged slidable nano‐ligands are assembled and then conjugated to a positively charged substrate via electrostatic interaction. The negatively charged slidable nano‐ligands are prepared by coating magnetic nanoparticles with a polymer linker and negatively charged RGD ligand. The nano‐ligand sliding is characterized under an external magnetic field, which spatiotemporally alters macroscale ligand density. To the best of knowledge, this is the first demonstration that magnetic maipulation of the macroscale ligand density inhibits inflammatory M1 phenotype but stimulates the adhesion and regenerative M2 phenotype of host macrophages. Furthermore, it is elucidated that the magnetic attraction of the slidable nano‐ligand facilitates the assembly of adhesion structures in macrophages, thereby stimulating their regenerative M2 phenotype. The design of ECM‐emulating materials that allow remote, spatiotemporal, and reversible controllability of macroscale ligand density provides an appealing strategy in the spatiotemporal regulation of immunomodulatory tissue‐regenerative responses to implants in vivo.
A slidable nano‐ligand is developed using magnetic nanoparticles coated with polymer linker and negatively charged ligand, which is electrostatically coupled to a positively charged substrate. It is demonstrated that magnetic attraction of slidable nano‐ligand manipulates macroscale ligand presentation in situ, which regulates the adhesion and polarization of macrophages, both in vitro and in vivo.
Abstract In this study, we introduced a simple method for polydopamine-mediated immobilization of dual bioactive factors for the preparation of functionalized vascular graft materials. Polydopamine ...was deposited on elastic and biodegradable poly(lactic acid-co-ε-caprolactone) (PLCL) films, and a cell adhesive RGD-containing peptide and basic fibroblast growth factor were subsequently immobilized by simple dipping. We used an enzyme-linked immunosorbent assay and fluorescamine assay to confirm that we had stably immobilized bioactive molecules on the polydopamine-coated PLCL film in a reaction time-dependent manner. When human umbilical vein endothelial cells (HUVEC) were cultured on the prepared substrates, the number of adherent cells and proliferation of HUVEC for up to 14 days were greatest on the film immobilized with dual factors. On the other hand, the film immobilized with RGD peptide exhibited the highest migration speed compared to the other groups. The expression of cluster of differentiation 31 and von Willebrand factor, which indicates maturation of endothelial cells, was highly stimulated in the dual factor-immobilized group, and passively adsorbed factors showed a negligible effect. The immobilization of bioactive molecules inspired by polydopamine was successful, and adhesion, migration, proliferation and differentiation of HUVEC were synergistically accelerated by the presence of multiple signaling factors. Collectively, our results have demonstrated that a simple coating with polydopamine enables the immobilization of multiple bioactive molecules for preparation of polymeric functionalized vascular graft materials.
Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion
. Herein, we designed charged mobile ...nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and
nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that
magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both
and
, with reversible control. Furthermore, we unravel that
magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes
.
Biodegradable metallic materials represent a potential step‐change technology that may revolutionize the treatment of broken bones. Implants made with biodegradable metals are significantly stronger ...than their polymer counterparts and fully biodegradable in vivo, removing the need for secondary surgery or long‐term complications. Here, it is shown how clinically approved Mg alloy promotes improved bone repair using an integrated state of the art fetal mouse metatarsal assay coupled with in vivo preclinical studies, second harmonic generation, secretome array analysis, perfusion bioreactor, and high‐resolution 3D confocal imaging of vasculature within skeletal tissue, to reveal a vascular‐mediated pro‐osteogenic mechanism controlling enhanced tissue regeneration. The optimized mechanical properties and corrosion rate of the Mg alloy lead to a controlled release of metallic Mg, Ca, and Zn ions at a rate that facilitates both angiogenesis and coupled osteogenesis for better bone healing, without causing adverse effects at the implantation site. The findings from this study support ongoing development and refinement of biodegradable metal systems to act as crucial portal technologies with significant potential to improve many clinical applications.
An integrated state‐of‐the‐art in vivo and in vitro approach reveals clinically approved Mg5Ca1Zn samples stimulate accelerated bone healing by releasing anabolic metallic ions into the surrounding tissues to enhance the growth of type H blood vessels, which localize at active sites of bone remodeling and actively recruit Osterix‐positive osteoprogenitors to the degrading implant site.
Numerous methods have been introduced to produce 3D cell cultures that can reduce the need for animal experimentation. This study presents a unique 3D culture platform that features bioinspired ...strands of electrospun nanofibers (BSeNs) and aquatic cell lines to compensate for shortcomings in the current cell spheroid generation techniques. The use of BSeNs in 3D zebrafish liver cell cultures is found to improve liver and reproductive functions through spheroid‐based in vitro assays such as whole transcriptome sequencing and reproductive toxicity testing, with optimized properties exhibiting results similar to those obtained for fish embryo acute toxicity (FET, OECD TG 236) following exposure to environmental endocrine‐disrupting chemicals (17β‐Estradiol (E2), 4‐hydroxytamoxifen (4‐HT), and bisphenol compounds (bisphenol A (BPA) and 9,9‐Bis(4‐hydroxyphenyl)fluorene (BPFL)). These findings indicate that the beneficial effects of bioinspired materials that closely mimic ECM environments can yield efficient zebrafish cells with intrinsic functions and xenobiotic metabolism similar to those of zebrafish embryos. As a closer analog for the in vivo conditions that are associated with exposure to potentially hazardous chemicals, the straightforward culture model introduced in this study shows promise as an alternative tool that can be used to further eco‐environmental assessment.
The beneficial effects of bioinspired strands of electrospun nanofibers (BSeNs) can compensate for shortcomings in the current cell spheroid generation techniques. Integrated 3D spheroids with BSeNs mitigate against the problems associated with hypoxia and the produced system is suitable for the testing of eco‐hazardous chemicals without the need for vertebrate platforms.
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