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Abstract Mimicking the mechanical properties of native tissue is an important requirement for tissue engineering scaffolds. Blood vessels are subject to repetitive dilation and contraction and possess a special nonlinear mechanical property due to their triple-layered structure. Fabrication of vascular grafts consisting of bioresorbable materials with biomimetic mechanical properties is an urgent demand, as well as a critical challenge. Inspired by the configuration and function of collagen and elastin in native blood vessels, a new type of triple-layered vascular graft (TLVG) was developed in this study. The TLVGs were composed of braided silk as the inner layer, polyacrylamide (PAM) hydrogel as the middle layer, and electrospun thermoplastic polyurethane (TPU) as the outer layer. The woven-structured silk fibers were able to mimic the properties of the loosely distributed collagen fibers, while the highly elastic PAM hydrogel and TPU nanofibers mimicked the elasticity of elastin in the blood vessel. With this specially designed microstructure and combination of rigid and elastic materials, the TLVGs successfully mimicked the nonlinear mechanical property of native blood vessels. Moreover, TLVGs possess sufficient suture retention strength for surgical implantation. The introduction of a PAM hydrogel layer effectively solved the leaking issue for conventional porous vascular grafts and greatly enhanced the burst pressure. In addition, all materials used have high biocompatibility to human endothelial cells, which indicates that the developed TLVGs have high potential to be used as readily available vascular grafts. Highlights • Triple-layered vascular grafts with biomimetic mechanical properties were prepared. • The grafts consist of braided silk fiber inner layer, PAM hydrogel middle layer and TPU outer layer. • Woven silk fibers result to non-linear physical property which resembles blood vessel. • The hydrogel layer prevents blood leaking and greatly enhanced burst pressure. [ABSTRACT FROM AUTHOR]

Mimicking the mechanical properties of native tissues is a critical criterion for an ideal tissue engineering scaffold. However, most biodegradable synthetic materials, including polyester-based polyurethanes (PUs), consist of rigid polyester chains and have high crystallinity. They typically lack the elasticity of most human tissues. In this study, a new type of biodegradable PU with excellent elasticity was synthesized based on the controlled crosslinking of poly(ester ether) triblock copolymer diols and polycaprolactone (PCL) triols using urethane linkages. Three-dimensional (3D) porous scaffolds with a defined geometry, tunable microstructures, and adjustable mechanical properties were synthesized in situ using an isocyanate-ended copolymer, a tri-armed PCL, and a chain extender. The mechanical properties of the scaffolds can be easily tuned by changing the ratio of reactants, varying the solution concentration, or using a porogen. Notably, all of these scaffolds, although mostly made of rigid PCL chains, showed remarkable elasticity and cyclical properties. With an optimized molecular design, a maximum recovery rate of 99.8% was achieved. This was because the copolymer provided molecular flexibility while the long chain crosslinking of PCL triol hindered crystallization, thus making the PU behave like an amorphous elastic material. Moreover, the in vitro cell culture of 3T3 fibroblasts and MG63 osteoblast-like cells confirmed the biocompatibility of these PU scaffolds and revealed that scaffolds with different stiffnesses can stimulate the proliferation of different types of cells. All of these attributes make PU scaffolds extremely suitable for the regeneration of tissues that experience dynamic loading. [ABSTRACT FROM AUTHOR]

Fabrication of highly porous, three-dimensional (3D) scaffolds with biomimicking microstructures for tissue engineering has received extensive attention lately. Although several studies have used silica as a filler material in various polymeric scaffold matrices for tissue engineering, there are no reports of 3D scaffolds fabricated solely with silica. In this study, we developed a method to fabricate fibrous silica sponges using a tetraethyl orthosilicate (TEOS)/polyvinyl alcohol (PVA) solution via self- assembly electrospinning and subsequent calcination. We then evaluated its potential application in tissue engineering. A detailed mechanism study revealed that appropriate crosslinking between hydrolyzed TEOS and PVA was the key to inducing 3D fiber stacking. The prepared silica sponges had a bulk density of 16 mg/cm 3 , a surface area of 6.45 m 2 /g, and a porosity of 98%, which endowed them with super-high absorbability. Cell culture results with 3T3 fibroblasts confirmed that the cells interacted strongly with the 3D silica fibers, showing a higher viability and proliferation rate than on 2D silica membranes, and that the cells migrated into the inner area of the sponge rapidly, indicating these silica sponges have potential to be used for 3D tissue regeneration. [ABSTRACT FROM AUTHOR]

Hydrogels currently used in electroactive tissues (cardiac tissues, skeletal muscles, and nerves) have certain shortcomings such as a lack of electrical conductivity and adhesiveness, both of which play a key role in the success of hydrogels in biomedical applications. In this study, chitosan (CS)/graphene oxide (GO) composite hydrogels with self-adhesive and self-healing properties, as well as electrical conductivity, were prepared by the incorporation of the mussel-inspired protein polydopamine (PDA). During the oxidizing process of dopamine (DA), graphene oxide was reduced by PDA and dispersed into the hydrogel network to form electric pathways. The covalent bonds, supramolecular interactions, hydrogen bonding, and π-π stacking gave the CS/GO composite hydrogels high stability, strong mechanical behaviors, good adhesiveness, self-healing properties, and a fast recovery ability. The electrical conductivity of the CS/GO reached 1.22 mS/cm and the adhesive strength of the composite hydrogel increased by 300% compared to CS-DA hydrogels. Cell culture results demonstrated that the conductive CS/GO hydrogels enhanced the cell viability and proliferation of human embryonic stem cell-derived fibroblasts (HEF1) and cardiomyocytes (CMs) compared to CS-DA hydrogels. Moreover, CMs showed a faster spontaneous beating rate than those in the control groups. Our work demonstrates a simple approach to fabricating polydopamine-based, adhesive, conductive, self-healing, and fast-recovering hydrogels that have great potential in electroactive tissue engineering applications. [ABSTRACT FROM AUTHOR]

In this study, parallel-aligned poly(propylene carbonate) (PPC) microfibers with a fiber diameter of 1.48 ± 0.42 μm were prepared by electrospinning and modified by oxygen plasma treatment. Next, chitosan nanofibers with a fiber diameter size of 278 ± 98 nm were introduced into the PPC fiber mats by freeze drying. Morphological analyses showed that the PPC scaffolds treated with 0.05 mg/ml chitosan solution provided the best micro and nanofiber structure with abundant chitosan nanofibers but without the formation of films. Surface chemical properties were analyzed by X-ray photoelectron spectroscopy (XPS). The initial water contact angle of the scaffolds decreased from 122.3 ± 0.4° for neat PPC scaffolds to 53.8 ± 1.6° for scaffolds with plasma treatment and chitosan nanofibers. The mechanical properties of the scaffolds were affected by plasma treatment with Young's modulus experiencing a reduction of 63%. Meanwhile, Young's modulus experienced a 26% improvement after the introduction of chitosan nanofibers. Fibroblast cells were cultured on the scaffolds to study the effects of both the plasma treatment and the introduction of chitosan nanofibers on cell adhesion, proliferation, and morphology. The scaffolds with PPC microfibers and chitosan nanofibers showed a superior cell response in terms of cell attachment, cell proliferation, and cell–scaffold interactions over the other scaffolds. [ABSTRACT FROM AUTHOR]

Tissue engineering provides a novel and promising approach to replace damaged tissue with an artificial substitute. Porous synthetic biodegradable polymers are the preferred materials for this substitution due to their microstructure, biocompatibility, biodegradability, and low cost. As a crucial element in tissue engineering, a scaffold acts as an artificial extracellular matrix (ECM) and provides support for cell migration, differentiation, and reproduction. The fabrication of viable scaffolds, however, has been a challenge in both clinical and academic settings. Methods such as solvent casting/particle leaching, thermally induced phase separation (TIPS), electrospinning, gas foaming, and rapid prototyping (additive manufacturing) have been developed or introduced for scaffold fabrication. Each method has its own advantages and disadvantages. In this review, the commonly used synthetic polymer scaffold fabrication methods will be introduced and discussed in detail, and recent progress regarding scaffold fabrication—such as combining different scaffold fabrication methods, combining various materials, and improving current scaffold fabrication methods—will be reviewed as well. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Abstract: Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications. [Copyright &y& Elsevier]

• Three dimensional fluffy nanofibrous scaffold was prepared by CO 2 escaping foaming. • Shih-kebab structure was successfully introduced onto 3D nanofibrous scaffold. • The developed 3D nanofibrous scaffolds possess low density, high surface area and porosity. • Fibroblast Cells were able to migrate into the inner of the scaffold effectively. Electrospun nanofibrous scaffolds are highly recognized in tissue engineering since they can mimic the structure of extracellular matrix (ECM). However, the nanofibers fail to resemble the three dimensional geometry of organs, and the surface nanotopography of collagen fibrils in ECM. In order to mimic the structure of ECM in both macroscale (3D geometry) and microscale (surface nanotopography), an ingenious approach was developed in this study. Electrospun nanofibers collected in ethanol bath was soaked in CO 2 saturated ethanol and subsequently foamed in a water bath, due to the escaping of CO 2 gas. This simple green method takes the advantage of solubility difference of carbon dioxide (CO 2) in ethanol and water, and is applicable to different materials. The foamed fluffy polycaprolactone (PCL) nanofibrous scaffolds achieved a low bulk density of 0.041 g/cm3 and a high porosity of 95.3%. To resemble the surface nanotopography of ECM, shish-kebab structure was introduced onto the fluffy PCL nanofibers by controlled crystallization. The shish-kebab structures greatly enhanced the surface area of scaffolds from 6.9 m2/g for 2D PCL to 10.9 m2/g for 3D SK-PCL. In addition, 3T3 fibroblast cell culture results confirmed that the cells interacted strongly with the 3D fluffy nanofibers and migrated into the inner area of the scaffolds rapidly. Moreover, human fibroblast cell culture results confirmed further enhancement in cell attachment and proliferation on the fluffy shish-kebab structured nanofibrous scaffolds, which indicates the developed biomimetic 3D scaffolds have high potential to be used for 3D tissue regeneration. [ABSTRACT FROM AUTHOR]

Bone is a nanocomposite comprised of two main components, nanohydroxyapatite (nHA) and Type I collagen. The aim of this study is to mimic the nanotopography of collagen fibrils in bone tissue and to modulate their cellular functions by nanoscale stimulation. Three-dimensional structures consisting of electrospun poly( $$ \varepsilon $$ -caprolactone) (PCL) and PCL/nHA composite nanofibers decorated by periodically spaced PCL crystal lamellae (shish-kebab structure) were created. It was found that the hierarchically decorated nanostructure not only enhanced the mechanical properties of the scaffolds but also changed the surface wettability behavior of the scaffolds. The enhanced surface wettability facilitated biomimetic mineralization through apatite deposition when exposed to simulated body fluids (SBF). MG-63, an osteosarcoma cell line which behaves similarly to osteoblasts, was used to study the cellular response to the scaffolds. Data suggest kebab crystal nanotopography facilitating cell attachment and proliferation. Functional assays, which quantify alkaline phosphatase (ALP) and calcium expression, revealed increased ALP activity and increased calcium expression on decorated nanofibers. In addition, compared with other scaffolds, the cells on PCL/nHA nanofibrous shish-kebab-structured scaffolds showed obvious extended pseudopodia of the filaments in the cytoskeleton study, demonstrating better interactions between cells and scaffolds. [ABSTRACT FROM AUTHOR]

Bi-modal pore structures were obtained by stepwise depressurization in batch foaming method. In this study, a novel method was developed to produce polylactic acid (PLA) foam with bi-modal pore structure by using multiple soaking temperature (MST) method based on one-step pressure release. The effects of soaking time and temperatures on the formation of bi-modal pore structure were investigated in detail. The formation of macro pores was attributed to the synergistic effect of the supercritical carbon dioxide (SC-CO 2 ) aggregation and the depressurization process. Moreover, bi-modal open-pore structures could be obtained at certain processing conditions. The PLA foams achieved porosity and open pore content as high as 87.9% and 82.4%, with average macro and micro pore size of 150 μm and 8 μm, respectively. The biocompatibility of the PLA open-pore foams was verified by 3T3 fibroblast cell culture. [ABSTRACT FROM AUTHOR]

Forced expression of transcription factors epigenetically reprograms somatic cells harvested from routine skin biopsies into induced pluripotent stem cells (iPSCs). Human iPSCs are key resources for drug discovery, regenerative medicine and tissue engineering. Here we developed a materials approach to explore how culture substrates could impact factor-mediated reprogramming of human fibroblasts. A materials library consisting of nanofibrous substrates with randomly oriented and aligned structures was prepared by electrospinning four polymers [polylactic acid (PLA), polycaprolactone (PCL), thermoplastic polyurethane (TPU) and polypropylene carbonate (PPC)] into nanofiber orientations. Adsorbing protein to each substrate permitted robust attachment of fibroblasts to all substrates. Fibroblasts on aligned substrates had elongated nuclei, but after reprogramming factor expression, nuclei became more circular. Reprogramming factors could override the nuclear shape constraints imposed by nanofibrous substrates, and the majority of substrates supported full reprogramming. Early culture on PCL and TPU substrates promoted reprogramming, and TGF-β repressed substrate effects. Partial least squares modeling of the biochemical and biophysical cues within our reprogramming system identified TGF-β and polymer identity as important cues governing cellular reprogramming responses. We believe that our approach of using a nanofibrous materials library can be used to dissect molecular mechanisms of reprogramming and generate novel substrates that enhance epigenetic reprogramming. [ABSTRACT FROM AUTHOR]

Nanofibrouspoly(propylene carbonate)(PPC)/gelatin composite scaffoldswere fabricated by the electrospinning process and characterized fortissue engineering applications. Using trifluoroethanol (TFE) as asolvent and at low mass content of gelatin, nanofibrous scaffold PPC/gelatinmembranes with improved wettability and hydrophilicity were produced,despite the fact that PPC is hydrophobic. However, phase separationoccurred when the mass content of gelatin was higher than 5%, resultingin a nonuniform fibrous structure and some large splash defects. Inspiredby the effect of pH on the behavior of dissolved gelatin, a smallamount of acetic acid was added to the PPC/gelatin solution, whichenabled the originally turbid solution to become clear immediately.The results showed that the miscibility of PPC and gelatin was enhancedby acetic acid. Using the treated solution, homogeneous PPC/gelatinnanofibers with a smooth surface and a more uniform diameter wereobtained, and they performed better in wettability and mechanicaltests. Cell culture experiments showed that fibroblast cells had morefavorable interactions on the PPC/gelatin composite scaffolds thanthose of pure PPC membranes. Furthermore, the introduction of aceticacid did not hinder cell growth and proliferation on the modifiedmembrane. The results of this study suggest the potential use of electrospunPPC/gelatin composite scaffolds in the tissue engineering field. [ABSTRACT FROM AUTHOR]