Porous Polyurethane Scaffolds Research Articles

Fabrication of 3D porous polyurethane-graphene oxide scaffolds by a sequential two-step processing for non-load bearing bone defects

Bone defects as a common orthopedic disease lead to severe pains over a long period. Scaffolds are novel approaches in tissue engineering to treat bone problems and deal with their challenges. Here, 3D porous polyurethane (PU) scaffolds containing graphene oxide (GO) with different percentages (0, 0.1, 0.3, and 0.5 wt%) were developed through a combination of freeze-drying and salt etching techniques for bone tissue engineering applications. The morphologies of scaffolds, physicochemical properties, the degree of crystallinity, and hydrophilicity were evaluated by SEM, FTIR, XRD, and water contact angle assay, respectively. The porosity, degradation behavior, compressive strength, and elastic modulus of 3D porous scaffolds were also determined. To assess the scaffold bioactivity, the morphology of the deposited calcium phosphate layer on the scaffold with macro-structure was evaluated by SEM images. The viability and adhesion of MG63 osteoblast-like cells cultured on the fabricated scaffolds were examined by MTT assay and SEM images, respectively. The results show that adding GO particles not only had no effect on the interconnectivity and porosity of 3D porous macroscopic structures of neat PU but also smaller and more uniformed microscopically pores were obtained. The crystallinity, water contact angle, and weight loss of scaffolds increased as the higher GO concentrations were employed. Followed by increasing GO contents from 0 to 0.5 wt%, the compressive strength and Young’s modulus were increased by 232% and 245%, respectively. The bioactivity of scaffolds was fostered as GO concentration increased. Although, the MTT assay proved the biocompatibility of PU scaffolds containing 0.1 and 0.3 wt% GO, the samples loaded with 0.5 GO had a negative impact on the viability of MG63 cell lines. In conclusion, the present study demonstrates a high potential of PU scaffolds loaded with 0.1 and 0.3 wt% GO particles in bone tissue engineering applications.

Porous Three-Dimensional Polyurethane Scaffolds Promote Scar-Free Endogenous Regeneration After Acute Brain Hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke and is associated with significant morbidity and mortality. Despite advances in the clinical treatment of ICH, limited progress has been made regarding endogenous brain regeneration after ICH. Failure of brain regeneration is mainly attributed to the inhibitive regenerative microenvironment caused by secondary injury after ICH. In this study, we investigated a three-dimensional biodegradable waterborne polyurethane (BWPU) scaffold as a tool to promote brain regeneration after ICH. After implantation into the cavity following hematoma evacuation, these implanted scaffolds could act as a reservoir; store a series of necrotic debris, cytokines, and chemokines; and attract microglia/macrophages to their pores. Subsequently, these microglia/macrophages were polarized into the M1-like subtype to eliminate these substances. This process disperses M1-like immune cells and prevents the formation of dense glial scar-free structures after ICH. Inflammatory cells in scaffolds include scar-free secreted growth factors and extracellular matrix (ECM) proteins, and further induce a M2-like immune cells enriched regeneration-predominant microenvironment to promote endogenous brain regeneration with functional recovery. In summary, in this work, we have revealed the potential and mechanism of the BWPU scaffold as a tool to promote endogenous brain tissue regeneration after ICH.

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air.

Devices for in vitro culture of three-dimensional (3D) skeletal muscle tissues have multiple applications, including tissue engineering and muscle-powered biorobotics. In both cases, it is crucial to recreate a biomimetic environment by using tailored scaffolds at multiple length scales and to administer prodifferentiative biophysical stimuli (e.g., mechanical loading). On the contrary, there is an increasing need to develop flexible biohybrid robotic devices capable of maintaining their functionality beyond laboratory settings. In this study, we describe a stretchable and perfusable device to sustain cell culture and maintenance in a 3D scaffold. The device mimics the structure of a muscle connected to two tendons: Tendon-Muscle-Tendon (TMT). The TMT device is composed of a soft (E ∼ 6 kPa) porous (pore diameter: ∼650 μm) polyurethane scaffold, encased within a compliant silicone membrane to prevent medium evaporation. Two tendon-like hollow channels interface the scaffold with a fluidic circuit and a stretching device. We report an optimized protocol to sustain C2C12 adhesion by coating the scaffold with polydopamine and fibronectin. Then, we show the procedure for the soft scaffold inclusion in the TMT device, demonstrating the device's ability to bear multiple cycles of elongations, simulating a protocol for cell mechanical stimulation. By using computational fluid dynamic simulations, we show that a flow rate of 0.62 mL/min ensures a wall shear stress value safe for cells (<2 Pa) and 50% of scaffold coverage by an optimal fluid velocity. Finally, we demonstrate the effectiveness of the TMT device to sustain cell viability under perfusion for 24 h outside of the CO2 incubator. We believe that the proposed TMT device can be considered an interesting platform to combine several biophysical stimuli, aimed at boosting skeletal muscle tissue differentiation in vitro, opening chances for the development of muscle-powered biohybrid soft robots with long-term operability in real-world environments.

3D biodegradable shape changing composite scaffold with programmable porous structures for bone engineering

This study developed a biodegradable composite porous polyurethane scaffold based on polycaprolactone and polyethylene glycol by sequential in-situ foaming salt leaching and freeze-drying process with responsive shape changing performance. Biomineral hydroxyapatite (HA) was introduced into the polyurethane matrix as inorganic fillers. Infrared spectroscopy results proved a successful synthesis, scanning electron microscopy showed that the scaffold’s porosity decreased with the addition of HA while the average pore size increased. X-ray diffraction and differential scanning calorimetry showed that the addition of HA lowered the melting point of the scaffold, resulting in a transition temperature close to the human body temperature. From the bending experiments, it could be demonstrated that PUHA20 has excellent shape memory performance with shape fixity ratio >98.9% and shape recovery ratio >96.2%. Interestingly, the shape-changing capacity could be influenced by the porous structures with variation of HA content. The shape recovery speed was further accelerated when the material was immersed in phosphate buffered saline at 37 °C. Additionally, in vitro mineralization experiments showed that the scaffold incorporating HA had good osteoconductivity, and implantation assessment proved that scaffolds had good in vivo biocompatibility. This scaffold is a promising candidate for implantation of bone defects.

Fabrication and Characterization of Alveolus-Like Scaffolds with Control of the Pore Architecture and Gas Permeability.

The micrometer scale sac-like alveoli are the most important and essential unit for gas exchange in the lung. Thus, design and fabrication of scaffolds for alveoli regeneration by tissue engineering approach should meet a few topography and functional requests such as large surface area, flexibility, and high gas permeability to their native counterpart. Testing the gas permeability of scaffolds through a fast and simple technique is also highly demanded to assist new scaffold development. This study fabricated alveolus-like scaffolds with regular pore shape, high pore connectivity, and high porosity produced by inverse opal technique alongside randomly distrusted porous scaffolds by salt leaching technique from two different materials (polyurethane and poly(L-lactic acid)). The scaffold surface was modified by immobilization of VEGF. A facile and new technique based on the bubble meter principle enabling to measure the gas permeability of porous scaffolds conveniently has been developed specifically. The cellular response of the scaffolds was assessed by culturing with bone marrow mesenchymal stem cells and coculturing with lung epithelial NL20 and endothelial HUVECs. Our results showed that the newly designed gas permeability device provided rapid, nondestructive, reproducible, and accurate assessment of gas permeability of different scaffolds. The porous polyurethane scaffolds made by inverse opal method had much better gas permeability than other scaffolds used in this study. The cellular work indicated that with VEGF surface modification, polyurethane inverse opal scaffolds induced alveolus-like tissues and have promising application in lung tissue engineering.

Engineering transplantable human lymphatic and blood capillary networks in a porous scaffold

Due to a relative paucity of studies on human lymphatic assembly in vitro and subsequent in vivo transplantation, capillary formation and survival of primary human lymphatic (hLEC) and blood endothelial cells (hBEC) ± primary human vascular smooth muscle cells (hvSMC) were evaluated and compared in vitro and in vivo. hLEC ± hvSMC or hBEC ± hvSMC were seeded in a 3D porous scaffold in vitro, and capillary percent vascular volume (PVV) and vascular density (VD)/mm2 assessed. Scaffolds were also transplanted into a sub-cutaneous rat wound with morphology/morphometry assessment. Initially hBEC formed a larger vessel network in vitro than hLEC, with interconnected capillaries evident at 2 days. Interconnected lymphatic capillaries were slower (3 days) to assemble. hLEC capillaries demonstrated a significant overall increase in PVV (p = 0.0083) and VD (p = 0.0039) in vitro when co-cultured with hvSMC. A similar increase did not occur for hBEC + hvSMC in vitro, but hBEC + hvSMC in vivo significantly increased PVV (p = 0.0035) and VD (p = 0.0087). Morphology/morphometry established that hLEC vessels maintained distinct cell markers, and demonstrated significantly increased individual vessel and network size, and longer survival than hBEC capillaries in vivo, and established inosculation with rat lymphatics, with evidence of lymphatic function. The porous polyurethane scaffold provided advantages to capillary network formation due to its large (300–600 μm diameter) interconnected pores, and sufficient stability to ensure successful surgical transplantation in vivo. Given their successful survival and function in vivo within the porous scaffold, in vitro assembled hLEC networks using this method are potentially applicable to clinical scenarios requiring replacement of dysfunctional or absent lymphatic networks.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical

Improving the colonization and functions of Wharton’s Jelly-derived mesenchymal stem cells by a synergetic combination of porous polyurethane scaffold with an albumin-derived hydrogel

The development of neo-tissues assisted by artificial scaffolds is continually progressing, but the reproduction of the extracellular environment surrounding cells is quite complex. While synthetic scaffolds can support cell growth, they lack biochemical cues that can prompt cell proliferation or differentiation. In this study, Wharton’s Jelly-derived mesenchymal stem cells are seeded on a polyurethane (PU) scaffold combined with a hydrogel based on bovine serum albumin (BSA). BSA hydrogel is obtained through thermal treatment. While such treatment leads to partial unfolding of the protein, we show that the extent of denaturation is small enough to maintain its bioactivity, such as protein binding. Therefore, BSA provides a suitable playground for cells inside the scaffold, allowing higher spreading, proliferation and matrix secretions. Furthermore, the poor mechanical properties of the hydrogel are compensated for by the porous PU scaffold, whose architecture is well controlled. We show that even though PU by itself can allow cell adhesion and protein secretion, cell proliferation is 3.5 times higher in the PU + BSA scaffolds as compared to pure PU after 21 d, along with the non-collagenous protein secretions (389 versus 134 μmmg−1). Conversely, the secretion of sulphated glycosaminoglycans is 12.3-fold higher in the scaffold made solely of PU. Thereby, we propose a simple approach to generating a hybrid material composed of a combination of PU and BSA hydrogel as a promising scaffold for tissue regeneration.

Functionalization of 3-D porous thermoplastic polyurethane scaffolds by two-stage polydopamine/hydroxyapatite composite nanoparticles

Functionalization of 3-D porous thermoplastic polyurethane scaffolds by two-stage polydopamine/hydroxyapatite composite nanoparticles

Paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell-like cells derived from adipose stromal cells

In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous polyurethane scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. Statement of significanceAdipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic polyurethane (D-PHI) scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial scaffold (e.g. D-PHI) based co-culture system containing monocytes.

Aligned 3D porous polyurethane scaffolds for biological anisotropic tissue regeneration.

A green fabrication process (organic solvent-free) of artificial scaffolds is required in tissue engineering field. In this work, a series of aligned three-dimensional (3D) scaffolds are made from biodegradable waterborne polyurethane (PU) emulsion via directional freeze–drying method to ensure no organic byproducts. After optimizing the concentration of polymer in the emulsion and investigating different freezing temperatures, an aligned PUs scaffold (PU14) generated from 14 wt% polymer content and processed at −196°C was selected based on the desired oriented porous structure (pore size of 32.5 ± 9.3 μm, porosity of 92%) and balanced mechanical properties both in the horizontal direction (strength of 41.3 kPa, modulus of 72.3 kPa) and in the vertical direction (strength of 45.5 kPa, modulus of 139.3 kPa). The response of L929 cells and the regeneration of muscle tissue demonstrated that such pure material-based aligned 3D scaffold can facilitate the development of orientated cells and anisotropic tissue regeneration both in vitro and in vivo. Thus, these pure material-based scaffolds with ordered architecture have great potentials in tissue engineering for biological anisotropic tissue regeneration, such as muscle, nerve, spinal cord and so on.

A new nanocomposite scaffold based on polyurethane and clay nanoplates for osteogenic differentiation of human mesenchymal stem cells in vitro

Bone tissue engineering as an alternative strategy, provides a great opportunity for regeneration of large bone tissue lesions. The use of biodegradable porous scaffolds along with stem cells, cytokines and growth factors improves cell survival, adhesion, proliferation and differentiation. In the present study, clay nanoplates (CNPs) were surface-modified (MCNPs) using phosphoric acid and calcium hydroxide, then porous polyurethane (PU) scaffolds and PU-MCNPs nanocomposite scaffolds were synthesized using solvent evaporation-dissolution technique. Physicochemical and morphological properties of scaffolds and MCNPs were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Moreover, thermal behavior of scaffolds was assessed by differential scanning calorimetry (DSC). Degradability, water uptake and mechanical behaviors of scaffolds were evaluated and hydrophilicity properties of them were obtained by contact angle technique. MTT assay and Acridine Orange/Ethidium Bromide (AO/EB) staining were used to assess the biocompatibility of MCNPs and PU scaffolds regarding cell attachment and proliferation support. Osteogenic differentiation of cultured human adipose derived mesenchymal stem cells (hADSCs) on MCNPs, PU and PU-MCNPs scaffolds was evaluated using common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium content assay, Alizarin Red staining, immunocytochemical analysis (ICC) and quantitative real-time PCR (qPCR). According to the results, the surface modification of CNPs and their presence into the PU scaffolds significantly enhanced proliferation and osteogenic differentiation of hADSCs. These results were obtained by higher ALP enzyme activity, biomineralization and expression of osteogenic related proteins and genes in differentiated hADSCs on PU-MCNPs scaffolds. In conclusion, our results revealed that these biocompatible nanocomposites porous scaffolds with proper cell adhesion and proliferation as well as effective osteogenic differentiation and which are able to provide a new and useful matrix for bone tissue engineering purposes.

Modulation of Cellular Colonization of Porous Polyurethane Scaffolds via the Control of Pore Interconnection Size and Nanoscale Surface Modifications.

Full-scale cell penetration within porous scaffolds is required to obtain functional connective tissue components in tissue engineering applications. For this aim, we produced porous polyurethane structures with well-controlled pore and interconnection sizes. Although the influence of the pore size on cellular behavior is widely studied, we focused on the impact of the size of the interconnections on the colonization by NIH 3T3 fibroblasts and Wharton's jelly-derived mesenchymal stem cells (WJMSCs). To render the material hydrophilic and allow good material wettability, we treated the material either by plasma or by polydopamine (PDA) coating. We show that cells weakly adhere on these surfaces. Keeping the average pore diameter constant at 133 μm, we compare two structures, one with LARGE (52 μm) and one with SMALL (27 μm) interconnection diameters. DNA quantification and extracellular matrix (ECM) production reveal that larger interconnections is more suitable for cells to move across the scaffold and form a three-dimensional cellular network. We argue that LARGE interconnections favor cell communication between different pores, which then favors the production of the ECM. Moreover, PDA treatment shows a truly beneficial effect on fibroblast viability and on matrix production, whereas plasma treatment shows the same effect for WJMSCs. We, therefore, claim that both pore interconnection size and surface treatment play a significant role to improve the quality of integration of tissue engineering scaffolds.

Abstract P3-13-11: The outcomes of ReFilx soft tissue filler as an immediate reconstruction technique for lumpectomy followed by radiotherapy

Abstract Introduction: Lumpectomy for breast cancer can often result in poor cosmetic outcomes which can lead to long-lasting impairment of quality of life. ReFilx is a synthetic porous degradable polyurethane scaffold that has mechanical properties comparable to that of native healthy breast tissue. It has been shown in two previous porcine studies to preserve breast shape and volume over 9 months when inserted into the cavities immediately after lumpectomy. We observed minimal foreign body reaction with good integration of the host tissue while the material degraded over time. In this study, we examined the healing process of lumpectomy treated with radiation. Radiotherapy is currently a standard adjuvant therapy after lumpectomy for breast cancers; and radiation is known to affect the healing process in general. Objective: To evaluate ReFilx, as soft tissue fillers for lumpectomy cavities in combination with standard radiotherapy. Hypothesis: ReFilx will preserve breast shape and volume by supporting tissue infiltration with minimal inflammation in the presence of clinically relevant radiotherapy. Methods: 3 female Yucatan minipigs received lumpectomies carried out using electrocautery to remove normal breast tissue of approximately 2 cm diameter, after which the cavities were filled with (case) or without ReFilx (sham control) (n=3 for each condition, each pig has 12-13 breasts). 6 weeks post-implantation, 2 of the pigs received radiation directed at the right half of their bodies (6 breasts per pig) for a total dose of 42.4 Gy delivered over 15 fractions using a clinical linear accelerator. The delivered doses to target sites and the adjacent tissue were confirmed with optically stimulated luminescent dosimeters (OSLDs). A third pig was maintained as a non-irradiated control. Ultrasound examinations were performed every 3 weeks post-implantation. At week 24 and 36, samples consisted of n=3 for irradiated and non-irradiated ReFilx and sham sites for the half-irradiated pigs, and n=3 for non-irradiated ReFilx and sham sites for the non-irradiated control pig were excised by mastecomy, the tissue samples were fixed in 10% buffered formalin for subsequent histological (H&amp;E, Masson's Trichrome) studies. Potential side effects were monitored by vital signs, pain control, wound checks, ultrasound and blood tests. Necropsies were performed at the conclusion of the study. Results: Ultrasound examination indicated no difference between ReFilx's ability to maintain breast shape and volume with or without the presence of radiation treatment, in contrast to the collapse of the sham sites by 24 weeks. Similarly, the histology of irradiated and non-irradiated ReFilx samples showed similar levels of tissue infiltration, inflammatory changes and degradation of ReFilx. There was no significant side effects observed. Conclusions: ReFilx's ability to act as a soft tissue filler for breast volume restoration post-lumpectomy does not appear to be significantly impacted by the presence of clinically relevant radiation treatment. Longer-term follow-up is currently in progress for this study. Acknowledgements: Connaught Innovation Award (University of Toronto) and Joule Innovation Fund (Canadian Medical Association). Citation Format: Leong WL, Battiston K, Cheung F, Fulton C, Lin A, Levin W, Done S, Santerre P. The outcomes of ReFilx soft tissue filler as an immediate reconstruction technique for lumpectomy followed by radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-13-11.

RGD-functionalized polyurethane scaffolds promote umbilical cord blood mesenchymal stem cell expansion and osteogenic differentiation.

Biomimetic materials are essential for the production of clinically relevant bone grafts for bone tissue engineering applications. Their ability to modulate stem cell proliferation and differentiation can be used to harness the regenerative potential of those cells and optimize the efficiency of engineered bone grafts. The arginyl-glycyl-aspartic acid (RGD) peptide has been recognized as the adhesion motif of various extracellular matrix proteins and can affect stem cell behaviour in biomaterials. Attempts to functionalize biomaterials with RGD have been limited to a maximum of 1- to 3-mm thickness scaffolds, overlooking the issue of core infiltration that represents a major hurdle in developing real thickness scaffolds. Herein, we present the cross-linking of RGD on the surface of "real thickness" (5×5×5mm) porous polyurethane scaffolds (PU-RGD), to be used for the expansion and osteogenic differentiation of umbilical cord blood mesenchymal stem cells (UCB MSCs). RGD-functionalized scaffolds increased initial cell adhesion (1.5-fold to twofold) and achieved a 3.4-fold increase in cell numbers at the end of culture compared with a 1.5-fold increase in non-functionalized controls. Homogenous cell infiltration to the scaffold core was observed in the PU-RGD scaffolds. Importantly, PU-RGD scaffolds were able to enhance the osteogenic differentiation of UCB MSCs. Osteogenic gene and protein expression increased in scaffolds functionalized with 100μg/ml RGD. Higher RGD concentrations (200μg/ml) were less efficient in stimulating osteogenic differentiation. We conclude that robust RGD tethering to 3D PU "real thickness" scaffolds is possible and that it promotes core infiltration, expansion, and osteogenic differentiation of UCB MSCs for the purposes of bone regeneration.

In-situ reduction of graphene oxide-wrapped porous polyurethane scaffolds: Synergistic enhancement of mechanical properties and piezoresistivity

Lightweight conductive graphene@polyurethane (PU) sponge with unique 3D structure and prominent piezoresistivity is a promising candidate for highly sensitive pressure sensor. However, the poor mechanical properties of PU skeleton and the use of toxic reductant for the reduction of graphene oxide (GO) greatly hampered its large-scale application. Here, we demonstrated for the first time that aramid nanofibers (ANFs) can be used as desirable building blocks to endow the layer-by-layer (LBL) assembled GO@PU nanocomposites with excellent mechanical properties. At the same time, the potassium hydroxide existed in ANFs solution could in-situ reduce the GO without extra reductants. The as-prepared rGO@PU/ANFs conductive nanocomposites exhibited excellent piezoresistive sensitivity and repeatability, enabling the nanocomposites to serve as flexible sensors for the application of human motions monitoring. This work opens up new opportunity for the facile fabrication of high performance graphene-based piezoresistive sensors and other electronic devices.

Fabrication and characterization of 3D-printed elastic auricular scaffolds: A pilot study.

Aesthetic reconstruction of the external ear is challenging due to the complex anatomical shape of the auricle. Recently, artificial scaffolds such as Medpor (Stryker, Kalamasoo, MI, USA) have become widely used in ear reconstruction. However, the Medpor scaffold is stiffer than the natural ear, which may lead to discomfort, and moreover has uniform design for every patient. In this study, we investigated whether three-dimensional (3D)-printed artificial polyurethane (PU) scaffolds are suitable for auricular reconstruction. PU scaffolds were fabricated using 3D printing according to a design derived from a digital imaging and communications in medicine (DICOM) image of the human auricle. The microstructure of the scaffolds was observed using scanning electron microscopy, and the porosity was examined. Cell proliferation on the scaffolds was assessed in vitro using tonsil-derived mesenchymal stem cells to evaluate the biocompatibility of the scaffolds. The scaffolds were implanted in C57BL/6 mice, and histological analysis was performed. The structural study revealed that the 3D-printed porous PU scaffolds have rectangular microstructure with regular pitch and line, as well as high porosity (56.46% ± 10.22%) with a pore diameter of 200 µm. The mechanical properties of the 3D-printed PU scaffolds were similar to those of the human auricle cartilage. Cell proliferation on the PU scaffolds was greater than that on Medpor scaffolds. Histological evaluation demonstrated that the porous parts of the PU scaffolds became filled with collagen and vascular tissue. Elastic, porous PU scaffolds can be obtained using 3D printing, have biomechanical properties similar to those of the natural ear, and are suitable for use in auricular reconstruction. NA Laryngoscope, 129:351-357, 2019.

Magnetically actuated graphene coated polyurethane foam as potential sorbent for oils and organics

Herein, we present Graphene-meso Iron Oxide composite incorporated Polyurethane foam (GPUF) as an elite sorbent for organic contaminants and oils. Anchoring Graphene-meso Iron Oxide composite switches Polyurethane foam to a super hydrophobic and super oleophilic moiety. Detailed structural, microscopic and wettability studies point the cooperative effect of the 3D porous polyurethane scaffold and the effect of Graphene-mesoporous Iron oxide composite on the adsorption dynamics. Benefitting from the hierarchical porous structure and heterogeneity, the as-fabricated sponge manifested superior selective adsorption capacity for a wide variety of oils and organic pollutants in the range 90–316 gg−1. Application of GPUF was demonstrated by the quick and selective removal of oils from water under magnetic field. In addition to this, the adsorbate can be released after sorption by simple squeezing without any deterioration in structure and performance, underlining the recyclability of the sorbent for over 150 cycles. Moreover, GPUF manifests appealing adsorption capacity in complex environments also. The results of the study promise a novel sorbent which can be easily scaled up for large scale treatment of oil spills.

Biocompatible Polyurethane Scaffolds Prepared from Glycerol Monostearate-Derived Polyester Polyol

Biodegradable polyester polyol was synthesized from oleochemical glycerol monostearate (GMS) and glutaric acid under a non-catalyzed and solvent-free polycondensation method. The chemical structure of GMS-derived polyester polyol (GPP) was elucidated by FTIR, 1H and 13C NMR, and molecular weight of GPP was characterized by GPC. The synthesized GPP with acid value of 3.03 mg KOH/g sample, hydroxyl value of 115.72 mg KOH/g sample and Mn of 1345 g/mol was incorporated with polyethylene glycol (PEG) and polycaprolactone diol (PCL diol) to produce a water-blown porous polyurethane system via one-shot foaming method. The polyurethanes were optimized by evaluating glycerol as a crosslinker, silicone surfactant and water blowing agent on tensile properties of polyurethanes. All polyurethanes underwent structural change, and crystalline hard segments of polyurethanes were shifted to higher temperature suggested that hard segments undergone re-ordering process during enzymatic treatment. In terms of biocompatibility, polyurethane scaffold produced by reacting 100% w/w of GPP with isophorone diisocyanate and additives showed the highest cells viability of 3T3 mouse fibroblast (94%, day 1), and MG63 human osteosarcoma (107%, day 1) and better cell adhesion as compared to reference polyurethane produced by only PEG and PCL diol (3T3 cell viability: 8%; MG63 cell viability: 2%). The current work demonstrated GPP synthesized from renewable and environmental friendly resources produced polyurethanes that allows improvement in physico-chemical, mechanical and biocompatibility properties. By blending with increasing content of GPP, the water-blown porous polyurethane scaffold has shown great potential as biomaterial for soft and hard tissue engineering.

A 3D bioinspired highly porous polymeric scaffolding system for in vitro simulation of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma is an aggressive disease with an extremely low survival rate. This is due to the (i) poor prognosis and (ii) high resistance of the disease to current treatment options. The latter is partly due to the very complex and dense tissue/tumour microenvironment of pancreatic cancer, which contributes to the disease's progression and the inhibition of apoptotic pathways. Over the last years, advances in tissue engineering and the development of three-dimensional (3D) culture systems have shed more light into cancer research by enabling a more realistic recapitulation of the niches and structure of the tumour microenvironment. Herein, for the first time, 3D porous polyurethane scaffolds were fabricated and coated with fibronectin to mimic features of the structure and extracellular matrix present in the pancreatic cancer tumour microenvironment. The developed 3D scaffold could support the proliferation of the pancreatic tumour cells, which was enhanced with the presence of fibronectin, for a month, which is a significantly prolonged in vitro culturing duration. Furthermore, in situ imaging of cellular and biomarker distribution showed the formation of dense cellular masses, the production of collagen-I by the cells and the formation of environmental stress gradients (e.g. HIF-1α) with similar heterogeneity trends to the ones reported in in vivo studies. The results obtained in this study suggest that this bioinspired porous polyurethane based scaffold has great potential for in vitro high throughput studies of pancreatic cancer including drug and treatment screening.