Xiumei Wang

Bio: Xiumei Wang is an academic researcher from Tsinghua University. The author has contributed to research in topics: Stem cell & Bone regeneration. The author has an hindex of 7, co-authored 12 publications receiving 230 citations.

Injectable and Self-Healing Thermosensitive Magnetic Hydrogel for Asynchronous Control Release of Doxorubicin and Docetaxel to Treat Triple-Negative Breast Cancer

Abstract: Integration of two or more drugs into a multiagent delivery system has been considered to have profound impact on both in vitro and in vivo cancer treatment due to their efficient synergistic effect. This study presents a cheap and simple chitosan hydrogel cross-linked with telechelic difunctional poly(ethylene glycol) (DF-PEG-DF) for synthesis of an injectable and self-healing thermosensitive dual-drug-loaded magnetic hydrogel (DDMH), which contains both doxorubicin (DOX) and docetaxel (DTX) for chemotherapy and iron oxide for magnetic hyperthermia induced stimuli responsive drug release. The as-prepared DDMH not only have good biocompatibility but also exhibit unique self-healing, injectable, asynchronous control release properties. Meanwhile, it shows an excellent magnetic field responsive heat-inducing property, which means that DDMH will produce a large amount of heat to control the surrounding temperature under the alternative magnetic field (AMF). A remarkably improved synergistic effect to triple ...

Neural tissue engineering: the influence of scaffold surface topography and extracellular matrix microenvironment

Abstract: During nervous system development, an extracellular matrix (ECM) plays a pivotal role through surface topography and microenvironment signals in neurons and neurites maturation. Topography and microenvironment signals act as physical and chemical guiding cues, respectively, for neural tissue formation and reconstruction. Imposed surface topography can affect neural stem cells by promoting adhesion, spreading, alignment, morphological changes, and specific gene expression. Therefore, fabrication of a biomimetic construct or scaffold to support neurite outgrowth and axon extension is a crucial and common strategy for neural tissue regeneration. Here, we review recent developments in biomaterials modification for simulating the microenvironment to promote neural cell adhesion and growth. The subtopics include those of potential cellular mechanisms of topographical response, topography on cellular organization and function, contact guidance in neurite outgrowth and axon growth, ECM microenvironment as regulatory cues, as well as challenges and future perspectives of nerve conduits that are now in clinical trials and usage.

An Antimicrobial Peptide-Loaded Gelatin/Chitosan Nanofibrous Membrane Fabricated by Sequential Layer-by-Layer Electrospinning and Electrospraying Techniques.

Abstract: Guided bone regeneration (GBR) technique is widely used in the treatment of bone defects caused by peri-implantitis, periodontal disease, etc. However, the GBR membranes commonly used in clinical treatments currently have no antibacterial activity. Therefore, in this study, sequential layer-by-layer electrospinning and electrospraying techniques were utilized to prepare a gelatin (Gln) and chitosan (CS) composite GBR membrane containing hydroxyapatite nanoparticles (nHAp) and antimicrobial peptide (Pac-525)-loaded PLGA microspheres (AMP@PLGA-MS), which was supposed to have osteogenic and antibacterial activities. The scanning electron microscope (SEM) observation showed that the morphology of the nanofibers and microspheres could be successfully produced. The diameters of the electrospun fibers with and without nHAp were 359 ± 174 nm and 409 ± 197 nm, respectively, and the mechanical properties of the membrane were measured according to the tensile stress-strain curve. Both the involvement of nHAp and the chemical crosslinking were able to enhance their tensile strength. In vitro cell culture of rat bone marrow mesenchymal stem cells (rBMSCs) indicated that the Gln/CS composite membrane had an ideal biocompatibility with good cell adhesion, spreading, and proliferation. In addition, the Gln/CS membrane containing nHAp could promote osteogenic differentiation of rBMSCs. Furthermore, according to the in vitro drug release assay and antibacterial experiments, the composite GBR membrane containing AMP@PLGA-MS exhibited a long-term sustained release of Pac-525, which had bactericidal activity within one week and antibacterial activity for up to one month against two kinds of bacteria, S. aureus and E. coli. Our results suggest that the antimicrobial peptide-loaded Gln/CS composite membrane (AMP@PLGA-MS@Gln/CS/nHAp) has a great promise in bone generation-related applications for the unique functions of guiding bone regeneration and inhibiting bacterial infection as well.

Manganese-Based Magnetic Layered Double Hydroxide Nanoparticle: A pH-Sensitive and Concurrently Enhanced T1/T2-Weighted Dual-Mode Magnetic Resonance Imaging Contrast Agent.

Abstract: The interference effect and lack of selectivity are the bottlenecks for dual-mode magnetic resonance imaging (MRI) contrast agent development. To address these challenges and overcome the single mode imaging contrast limitations, a novel MgMnAl-layered double hydroxide@iron oxide nanoparticle (MgMnAl-LDH@IO NP) has been successfully synthesized as a concurrently enhanced dual-mode contrast agent for MRI of tumor tissues with sensitive pH response and high efficacy. The attachment of iron oxide nanoparticles on the surface of MgMnAl-LDH NPs led to the increased local magnetic field intensity, inducing the concurrent enhancement of both T1 and T2 relaxivity. The in vitro MRI demonstrated that the MgMnAl-LDH@IO NP could act as a pH-sensitive contrast agent for both T1- and T2-weighted MR imaging (r1, 5.67 mM-1 s-1 under pH 5.0 and 1.98 mM-1 s-1 under pH 7.4; r2, 369.12 mM-1 s-1 under pH 5.0 and 225.29 mM-1 s-1 under pH 7.4). The biocompatibility of the dual-mode contrast agent was revealed by the cytotoxicity test on fibroblast cells. Further in vivo dual-mode MR imaging exhibited that the MgMnAl-LDH@IO NP showed clear T1- and T2-weighted MR imaging of tumor tissues in breast-tumor-bearing mice. The facile synthetic method, desirable biocompatibility, sensitive stimuli response, and concurrently enhanced T1/T2 MRI signals both in vitro and in vivo encourage the great potential biomedical and clinical applications of MgMnAl-LDH@IO NP in MR imaging with improved accuracy.

Mesenchymal Stem Cell-Laden Hydrogel Microfibers for Promoting Nerve Fiber Regeneration in Long-Distance Spinal Cord Transection Injury.

Abstract: Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration, and differentiation of stem cells after implantation represent major challenges toward the clinical deployment of this approach. In this study, we fabricated three-dimensional MSC-laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior, and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSC carrier though a rotating method and the aligned fiber structure induced the MSC-aligned adhesion on the surface of the hydrogel to form microscale cell fibers. The MSC-laden microfiber implantation enhanced the donor MSC neural differentiation, encouraged the migration of host neurons into the injury gap and significantly promoted nerve fiber regeneration across the injury site. Abundant GAP-43- and NF-positive nerve fibers were observed to regenerate in the caudal, rostral, and middle sites of the injury position 8 weeks after the surgery. The NF fiber density reached to 29 ± 6 per 0.25 mm2 at the middle site, 82 ± 13 per 0.25 mm2 at the adjacent caudal site, and 70 ± 23 at the adjacent rostral site. Similarly, motor axons labeled with 5-hydroxytryptamine were significantly regenerated in the injury gap, which was 122 ± 22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSC-laden microfibers significantly improved electrophysiological expression and re-established limb motor function. These findings highlight the combination of MSCs with microhydrogel fibers, the use of which may become a promising method for MSC implantation and SCI repair.

Materials design for bone-tissue engineering

Abstract: Successful materials design for bone-tissue engineering requires an understanding of the composition and structure of native bone tissue, as well as appropriate selection of biomimetic natural or tunable synthetic materials (biomaterials), such as polymers, bioceramics, metals and composites. Scalable fabrication technologies that enable control over construct architecture at multiple length scales, including three-dimensional printing and electric-field-assisted techniques, can then be employed to process these biomaterials into suitable forms for bone-tissue engineering. In this Review, we provide an overview of materials-design considerations for bone-tissue-engineering applications in both disease modelling and treatment of injuries and disease in humans. We outline the materials-design pathway from implementation strategy through selection of materials and fabrication methods to evaluation. Finally, we discuss unmet needs and current challenges in the development of ideal materials for bone-tissue regeneration and highlight emerging strategies in the field. Design of bone-tissue-engineering materials involves consideration of multiple, often conflicting, requirements. This Review discusses these considerations and highlights scalable technologies that can fabricate natural and synthetic biomaterials (polymers, bioceramics, metals and composites) into forms suitable for bone-tissue-engineering applications in human therapies and disease models.

Toward Stimuli-Responsive Dynamic Thermosets through Continuous Development and Improvements in Covalent Adaptable Networks (CANs)

Abstract: Covalent adaptable networks (CANs), unlike typical thermosets or other covalently crosslinked networks, possess a unique, often dormant ability to activate one or more forms of stimuli-responsive, dynamic covalent chemistries as a means to transition their behavior from that of a viscoelastic solid to a material with fluid-like plastic flow. Upon application of a stimulus, such as light or other irradiation, temperature, or even a distinct chemical signal, the CAN responds by transforming to a state of temporal plasticity through activation of either reversible addition or reversible bond exchange, either of which allows the material to essentially re-equilibrate to an altered set of conditions that are distinct from those in which the original covalently crosslinked network is formed, often simultaneously enabling a new and distinct shape, function, and characteristics. As such, CANs span the divide between thermosets and thermoplastics, thus offering unprecedented possibilities for innovation in polymer and materials science. Without attempting to comprehensively review the literature, recent developments in CANs are discussed here with an emphasis on the most effective dynamic chemistries that render these materials to be stimuli responsive, enabling features that make CANs more broadly applicable.

Stimuli-Responsive Biomolecule-Based Hydrogels and Their Applications

Abstract: This Review presents polysaccharides, oligosaccharides, nucleic acids, peptides, and proteins as functional stimuli-responsive polymer scaffolds that yield hydrogels with controlled stiffness. Different physical or chemical triggers can be used to structurally reconfigure the crosslinking units and control the stiffness of the hydrogels. The integration of stimuli-responsive supramolecular complexes and stimuli-responsive biomolecular units as crosslinkers leads to hybrid hydrogels undergoing reversible triggered transitions across different stiffness states. Different applications of stimuli-responsive biomolecule-based hydrogels are discussed. The assembly of stimuli-responsive biomolecule-based hydrogel films on surfaces and their applications are discussed. The coating of drug-loaded nanoparticles with stimuli-responsive hydrogels for controlled drug release is also presented.