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            Sacrificial strategy towards the formation of vascular‐like networks in volumetric tissue constructsAbstract The fields of tissue engineering and regenerative medicine have made astounding progress in recent years, evidenced by cutting‐edge 4D printing technologies, precise gene editing tools, and sustained long‐term functionality of engineered tissue grafts. Despite these fantastic feats, the clinical success of tissue‐engineered constructs so far remains limited to only those relatively simple types of tissues such as thin bilayer skin equivalents or avascular cartilage. On the other hand, volumetric tissues (larger than a few millimeters in all dimensions), which are highly desirable for clinical utility, suffer from poor oxygen supply due to limited dimensional diffusion. Notably, large, complex tissues typically require a vascular network to supply the growing cells with nutrients for metabolic demands to prolong viability and support tissue formation. In recognition, extensive efforts have been made to create vascular‐like networks in order to facilitate mass exchange through volumetric scaffolds. This review underlines the urgent need for continued research to create more complex and functional vascular networks, which is crucial for generating viable volumetric tissues, and highlights the recent advances in sacrificial template‐enabled formation of vascular‐like networks.more » « less
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            Abstract In search of effective therapeutics for breast cancers, establishing physiologically relevant in vitro models is of great benefit to facilitate the clinical translation. Despite extensive progresses, it remains to develop the tumor models maximally recapturing the key pathophysiological attributes of their native counterparts. Therefore, the current study aimed to develop a microsphere‐enabled modular approach toward the formation of in vitro breast tumor models with the capability of incorporating various selected cells while retaining spatial organization. Poly (lactic‐co‐glycolic acid) microspheres (150‐200 mm) with tailorable pore size and surface topography are fabricated and used as carriers to respectively lade with breast tumor‐associated cells. Culture of cell‐laden microspheres assembled within a customized microfluidic chamber allowed to form 3D tumor models with spatially controlled cell distribution. The introduction of endothelial cell‐laden microspheres into cancer‐cell laden microspheres at different ratios would induce angiogenesis within the culture to yield vascularized tumor. Evaluation of anticancer drugs such as doxorubicin and Cediranib on the tumor models do demonstrate corresponding physiological responses. Clearly, with the ability to modulate microsphere morphology, cell composition and spatial distribution, microsphere‐enabled 3D tumor tissue formation offers a high flexibility to satisfy the needs for pathophysiological study, anticancer drug screening or design of personalized treatment.more » « less
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            Abstract Porous noble metal nanoparticles have received particular attention recently for their unique optical, thermal, and catalytic functions in biomedicine. However, limited progress has been made to synthesize such porous metallic nanostructures with large mesopores (≥25 nm). Here, a green yet facile synthesis strategy using biocompatible liposomes as templates to mediate the formation of mesoporous metallic nanostructures in a controllable fashion is reported. Various monodispersed nanostructures with well‐defined mesoporous shape and large mesopores (≈ 40 nm) are successfully synthesized from mono‐ (Au, Pd, and Pt), bi‐ (AuPd, AuPt, AuRh, PtRh, and PdPt), and tri‐noble metals (AuPdRh, AuPtRh, and AuPdPt). Along with a successful demonstration of its effectiveness in synthesis of various mesoporous nanostructures, the possible mechanism of liposome‐guided formation of such nanostructures via time sectioning of the synthesis process (monitoring time‐resolved growth of mesoporous structures) and computational quantum molecular modeling (analyzing chemical interaction energy between metallic cations and liposomes at the enthalpy level) is also revealed. These mesoporous metallic nanostructures exhibit a strong photothermal effect in the near‐infrared region, effective catalytic activities in hydrogen peroxide decomposition reaction, and high drug loading capacity. Thus, the liposome‐templated method provides an inspiring and robust avenue to synthesize mesoporous noble metal‐based nanostructures for versatile biomedical applications.more » « less
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            We have been studying the complexation between cationic antimicrobials and polyanionic microgels to create self-defensive surfaces that responsively resist bacterial colonization. An essential property is the stable sequestration of the loaded (complexed) antimicrobial within the microgel under physiological ionic strength. Here we assess the complexation strength between poly(acrylic acid) [PAA] microgels and a series of cationic peptoids that display supramolecular structures ranging from an oligomeric monomer to a tetramer. We follow changes in loaded microgel diameter with increasing [Na+] as a measure of the counterion doping level. Consistent with prior findings on colistin/PAA complexation, we find that a monomeric peptoid is fully released at ionic strengths well below physiological conditions despite its +5 charge. In contrast, progressively higher degrees of peptoid supramolecular structure display progressively greater resistance to salting out, which we attribute to the greater entropic stability associated with the complexation of multimeric peptoid bundles.more » « less
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            Injuries to the peripheral nervous system are a common clinical issue, causing dysfunctions of the motor and sensory systems. Surgical interventions such as nerve autografting are necessary to repair damaged nerves. Even with autografting, i.e., the gold standard, malfunctioning and mismatches between the injured and donor nerves often lead to unwanted failure. Thus, there is an urgent need for a new intervention in clinical practice to achieve full functional recovery. Nerve guidance conduits (NGCs), providing physicochemical cues to guide neural regeneration, have great potential for the clinical regeneration of peripheral nerves. Typically, NGCs are tubular structures with various configurations to create a microenvironment that induces the oriented and accelerated growth of axons and promotes neuron cell migration and tissue maturation within the injured tissue. Once the native neural environment is better understood, ideal NGCs should maximally recapitulate those key physiological attributes for better neural regeneration. Indeed, NGC design has evolved from solely physical guidance to biochemical stimulation. NGC fabrication requires fundamental considerations of distinct nerve structures, the associated extracellular compositions (extracellular matrices, growth factors, and cytokines), cellular components, and advanced fabrication technologies that can mimic the structure and morphology of native extracellular matrices. Thus, this review mainly summarizes the recent advances in the state-of-the-art NGCs in terms of biomaterial innovations, structural design, and advanced fabrication technologies and provides an in-depth discussion of cellular responses (adhesion, spreading, and alignment) to such biomimetic cues for neural regeneration and repair.more » « less
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