Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

The 3D printed conductive grooved topography hydrogel combined with electrical stimulation for synergistically enhancing wound healing of dermal fibroblast cells.

Patients with extensive cutaneous damage resulting from poor wound healing often have other comorbidities such as diabetes that may lead to impaired skin functions and scar formation. Many recent studies have shown that the application of electrical stimulation (ES) to cutaneous lesions significantly improves skin regeneration via activation of AKT intracellular signaling cascades and secretion of regeneration-related growth factors. In this study, we fabricated varying concentrations of gelatin-methacrylate (GelMa) hydrogels with poly(3,4-ethylenedioxythiophene) (PEDOT): polystyrene sulfonate (PSS), which is a conductive material commonly used in tissue engineering due to its efficiency among conductive thermo-elastic materials. The results showed successful modification of PEDOT:PSS with GelMa while retaining the original structural characteristics of the GelMa hydrogels. In addition, the incorporation of PEDOT:PSS increased the interactions between both the materials, thus leading to enhanced mechanical strength, improved swelling ratio, and decreased hydrophilicity of the scaffolds. Our GelMa/PEDOT:PSS scaffolds were designed to have micro-grooves on the surfaces of the scaffolds for the purpose of directional guiding. In addition, our scaffolds were shown to have excellent electrical conductivity, thus leading to enhanced cellular proliferation and directional migration and orientation of human dermal fibroblasts. In vivo studies revealed that the GelMa/PEDOT:PSS scaffolds with electrical stimulation were able to induce full skin thickness regeneration, as seen from the various stainings. These results indicate the potential of GelMa/PEDOT:PSS as an electro-conductive biomaterial for future skin regeneration applications.

The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration.

The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration.

Higher DHEAS Levels Associated with Long-Term Practicing of Tai Chi.

Tai Chi has many benefits for middle-aged/older individuals including improvements to muscle strength and various body lipid components. DHEAS and testosterone have anti-obesity/anti-aging characteristics and also improve libido, vitality and immunity levels. Thus, the aim of the present study was to investigate the differences between middle-aged Tai Chi practitioners (n = 17) and sedentary individuals (n = 17) in terms of leg strength, blood levels of cholesterol, triglyceride, HDL, as well as DHEAS, testosterone and cortisol. Unpaired t-tests were used to identify significant differences between the two groups. There were no significant differences in body composition, leg strength, blood lipid components and testosterone. However, the Tai Chi practitioners had higher levels of DHEAS (P < 0.01) and lower levels of cortisol (P < 0.05). Thus, Tai Chi practitioners have a higher ratio of DHEAS to cortisol, which might have potential benefits in terms of improving an individual's health-related quality of life during the aging.

A facile approach toward protein-resistant biointerfaces based on photodefinable poly-p-xylylene coating.

A facile and versatile tool is reported that uses a photodefinable polymer, poly(4-benzoyl-p-xylylene-co-p-xylylene) to immobilize antifouling materials, such as poly(ethylene glycol), poly(ethylene glycol) methyl ether methacrylate, dextran, and ethanolamine. This immobilization process requires the polymer's photoactivated carbonyl groups, which can facilitate light-induced molecular crosslinking and can rapidly react via insertion into CH or NH bonds upon photo-illumination at 365 nm. Importantly, the process does not require additional functional groups on the antifouling materials. The immobilized fouling materials were characterized using X-ray photoelectron spectroscopy (XPS) and infrared reflection absorption spectroscopy (IRRAS), and the resulting antifouling properties were examined through protein adsorption studies on fibrinogen and bovine serum albumin at surfaces that were spatially modified using a photomask during the photochemical process. In addition, the adsorbed fibrinogen was quantitatively analyzed using a quartz crystal microbalance (QCM), and the adsorption values were reduced to 32.8 ± 4.9 ng cm(-2), 5.5 ± 3.9 ng cm(-2), 21.4 ± 4.5 ng cm(-2), and 16.9 ± 3.4 ng cm(-2) for poly(ethylene glycol) (PEG), poly(ethylene glycol) methyl ether methacrylate (PEGMA), dextran, and ethanolamine, respectively. Finally, this antifouling modification technology was demonstrated on an unconventional substrate for a stent that was modified by PEGMA at selected areas using a microscopic patterning technique during photoimmobilization. Low levels of fibrinogen and BSA adsorption were also observed at the areas where PEGMA was attached.

Compatibility balanced antibacterial modification based on vapor-deposited parylene coatings for biomaterials.

Advanced antibacterial surfaces are designed based on covalently attached antibacterial agents, avoiding potential side effects associated with overdosed or eluted agents. The technique is widely applicable regardless of the underlying substrate material. In addition, antibacterial surfaces are effective against the early stages of bacterial adhesion and can significantly reduce the formation of biofilm, without compromising biocompatibility. Here, this concept was realized by employing a benzoyl-functionalized parylene coating. The antibacterial agent chlorhexidine was used as a proof of concept. Chlorhexidine was immobilized by reaction with photoactivated benzoyl-functionalized surfaces, including titanium alloy, stainless steel, polyether ether ketone, polymethyl methacrylate, and polystyrene. A low concentration of chlorhexidine (1.4 ± 0.08 nmol cm-2) covalently bound to surfaces rendered them sufficiently resistant to an Enterobacter cloacae inoculum and its adherent biofilm. Compared to unmodified surfaces, up to a 30-fold reduction in bacterial attachment was achieved with this coating technology. The immobilization of chlorhexidine was verified with infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS), and a leaching test was performed to confirm that the chlorhexidine molecules were not dislodged. Cell compatibility was examined by culturing fibroblasts and osteoblasts on the modified surfaces, revealing greater than 93% cell viability. This coating technology may be broadly applicable for a wide range of other antibacterial agents and allow the design of new biomaterials.

Synthesis of boron-containing primary amines.

In this study, boron-containing primary amines were synthesized for use as building blocks in the study of peptoids. In the first step, Gabriel synthesis conditions were modified to enable the construction of seven different aminomethylphenyl boronate esters in good to excellent yields. These compounds were further utilized to build peptoid analogs via an Ugi four-component reaction (Ugi-4CR) under microwave irradiation. The prepared Ugi-4CR boronate esters were then successfully converted to the corresponding boronic acids. Finally, the peptoid structures were successfully modified by cross-coupling to aryl/heteroaryl chlorides via a palladium-mediated Suzuki coupling reaction to yield the corresponding derivatives in moderate to good yields.

Vapor-based tri-functional coatings.

The tri-functional coating synthesized via CVD copolymerization is comprised of distinguished anchoring sites of acetylene, maleimide, and ketone that can synergically undergo specific conjugation reactions to render surfaces with distinct biological functions, simultaneously. In addition, these tri-functional coatings can be fabricated in a micro-structured fashion on non-conventional surfaces.