Development of an In Situ Photo-Crosslinking Antimicrobial Collagen Hydrogel for the Treatment of Infected Wounds.

Antimicrobial hydrogels have received considerable attention in the treatment of bacteria-infected wounds. Herein, we develop a neutral, soluble collagen via modification with maleic anhydride, serving as a hydrogel precursor. Maleic anhydride-modified collagen (ColME) could form a gel after exposure to UV light and be loaded with the antimicrobial agents, nisin and levofloxacin, to acquire antimicrobial ability. The ColME hydrogel containing nisin and levofloxacin had good cytocompatibility and effectively killed pathogenic bacterial strains, such as Escherichia coli and Staphylococcus aureus. The antimicrobial ColME hydrogels effectively supported the healing of a full-thickness skin wound infected with S. aureus in a mouse model. Our results demonstrate the potential of antimicrobial hydrogels as effective wound dressings via in situ photogelation for the healing of infected wounds.

Fabrication of Transparent PEGylated Antifouling Coatings via One-Step Pyrogallol Deposition.

Antifouling coatings are critical for many biomedical devices. A simple and universal technique used to anchor antifouling polymers is important in order to expand its applications. In this study, we introduced the pyrogallol (PG)-assisted immobilization of poly(ethylene glycol) (PEG) to deposit a thin antifouling layer on biomaterials. Briefly, biomaterials were soaked in a PG/PEG solution and PEG was immobilized onto the biomaterial surfaces via PG polymerization and deposition. The kinetics of PG/PEG deposition started with the deposition of PG on the substrates, followed by the addition of a PEG-rich adlayer. However, prolonged coating added a top-most PG-rich layer, which deteriorated the antifouling efficacy. By controlling the amounts of PG and PEG and the coating time, the PG/PEG coating was able to reduce more than 99% of the adhesion of L929 cells and the adsorption of fibrinogen. The ultrathin (tens of nanometers) and smooth PG/PEG coating was easily deposited onto a wide variety of biomaterials, and the deposition was robust enough to survive harsh sterilization conditions. Furthermore, the coating was highly transparent and allowed most of the UV and Vis light to pass through. The technique has great potential to be applied to biomedical devices that need a transparent antifouling coating, such as intraocular lenses and biosensors.

The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel.

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-ß3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type channel subunit CaV1.2 (CACNA1C) and Serca2 pump (ATP2A2) genes, and their balance was kept more stable. Due to the lower susceptibility to mechanical load, BMMSCs in CS-Tyr/Gel hydrogel may have an advantage over chondrocytes in application for cartilage regeneration purposes. The mechanical overload related cartilage damage in vivo and the vague regenerative processes of OA chondrocytes might be associated to the inefficient control of iCa2+ regulating channels.

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.

The Impact of Polyethylene Glycol-Modified Chitosan Scaffolds on the Proliferation and Differentiation of Osteoblasts.

The objective of this study was to investigate the influence of polyethylene glycol (PEG) incorporated chitosan scaffolds on osteoblasts proliferation and differentiation. The chitosan polymer was initially modified by the predetermined concentration of the photoreactive azido group for UV-crosslinking and with RGD peptides (N-acetyl-GRGDSPGYG-amide). The PEG was mixed at different ratios (0, 10, and 20 wt%) with modified chitosan in 96-well tissue culture polystyrene plates to prepare CHI-100, CHI-90, and CHI-80 scaffolds. PEG-containing scaffolds exhibited bigger pore size and higher water content compared to unmodified chitosan scaffolds. After 10 days of incubation, the cell number of CHI-90 (1.1 × 106 cells/scaffold) surpasses that of CHI-100 (9.2 × 105 cells/scaffold) and the cell number of CHI-80 (7.6 × 105 cells/scaffold) were significantly lower. The ALP activity of CHI-90 was the highest on the fifth day indicating the favored osteoblasts' early-stage differentiation. Moreover, after 14 days of osteogenic culture, calcium deposition in the CHI-90 scaffolds (2.7 µmol Ca/scaffold) was significantly higher than the control (2.2 µmol Ca/scaffold) whereas on CHI-80 was 1.9 µmol/scaffold. The results demonstrate that PEG-incorporated chitosan scaffolds favored osteoblasts proliferation and differentiation; however, mixing relatively excess PEG (≥20% wt.) had a negative impact on osteoblasts proliferation and differentiation.

Polycarboxybetaine-Based Hydrogels for the Capture and Release of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are indicators for the detection, diagnosis, and monitoring of cancers and offer biological information for the development of personalized medicine. Techniques for the specific capture and non-destructive release of CTCs from millions of blood cells remain highly desirable. Here, we present a CTC capture-and-release system using a disulfide-containing poly(carboxybetaine methacrylate) (pCB) hydrogel. The non-fouling characteristic of pCB prevents unwanted, nonspecific cell binding, while the carboxyl functionality of pCB is used for the conjugation of anti-epithelial cell adhesion molecule (anti-EpCAM) antibodies for the capture of CTCs. The results demonstrated that the anti-EpCAM-conjugated pCB hydrogel captured HCT116 cells from blood, and the capture ratio reached 45%. Furthermore, the captured HCT116 cells were released within 30 min from the dissolution of the pCB hydrogel by adding cysteine, which breaks the disulfide bonds of the crosslinkers. The cells released were viable and able to grow. Our system has potential in the development of a device for CTC diagnosis.

Fabrication of Polysulfobetaine Gradient Coating via Oxidation Polymerization of Pyrogallol To Modulate Biointerfaces.

A surface with a gradient physical or chemical feature, such as roughness, hardness, wettability, and chemistry, serves as a powerful platform for high-throughput investigation of cell responses to a biointerface. In this work, we developed a continuous antifouling gradient surface using pyrogallol (PG) chemistry. A copolymer of a zwitterionic monomer, sulfobetaine methacrylate, and an amino monomer, aminoethyl methacrylate, were synthesized (pSBAE) and deposited on glass slides via the deposition of self-polymerized PG. A gradient of pSBAE was fabricated on glass slides in 7 min in the presence of an oxidant, ammonium persulfate, by withdrawing the reaction solution. The modified glass slide showed a wettability gradient, determined by measuring the water contact angle. Cell adhesion and protein adsorption were well correlated with surface wettability. We expect that this simple and faster method for the fabrication of a continuous chemical gradient is applicable for high-throughput screening of surface properties to modulate biointerfaces.

Fabrication of Low-Fouling Surfaces on Alkyne-Functionalized Poly-(p-xylylenes) Using Click Chemistry.

A facial, versatile, and universal method that breaks the substrate limits is desirable for antifouling treatment. Thin films of functional poly-p-xylylenes (PPX) that are deposited using chemical vapor deposition (CVD) provide a powerful platform for surface immobilization of molecules. In this study, we prepared an alkyne-functionalized PPX coating on which poly (sulfobetaine methacrylate-co-Az) could be conjugated via click chemistry. We found that the conjugated polymers were very stable and inhibited cell adhesion and protein adsorption effectively. The same conjugation strategy could also be applied to conjugate azide-containing poly (ethylene glycol) and poly (NIPAAm). The results indicate that our method provides a simple and robust tool for fabricating antifouling surfaces on a wide range of substrates using CVD technology of functionalized poly (p-xylylenes) for biosensor, diagnostics, immunoassay, and other biomaterial applications.

One-step electrochemical deposition of antifouling polymers with pyrogallol for biosensing applications.

Electrochemical techniques are highly sensitive and label-free sensing methods for the detection of various biomarkers, toxins, or pathogens. An ideal sensing element should be electroconductive, nonfouling, and readily available for conjugation of ligands. In this work, we have developed a facile, one-step electrodeposition method based on pyrogallol polymerization for preparation of a nonfouling and biotinylated surface on indium tin oxide (ITO). A copolymer of sulfobetaine methacrylate and aminoethyl methacrylate (pSBAE) was synthesized and deposited on ITO in the presence of pyrogallol via cyclic voltammetry. The deposition took less than 15 minutes to sufficiently inhibit cell adhesion. Using biotinylated pSBAE, the modified surface resisted nonspecific protein adsorption from the fetal bovine serum solution and detected added avidin concentrations. The results show an efficient platform to fabricate an electrochemical biosensor for the detection of biomarkers. We expect that this facile one-step technology could be applied to conjugate various biosensing elements for nonfouling biosensors.

Conjugation of Polysulfobetaine via Poly(pyrogallol) Coatings for Improving the Antifouling Efficacy of Biomaterials.

Antifouling treatment is critical to certain biomedical devices for their functions and patients' life. Facial, versatile, and universal coating methods to conjugate antifouling materials on a wide variety of biomaterials are beneficial for the fabrication of low-fouling biomedical devices. We developed a simple one-step coating method for surface conjugation of zwitterionic poly(sulfobetaine) via deposition of self-polymerized pyrogallol (PG). Poly(pyrogallol) could deposit copolymers of sulfobetaine methacrylate and aminoethyl methacrylate (pSBAE) on various biomaterials. pSBAE coatings inhibited as high as 99.8% of the adhesion of L929 cells and reduced protein adsorption significantly. The resistance against L929 cell adhesion was increased with increasing coating time and was positively correlated with the surface hydrophilicity and film thickness. Such a coating was robust to resist harsh sterilization conditions and stable for long-term storage in phosphate-buffered saline. We expect that the simple low-fouling pSBAE coating is applicable to the manufacture of medical devices.

Harnessing the perinuclear actin cap (pnAC) to influence nanocarrier trafficking and gene transfection efficiency in skeletal myoblasts using nanopillars.

Gene transfection is important in biotechnology and is used to modify cells intrinsically. It can be conducted in cell suspension or after cell adhesion, where the efficiency is dependent on many factors such as the type of nanocarrier used and cell division processes. Anchor-dependent cells are sensitive to the substrate they are attached to and adapt their behavior accordingly, including plasmid trafficking during gene transfection. Previously, it was shown in our group that the cytoskeleton is an essential factor in influencing gene transfection in skeletal myoblasts using nanogrooves as a substrate. In this study, the effect of the cytoskeleton on gene transfection efficiency of skeletal myoblasts was studied using various nanopillars and nanocarriers. Nanopillars with different diameters (200-1000 nm) and depths (200 or 400 nm) were fabricated using colloidal self-assembly and reactive ion etching. All surfaces were treated with oxygen plasma or polydopamine (PD) to further control cell morphology. Plasmid DNA was delivered into cells using jetPRIME or Lipofectamine 3000 nanocarriers. After screening hundreds of images, two distinguishable F-actin distributions were found, i.e., cells with or without a perinuclear actin cap (pnAC). Cells attached to nanopillars, especially the deep pillars, had a smaller spreading area, shorter F-actin, more 3D-like cell nuclei, and a lower percentage of pnAC, which lead to a higher gene transfection efficiency using jetPRIME. On the other hand, cells attached to the shallow nanopillars or flat surfaces had a larger spreading area, longer F-actin, more 2D-like cell nuclei, and a higher percentage of pnAC that facilitates gene transfection using Lipofectamine. The effects of cell density, cytoskeleton (cytoD), and focal adhesions (RGD) on gene transfection were also studied, and the results were consistent with our hypothesis that F-actin distribution is one of the critical factors in gene transfection. In conclusion, pnAC plays a vital role in the intracellular trafficking of nanocarrier/plasmid complexes and this study provides new insights into gene transfection in anchor-dependent cells. STATEMENT OF SIGNIFICANCE: This study provides a new perspective in gene transfection using attached cells where perinuclear actin cap (pnAC) is an essential factor involved in transfection efficiency. A series of nanopillars were used to harness cell and cytoskeleton morphology. Two distinguishable cytoskeletal structures were found including cells with or without pnAC. 2D-like cells with pnAC facilitate gene delivery using liposome-based nanocarriers, while 3D-like cells without pnAC benefit gene delivery using cationic polymer-based nanocarriers. This study reveals the importance of the cytoskeleton during gene transfection that is beneficial in tissue transfection.

Aminomalononitrile-Assisted Multifunctional Antibacterial Coatings.

Medical device associated infections remain a significant problem for all classes of devices at this point in time. Here, we have developed a surface modification technique to fabricate multifunctional coatings that combine antifouling and antimicrobial properties. Zwitterionic polymers providing antifouling properties and quaternary ammonium containing polymers providing antimicrobial properties were combined in these coatings. Throughout this study, aminomalononitrile (AMN) was used to achieve one-step coatings incorporating different polymers. The characterization of coatings was carried out using static water contact angle (WCA) measurements, X-ray photoelectron spectroscopy (XPS), profilometry, and scanning electron microscopy (SEM), whereas the biological response in vitro was analyzed using Staphylococcus epidermidis and Escherichia coli as well as L929 fibroblast cells. Zwitterionic polymers synthesized from sulfobetaine methacrylate and 2-aminoethyl methacrylate were demonstrated to reduce bacterial attachment when incorporated in AMN assisted coatings. However, bacteria in suspension were not affected by this approach. On the other hand, alkylated polyethylenimine polymers, synthesized to provide quaternary ammonium groups, were demonstrated to have contact killing properties when incorporated in AMN assisted coatings. However, the high bacterial attachment observed on these surfaces may be detrimental in applications requiring longer-term bactericidal activity. Therefore, AMN-assisted coatings containing both quaternary and zwitterionic polymers were fabricated. These multifunctional coatings were demonstrated to significantly reduce the number of live bacteria not only on the modified surfaces, but also in suspension. This approach is expected to be of interest in a range of biomedical device applications.

Modulation of Neural Differentiation through Submicron-Grooved Topography Surface with Modified Polydopamine.

Surface topography and bioactive molecules can generate physicochemical cues that control proliferation and differentiation of neural cells. In this study, polystyrene (PS) submicron-patterns with different widths (400 and 800 nm) and depths (100 and 400 nm) were prepared and subsequently modified with polydopamine (PDA) by a coating method. We examined neurites of PC12 cells and human adipose-derived stem cells (hADSCs) incubated in neuronal induction medium containing nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), respectively. Then the differentiated cells on different grooved topographies were immunologically stained by Tuj-1 (a neuron marker) to compare the extent of neuronal differentiation. Our results showed that PC12 cells on grooved topography have predominantly bipolar neurite extension and align along the direction of the patterns, while flat surface has multipolar neurites. We demonstrated that the depths of topography have a strong impact on neurite outgrowth and alignment. In terms of the number of neurites, neurite length, and percentage of Tuj-1 positive cells, the 400/400 and 800/400 nm (widths/depths) PS grooves are appropriate for the cultivations of PC12 cells and hADSCs relative to those of other groups. In conclusion, the submicron-grooved topography and neurotrophic growth factors supported neurites outgrown and differentiated into neuron-like cells.

One-Step Aminomalononitrile-Based Coatings Containing Zwitterionic Copolymers for the Reduction of Biofouling and the Foreign Body Response.

Many biomedical devices benefit from antibiofouling coatings, which can reduce biointerfacial interactions such as protein adsorption and cell attachment. In this study, we synthesized zwitterionic copolymers consisting of sulfobetaine methacrylate (SB) and 2-aminoethyl methacrylate (AE) via free radical polymerization and combined these copolymers in solution with aminomalononitrile to form zwitterionic coatings in an autopolymerization process. The successful deposition of coatings containing different SB/AE ratios was demonstrated by X-ray photoelectron spectroscopy. The one-step surface modification process was carried out on polydimethylsiloxane (PDMS), tissue culture polystyrene, and gold substrates, demonstrating that this method can be transferred to different substrate materials. The ability of optimized coatings to reduce serum protein adsorption was demonstrated by quartz crystal microbalance measurements while the ability to resist cell attachment for 24 h was demonstrated using L929 mouse fibroblasts. The stability of the coatings under physiological conditions was investigated, and resistance to cell attachment was maintained over a period of 45 days. Furthermore, the resistance of the copolymer coating to cell attachment was maintained after both ethylene oxide sterilization and autoclaving. Finally, copolymer-modified PDMS samples were investigated with regard to their ability to reduce the foreign body response in vivo. Here, a significant reduction in the capsule thickness (approximately 50%) was observed in nude mice after 2 and 4 weeks. It is expected that the one-step, facile, and versatile surface modification strategy discussed here will find applications in biomedical devices.

Modification and crosslinking of gelatin-based biomaterials as tissue adhesives.

Tissue adhesives have been developed to overcome the difficulties of conventional wound closure techniques (e.g. sutures and staples), such as the potential for collateral damage and difficulty of stopping body fluid and gas. At the same time, it provides advantages such as simpler implementation, less painful, and does not require removal. However, representative adhesives such as cyanoacrylates and fibrin glues are plagued by cytotoxicity and low adhesion. In this study, we choose instead gelatin as the backbone of adhesive, due to its biocompatibility, biodegradability, and low cost. Firstly, catechol-modified gelatin and phenol-modified gelatin were synthesized via an EDC/NHS chemistry. Then, gelatin-based adhesives were prepared via ruthenium-based photochemistry, including photo-crosslinked gelatin (PG), phenol-modified gelatin (PPG), and catechol-modified gelatin (PCG). We also compared the photo-crosslinked adhesives to the recently reported ion-crosslinked catechol-modified gelatin. Our results indicate that gelatin-based adhesives demonstrate lower swelling index, great degradability, and low cytotoxicity. This shows that gelatin-based adhesives demonstrate great potential for wound closure and healing.

Immobilization of functional polymers on poly(4-benzoyl-pxylylene-co-p-xylylene) films via photochemical conjugation for modulation of cell adhesion.

Surface modification with functional materials, such as anti-fouling or thermal responsive polymers, on biomedical devices benefits their clinical performance. Simple and versatile technologies, which could be applied to a wide variety of substrates, are still highly desirable. Chemical vapor deposition (CVD) of 4-benzoyl-[2,2]paracyclophane (Benzoyl-PPX) layers attracts much attention because the photoreactive platform could be deposited onto almost every substrate for the conjugation of functional molecules. In this study, poly(ethylene glycol) (PEG) was conjugated onto Benzoyl-PPX via UV illumination. The deposited PEG films could effectively reduce protein adsorption and cell attachment. The low-fouling properties of the PEG films were positively correlated with the molecular weight and concentration of PEG. We found that a PEG film, thicker than 16 nm and with a water contact angle of 30°, is a prerequisite for effective inhibition of cell attachment. We also demonstrated that the PEG coating was stable under acidic and basic environments. Furthermore, poly(N-isopropyl acrylamide), PNIPAAm, could be also tethered on the Benzoyl-PPX via UV illumination, and possessed thermal-responsive properties. Intact cell sheets could be released from the PNIPAAm film by decreasing culture temperature. The results indicate that Benzoyl-PPX is an excellent photoreactive platform for the conjugation of functional polymers for modulation of cell attachment.

Methylene-Blue-Encapsulated Liposomes as Photodynamic Therapy Nano Agents for Breast Cancer Cells.

Methylene blue (MB) is a widely used dye and photodynamic therapy (PDT) agent that can produce reactive oxygen species (ROS) after light exposure, triggering apoptosis. However, it is hard for the dye to penetrate through the cell membrane, leading to poor cellular uptake; thus, drug carriers, which could enhance the cellular uptake, are a suitable solution. In addition, the defective vessels resulting from fast vessel outgrowth leads to an enhanced permeability and retention (EPR) effect, which gives nanoscale drug carriers a promising potential. In this study, we applied poly(12-(methacryloyloxy)dodecyl phosphorylcholine), a zwitterionic polymer-lipid, to self-assemble into liposomes and encapsulate MB (MB-liposome). Its properties of high stability and fast intracellular uptake were confirmed, and the higher in vitro ROS generation ability of MB-liposomes than that of free MB was also verified. For in vivo tests, we examined the toxicity in mice via tail vein injection. With the features found, MB-liposome has the potential of being an effective PDT nano agent for cancer therapy.

Fabrication of Chlorophyll-Incorporated Nanogels for Potential Applications in Photothermal Cancer Therapy.

Nanogels have been widely used in biomedical applications, such as carriers for hyperthermia cancer treatment, drug delivery, and imaging. Owing to the enhanced permeability and retention effect, nanogels have shown a great potential in cancer therapy. In this study, sodium copper chlorophyllin (SCC), a low cytotoxicity and biodegradable photothermal agent, was copolymerized with a nanogel of N-[3-(dimethylamino)propyl]methacrylamide. The nanogels could produce heat under exposure to a green laser with a 532 nm wavelength. The positively charged nature of the nanogels enhanced the endocytosis of the nanogels. The cell mortality was greatly enhanced with the treatment of the SCC-containing nanogels and green light illumination. Our results suggest the potential of SCC-containing nanogels in photothermal cancer therapy.

A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model.

To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG). However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB-lipid) synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid-IR-780). Our results demonstrated that PCB-lipid-IR-780 nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser irradiation. The biodistribution of PCB-lipid-IR-780 showed higher accumulation of PCB-lipid-IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid-IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.

Regulation of mesenchymal stem cell functions by micro-nano hybrid patterned surfaces.

Micro- and nano-structured substrates have been widely used in the biomedical engineering field. Their precise control of cell morphology makes them promising for investigating various cell behaviors. However, regulation of cell functions using micro-nano hybrid patterns is rarely achieved. Since the cell microenvironment in vivo has complex micro- and nano-structures, it is desirable to use micro-nano hybrid patterns to mimic the microenvironment to control cell morphology and disclose its influence on stem cell differentiation. In this study, poly(vinyl alcohol) (PVA) micro-stripes with different spacings (50 µm, 100 µm and 200 µm) were constructed on polystyrene (PS) nano-grooves to prepare micro-nano hybrid patterns where the direction of the PVA micro-stripes and PS nano-grooves was parallel or orthogonal. Human bone marrow-derived mesenchymal stem cells (hMSCs) cultured on the micro-nano hybrid patterns showed a different cell alignment and elongation dependent on the PVA micro-stripe spacing and orientation of the PS nano-grooves. Comparison of the influence of cell alignment and aspect ratio on differentiation of hMSCs indicated that myogenic differentiation was predominantly regulated by cell alignment and osteogenic differentiation by cell elongation, while adipogenic differentiation was regulated neither by cell alignment nor by cell elongation.