Photoactivatable Adhesive Ligands for Light-Guided Neuronal Growth.

Neuro-regeneration after trauma requires growth and reconnection of neurons to reestablish information flow in particular directions across the damaged tissue. To support this process, biomaterials for nerve tissue regeneration need to provide spatial information to adhesion receptors on the cell membrane and to provide directionality to growing neurites. Here, photoactivatable adhesive peptides based on the CASIKVAVSADR laminin peptidomimetic are presented and applied to spatiotemporal control of neuronal growth to biomaterials in vitro. The introduction of a photoremovable group [6-nitroveratryl (NVOC), 3-(4,5-dimethoxy-2-nitrophenyl)butan-2-yl (DMNPB), or 2,2'-((3'-(1-hydroxypropan-2-yl)-4'-nitro-[1,1'-biphenyl]-4-yl)azanediyl)bis(ethan-1-ol) (HANBP)] at the amino terminal group of the K residue temporally inhibited the activity of the peptide. The bioactivity was regained through controlled light exposure. When used in neuronal culture substrates, the peptides allowed light-based control of the attachment and differentiation of neuronal cells. Site-selective irradiation activated adhesion and differentiation cues and guided seeded neurons to grow in predefined patterns. This is the first demonstration of ligand-based light-controlled interaction between neuronal cells and biomaterials.

[Application of modified lateral window for maxillary sinus floor augmentation].

Objective: To evaluate the clinical efficacy of modified lateral window for maxillary sinus floor augmentation (MSFA). Methods: Fifty-five patients who visited the Stomatology Hospital Affiliated to Zhejiang University School of Medicine between June 2012 and October 2014 were enrolled in the study. Patients underwent MSFA with Bio-Oss grafts based on modified access window. During the operation the vertical height of the bony window was reduced from 6-8 mm of conventional oval window to 4-5 mm of slot-shaped window. The sinus membrane was detached completely via the lateral access and large particle Bio-Oss graft was placed in the sub-mucosal space. The implant survival, graft height, graft volume and resorption rates were measured. Intra-op and post-op complications were recorded. Results: There were 86 implants inserted. The 2-4 year cumulative survival rates were 97.67% by implant-based analysis and 96.36% by patient-based analysis. The residual bone height was (4.7±2.6) mm and bone width was (8.4±2.7) mm. The bone height of implantation site immediately after operation was (16.1±2.5) mm and it was (16.2±2.2) mm at restoration. The bone heights at 1 and 2 years after operation were (14.9±2.5) mm and (13.6±2.6) mm, respectively. The graft height was (10.6±2.8) mm and the graft volume was (1569±745) mm3 immediately after operation. The resorption rate of graft height 6 months after operation was 3.79% and that of graft volume was 7.87%. The 1-year accumulative resorption rate of graft height was 6.63% and that of graft volume was 10.89%. The 2-year accumulative resorption rate of graft height was 7.58% and that of graft volume was 15.26%. Small membrane perforation during MSFA was observed in 5 cases and all were successfully repaired by a collagen Bio-Gide membrane. Conclusion: The modified lateral technique obtains high implant survival rate, excellent graft stability and low complication rate at 2-4 year clinical follow-up, indicating that it is a safe, predictable and minimally invasive surgical method for severe atrophic maxillary posterior dentition.

Discovery of Novel Isoquinoline Analogues as Dual Tubulin Polymerization/V-ATPase Inhibitors with Immunogenic Cell Death Induction.

Cancer immunotherapy has revolutionized clinical advances in a variety of cancers. Due to the low immunogenicity of the tumor, only a few patients can benefit from it. Specific microtubule inhibitors can effectively induce immunogenic cell death and improve immunogenicity of the tumor. A series of isoquinoline derivatives based on the natural products podophyllotoxin and diphyllin were designed and synthesized. Among them, F10 showed robust antiproliferation activity against four human cancer cell lines, and it was verified that F10 exerted antiproliferative activity by inhibiting tubulin and V-ATPase. Further studies indicated that F10 is able to induce immunogenic cell death in addition to apoptosis. Meanwhile, F10 inhibited tumor growth in an RM-1 homograft model with enhanced T lymphocyte infiltration. These results suggest that F10 may be a promising lead compound for the development of a new generation of microtubule drugs.

Design and biological evaluation of dual tubulin/HDAC inhibitors based on millepachine for treatment of prostate cancer.

In this work, a novel of dual tubulin/HDAC inhibitors were designed and synthesized based on the structure of natural product millepachine, which has been identified as a tubulin polymerization inhibitor. Biological evaluation revealed that compound 9n exhibited an impressive potency against PC-3 cells with the IC50 value of 16 nM and effectively inhibited both microtubule polymerization and HDAC activity. Furthermore, compound 9n not only induced cell cycle arrest at G2/M phase, but also induced PC- 3 cells apoptosis. Further study revealed that the induction of cell apoptosis by 9n was accompanied by a decrease in mitochondrial membrane potential and an elevation in reactive oxygen species levels in PC-3 cells. Additionally, 9n exhibited inhibitory effects on tumor cell migration and angiogenesis. In PC-3 xenograft model, 9n achieved a remarkable tumor inhibition rate of 90.07%@20 mg/kg, significantly surpassing to that of CA-4 (55.62%@20 mg/kg). Meanwhile, 9n exhibited the favorable drug metabolism characteristics in vivo. All the results indicate that 9n is a promising dual tubulin/HDAC inhibitor for chemotherapy of prostate cancer, deserving the further investigation.

Design, synthesis and biological evaluation of CDC20 inhibitors for treatment of triple-negative breast cancer.

The involvement of CDC20 in promoting tumor growth in different types of human cancers and it disturbs the process of cell division and impedes tumor proliferation. In this work, a novel of Apcin derivatives targeting CDC20 were designed and synthesized to evaluate for their biological activities. The inhibitory effect on the proliferation of four human tumor cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and A549) was observed. Among them, compound E1 exhibited the strongest inhibitory effect on the proliferation of MDA-MB-231 cells with an IC50 value of 1.43 µM, which was significantly superior to that of Apcin. Further biological studies demonstrated that compound E1 inhibited cancer cell migration and colony formation. Furthermore, compound E1 specifically targeted CDC20 and exhibited a higher binding affinity to CDC20 compared to that of Apcin, thereby inducing cell cycle arrest in the G2/M phase of cancer cells. Moreover, it has been observed that compound E1 induces autophagy in cancer cells. In 4T1 Xenograft Models compound E1 exhibited the potential antitumor activity without obvious toxicity. These findings suggest that E1 could be regarded as a CDC20 inhibitor deserved further investigation.

Effects of magnesium-substituted nanohydroxyapatite coating on implant osseointegration.

OBJECTIVE: The objective of this study was to compare magnesium-substituted and pure hydroxyapatite coatings on the promotion of osteogenesis in vitro and on the osseointegration in vivo. METHODS: Electrochemically deposited pure hydroxyapatite (EDHA) or electrochemically deposited magnesium-substituted hydroxyapatite (EDMHA) coatings were formed on the surface of pure titanium disks or implants. MC3T3-E1 preosteoblasts were cultured in the EDHA and EDMHA coated disks, and cell growth, alkaline phosphatase (ALP) activity, and osteocalcin secretion were measured at various time points. For studies on osseointegration, 30 roughened implants coated either with EDHA or EDMHA (n = 15 for each coating) were implanted in the femurs of 15 NZW rabbits. After 2, 4, and 8 weeks, femurs were retrieved and prepared for histomorphometric evaluation (n = 5 for each coating at each time point). RESULTS: MC3T3-E1 cells cultured on EDMHA coated disks showed increased cell number, ALP, and osteocalcin secretion compared with the EDHA coated disks at all time points (P < 0.05 for all). Histologic observation of the coated implants showed woven bone in direct contact with both implant surfaces after 2 weeks and mature bone after 8 weeks. While there were no differences in the amount of bone between the threads at any time point, the percentage of implant in direct contact with bone (bone implant contact) was slightly higher along the EDMHA coated implants at 2 weeks (P = 0.086), although this difference was no longer seen at 4 and 8 weeks. CONCLUSION: Mg-substituted HA coated surfaces promote osteogenic differentiation of preosteoblasts in vitro and may improve implant osseointegration during the early stages of bone healing compared with pure EDHA coated surfaces.

Bone response to the multilayer BMP-2 gene coated porous titanium implant surface.

OBJECTIVES: Evaluate hBMP-2 expression following gene delivery from plasmid multilayers formed on sandblasted titanium in vitro and bone formation around similarly prepared implant surfaces in vivo. MATERIALS AND METHODS: Multilayers of cationic lipid/rhBMP-2 plasmid DNA complex (LDc) and anionic hyaluronic acid (HA) was assembled on sandblasted-dual acid etched pure titanium disks or implant surfaces using layer-by-layer (LBL) assembly. Gene delivery and hBMP-2 expression in cells exposed to the LDc multilayers was measured in vitro. To determine the effect of BMP delivery from such multilyaers in vivo, roughened implants coated with BMP-2 LDc multilayers or uncoated control implants (n = 15 for both) were implanted in the femurs of NZW rabbits. After 2, 4, 8 weeks, femurs were retrieved and prepared for histomorphometric evaluation (n = 5 rabbits per time point). RESULTS: MC3T3-E1 cells cultured directly on the BMP-2 LDc coated titanium disks showed EGFP and hBMP-2 expression after 48 h in culture. Increased gene delivery occurred by increasing the number of assembly layers when cells were cultured for 48 h. Cells cultured on LDc coated surfaces had significantly higher cell viability than control cells cultured on uncoated porous titanium surfaces. Histologic observation of the implants showed that after 4 weeks healing, the bone to implant contact (BIC) on the LDc coated surface was much lower than that on the control surface, but didn't reach significant. In contrast, the percentage of bone within the implant's threads was significantly higher than the control group (P = 0.047). CONCLUSION: The BMP-2 gene coated sandblasted dual acid etched titanium implants slightly accelerated early bone formation around implants.

Discovery of Novel Potent Covalent Glutathione Peroxidase 4 Inhibitors as Highly Selective Ferroptosis Inducers for the Treatment of Triple-Negative Breast Cancer.

Glutathione peroxidase 4 (GPX4) is a promising target to induce ferroptosis for the treatment of triple-negative breast cancer (TNBC). We designed and synthesized a novel series of covalent GPX4 inhibitors based on RSL3 and ML162 by structural integration and simplification strategies. Among them, compound C18 revealed a remarkable inhibitory activity against TNBC cells and significantly inhibited the activity of GPX4 compared to RSL3 and ML162. Moreover, it was identified that C18 could notably induce ferroptosis with high selectivity by increasing the accumulation of lipid peroxides (LPOs) in cells. Further study demonstrated that C18 covalently bound to the Sec46 of GPX4. Surprisingly, C18 exhibited an outstanding potency of tumor growth inhibition in the MDA-MB-231 xenograft model with a TGI value of 81.0%@20 mg/kg without obvious toxicity. Overall, C18 could be a promising GPX4 covalent inhibitor to induce ferroptosis for the treatment of TNBC.

[Construction of a multiple-scale implant surface with super-hydrophilicity].

OBJECTIVE: To construct a multiple-scale organized implant surface with super-hydrophilicity. METHODS: The SiC paper polished titanium disc was sandblasted and treated with HF/HNO3 and HCl/H2SO4, then acid-etched with H2SO4/H2O2. The physicochemical properties of the surfaces were characterized by scanning electron microscope, static state contact angle and X-ray diffraction. MC3T3-E1 cells were used to evaluate the effects of the surface on the cell adhesion, proliferation and differentiation. RESULTS: The acid-etching process with a mixture of H2SO4/H2O2 superimposed the nano-scale structure on the micro-scale texture. The multiple-scale implant surface promoted its hydrophilicity and was more favorable to the responses of osteoprogenitor cells, characterized by increased DNA content, enhanced ALP activity and promoted OC production. CONCLUSION: A multiple-scale implant surface with super-hydrophilicity has been constructed in this study, which facilitates cell proliferation and adhesion.

Discovery of Novel N-Heterocyclic-Fused Deoxypodophyllotoxin Analogues as Tubulin Polymerization Inhibitors Targeting the Colchicine-Binding Site for Cancer Treatment.

Natural products are a major source of anticancer agents and play critical roles in anticancer drug development. Inspired by the complexity-to-diversity strategy, novel deoxypodophyllotoxin (DPT) analogues were designed and synthesized. Among them, compound C3 exhibited the potent antiproliferative activity against four human cancer cell lines with IC50 values in the low nanomolar range. Additionally, it showed marked activity against paclitaxel-resistant MCF-7 cells and A549 cells. Moreover, compound C3 can inhibit tubulin polymerization by targeting the colchicine-binding site of tubulin. Further study revealed that compound C3 could arrest cancer cells in the G2/M phase and disrupt the angiogenesis in human umbilical vein endothelial cells. Meanwhile, C3 remarkably inhibited cancer cell motility and migration, as well as considerably inhibited tumor growth in MCF-7 and MCF-7/TxR xenograft model without obvious toxicity. Collectively, these results indicated that compound C3 may be a promising tubulin polymerization inhibitor development for cancer treatment.

Mechanical and histomorphometric evaluations of rough titanium implants treated with hydrofluoric acid/nitric acid solution in rabbit tibia.

PURPOSE: The aim of this study was to investigate the bone response to rough titanium implants treated with hydrofluoric acid/nitric acid (HF/HNO3) solution. MATERIALS AND METHODS: Implants were treated with HF/HNO3 solution (test implants) or without HF/HNO3 solution (control implants). Forty-five test and 45 control implants were inserted into both tibias of 15 rabbits. After 2, 4, and 8 weeks in situ, tibias were retrieved and prepared for removal torque testing and histomorphometric evaluation. The removed implants were prepared and observed with an electron microscope. RESULTS: Mechanical tests showed that mean removal torque values for the test implants were higher than those of the control implants after 8 weeks (33.1 Ncm versus 25.7 Ncm, P = .012). Histomorphometric analysis showed that the bone area in the threads of the cortical bone region was significantly higher for test implants (81.99% and 86.38%) than for control implants (75.33% and 81.62%) after 4 and 8 weeks of healing, respectively. The implant-bone contact rate in the cortical region was higher for test implants than for control implants after 8 weeks in situ (79.56% versus 68.45%, P = .003). CONCLUSIONS: The treatment with HF/HNO3 solution promotes bone formation and osseointegration after 4 and 8 weeks of bone healing in the rabbit tibia model.

In vivo comparison of bone formation on titanium implant surfaces coated with biomimetically deposited calcium phosphate or electrochemically deposited hydroxyapatite.

PURPOSE: The purpose of this study was to investigate and compare bone formation on titanium implant surfaces coated with biomimetically deposited calcium phosphate (BDCaP) or electrochemically deposited hydroxyapatite (EDHA). MATERIALS AND METHODS: The implants were separated into three groups: a control group, a BDCaP group, and an EDHA group. Surface analysis was performed by field-emission scanning electron microscopy, x-ray diffractometry, and Fourier transform infrared spectroscopy. Implants were inserted in a randomized arrangement into rabbit tibiae. After 2, 4, and 8 weeks, the tibiae were retrieved and prepared for histomorphometric evaluation. RESULTS: Field-emission scanning electron microscopy showed that the BDCaP crystals were flakelike and the EDHA crystals were rodlike with a hexagonal cross section. X-ray diffractometric patterns and Fourier transform infrared spectroscopy spectra showed that the BDCaP coating consisted of HA and octacalcium phosphate, whereas the EDHA coating consisted of HA. Histologic observation showed that new bone on the EDHA-coated implant became mature after 4 weeks, while new bone on the control and BDCaP-coated implants was mature after 8 weeks. The EDHA implant showed significantly greater BIC and bone area compared to the control and BDCaP implants during 4 to 8 weeks. The BDCaP coating failed to show increased bone formation during the test period. CONCLUSION: The present EDHA coating has good bone formation properties, while the BDCaP coating has weaker bone formation properties.

Cell response of titanium implant with a roughened surface containing titanium hydride: an in vitro study.

PURPOSE: The purpose of this study was to investigate the effect of surface chemistry of a sandblasted and acid-etched implant (with and without titanium hydride [TiH(2)]) on cell attachment, proliferation, and differentiation of preosteoblasts (MC3T3-E1). MATERIALS AND METHODS: Sandblasted and dual acid-etched titanium discs comprised the test group, whereas sandblasted, acid-etched, and heat-treated discs comprised the control group. Both groups' discs were sent for surface characterization. MC3T3-E1 cells were cultured on these 2 groups' discs, and then cell attachment, cell proliferation, and cell differentiation were analyzed. RESULTS: Scanning electron microscope analysis showed that the titanium discs in the 2 groups shared the same surface topography; however, x-ray diffraction examination showed that the TiH(2) diffractions only appeared in the test group. Cell attachment and cell proliferation were much better in the test group than in the control group at all time points investigated (P < .05). The expressions of alkaline phosphatase and osteocalcin were significantly higher in the test group than in the control group for both protein and transcription level at every time point (P < .05 or P < .01). CONCLUSIONS: These results suggested that surface chemistry played a significant role in cell response to the sandblasted and acid-etched surface and the presence of TiH(2) might promote the attachment, proliferation, and differentiation of preosteoblasts.

Biomechanical comparison of biomimetically and electrochemically deposited hydroxyapatite-coated porous titanium implants.

PURPOSE: The purpose of this study was to investigate the effects of biomimetically and electrochemically deposited hydroxyapatite on the fixation of an implant with bone tissue. MATERIALS AND METHODS: Implants were separated into 3 groups: roughened group, biomimetically deposited calcium-phosphorus (BDCaP) group, and electrochemically deposited hydroxyapatite (EDHA) group. We randomly inserted 90 implants into the femurs of 45 rabbits. After 2, 4, and 8 weeks, the femurs were retrieved and prepared for removal torque tests (RTQs) and field-emission scanning electron microscopy observation. RESULTS: During the test period, the EDHA group showed significantly greater RTQ values than did the roughened group and BDCaP group. The BDCaP group failed to increase the RTQ values compared with the roughened group. Field-emission scanning electron microscopy observation showed that the amount of attached bone tissue on the EDHA-coated implant surface was more than that on the roughened and BDCaP-coated implant surfaces during the test period. CONCLUSION: The electrochemical hydroxyapatite coating contributes to the fixation between bone and implant compared with the roughened surface, whereas the biomimetic calcium-phosphorus coating has little effect on the fixation.

Effect of electrochemically deposited nanohydroxyapatite on bone bonding of sandblasted/dual acid-etched titanium implant.

PURPOSE: The aim of this study was to evaluate the effect of an electrochemically deposited nanohydroxyapatite (EDHA) coating on the bone bonding of sandblasted and dual acid-etched titanium implants. MATERIALS AND METHODS: One hundred EDHA-coated and uncoated sandblasted/dual acid-etched implants (3 mm in diameter, 10 mm long) were inserted into the femoral condyles of 50 rabbits. The osteotomy sites were enlarged to 3 mm in diameter via a sequence of drills. After 2, 4, 6, 8, and 12 weeks of bone healing, removal torque testing was performed to evaluate the interfacial shear strength of each implant type. The removed implants were prepared and observed with an electron microscope equipped with an energy dispersive electron probe x-ray microanalyzer. RESULTS: The mean removal torque values for the EDHA-coated implants were 39.6 Ncm at 2 weeks and 40.4 Ncm at 4 weeks; corresponding values for the control implants were 21.1 Ncm and 24.1 Ncm. Removal torque values of the EDHA-coated implants were 87% higher than those of control implants after 2 weeks of healing (P = .015). However, the mean removal torque values for both types of implants were similar after 6, 8, or 12 weeks of healing (no significant differences between the implant surfaces; P > .05). CONCLUSIONS: The EDHA nanocrystal coating had a beneficial effect on interfacial shear strength during the early stages of bone healing.

[Cross-talk between Notch1 and epidermal growth factor receptor signalling in regulating cell proliferation of human tongue squamous carcinoma cells].

OBJECTIVE: To investigate the cross-talk between Notch1 and epidermal growth factor receptor (EGFR) signaling in regulating the cellular proliferation of human tongue squamous cell carcinoma (SCC). METHODS: Human tongue SCC cell line Tca8113 cells was transiently transfected with the vector encoding exogenous intracellular fragment of Notch1 and the vector encoding the specific short hairpin RNA (shRNA) targeting EGFR respectively and were treated by AG1478, an inhibitor of receptor tyrosine kinases, for elucidating the effects of constitutive activation, EGFR gene silencing and blocking EGFR signaling upon cellular proliferation and expression of Notch1 and EGFR. The mRNA and protein levels of Notch1 and EGFR were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. The cellular proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: Constitutive activation of Notch1 resulted in inhibition of cellular proliferation, and up-regulation of Notch1 (1.102 +/- 0.135, 0.243 +/- 0.032, P < 0.05) but down-regulation of EGFR (0.083 +/- 0.009, 0.605 +/- 0.075, P < 0.05) at the the mRNA and protein levels. Silencing of EGFR gene resulted in inhibition of cell proliferation, and down-regulation of EGFR (0.148 +/- 0.019, 1.175 +/- 0.132, P < 0.05) but up-regulation of Notch1 (0.978 +/- 0.115, 0.083 +/- 0.009, P < 0.05) at the mRNA and protein levels. Blocking EGFR signaling had no significant effect upon EGFR expression (P > 0.05), but resulted in inhibition of cellular proliferation and up-regulation of Notch1 (P < 0.05) at the mRNA and protein levels. CONCLUSION: There might be a cross-talk of bi-directional control between Notch1 and EGFR signaling in regulating the cellular proliferation of human tongue SCC cells.

Microstructure and Isothermal Oxidation of Ir-Rh Spark Plug Electrodes.

High-temperature oxidation tests were performed on pure iridium, rhodium, and the iridium alloys, IrRh10, IrRh25, and IrRh40, at 1100 °C in a stable air environment for 60 h. The results of the oxidation were analyzed by X-ray photoelectron spectroscopy (XPS). Microstructural changes of the Ir-Rh alloys were characterized by scanning electron microscopy (SEM). XPS analysis results show that the main oxide of the Ir-Rh alloy in a 1100 °C environment was Rh2O3, and SEM analysis shows that the surfaces of the Ir-Rh alloys after oxidation formed both linear and ellipse-shaped corrosion pits, and had the same direction with the wire-drawing process. The oxidation behavior of Ir-Rh alloys, including the mass change, the reason for the mass loss, and the role of Rh in improving oxidation resistance performance, are discussed.

Effect of H2O2/HCl heat treatment of implants on in vivo peri-implant bone formation.

PURPOSE: To investigate the effect of H2O/HCl heat treatment on peri-implant bone formation in vivo. MATERIALS AND METHODS: Twenty Ti-6Al-4V implants and 30 Ti-6Al-4V discs were used in this study. The implants and discs were separated into 2 groups: sandblasted and dual acid-etched group (control group) and sandblasted, dual acid-etched and H2O2/HCl heat-treated group (test group). Surface morphology, roughness, and crystal structure of the discs were analyzed by field-emission scanning electron microscopy, atomic force microscopy, and low angle X-ray diffractometry. The implants were inserted into the femurs of 10 adult white rabbits. Animals were injected with fluorescent bone labels at 1, 5, and 7 weeks following surgery to monitor progress of bone formation. Animals were euthanized 8 weeks postsurgery, and block biopsies were prepared for histologic and histometric analysis. RESULTS: Microscopic evaluation showed the surfaces were quite irregular for both techniques; however, the test surface demonstrated consistently smaller surface irregularities. The differences in Sa values were significant (P = .022). No significant differences were found in the maximum peak-to-valley ratio values (P = .258). X-ray diffractometry analysis showed that titanium dioxide was found on the test surface. New bone was formed on both implant surfaces. The bone-implant contact pattern appeared to produce a broad-based direct contact. Test implants demonstrated 7.13% more bone to implant contact (P = .003) and 15.42% more bone to implant contact for 3 consecutive threads (P = .001) than control implants. Test implants demonstrated 37.04% more bone area 500 microm outside of implant threads (P = .004) and 51.97% more bone area within 3 consecutive threads (P = .001) than control implants. No significant differences were found in bone area within all implant threads between the two groups (P = .069). CONCLUSION: This study demonstrated that implants heat-treated with H2O2/HCl solution enhanced peri-implant bone formation.

Toward Light-Regulated Living Biomaterials.

Living materials are an emergent material class, infused with the productive, adaptive, and regenerative properties of living organisms. Property regulation in living materials requires encoding responsive units in the living components to allow external manipulation of their function. Here, an optoregulated Escherichia coli (E. coli)-based living biomaterial that can be externally addressed using light to interact with mammalian cells is demonstrated. This is achieved by using a photoactivatable inducer of gene expression and bacterial surface display technology to present an integrin-specific miniprotein on the outer membrane of an endotoxin-free E. coli strain. Hydrogel surfaces functionalized with the bacteria can expose cell adhesive molecules upon in situ light-activation, and trigger cell adhesion. Surface immobilized bacteria are able to deliver a fluorescent protein to the mammalian cells with which they are interacting, indicating the potential of such a bacterial material to deliver molecules to cells in a targeted manner.

In Situ, Light-Guided Axon Growth on Biomaterials via Photoactivatable Laminin Peptidomimetic IK(HANBP)VAV.

The ability to guide the growth of neurites is relevant for reconstructing neural networks and for nerve tissue regeneration. Here, a biofunctional hydrogel that allows light-based directional control of axon growth in situ is presented. The gel is covalently modified with a photoactivatable derivative of the short laminin peptidomimetic IKVAV. This adhesive peptide contains the photoremovable group 2-(4'-amino-4-nitro-[1,1'-biphenyl]-3-yl)propan-1-ol (HANBP) on the Lys rest that inhibits its activity. The modified peptide is highly soluble in water and can be simply conjugated to -COOH containing hydrogels via its terminal -NH2 group. Light exposure allows presentation of the IKVAV adhesive motif on a soft hydrogel at desired concentration and at defined position and time point. The photoactivated gel supports neurite outgrowth in embryonic neural progenitor cells culture and allows site-selective guidance of neurites extension. In situ exposure of cell cultures using a scanning laser allows outgrowth of neurites in desired pathways.