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3D bioprinting, a significant advancement in biofabrication, is renowned for its precision in creating tissue constructs. Collagen, despite being a gold standard biomaterial, faces challenges in bioink formulations due to its unique physicochemical properties. This study introduces a novel, neutral-soluble, photocrosslinkable collagen maleate (ColME) that is ideal for 3D bioprinting. ColME was synthesized by chemically modifying bovine type I collagen with maleic anhydride, achieving a high substitution ratio that shifted the isoelectric point to enhance solubility in physiological pH environments. This modification was confirmed to preserve the collagen's triple-helix structure substantially. Bioprinting parameters for ColME were optimized, focusing on adjustments to the bioink concentration, extrusion pressure, nozzle speed, and temperature. Results demonstrated that lower temperatures and smaller nozzle sizes substantially improved the print quality of grid structures. Additionally, the application of intermittent photo-crosslinking facilitated the development of structurally robust 3D multilayered constructs, enabling the stable fabrication of complex tissues. Cell viability assays showed that encapsulated cells within the ColME matrix maintained high viability after printing. When compared to methacrylated gelatin, ColME exhibited superior mechanical strength, resistance to enzymatic digestion, and overall printability, positioning it as an outstanding bioink for the creation of durable, bioactive 3D tissues.

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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.

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Intraocular surgery is tabooed in retinoblastoma management, due to the concern of lethal extraocular spread. We reviewed the outcomes of consecutive children with intraocular retinoblastoma diagnosed at 29 Chinese centers between 2012-2014. We compared the outcomes of three categories of treatment: eye salvage including tylectomy (Group I), eye salvage without tylectomy (Group II), and primary enucleation (Group III). A total of 960 patients (1243 eyes) were diagnosed: 256 in Group I, 370 in Group II, and 293 in Group III; 41 patients abandoned treatment upfront. The estimated 5-year overall survivals (OS) were, for Group I, 94%, for Group II 89%, and for Group III 95%. The estimated 5-year disease-specific survivals (DSS) were, for Group I, 96%, for Group II 90%, and for Group III 95%. Patients in Group I had a significantly higher 5-year DSS than patients in Group II (p = 0.003) and not significantly different than patients in Group III (p = 0.367). Overall survival was not compromised by the inclusion of tylectomy in eye salvage therapy compared to eye salvage without tylectomy or primary enucleation. Disease-specific survival was better when tylectomy was included in eye salvage treatments. Tylectomy as part of multimodal treatment may contribute to the care of retinoblastoma patients with chemotherapy-resistant tumor, eyes with concomitant ocular complications, or at the risk of treatment abandonment.

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Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-conductive gelatin. The as-synthesized PAMB-G copolymer is self-doped in physiological pH environments, making it an electrically active material in biological tissues. This copolymer is cross-linked by carbodiimide to form an injectable conductive hydrogel (PAMB-G hydrogel). The un-grafted gelatin hydrogel is prepared in a similar manner as a control. Both test hydrogels not only provide an optimal matrix for CM adhesion and growth but also maintain CM morphology and functional proteins. The conductivity of PAMB-G hydrogel is ca. 12 times higher than that of gelatin hydrogel. Microelectrode array analyses reveal that a heart placed on the PAMB-G hydrogel has a higher field potential amplitude than that placed on the gelatin hydrogel and can pass current from one heart to excite another heart at a distance. The injection of PAMB-G hydrogel into the scar zone following an MI in a rat heart improves electrical impulse propagation over that in a heart that has been treated with gelatin hydrogel, and synchronizes heart contraction, leading to preservation of the ventricular function and reduction of cardiac arrhythmia, demonstrating its potential for use in treating MI.

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AIM: To investigate the therapeutic effects of nanophthalocyanine photosensitizers on an experimental rat choroidal neovescularization (CNV) model, as well as to evaluate the cytotoxicity of which on human retinal pigment epithelia (HRPE) and human retinal endothelial cells (HRECs). METHODS: Two types of photosensitizers, G(1)-ZnPc(COOH)(8) and G(1)-ZnPc(COOH)(8)/m respectively, were administrated for photodynamic therapy (PDT) after a successful establishment of CNV model on Brown-Norway (BN) rats via fundus photocoagulation. The therapeutic effects of the two drugs were assessed through optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and transmission electron microscopy (TEM). For cytotoxicity tests, cell counting kit-8 (CCK-8) assays and changes of mitochondrial transmembrane potential (△Ψm) were conducted on HRPE and HRECs after initial uptake of the two drugs. RESULTS: Both photosensitizers demonstrated an improvement of vascular leakage and closure of CNV 1 week after PDT as confirmed by fundus image, OCT, FFA and TEM. Two weeks after PDT, G(1)-ZnPc(COOH)(8)/m showed a better CNV closure effect versus G(1)-ZnPc(COOH)(8) (P<0.05). A significant difference (P<0.01) was found in uptake of the two drugs in HRPE and HRECs, with no difference between the drugs (P>0.05). Both photosensitizers showed cytotoxicity on HRPE, but G(1)-ZnPc(COOH)(8)/m induced a lower cell viability. CONCLUSION: G(1)-ZnPc(COOH)(8)/m mediated PDT is better than G(1)-ZnPc(COOH)(8) in CNV closure and also have the advantage of fast metabolism leading to less side effect.