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In situ tissue regeneration approach aims to exploit the body’s own biological resources and reparative capability and recruit host cells by utilizing cell-instructive biomaterials. In order to immobilize and release bioactive factors in biomaterials, it is important to engineer the load effectiveness, release kinetics and cell recruiting capabilities of bioactive molecules by using suitable bonding strategies. Stromal cell-derived factor 1α (SDF-1α) is one of the most potent chemokines for stem cell recruitment, and SDF-1α-loaded scaffolds have been used for the regeneration of many types of tissues. This review summarizes the strategies to incorporate SDF-1α into scaffolds, including direct loading or adsorption, polyion complexes, specific heparin-mediated interaction and particulate system, which may be applied to the immobilization of other chemokines or growth factors. In addition, we discuss the application of these strategies in the regeneration of tissues such as blood vessel, myocardium, cartilage and bone.

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The increasing evidence supports the fact that lactate in the tumor microenvironment (TME) plays a vital role in tumor proliferation, metastasis, and recurrence, which in turn is emerging as one of the most interesting molecular targets for tumor treatment. Here, hierarchical porous zeolitic imidazolate framework-8 (ZIF-8) as the nanocarrier is fabricated to simultaneously load lactate oxidase (LOD) and Fe3O4 nanoparticles (NPs), called LOD & Fe3O4@ZIF-8 NPs (LFZ NPs), for tumor therapy. On one hand, the sharp consumption of lactate in the TME by LOD will change the essential “soil” where tumor cells live so as to suppress tumor rapid growth. On the other hand, hydrogen peroxide (H2O2) is produced in the TME from the oxidation of lactate catalyzed by LOD and subsequently converted to highly toxic hydroxyl radicals (•OH) catalyzed by Fe3O4 NPs via Fenton-like reactions to kill tumor cells. Based on the endogenous catalysis, this dual-modal strategy of tumor therapy based on lactate is simple, safe, and effective, which deserves to be well concerned.

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Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. Methods In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipa lmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol) in a fluid state, and intact bacterial cells, by lipid mixing assay. Results The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66%) or P. aeruginosa (44%) seems to be correlated to their outer membrane phosphatidylethanolamine (PE) phospholipids composition (91% and 71%, respectively). Divalent cations increased the degree of fusion in the sequence Fe 2+ > Mg 2+ > Ca 2+ > Ba 2+ whereas temperatures lower than the phase transition temperature of DPPC/DMPG (9:1) vesicles decreased their fusion capacity. Acidic as well as basic pHs conferred higher degrees of fusion (54% and 45%, respectively) when compared to neutral pH (35%). Conclusion Based on the results of this study, a possible mechanism involving cationic bridging between bacterial negatively charged lipopolysaccharide and fluid liposomes DMPG phospholipids was outlined. Furthermore, the fluid liposomal-encapsulated tobramycin was prepared, and the in vitro bactericidal effects were also investigated.

Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion:The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections.