Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver or bone. The immobilization or delivery of growth factors has been explored to improve vascularization capacity of tissue engineered constructs, however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications such as immunological responses and cancer. Here, a new method of preparing water-insoluble silk protein scaffolds with vascularization capacity using an all aqueous process is reported. Acid was added temporally to tune the self-assembly of silk in lyophilization process, resulting in water insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk-based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.

cChronic wound infections are associated with biofilm formation, which in turn has been correlated with drug resistance. However, the mechanism by which bacteria form biofilms in clinical environments is not clearly understood. This study was designed to investigate the biofilm formation potency of Acinetobacter baumannii and the potential association of biofilm formation with genes encoding efflux pumps, quorum-sensing regulators, and outer membrane proteins. A total of 48 clinically isolated A. baumannii strains, identified by enterobacterial repetitive intergenic consensus (ERIC)-PCR as types A-II, A-III, and A-IV, were analyzed. Three representative strains, which were designated A. baumannii ABR2, ABR11, and ABS17, were used to evaluate antimicrobial susceptibility, biofilm inducibility, and gene transcription (abaI, adeB, adeG, adeJ, carO, and ompA). A significant increase in the MICs of different classes of antibiotics was observed in the biofilm cells. The formation of a biofilm was significantly induced in all the representative strains exposed to levofloxacin. The levels of gene transcription varied between bacterial genotypes, antibiotics, and antibiotic concentrations. The upregulation of adeG correlated with biofilm induction. The consistent upregulation of adeG and abaI was detected in A-III-type A. baumannii in response to levofloxacin and meropenem (1/8 to 1/2؋ the MIC), conditions which resulted in the greatest extent of biofilm induction. This study demonstrates a potential role of the AdeFGH efflux pump in the synthesis and transport of autoinducer molecules during biofilm formation, suggesting a link between low-dose antimicrobial therapy and a high risk of biofilm infections caused by A. baumannii. This study provides useful information for the development of antibiofilm strategies.

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Improved and more rapid healing of full-thickness skin wounds remains a major clinical need. Silk fibroin (SF) is a natural protein biomaterial that has been used in skin repair. However, there has been little effort aimed at improving skin healing through tuning the hierarchical microstructure of SF-based matrices and introducing multiple physical cues. Recently, enhanced vascularization was achieved with SF scaffolds with nanofibrous structures and tunable secondary conformation of the matrices. We hypothesized that anisotropic features in nanofibrous SF scaffolds would promote cell migration, neovascularization, and tissue regeneration in wounds. To address this hypothesis, SF nanofibers were aligned in an electric field to form anisotropic porous scaffolds after lyophilization. In vitro and in vivo studies indicated good cytocompatibility, and improved cell migration and vascularization than nanofibrous scaffolds without these anisotropic features. These improvements resulted in more rapid wound closure, tissue ingrowth, and the formation of new epidermis, as well as higher collagen deposition with a structure similar to the surrounding native tissue. The new epidermal layers and neovascularization were achieved by day 7, with wound healing complete by day 28. It was concluded that anisotropic SF scaffolds alone, without a need for growth factors and cells, promoted significant cell migration, vascularization, and skin regeneration and may have the potential to effectively treat dermal wounds.

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