Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites

Introducing a 3-dimensionally Printed, Tissue-Engineered Graft for Airway Reconstruction: A Pilot Study

OBJECTIVE: To use 3-dimensional (3D) printing and tissue engineering to create a graft for laryngotracheal reconstruction (LTR). STUDY DESIGN: In vitro and in vivo pilot animal study. SETTING: Large tertiary care academic medical center. SUBJECTS AND METHODS: A 3D computer model of an anterior LTR graft was designed. That design was printed with polylactic acid on a commercially available 3D printer. The scaffolds were seeded with mature chondrocytes and collagen gel and cultured in vitro for up to 3 weeks. Scaffolds were evaluated in vitro for cell viability and proliferation. Anterior graft LTR was performed on 9 New Zealand white rabbits with the newly created scaffolds. Three animals were sacrificed at each time point (4, 8, and 12 weeks). The in vivo graft sites were assessed via bronchoscopy and histology. RESULTS: The in vitro cell proliferation assay demonstrated initial viability of 87.5%. The cells proliferated during the study period, doubling over the first 7 days. Histology revealed that the cells retained their cartilaginous properties during the 21-day study period. In vivo testing showed that all animals survived for the duration of the study. Bronchoscopy revealed a well-mucosalized tracheal lumen with no evidence of scarring or granulation tissue. Histology indicated the presence of newly formed cartilage in the region where the graft was present. CONCLUSIONS: Our results indicate that it is possible to produce a custom-designed, 3D-printed, tissue-engineered graft for airway reconstruction

A full orthotropic bond-based peridynamic formulation for linearly elastic solids

An original full orthotropic model for in-plane linear elasticity is proposed in the micropolar peridynamic analysis framework. The analytical formulation is derived from the definition of a specific microe-lastic energy function for micropolar nonlocal lattices which allows to obtain, for the first time, an orthotropic bond-based model characterized by four independent elastic moduli. An important feature of the model is that the bond properties, i.e. the elastic constants, are continuous functions of the bond orientation in the principal material axes. The introduction of the bond shear stiffness and the definition of a bond shear deformation measure which accounts for particle’s rotation, on one hand eliminates the restriction of two independent constants that affects other bond-based orthotropic peridynamic formulations, and on the other makes the model suitable in predicting the mechanical behavior of a wide variety of Cauchy orthotropic materials undergoing homogeneous and non-homogeneous deformations. The accuracy of the proposed model in linear elasticity has been verified through simulating uniaxial extension test of a composite lamina with a central circular hole and natural frequency analyses considering different orientations of the principal material reference system

Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response to iron availability using genome-wide measurements. Integrative data analysis reveals that a total of 81 genes in 42 transcription units are directly regulated by three different modes of Fur regulation, including apo- and holo-Fur activation and holo-Fur repression. We show that Fur connects iron transport and utilization enzymes with negative-feedback loop pairs for iron homeostasis. In addition, direct involvement of Fur in the regulation of DNA synthesis, energy metabolism and biofilm development is found. These results show how Fur exhibits a comprehensive regulatory role affecting many fundamental cellular processes linked to iron metabolism in order to coordinate the overall response of E. coli to iron availability