Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration

Biomaterials without exogenous cells or therapeutic agents often fail to achieve rapid endogenous bone regeneration with high quality. Here, we reported a class of three-dimensional (3D) nanofiber scaffolds with hierarchical structure and controlled alignment for effective endogenous cranial bone regeneration. 3D scaffolds consisting of radially aligned nanofibers guided and promoted the migration of bone marrow stem cells from the surrounding region to the center in vitro. These scaffolds showed the highest new bone volume, surface coverage, and mineral density among the tested groups in vivo. The regenerated bone exhibited a radially aligned fashion, closely recapitulating the scaffold’s architecture. The organic phase in regenerated bone showed an aligned, layered, and densely packed structure, while the inorganic mineral phase showed a uniform distribution with smaller pore size and an even distribution of stress upon the simulated compression. We expect that this study will inspire the design of next-generation biomaterials for effective endogenous bone regeneration with desired quality

Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology

A cornerstone of biotechnology is the use of microorganisms for the efficient production of chemicals and the elimination of harmful waste. Pseudomonas putida is an archetype of such microbes due to its metabolic versatility, stress resistance, amenability to genetic modifications, and vast potential for environmental and industrial applications. To address both the elucidation of the metabolic wiring in P. putida and its uses in biocatalysis, in particular for the production of non-growth-related biochemicals, we developed and present here a genome-scale constraint-based model of the metabolism of P. putida KT2440. Network reconstruction and flux balance analysis (FBA) enabled definition of the structure of the metabolic network, identification of knowledge gaps, and pin-pointing of essential metabolic functions, facilitating thereby the refinement of gene annotations. FBA and flux variability analysis were used to analyze the properties, potential, and limits of the model. These analyses allowed identification, under various conditions, of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. The model was validated with data from continuous cell cultures, high-throughput phenotyping data, 13C-measurement of internal flux distributions, and specifically generated knock-out mutants. Auxotrophy was correctly predicted in 75% of the cases. These systematic analyses revealed that the metabolic network structure is the main factor determining the accuracy of predictions, whereas biomass composition has negligible influence. Finally, we drew on the model to devise metabolic engineering strategies to improve production of polyhydroxyalkanoates, a class of biotechnologically useful compounds whose synthesis is not coupled to cell survival. The solidly validated model yields valuable insights into genotype–phenotype relationships and provides a sound framework to explore this versatile bacterium and to capitalize on its vast biotechnological potential

Cost Analysis in Shoulder Arthroplasty Surgery

Cost in shoulder surgery has taken on a new focus with passage of the Patient Protection and Affordable Care Act. As part of this law, there is a provision for Accountable Care Organizations (ACOs) and the bundled payment initiative. In this model, one entity would receive a single payment for an episode of care and distribute funds to all other parties involved. Given its reproducible nature, shoulder arthroplasty is ideally situated to become a model for an episode of care. Currently, there is little research into cost in shoulder arthroplasty surgery. The current analyses do not provide surgeons with a method for determining the cost and outcomes of their interventions, which is necessary to the success of bundled payment. Surgeons are ideally positioned to become leaders in ACOs, but in order for them to do so a methodology must be developed where accurate costs and outcomes can be determined for the episode of care

Expanding Two-Dimensional Electrospun Nanofiber Membranes in the Third Dimension By a Modified Gas-Foaming Technique

Electrospun nanofibers have shown great potential as scaffolds for regenerative medicine because of its biomimicry. However, traditional two-dimensional electrospun nanofiber mats inhibit their applications because of the dense structure and lack of effective cell infiltration. Herein, we report a new method of expanding electrospun nanofiber mats in the third dimension using a modified gas-foaming technique. The resulting nanofiber scaffolds show layered structures with controllable gap widths and layer thicknesses on the order of microns. Expanded nanofiber scaffolds possess significantly higher porosity than traditional two-dimensional nanofiber membranes, while simultaneously maintaining nanotopographic cues. The distributions of gap widths and layer thicknesses are directly dependent on the processing time of nanofiber mats within the gas bubble forming solution. In vitro testing demonstrates robust cellular infiltration and proliferation within expanded nanofiber scaffolds as compared to limited cellular proliferation on the surface of traditional nanofiber mats. Importantly, cell alignment was observed throughout the expanded and aligned nanofiber scaffolds after incubation for 7 days. The presented method was further applied to fabricate tubular scaffolds composed of expanded nanofibers. Together, this novel class of scaffolds holds significant promise for applications in regenerative medicine and building 3D in vitro tissue models for drug screening and biological study

Binary Doping of Strontium and Copper Enhancing Osteogenesis and Angiogenesis of Bioactive Glass Nanofibers while Suppressing Osteoclast Activity

Electrospun bioactive glass fibers show great potential as scaffolds for bone tissue engineering due to their architectural biomimicry of the bone extracellular matrix and their composition capable of providing soluble bioactive cues for bone regeneration and remodeling. Trace elements can be doped to further promote osteogenesis and angiogenesis during bone regeneration. Cationic substitution of strontium for calcium in bioactive glass positively enhances osteoblast phenotype, while suppressing osteoclast activity. Further, the addition of copper spontaneously improves the vascularization during neobone formation. The objective of this study was to fabricate and characterize electrospun bioactive glass fibers doped with strontium and copper and evaluate their potential for bone repair/regeneration in vitro. Different ratios of strontium and copper were doped in electrospun bioactive glass fibers. The released strontium and copper from doped fibers could reach effective concentrations within 40 h and last for 4 weeks. These bioactive glass fibers demonstrate their bioactivity by promoting osteoblastic and endothelial cell activity and inhibiting the formation of osteoclasts or bone resorbing cells. Additionally, in vitro cell culture of different cell types in the presence of extraction solutions of the electrospun bioactive glass fibers showed that the dopants achieved their individual goals without causing significant cytotoxicity. Altogether, this novel class of bioactive glass fibers holds great promise for bone regeneration