Periosteal Flaps Enhance Prefabricated Engineered Bone Reparative Potential

The clinical translation of bone tissue engineering for reconstructing large bone defects has not advanced without hurdles. The in vivo bioreactor (IVB) concept may therefore bridge between bone tissue engineering and reconstructive surgery by employing the patient body for prefabricating new prevascularized tissues. Ideally, IVB should minimize the need for exogenous growth factors/cells. Periosteal tissues are promising for IVB approaches to prefabricate tissue-engineered bone (TEB) flaps. However, the significance of preserving the periosteal vascular supply has not been adequately investigated. This study assessed muscle IVB with and without periosteal/pericranial grafts and flaps for prefabricating TEB flaps to reconstruct mandibular defects in sheep. The sheep (n = 14) were allocated into 4 groups: muscle IVB (M group; n(M) = 3), muscle + periosteal graft (MP group; n(MP) = 4), muscle + periosteal flap (MVP group; n(MVP) = 4), and control group (n(Control) = 3). In the first surgery, alloplastic bone blocks were implanted in the brachiocephalic muscle (M) with a periosteal graft (MP) or with a vascularized periosteal flap (MVP). After 9 wk, the prefabricated TEB flaps were transplanted to reconstruct a mandibular angle defect. In the control group, the defects were reconstructed by non-prevascularized bone blocks. Computed tomography (CT) scans were performed after 13 wk and after 23 wk at termination, followed by micro-CT (mu CT) and histological analyses. Both CT and mu CT analysis revealed enhanced new bone formation and decreased residual biomaterial volume in the MVP group compared with control and MP groups, while the M group showed less new bone formation and more residual biomaterial. The histological analysis showed that most of the newly formed bone emerged from defect edges, but larger areas of new bone islands were found in MP and MVP groups. The MVP group showed enhanced vascularization and higher biomaterial remodeling rates. The periosteal flaps boosted the reconstructive potential of the prefabricated TEB flaps. The regenerative potential of the periosteum was manifested after the transplantation into the mechanically stimulated bony defect microenvironment.Peer reviewe

Future Perspectives of Bone Tissue Engineering with Special Emphasis on Extracellular Vesicles

Peer reviewe

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions

10.1155/2017/6909163Stem Cells International20176909163

Novel polypyrrole-coated polylactide scaffolds enhance adipose stem cell proliferation and early osteogenic differentiation

An electrically conductive polypyrrole (PPy) doped with a bioactive agent is an emerging functional biomaterial for tissue engineering. We therefore used chondroitin sulfate (CS)-doped PPy coating to modify initially electrically insulating polylactide resulting in novel osteogenic scaffolds. In situ chemical oxidative polymerization was used to obtain electrically conductive PPy coating on poly-96L/4D-lactide (PLA) nonwoven scaffolds. The coated scaffolds were characterized and their electrical conductivity was evaluated in hydrolysis. The ability of the coated and conductive scaffolds to enhance proliferation and osteogenic differentiation of human adipose stem cells (hASCs) under electrical stimulation (ES) in three-dimensional (3D) geometry was compared to the noncoated PLA scaffolds. Electrical conductivity of PPy-coated PLA scaffolds (PLA-PPy) was evident at the beginning of hydrolysis, but decreased during the first week of incubation due to de-doping. PLA-PPy scaffolds enhanced hASC proliferation significantly compared to the plain PLA scaffolds at 7 and 14 days. Furthermore, the alkaline phosphatase (ALP) activity of the hASCs was generally higher in PLA-PPy seeded scaffolds, but due to patient variation, no statistical significance could be determined. ES did not have a significant effect on hASCs. This study highlights the potential of novel PPy-coated PLA scaffolds in bone tissue engineering

On the relationship between valence and arousal in samples across the globe

Affect is involved in many psychological phenomena, but a descriptive structure, long sought, has been elusive. Valence and arousal are fundamental, and a key question-the focus of the present study-is the relationship between them. Valence is sometimes thought to be independent of arousal, but, in some studies (representing too few societies in the world) arousal was found to vary with valence. One common finding is that arousal is lowest at neutral valence and increases with both positive and negative valence: a symmetric V-shaped relationship. In the study reported here of self-reported affect during a remembered moment (N = 8,590), we tested the valence-arousal relationship in 33 societies with 25 different languages. The two most common hypotheses in the literature-independence and a symmetric V-shaped relationship-were not supported. With data of all samples pooled, arousal increased with positive but not negative valence. Valence accounted for between 5% (Finland) and 43% (China Beijing) of the variance in arousal. Although there is evidence for a structural relationship between the two, there is also a large amount of variability in this relation

On the relationship between valence and arousal in samples across the globe

Affect is involved in many psychological phenomena, but a descriptive structure, long sought, has been elusive. Valence and arousal are fundamental, and a key question–the focus of the present study–is the relationship between them. Valence is sometimes thought to be independent of arousal, but, in some studies (representing too few societies in the world) arousal was found to vary with valence. One common finding is that arousal is lowest at neutral valence and increases with both positive and negative valence: a symmetric V-shaped relationship. In the study reported here of self-reported affect during a remembered moment (N = 8,590), we tested the valence-arousal relationship in 33 societies with 25 different languages. The two most common hypotheses in the literature–independence and a symmetric V-shaped relationship–were not supported. With data of all samples pooled, arousal increased with positive but not negative valence. Valence accounted for between 5% (Finland) and 43% (China Beijing) of the variance in arousal. Although there is evidence for a structural relationship between the two, there is also a large amount of variability in this relation