Biomimetic hematoma delivers an ultra-low dose of rhBMP-2 to successfully regenerate large femoral bone defects in rats.

Successful repair of large bone defects remains a clinical challenge. Following fractures, a bridging hematoma immediately forms as a crucial step that initiates bone healing. In larger bone defects the micro-architecture and biological properties of this hematoma are compromised, and spontaneous union cannot occur. To address this need, we developed an ex vivo Biomimetic Hematoma that resembles naturally healing fracture hematoma, using whole blood and the natural coagulants calcium and thrombin, as an autologous delivery vehicle for a very reduced dose of rhBMP-2. When implanted into a rat femoral large defect model, complete and consistent bone regeneration with superior bone quality was achieved with 10-20× less rhBMP-2 compared to that required with the collagen sponges currently used. Moreover, calcium and rhBMP-2 demonstrated a synergistic effect enhancing osteogenic differentiation, and fully restored mechanical strength 8 weeks after surgery. Collectively, these findings suggest the Biomimetic Hematoma provides a natural reservoir for rhBMP-2, and that retention of the protein within the scaffold rather than its sustained release might be responsible for more robust and rapid bone healing. Clinically, this new implant, using FDA-approved components, would not only reduce the risk of adverse events associated with BMPs, but also decrease treatment costs and nonunion rates.

Fracture hematoma micro-architecture influences transcriptional profile and plays a crucial role in determining bone healing outcomes.

The hematoma that forms between broken fragments of bone serves as a natural fibrin scaffold, and its removal from the defect site delays bone healing. The hypothesis of this study is that the microarchitectural and mechanical properties of the initially formed hematoma has a significant effect on the regulation of the biological process, which ultimately determines the outcome of bone healing. To mimic three healing conditions in the rat femur (normal, delayed, and non-healing bone defects), three different defect sizes of 0.5, 1.5, and 5.0 mm, are respectively used. The analysis of 3-day-old hematomas demonstrates clear differences in fibrin clot micro-architecture in terms of fiber diameter, fiber density, and porosity of the formed fibrin network, which result in different mechanical properties (stiffness) of the hematoma in each model. Those differences directly affect the biological processes involved. Specifically, RNA-sequencing reveals almost 700 differentially expressed genes between normally healing and non-healing defects, including significantly up-regulated essential osteogenic genes in normally healing defects, also differences in immune cell populations, activated osteogenic transcriptional regulators as well as potential novel marker genes. Most importantly, this study demonstrates that the healing outcome has already been determined during the hematoma phase of bone healing, three days post-surgery.

Classification of fractional order biomarkers for anomalous diffusion using q-space entropy.

In this study, we applied continuous random walk theory (CTRW) to develop a new model that characterizes anomalous diffusion in magnetic resonance imaging experiments. Furthermore, we applied a classification scheme based on information theoretic a techniques to characterize the degree of heterogeneity and complexity in biological tissues. From a CTRW approach, the Fourier transform of the generalized solution to the diffusion equation comes in the form of the Mittag-Leffler function. In this solution form, the relative stochastic uncertainty in the diffusion process can be computed with spectral entropy. We interrogated both white and gray matter regions of a fixed rat brain with diffusion - weighted magnetic resonance imaging experiments up to 26,000 s/mm² by independently weighting q and Δ. to investigate the effects on the diffusion phenomena. Our model fractional order parameters, α and ß, and entropy measure, H(q, Δ), differentiated between tissue types and extracted differing information within a region of interest based on the type of diffusion experiment performed. By combining fractional order modeling and information theory, new and powerful biomarkers are available to characterize tissue microstructure and provide contextual information about the anatomical complexity.

General strategy for self-assembly of highly oriented nanocrystalline semiconducting polymers with high mobility.

Solution processable semiconducting polymers with excellent film forming capacity and mechanical flexibility are considered among the most progressive alternatives to conventional inorganic semiconductors. However, the random packing of polymer chains and the disorder of the polymer matrix typically result in low charge transport mobilities (10(-5)-10(-2) cm(2) V(-1) s(-1)). These low mobilities compromise their performance and development. Here, we present a strategy, by utilizing capillary action, to mediate polymer chain self-assembly and unidirectional alignment on nanogrooved substrates. We designed a sandwich tunnel system separated by functionalized glass spacers to induce capillary action for controlling the polymer nanostructure, crystallinity, and charge transport. Using capillary action, we demonstrate saturation mobilities with average values of 21.3 and 18.5 cm(2) V(-1 )s(-1) on two different semiconducting polymers at a transistor channel length of 80 µm. These values are limited by the source-drain contact resistance, Rc. Using a longer channel length of 140 µm where the contact resistance is less important, we measured µh = 36.3 cm(2) v(-1) s(-1). Extrapolating to infinite channel length where Rc is unimportant, the intrinsic mobility for poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiadiazolo[3,4-c]pyridine] (Mn = 140 kDa) at this degree of chain alignment and structural order is µh ≈ 47 cm(2 )v(-1) s(-1). Our results create a promising pathway toward high performance, solution processable, and low-cost organic electronics.

High-mobility field-effect transistors fabricated with macroscopic aligned semiconducting polymers.

A record high OFET hole mobility, as high as 23.7 cm(2) /Vs, is achieved in macroscopic aligned semiconducting polymers. The high mobility is insensitive to the polymer molecular weight. Polymer chains are aligned along the fiber to facilitate intrachain charge transport.

Solvent additive effects on small molecule crystallization in bulk heterojunction solar cells probed during spin casting.

Solvent additive processing can lead to drastic improvements in the power conversion efficiency (PCE) in solution processable small molecule (SPSM) bulk heterojunction solar cells. In situ grazing incidence wide-angle X-ray scattering is used to investigate the kinetics of crystallite formation during and shortly after spin casting. The additive is shown to have a complex effect on structural evolution invoking polymorphism and enhanced crystalline quality of the donor SPSM.

Narrow-band-gap conjugated chromophores with extended molecular lengths.

The influence of extending the molecular length of donor-acceptor chromophores on properties relevant to organic optoelectronic devices has been studied by using two new narrow-band-gap systems. Most significantly, we find that the higher molecular weight systems exhibit higher thermal stabilities (beyond 200 °C) when introduced into field effect transistor devices. It is also possible to fabricate bulk heterojunction solar cells using PC(61)BM with power conversion efficiencies >6%. These high values are not heavily influenced by the blend composition and are achieved without the influence of solvent additives or postdeposition thermal annealing.

High mobility field effect transistors based on macroscopically oriented regioregular copolymers.

Field-effect transistors fabricated from semiconducting conjugated polymers are candidates for flexible and low-cost electronic applications. Here, we demonstrate that the mobility of high molecular weight (300 kDa) regioregular, poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiadiazolo[3,4-c]pyridine] can be significantly improved by introducing long-range orientation of the polymer chains. By annealing for short periods, hole mobilities of 6.7 cm(2)/(V s) have been demonstrated. The transport is anisotropic, with a higher mobility (approximately 6:1) parallel to the polymer backbone than that perpendicular to the polymer backbone.

Solar cell efficiency, self-assembly, and dipole-dipole interactions of isomorphic narrow-band-gap molecules.

We examine the correlations of the dipole moment and conformational stability to the self-assembly and solar cell performance within a series of isomorphic, solution-processable molecules. These charge-transfer chromophores are described by a D(1)-A-D-A-D(1) structure comprising electron-rich 2-hexylbithiophene and 3,3'-di-2-ethylhexylsilylene-2,2'-bithiophene moieties as the donor units D(1) and D, respectively. The building blocks 2,1,3-benzothiadiazole (BT) and [1,2,5]thiadiazolo[3,4-c]pyridine (PT) were used as the electron-deficient acceptor units A. Using a combination of UV-visible spectroscopy, field-effect transistors, solar cell devices, grazing incident wide-angle X-ray scattering, and transmission electron microscopy, three PT-containing compounds (1-3) with varying regiochemistry and symmetry, together with the BT-based compound 5,5'-bis{(4-(7-hexylthiophen-2-yl)thiophen-2-yl)-[1,2,5]thiadiazolobenzene}-3,3'-di-2-ethylhexylsilylene-2,2'-bithiophene (4), are compared and contrasted in solution, in thin films, and as blends with the electron acceptor [6,6]-phenyl-C(70)-butyric acid methyl ester. The molecules with symmetric orientations of the PT acceptor, 1 and 2, yield highly ordered blended thin films. The best films, processed with the solvent additive 1,8-diiodooctane, show donor "crystallite" length scales on the order of 15-35 nm and photovoltaic power conversion efficiencies (PCEs) of 7.0 and 5.6%, respectively. Compound 3, with an unsymmetrical orientation of PT heterocycles, shows subtle differences in the crystallization behavior and a best PCE of 3.2%. In contrast, blends of the BT-containing donor 4 are highly disordered and give PCEs below 0.2%. We speculate that the differences in self-assembly arise from the strong influence of the BT acceptor and its orientation on the net dipole moment and geometric description of the chromophore.

Regioregular pyridal[2,1,3]thiadiazole π-conjugated copolymers.

π-Conjugated, narrow band gap copolymers containing pyridal[2,1,3]thiadiazole (PT) were synthesized via starting materials that prevent random incorporation of the PT heterocycles relative to the backbone vector. Two regioregular structures could be obtained: in one the PTs are oriented in the same direction, and in the other the orientation of the PTs alternates every other repeat unit. Compared to their regiorandom counterparts, the regioregular polymers exhibit a 2 orders of magnitude increase of the hole mobilites, from 0.005 to 0.6 cm(2) V(-1) s(-1), as determined by field-effect transistor measurements.