No abstract

Biomaterial scaffolds are fundamental components of strategies aimed at engineering a wide range of tissues. Scaffolds possessing uniform, oriented microtubular architectures could be ideal for multiple tissues, but are challenging to produce. Therefore, we developed hydrogel scaffolds possessing regular, tubular microstructures from self-assembled copper-capillary alginate gel (CCAG). To abrogate the rapid dissolution of CCAG in cell culture media, we treated it with oligochitosan and created a stable oligochitosan-CCAG (OCCAG) polyelectrolyte complex. Fourier transform infrared spectroscopy confirmed polyelectrolyte complexation between alginate and oligochitosan. OCCAG retained capillary morphology, shrank anisotropically in bulk, lost Cu(2+) ions, and maintained (71.9 +/- 5.65)% of its mass in cell culture media. Next, we seeded mouse embryonic stem (ES) cells within OCCAG scaffolds, and examined cell morphology and quantified cell growth and viability over four days. ES cells were guided to form cylindrical structures of staggered cells within scaffold capillaries. Analysis of the total cells recovered from the scaffolds revealed exponential cell growth (normalized to day 0) that was statistically similar to gelatinized-plate controls. OCCAG-cultured ES cell viability was also not significantly different from controls at day 4. CCAG-derived scaffolds can therefore serve as a unique platform for stem cell-based tissue engineering.

Nearly 12 million wounds are treated in emergency departments throughout the United States every year. The limitations of current treatments for complex, full-thickness wounds are the driving force for the development of new wound treatment devices that result in faster healing of both dermal and epidermal tissue. Here, a bilayered, biodegradable hydrogel dressing that uses microarchitecture to guide two key steps in the proliferative phase of wound healing, re-epithelialization, and revascularization, was evaluated in vitro in a cell migration assay and in vivo in a bipedicle ischemic rat wound model. Results indicate that the Sharklet TM -micropatterned apical layer of the dressing increased artificial wound coverage by up to 64%, P ¼ 0.024 in vitro. In vivo evaluation demonstrated that the bilayered dressing construction enhanced overall healing outcomes significantly compared to untreated wounds and that these outcomes were not significantly different from a leading clinically available wound dressing.Collectively, these results demonstrate high potential for this new dressing to effectively accelerate wound healing.Keywords: Micropattern, wound healing, biomaterials, hydrogel, gelatin, microarchitectureExperimental Biology and Medicine 2016; 241: 986-995.

In severe hypoxic–ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper–capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain.

Colorimetric detection of arboviruses and vector mosquito species. (A) Aptamer-gold nanoparticle conjugates, (B) mosquito salivary protein, (C) Zika envelope protein, (D) visible color change, (E) imbibed diagnostic and (F) diagnostic cards.

A polydimethylsiloxane-based microfluidic device has been developed for the multiplex detection of viral envelope proteins such as Zika and chikungunya on a single platform using aptamer–analyte interactions. The channel is integrated with microsized pillars that increase the surface area allowing more aptamers to attach to the incoming envelope protein molecules, thus increasing the overall sensitivity of the system. The working of the device depends on the formation of protein-mediated sandwich morphology that is obtained using an aptamer and aptamer-functionalized gold nanoparticle (AuNP) pair. The colorimetric signal is obtained upon introduction of silver reagents into the channel, which are selectively deposited on the AuNP surface, providing a gray contrast in the testing zone. The microfluidic channel approach successfully detected clinically relevant concentrations of Zika and chikungunya envelope proteins in phosphine-buffered saline (1 pM) and calf blood (100 pM) with high specificity using gold-decorated aptamers integrated in a microfluidic channel.

Morphological modification of gold nanoparticles to obtain a highly efficient paper based sensor for colorimetric detection of epinephrine (LOD – Limit of Detection).

Background A new post–myocardial infarction (MI) therapy is injection of high-water content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. Methods We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48 hours) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4 weeks (week 4) to evaluate left ventricular function. Results Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4 weeks, but was minimal at 8 weeks. The remaining gel was heavily populated by CD68+ macrophages with CD206+ clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90 days. Conclusions Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).