Advances in regenerative medicine have improved the potential of using cellular therapy for treating several diseases. However, the effectiveness of new cellular therapies is largely limited by low cell engraftment and inadequate localization. To improve upon these limitations, we developed a novel delivery mechanism using cell-seeded biological sutures. Herein, we demonstrate the ability of cell-seeded biological sutures to efficiently implant human mesenchymal stem cells (hMSCs) to specific regions within the beating heart; a tissue known to have low cell retention and engraftment shortly after delivery. Cell-seeded biological sutures were developed by bundling discrete microthreads extruded from extracellular matrix proteins, attaching a surgical needle to the bundle, and seeding the bundle with hMSCs. Prior to cell preparation, hMSCs were loaded with quantum dot (QD) nanoparticles for cell tracking within the myocardium. Each biological suture contained an average of 5,903 ± 1,966 hMSCs/cm suture length. Delivery efficiency was evaluated by comparing cell-seeded biological suture implantation with intramyocardial cell injections (10,000 hMSCs in 35 µL) into the left ventricle of normal, non-infarcted rat hearts after one hour. Delivery efficiency of hMSCs by biological sutures (63.6 ± 10.6%) was significantly higher than intramyocardial injection (11.8 ± 6.2%; p < 0.05). Cell-tracking analysis indicated suture-delivered hMSCs were found throughout the thickness of the ventricular myocardium; along the entire length of the biological suture track, localizing closely with native myocardium. These results suggest cell-seeded biological sutures can deliver cells to the heart more efficiently than conventional methods, demonstrating an effective delivery method for implanting cells in soft tissue.

Engineered cardiac tissues have been constructed with primary or stem cell-derived cardiac cells on natural or synthetic scaffolds. They represent a tremendous potential for treatment of injured areas through addition of tensional support and delivery of sufficient cells. In this study 1 to 6 million (M) neonatal cardiac cells were seeded on fibrin gels to fabricate cardiac tissue patches, and the effects of culture time and cell density on spontaneous contraction rates, twitch forces and paced response frequencies were measured. Electrocardiograms and signal volume index of connexin 43 were also analyzed. Patches of 1–6M cell densities exhibited maximal contraction rates between 305–410 bpm within the first 4 days after plating; low cell densities (1–3M) patches sustained rhythmic contraction longer than high cell densities (4–6M). Patches with 1–6 M cell densities generated contractile forces in the range 2.245–14.065 mN/mm3 on days 4–6. Upon patch formation, a paced response frequency of approximately 6 Hz was obtained, and decreased to approximately 3 Hz after 6 days of culture. High cell density patches contained a thicker real cardiac tissue layer which generated higher R wave amplitudes; however, low density patches had a greater signal volume index of connexin 43. In addition, all patches manifested endothelial cell growth and robust nuclear division. The present study demonstrates that the proper time for in vivo implantation of this cardiac construct is just at patch formation and patches with 3–4M cell densities are the best candidates.

The antifungal properties and mechanism of three types of chitosan against the rice sheath blight pathogen, Rhizoctonia solani, were evaluated. Each chitosan had strong antifungal activity against R. solani and protected rice seedlings from sheath blight, in particular, two types of acid-soluble chitosan caused a 60-91 % inhibition in mycelial growth, 31-84 % inhibition of disease incidence, and 66-91 % inhibition in lesion length. The mechanism of chitosan in protection of rice from R. solani pathogen was attributed to direct destruction of the mycelium, evidenced by scanning and transmission electron microscopic observations and pathogenicity testing; indirect induced resistance was evidenced by the changes in the activities of the defense-related phenylalanine ammonia lyase, peroxidase and polyphenol oxidase in rice seedling. To our knowledge, this is the first report on the antifungal activity of chitosan against rice R. solani.

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