Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.

Evaluation of biocompatibility of the AC8 peptide and its potential use as a drug carrier.

Peptide-based nanoparticles have emerged as promising drug delivery systems for targeted cancer therapy. Yet, the biocompatibility of these nanoparticles has not been elucidated. Here, the in vitro biocompatibility and toxicity and in vivo immunocompatibility and bioactivity of the self/coassembling peptide AC8 in its nanoparticle form are evaluated. AC8 showed minimal hemolytic activity (5%) and did not cause aggregation of red blood cells. The in vitro assay revealed that AC8 did not activate the complement system via the classical or alternative pathway but did activate the lectin pathway to a small extent. However, AC8 showed no C3a and C5a anaphylotoxin activation suggesting that complement activation did not proceed to the later, inflammatory, stages. The in vivo immune response assay showed that administration of AC8 to BALB/c mice had no effect on the weight of immune organs or body weight of mice at doses less than 0.1 mg/kg. This peptide also did not have any effect on the expression of CD3+ T-cells and natural killer (NK) cells, the ratio of CD4+/CD8+ T-cell, and the proliferation of B-cells. These results suggest that AC8 can be a potential carrier candidate for drug delivery.

Biocompatibility of engineered nanoparticles for drug delivery.

The rapid advancement of nanotechnology has raised the possibility of using engineered nanoparticles that interact within biological environments for treatment of diseases. Nanoparticles interacting with cells and the extracellular environment can trigger a sequence of biological effects. These effects largely depend on the dynamic physicochemical characteristics of nanoparticles, which determine the biocompatibility and efficacy of the intended outcomes. Understanding the mechanisms behind these different outcomes will allow prediction of the relationship between nanostructures and their interactions with the biological milieu. At present, almost no standard biocompatibility evaluation criteria have been established, in particular for nanoparticles used in drug delivery systems. Therefore, an appropriate safety guideline of nanoparticles on human health with assessable endpoints is needed. In this review, we discuss the data existing in the literature regarding biocompatibility of nanoparticles for drug delivery applications. We also review the various types of nanoparticles used in drug delivery systems while addressing new challenges and research directions. Presenting the aforementioned information will aid in getting one step closer to formulating compatibility criteria for biological systems under exposure to different nanoparticles.

A new amphipathic, amino-acid-pairing (AAP) peptide as siRNA delivery carrier: physicochemical characterization and in vitro uptake.

RNA interference has emerged as a powerful tool in biological and pharmaceutical research; however, the enzymatic degradation and polyanionic nature of short interfering RNAs (siRNAs) lead to their poor cellular uptake and eventual biological effects. Among nonviral delivery systems, cell-penetrating peptides have been recently employed to improve the siRNA delivery efficiency. Here we introduce an 18-mer amphipathic, amino-acid-pairing peptide, C6, as an siRNA delivery carrier. Peptide C6 adopted a helical structure upon coassembling with siRNA. The C6-siRNA coassembly showed a size distribution between 50 and 250 nm, confirmed by dynamic light scattering and atomic force microscopy. The C6-siRNA interaction enthalpy and stoichiometry were 8.8 kJ·mol(-1) and 6.5, respectively, obtained by isothermal titration calorimetry. A minimum C6/siRNA molar ratio of 10:1 was required to form stable coassemblies/complexes, indicated by agarose gel shift assay and fluorescence spectroscopy. Peptide C6 showed lower toxicity and higher efficiency in cellular uptake of siRNA compared with Lipofectamine 2000. Fluorescence microscopy images also confirmed the localization of C6-siRNA complexes in the cytoplasm using Cy3-labeled siRNAs. These results indicate high capabilities of C6 in forming safe and stable complexes with siRNA and enhancing its cellular uptake.