Anticancer Therapeutic Alginate-Based Tissue Sealants for Lung Repair

Abstract

Injury to the connective tissue that lines the lung, the pleura, or to the lung itself can occur from many causes including trauma or surgery, as well as lung diseases or cancers. To address current limitations for patching lung injuries, to stop air or fluid leaks, an adherent hydrogel sealant patch system was developed, based on methacrylated alginate (AMA) and AMA di-aldehyde (AMA-DA) blends, which is capable of sealing damaged tissues and sustaining physiological pressures. Methacrylation of alginate hydroxyl groups rendered the polysaccharide capable of photo-crosslinking when mixed with an eosin Y-based photo-initiator system, and exposed to visible green light. Oxidation of alginate yields functional aldehyde groups capable of imine bond formation with proteins found in many tissues. The alginate-based patch system was rigorously tested on a custom burst pressure testing device. Blending of non-oxidized material with oxidized (aldehyde modified) alginates yielded patches with improved burst pressure performance, and decreased delamination as compared with pure AMA. Human mesothelial cell (MeT-5A) viability and cytotoxicity were retained when cultured with the hydrogel patches. The release and bioactivity of doxorubicin-encapsulated sub-microspheres enabled the fabrication of drug-eluting adhesive patches, and were effective in decreasing human lung cancer cell (A549) viability.

How to build a lung: latest advances and emerging themes in lung bioengineering

“…Furthermore, there has been work on the development of biomaterials that can serve as artificial pleuras for diseases and acute conditions that affect the visceral pleura (e.g. pneumothorax and mesothelioma) [170,171]. Thus, there may be potential clinical impact for partial reconstruction or replacement of lung tissue with tissue-engineered products in patients where only certain regions of the lung are damaged.…”

Physico-mechanical Characterization of Liquid versus Solid Applications of Visible Light Cross-Linked Tissue Sealants

“…Polymer concentrations were selected based on viscosity values, to maintain injectable formulations. The polymer and blend concentrations were chosen based on our earlier work; in addition, our focus was to investigate the differences between alginate, chitosan, and the effect of blending the two polymers. − Some of the hydrogel groups were prepared with or without the short-chain cross-linker MBAA (6% w/w). The concentration of MBAA was kept constant in all group to determine whether it can have a significant effect on the properties of the hydrogels. − Photosensitive initiator solution was prepared in PBS, pH 7.4, under red light to prevent premature photo-cross-linking.…”

“…The solution with the highest absorbance at 530 nm was chosen as the photoinitiator system for subsequent tests. According to previously published studies, the photosensitive initiator solution was prepared as follows: EY (1 mmol L-1, photosensitizer), TEOA (125 mmol L-1, initiator), VP (20 mmol L-1, catalyst). ,,, The hydrogel precursor solutions (PBS, pH 7.4) were prepared with the photosensitive initiator solution, which were then used for the liquid-based tissue sealants. To fabricate tissue sealant hydrogel patches, the polymer precursor solutions were prepared with the photosensitive initiator solution and injected between two sheets of polytetra­fluoroethylene (Teflon) with a 1 mm spacer using a syringe and 20-gauge needle, taking care to avoid the formation of air bubbles.…”

“…Quantitative burst pressure testing was performed on hydrogels, from liquid-based and solid-based sealants ( n = 3), according to standard ASTM F2392–04. A custom-built burst pressure testing device was employed as previously described and set up in an incubator at 37 °C. , All burst pressure tests were conducted a 37 °C. Collagen-rich substrates (Collagen Casings, The Sausage Maker Inc.) were used as an in vitro test membrane and were hydrated for 30 min prior to testing.…”

Injectable and Biocompatible Mussel‐Inspired Adhesive for Enhanced Reendothelialization of Injured Artery

“…[ 3 ] As alternative devices to avoid second injury, bioadhesives attract tremendous attentions due to their applications in wound closure, hemostatic, tissue repair, and especially targeted delivery of therapeutic agents to lesion location. [ 4–8 ] However, the moist environment in tissue and body fluid has severely reduced the adhesive strength, and thereby limited the real‐world application of adhesive‐based drug transporter.…”