Distinct Effects of Heparin and Interleukin-4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats.

Two of the greatest challenges for successful application of small-diameter in situ tissue-engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual-functionalized with anti-thrombogenic heparin (hep) and anti-inflammatory interleukin 4 (IL-4) using a supramolecular approach. The regenerative capacity of IL-4/hep, hep-only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow-up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months). Routine analyses are augmented with Raman microspectroscopy, in order to acquire the local molecular fingerprints of the resorbing scaffold and developing tissue. Thrombosis is found not to be a confounding factor in any of the groups. Hep-only-functionalized grafts resulted in adverse tissue remodeling, with cases of local intimal hyperplasia. This is negated with the addition of IL-4, which promoted M2 macrophage polarization and more mature neotissue formation. This study shows that with bioactive functionalization, the early inflammatory response can be modulated and affect the composition of neotissue. Nevertheless, variability between graft outcomes is observed within each group, warranting further evaluation in light of clinical translation.

Cyclic Strain Affects Macrophage Cytokine Secretion and Extracellular Matrix Turnover in Electrospun Scaffolds.

IMPACT STATEMENT: Electrospun elastomeric scaffolds are being used for a variety of in situ tissue engineering applications, in which biomechanical loads play a dominant in vivo role, such as cardiovascular replacements (e.g., heart valve and blood vessel prostheses) and pelvic floor reconstruction. The findings of this study underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, for example, in terms of stiffness and compliance, to support a desirable proregenerative macrophage phenotype. Moreover, this research contributes to the general understanding of pathophysiological macrophage phenotypes in cyclically strained tissues (e.g., atherosclerotic plaques), and their role in tissue regeneration and degeneration.

Effects of polarization and apodization on laser induced optical breakdown threshold.

We investigated the influence of polarization and apodization on laser induced optical breakdown threshold in transparent and diffuse media using linearly and radially polarized light. We demonstrate a lower irradiance threshold for optical breakdown using radially polarized light. The dominance of radial polarization in higher-order multiphoton ionization has important medical applications where a lower irradiance threshold may allow reaching deeper layers inside the skin with less risk of collateral damage and thereby improving safety and efficacy of treatment.