Hydrogel foam dressings with angiogenic and immunomodulatory factors from mesenchymal stem cells.

Stem cell therapy and skin substitutes address the stalled healing of chronic wounds in order to promote wound closure; however, the high cost and regulatory hurdles of these treatments limit patient access. A low-cost method to induce bioactive healing has the potential to substantially improve patient care and prevent wound-induced limb loss. A previous study reported that bioactive factors derived from apoptotic-like mesenchymal stem cells (MSCs) demonstrated anti-inflammatory and proangiogenic effects and improved ischemic muscle regeneration. In this work, these MSC-derived bioactive factors were loaded into a hydrogel foam to harness immunomodulatory and angiogenic properties from MSC components to facilitate chronic wound healing without the high cost and translational challenges of cell therapies. After incorporation of bioactive factors, the hydrogel foam retained high absorbency, moisture retention, and target water vapor transmission rate. High loading efficiency was confirmed and release studies indicated that over 90% of loaded factors were released within 24 h. Ethylene oxide sterilization and 4-week storage did not affect the bioactive factor release profile or physical properties of the hydrogel foam dressing. Bioactivity retention of the released factors was also confirmed for as-sterilized, 4°C-stored, and -20°C-stored bioactive hydrogel foams as determined by relevant gene expression levels in treated pro-inflammatory (M1) macrophages. These results support the use of the bioactive dressings as an off-the-shelf product. Overall, this work reports a new method to achieve a first-line wound dressing with the potential to reduce persistent inflammation and promote angiogenesis in chronic wounds.

UCR-Net: U-shaped context residual network for medical image segmentation.

Medical image segmentation prerequisite for numerous clinical needs is a critical step in biomedical image analysis. The U-Net framework is one of the most popular deep networks in this field. However, U-Net's successive pooling and downsampling operations result in some loss of spatial information. In this paper, we propose a U-shaped context residual network, called UCR-Net, to capture more context and high-level information for medical image segmentation. The proposed UCR-Net is an encoder-decoder framework comprising a feature encoder module and a feature decoder module. The feature decoder module contains four newly proposed context attention exploration(CAE) modules, a newly proposed global and spatial attention (GSA) module, and four decoder blocks. We use the proposed CAE module to capture more multi-scale context features from the encoder. The proposed GSA module further explores global context features and semantically enhanced deep-level features. The proposed UCR-Net can recover more high-level semantic features and fuse context attention information from CAE and global and spatial attention information from GSA module. Experiments on the retinal vessel, femoropopliteal artery stent, and polyp datasets demonstrate that the proposed UCR-Net performs favorably against the original U-Net and other advanced methods.

Use of Oppositely Polarized External Magnets To Improve the Accumulation and Penetration of Magnetic Nanocarriers into Solid Tumors.

Drug delivery to solid tumors is hindered by hydrostatic and physical barriers that limit the penetration of nanocarriers into tumor tissue. When exploiting the enhanced permeability and retention (EPR) effect for passive targeting of nanocarriers, the increased interstitial fluid pressure and dense extracellular matrix in tumors limits the distribution of the nanocarriers to perivascular regions. Previous strategies have shown that magnetophoresis enhances accumulation and penetration of nanoparticles into solid tumors. However, because magnetic fields fall off rapidly with distance from the magnet, these methods have been limited to use in superficial tumors. To overcome this problem, we have developed a system comprising two oppositely polarized magnets that enables the penetration of magnetic nanocarriers into more deeply seeded tumors. Using this method, we demonstrate a 5-fold increase in the penetration and a 3-fold increase in the accumulation of magnetic nanoparticles within solid tumors compared to EPR.

In Vivo Characterization of Poly(ethylene glycol) Hydrogels with Thio-ß Esters.

Resorbable hydrogels have numerous potential applications in tissue engineering and drug delivery due to their highly tunable properties and soft tissue-like mechanical properties. The incorporation of esters into the backbone of poly(ethylene glycol) hydrogels has been used to develop libraries of hydrogels with tunable degradation rates. However, these synthetic strategies used to increase degradation rate often result in undesired changes in the hydrogel physical properties such as matrix modulus or swelling. In an effort to decouple degradation rate from other hydrogel properties, we inserted thio-ß esters into the poly(ethylene glycol)-diacrylate backbone to introduce labile bonds without changing macromer molecular weight. This allowed the number of hydrolytically labile thio-ß esters to be controlled through changing the ratios of this modified macromer to the original macromer without affecting network properties. The retention of hydrogel properties at different macromer ratios was confirmed by measuring gel fraction, swelling ratio, and compressive modulus. The tunable degradation profiles were characterized both in vitro and in vivo. Following confirmation of cytocompatibility after exposure to the hydrogel degradation products, the in vivo host response was evaluated in comparison to medical grade silicone. Collectively, this work demonstrates the utility and tunability of these hydrolytically degradable hydrogels for a wide variety of tissue engineering applications.