Elastogenic cues and methods for using same

Disclosed are elastogenic cues that can be utilized to encourage growth and development of elastin-containing cellular constructs. The elastogenic cues include hyaluronan fragments and oligomers, optionally in conjunction with growth factors and/or a source of copper ions. The elastogenic cues can up-regulate elastin matrix synthesis and by vascular smooth muscle cells. In addition to encouraging synthesis of elastin in a cellular matrix and organization into elastic fibers, the elastogenic cues can also stabilize the formed ECM matrix through suppression of elastin-laminin receptor (ELR). In addition, the elastogenic cues can inhibit cell hyper-proliferation (e.g., hyperplasia) common in inflammatory vascular disease

Delivery of Mesenchymal Stem Cells from Gelatin–Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICCs) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric emptying. Regenerating these fundamental structures with mesenchymal stem cell (MSC) therapy would be helpful to restore gastric function in GP. MSCs have been successfully used in animal models of other gastrointestinal (GI) diseases, including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored whether mouse MSCs can be delivered from a hydrogel scaffold to the luminal surfaces of mice stomach explants. Mouse MSCs were seeded atop alginate–gelatin, coated with poly-l-lysine. These cell–gel constructs were placed atop stomach explants facing the luminal side. MSCs grew uniformly all across the gel surface within 48 h. When placed atop the lumen of the stomach, MSCs migrated from the gels to the tissues, as confirmed by positive staining with vimentin and N-cadherin. Thus, the feasibility of transplanting a cell–gel construct to deliver stem cells in the stomach wall was successfully shown in a mice stomach explant model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with cells and growth factors

A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering

In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL) filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC) to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF) showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC

Development of in vitro cardiovascular tissue models within capillary circuit microfluidic devices fabricated with 3D stereolithography printing

Abstract This study presents the development and morphology analysis of bioinspired 3D cardiovascular tissue models cultured within a dynamic capillary circuit microfluidic device. This study is significant because our in vitro 3D cardiovascular tissue models retained within a capillary circuit microfluidic device provide a less expensive, more controlled, and reproducible platform for more physiologically-relevant evaluation of cellular response to microenvironmental stimuli. The overall aim of our study is to demonstrate our cardiovascular tissue model (CTM) and vascular tissue model (VTM) actively changed their cellular morphology and exhibited structural reorganization in response to biophysical stimuli provided by microposts within the device tissue culture chambers during a 5-day period. The microfluidic device in this study was designed with the Young–Laplace and Navier–Stokes principles of capillary driven fluid flow and fabricated with 3D stereolithography (SLA) printing. The cardiac tissue model and vascular tissue model presented in this study were developed by encapsulating AC16 cardiomyocytes (CTM) and Human umbilical vein endothelial cells (VTM) in a fibrin hydrogel which were subsequently loaded into a capillary circuit microfluidic device. The cardiovascular tissue models were analyzed with fluorescent microscopy for morphological differences, average tube length, and cell orientation. We determined the VTM displayed capillary-like tube formation and the cells within both cardiovascular tissue models continued to elongate around microposts by day-5 which indicates the microfluidic system provided biophysical cues to guide cell structure and direction-specific organization

Cardioprotective Effect of Glycyrrhizin on Myocardial Remodeling in Diabetic Rats

Myocardial fibrosis is one of the major complications of long-term diabetes. Hyperglycemia induced cardiomyocyte atrophy is a frequent pathophysiological indicator of diabetic heart. The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in diabetic rats and assess the anti-inflammatory and anti-fibrotic effect of GLC. Our study demonstrates that hyperglycemia can elevate cardiac atrophy in diabetic animals. Type 2 diabetic fatty and the lean control rats were evaluated for cardiac damage and inflammation at 8–12 weeks after the development of diabetes. Western blot and immunohistochemical studies revealed that gap junction protein connexin-43 (CX43), cardiac injury marker troponin I, cardiac muscle specific voltage gated sodium channel NaV1.5 were significantly altered in the diabetic heart. Furthermore, oxidative stress mediator receptor for advanced glycation end-products (RAGE), as well as inflammatory mediator phospho-p38 MAPK and chemokine receptor CXCR4 were increased in the diabetic heart whereas the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), the antioxidant proteins that protect against oxidative damage was reduced. We also observed an increase in the expression of the pleiotropic cytokine, transforming growth factor beta (TGF-β) in the diabetic heart. GLC treatment exhibited a decrease in the expression of phospho-p38 MAPK, RAGE, NaV1.5 and TGF-β and it also altered the expression of CX43, CXCR4, Nrf2 and troponin I. These observations suggest that GLC possesses cardioprotective effects in diabetic cardiac atrophy and that these effects could be mediated through activation of Nrf2 and inhibition of CXCR4/SDF1 as well as TGF-β/p38MAPK signaling pathway