Pores are key features of natural tissues and the development of tissues scaffolds with biomimetic properties (pore structures and chemical/mechanical properties) offers a route to engineer implantable biomaterials for specific niches in the body. Here we report the use of sacrificial crystals (potassium dihydrogen phosphate or urea) that act as templates to impart pores to hyaluronic acid-based hydrogels. The mechanical properties of the hydrogels were analogous to the nervous system (in the Pascal regime), and we investigated the use of the potassium dihydrogen phosphate crystaltemplated hydrogels as scaffolds for neural progenitor cells (NPCs), and the use of urea crystal-templated hydrogels as scaffolds for Schwann cells. For NPCs cultured inside the porous hydrogels, assays for the expression of Nestin are inconclusive, assays for GFAP and BIII-tubulin expression suggest that the NPCs maintain their undifferentiated phenotype more effectively than the controls (with glial fibrillary acidic protein (GFAP) and BIII-tubulin expression at ca. 50% relative to the chemically/mechanically equivalent not templated control hydrogels). For Schwann cells cultured within these hydrogels, assays for the expression of S100 protein or Myelin basic protein confirm the expression of both proteins, albeit at lower levels on the templated hydrogels (ca. 50%) than on the chemically/mechanically equivalent not templated control hydrogels. Such sacrificial crystal templated hydrogels represent platforms for biomimetic 3D tissue scaffolds for the nervous system.
Calcium phosphate-based cements with enhanced regenerative potential are promising biomaterials for the healing of bone defects in procedures such as percutaneous vertebroplasty. With a view to the use of such cements for low load bearing applications such as sinus augmentation or filling extraction sites. However, the inclusion of certain species into bone cement formulations has the potential to diminish the mechanical properties of the formulations and thereby reduce their prospects for clinical translation. Consequently, we have prepared α-tricalcium phosphate (α-TCP)-based bone cements including materials that we would expect to improve their regenerative potential, and describe the mechanical properties of the resulting formulations herein. Formulations incorporated α-TCP, hydroxyapatite, biopolymer-thickened wetting agents, sutures, and platelet poor plasma. The mechanical properties of the composites were composition dependent, and optimized formulations had clinically relevant mechanical properties. Such calcium phosphate-based cements have potential as replacements for cements such as those based on polymethylmethacrylate.
BackgroundVA-ECMO with concomitant Impella support (ECpella) is an emerging treatment modality for cardiogenic shock (CS). Survival outcomes by CS etiology with ECpella support have not been well-described.MethodsThis study was a retrospective, single-center analysis of patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) or decompensated heart failure (ADHF-CS) supported with ECpella from December 2020 to January 2023. Primary outcomes included 90-day survival post-discharge and destination after support. Secondary outcomes included complications post-ECpella support.ResultsA total of 44 patients were included (AMI-CS,n =20, and ADHF-CS,n= 24). Patients with AMI-CS and ADHF-CS had similar survival 90 days post-discharge (p= .267) with similar destinations after ECpella support (p =.220). Limb ischemia and acute kidney injury occurred more frequently in patients presenting with AMI-CS (p=.013;p= .030). Patients with initial Impella support were more likely to survive ECpella support and be bridged to transplant (p=.033) and less likely to have a cerebrovascular accident(p=.016). Sub-analysis of ADHF-CS patients into acute-on-chronic decompensated heart failure and de novo heart failure demonstrated no difference in survival or destination.ConclusionECpella can be used to successfully manage patients with CS. There is no difference in survival or destination for AMI-CS and ADHF-CS in patients with ECpella support. Patients with initial Impella support are more likely to survive ECpella support and bridge to transplant. Future multicenter studies are required to fully analyze the differences between AMI-CS and ADHF-CS with ECpella support.Clinical PerspectivesWhat is New?ECpella support is a feasible support strategy for allcomers in severe cardiogenic shock. This study demonstrates that ECpella can be utilized not only as a salvage therapy and venting strategy for those in cardiogenic shock on VA-ECMO, but also can be utilized as a method for additional cardiac support for patients with initial Impella support. There were no differences in survival between cardiogenic shock secondary to acute myocardial infarction and cardiogenic secondary to acute decompensated heart failure.What are the clinical implications?Although ECpella patients that received initial Impella support have higher success in bridging to heart transplant, allcomers on ECpella support should be evaluated for advanced therapies early in their clinical course. Further studies are required to ascertain the differences in pathophysiology between cardiogenic shock secondary to acute myocardial infarction and cardiogenic secondary to acute decompensated heart failure and determine appropriate support strategies for differing cardiogenic shock phenotypes.
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