Multi-step connective tissue stabilization method and stabilized tissue formed thereby

A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator

Vascular biomaterial devices and methods

Vascular biomaterial structures may be coated with a plasma-induced layer on their surface. Vascular biomaterial structures may include cardiovascular devices such as heart valves, stents, vascular graphs, and the like. Devices coated with a plasma polymerized coating may show reduced amounts of undesirable coagulation of blood at the surface of the device. A reduced amount of thrombosis may be observed for such plasma coated medical devices

Pediatric Cardiac Devices: Recent Progress and Remaining Problems

Pediatric cardiology is a field that largely relies on translation of innovation in its adult counterpart in order to improve patient outcomes and introduce new technology to the field. Few FDA-approved pediatric cardiac devices are available for clinical use, thus leading to widespread off-label use within the field. Nonetheless, adaption of devices and technology from the adult field has proven to improve patient outcomes and overall wellness. However, the diversity of congenital heart disease, in terms of basic anatomy and treatment response, continues to complicate results. The combination of diversity of anatomy and small population size make it difficult for identifying control populations on which to test new devices, thus limiting the amount of safety and efficacy data that can be gathered. With little guidance and long-term data due to off-label use and poor reporting infrastructure, physicians are often left to devise solutions on a case-by-case basis. While surgery continues to be a mainstay of pediatric cardiology, transcatheter approaches to treating congenital heart disease have continued to gain momentum. With increasing data and multiplying device options, physicians have various options for approaching congenital heart disease. More recently, the creation of large databases such as Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) has made evaluating the safety and efficacy of pediatric cardiac devices more realistic. In this review, various approaches to surgical and device treatment of congenital heart diseases and conditions will be explored in order to shed light on the current status of pediatric cardiac devices

Future treatments for the arteriopathy of ectopic calcification disorders

Ectopic calcification disorders, including Generalized Arterial Calcification of Infancy (GACI) and Pseudoxanthoma Elasticum are rare but impactful on individuals, healthcare and society, with significant associated morbidity, mortality and healthcare costs. Available therapies are not curative and focus on reducing extracellular calcification to limit progression of the arteriopathy that is responsible for much of the morbidity and, in the case of GACI, significant early mortality (approximately 50% in infancy). In this article, current and emerging medical approaches are reviewed and critiqued, including dietary manipulation, phosphate binders, bisphosphonates, tissue nonspecific alkaline phosphatase inhibitors, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement, allele-specific therapies, gene therapies, and antibody targeted treatment. Available therapies may limit further arterial calcification, but in GACI in particular, significant calcification can be present at birth, contributing to high infant mortality. This highlights the need for new approaches that aim to reverse established calcification, rather than merely slow its progression. Recently, a promising new class of antibody-targeted nanoparticle therapeutics has emerged that can reverse established arterial calcification in animals, restoring arterial elasticity. In one realization, nanoparticles carry established chelators, such as ethylenediaminetetraacetic disodium acid, to sites of arterial damage, concentrating the impact of the chelator where it is needed and limiting off-target effects. Such drugs would complement existing and emerging therapies, such as ENPP1 enzyme replacement, that slow or prevent progression of calcification, by offering an opportunity to “reset” arterial health in ectopic calcification disorders. At present, ectopic calcification disorders are challenging to treat effectively and carry a high burden of morbidity and mortality, particularly in GACI. Recent drug developments offer good reason to be hopeful for a new era of effective therapeutics that may reverse established arterial disease as well as halt its progression

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice.

AimAbdominal aortic aneurysms (AAA) is a life-threatening weakening and expansion of the abdominal aorta due to inflammatory cell infiltration and gradual degeneration of extracellular matrix (ECM). There are no pharmacological therapies to treat AAA. We tested the hypothesis that nanoparticle (NP) therapy that targets degraded elastin and delivers anti-inflammatory, anti-oxidative, and ECM stabilizing agent, pentagalloyl glucose (PGG) will reverse advance stage aneurysm in an elastase-induced mouse model of AAA.Method and resultsPorcine pancreatic elastase (PPE) was applied periadventitially to the infrarenal aorta in mice and AAA was allowed to develop for 14 days. Nanoparticles loaded with PGG (EL-PGG-NPs) were then delivered via IV route at 14-day and 21-day (10 mg/kg of body weight). A control group of mice received no therapy. The targeting of NPs to the AAA site was confirmed with fluorescent dye marked NPs and gold NPs. Animals were sacrificed at 28-d. We found that targeted PGG therapy reversed the AAA by decreasing matrix metalloproteinases MMP-9 and MMP-2, and the infiltration of macrophages in the medial layer. The increase in diameter of the aorta was reversed to healthy controls. Moreover, PGG treatment restored degraded elastic lamina and increased the circumferential strain of aneurysmal aorta to the healthy levels.ConclusionOur results support that site-specific delivery of PGG with targeted nanoparticles can be used to treat already developed AAA. Such therapy can reverse inflammatory markers and restore arterial homeostasis

Macromonomer for preparation of a degradable hydrogel

A degradable hydrogel and a method of making a degradable hydrogel is disclosed herein. The method comprises obtaining a hydrophilic polymer having at least two hydroxyl groups, reacting the hydrophilic polymer with a di-functional monomer comprised of an acid halide group and an alkyl halide group to form an intermediate having an ester bond and a terminal alkyl halide group, reacting the terminal alkyl halide group of the intermediate with a metallic salt of a vinyl acid monomer to form a macromonomer comprised of an ester, an alkyl group spacer, and a terminal vinyl group, and polymerizing the macromonomer to form a degradable hydrogel. A method is also disclosed for varying the degradation rate of the hydrogel as a function of the chemical composition of the alkyl group spacer in the terminal linkage of the macromonomer