Factor XIII Cross-Linked Hyaluronan Hydrogels for Cartilage Tissue Engineering

ISSN:2373-987

Chemical design of non-ionic polymer brushes as biointerfaces : poly(2-oxazine)s outperform both poly(2-oxazoline)s and PEG

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation

Influence of N-methyl pyrrolidone on the activity of the pulp-dentine complex and bone integrity during osteoporosis

AIM To analyze the effect of systemic application of N-methyl pyrrolidone (NMP) on the pulp-dentine complex and on the jawbone of ovariectomized rats. METHOD Female Sprague-Dawley rats were randomly divided into a sham-operated group (Sham n=6) and an estrogen depletion by ovariectomy (OVX n=12) group. In 6 of the ovariectomized animals N-methyl pyrrolidone (NMP) in phosphate-buffered saline (PBS) was administered systemically weekly by intraperitoneal injection (i.p.); the other 6 were injected with PBS (Veh). After 15 weeks of injections the jaw bones were collected and pulps extracted from the incisors teeth. Histology was used to determine pre-dentine thickness in teeth and radiography to determine alveolar bone mass. Immunohistological staining and RT-PCR were performed to verify the presence and localization of the odontoblast specific dentine sialoprotein and to quantify its expression in the dentine pulp complex. Mandibular cortical width and mandibular height was evaluated by means of X-ray analysis. Statistical analysis was performed with analysis of variance (ANOVA). RESULTS Both pre-dentine (P=0.029) and alveolar bone structures (P=0.049) were significantly reduced due to estrogen deficiency in OVX Veh and OVX NMP treatment normalized these parameters to the Sham level. DSPP expression in OVX NMP animals was significantly higher (P=0.046) than in OVX Veh. X-ray analysis confirmed that ovariectomy significantly reduced the mandibular cortical width in the OVX Veh group compared to the Sham Veh and OVX NMP (P=0.020). CONCLUSION N-methyl pyrrolidone (NMP) had a remarkable anti-osteoporotic ability preserving the activity in the pulp-dentine complex and preventing jawbone loss. These effects make NMP a promising candidate for the preservation of the activity of the pulp-dentine complex and the jawbone thickness in postmenopausal females. This article is protected by copyright. All rights reserved

The role of poly(2-alkyl-2-oxazoline)s in hydrogels and biofabrication

Poly(2-alkyl-2-oxazoline)s (PAOXAs) have been rapidly emerging as starting materials in the design of tissue engineering supports and for the generation of platforms for cell cultures, especially in the form of hydrogels. Thanks to their biocompatibility, chemical versatility and robustness, PAOXAs now represent a valid alternative to poly(ethylene glycol)s (PEGs) and their derivatives in these applications, and in the formulation of bioinks for three-dimensional (3D) bioprinting. In this review, we summarize the recent literature where PAOXAs have been used as main components for hydrogels and biofabrication mixtures, especially highlighting how their easily tunable composition could be exploited to fabricate multifunctional biomaterials with an extremely broad spectrum of properties.ISSN:2047-4830ISSN:2047-484

An injectable heparin-conjugated hyaluronan scaffold for local delivery of transforming growth factor β1 promotes successful chondrogenesis.

Cartilage lacks basic repair mechanisms and thus surgical interventions are necessary to treat lesions. Minimally-invasive arthroscopic procedures require the development of injectable biomaterials to support chondrogenesis of implanted cells. However, most cartilage tissue engineering approaches rely on pre-culture of scaffolds in media containing growth factors (GFs) such as transforming growth factor (TGF)-β1, which are crucial for cartilage formation and homeostasis. GFs media-supplementation is incompatible with injectable approaches and has led to a knowledge gap about optimal dose of GFs and release profiles needed to achieve chondrogenesis. This study aims to determine the optimal loading and release kinetics of TGF-β1 bound to an engineered GAG hydrogel to promote optimal cartilaginous matrix production in absence of TGF-β1 media-supplementation. We show that heparin, a GAG known to bind a wide range of GFs, covalently conjugated to a hyaluronan hydrogel, leads to a sustained release of TGF-β1. Using this heparin-conjugated hyaluronan hydrogel, 0.25 to 50 ng TGF-β1 per scaffold was loaded and cell viability, proliferation and cartilaginous matrix deposition of the encapsulated chondroprogenitor cells were measured. Excellent chondrogenesis was found when 5 ng TGF-β1 per scaffold and higher were used. We also demonstrate the necessity of a sustained release of TGF-β1, as no matrix deposition is observed upon a burst release. In conclusion, our biomaterial loaded with an optimal initial dose of 5 ng/scaffold TGF-β1 is a promising injectable material for cartilage repair, with potentially increased safety due to the low, locally administered GF dose. STATEMENT OF SIGNIFICANCE: Cartilage cell-based products are dependent on exogenous growth factor supplementation in order for proper tissue maturation. However, for a one-step repair of defects without need for expensive tissue maturation, an injectable, growth factor loaded formulation is required. Here we show development of an injectable hyaluronan hydrogel, which achieves a sustained release of TGF-β1 due to covalent conjugation of heparin. These grafts matured into cartilaginous tissue in the absence of growth factor supplementation. Additionally, this system allowed us to screen TGF-β1 concentrations to determine the mimimum amount of growth factor required for chondrogenesis. This study represents a critical step towards development of a minimally-invasive, arthroscopic treatment for cartilage lesions

Hydrogels Generated from Cyclic Poly(2-Oxazoline)s Display Unique Swelling and Mechanical Properties

Cyclic macromolecules do not feature chain ends and are characterized by a higher effective intramolecular repulsion between polymer segments, leading to a higher excluded-volume effect and greater hydration with respect to their linear counterparts. As a result of these unique properties, hydrogels composed of cross-linked cyclic polymers feature enhanced mechanical strength while simultaneously incorporating more solvent with respect to networks formed from their linear analogues with identical molar mass and chemical composition. The translation of topology effects by cyclic polymers into the properties of polymer networks provides hydrogels that ideally do not include defects, such as dangling chain ends, and display unprecedented physicochemical characteristics