Combination of a Collagen Scaffold and an Adhesive Hyaluronan-Based Hydrogel for Cartilage Regeneration: A Proof of Concept in an Ovine Model.

Objective: Hyaluronic acid-transglutaminase (HA-TG) is an enzymatically crosslinkable adhesive hydrogel with chondrogenic properties demonstrated and in an ectopic mouse model. In this study, we investigated the feasibility of using HA-TG in a collagen scaffold to treat chondral lesions in an ovine model, to evaluate cartilage regeneration in a mechanically and biologically challenging joint environment, and the influence of the surgical procedure on the repair process.

Design: Chondral defects of 6-mm diameter were created in the stifle joint of skeletally mature sheep.

Tyrosinase-crosslinked, tissue adhesive and biomimetic alginate sulfate hydrogels for cartilage repair.

The native cartilage extracellular matrix (ECM) is enriched in sulfated glycosaminoglycans with important roles in the signaling and phenotype of resident chondrocytes. Recapitulating the key ECM components within engineered tissues through biomimicking strategies has potential to improve the regenerative capacity of encapsulated cells and lead to better clinical outcome. Here, we developed a double-modified, biomimetic and tissue adhesive hydrogel for cartilage engineering.

Chondrocytes From Device-Minced Articular Cartilage Show Potent Outgrowth Into Fibrin and Collagen Hydrogels.

Background: Transplantation of autologous minced cartilage is an established procedure to repair chondral lesions. It relies on the migration of chondrocytes out of cartilage particles into a biomaterial. So far, there is no efficient way to finely mince cartilage.

Characterization of polydactyly chondrocytes and their use in cartilage engineering.

Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-β transduced polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns.

Growth of Epithelial Organoids in a Defined Hydrogel.

Epithelial organoids are simplified models of organs grown in vitro from embryonic and adult stem cells. They are widely used to study organ development and disease, and enable drug screening in patient-derived primary tissues. Current protocols, however, rely on animal- and tumor-derived basement membrane extract (BME) as a 3D scaffold, which limits possible applications in regenerative medicine.

Cell-Instructive Alginate Hydrogels Targeting RhoA.

Cellular processes involve dynamic rearrangement of the cytoskeleton. The GTPase RhoA plays a fundamental role in controlling cytoskeletal architecture. The phenotypic stability of chondrocytes is enhanced through inhibition of RhoA, whereas RhoA activation leads to dedifferentiation.

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.

Cyclic Polymer Grafts That Lubricate and Protect Damaged Cartilage.

Tissue-reactive graft copolymers were designed to protect the cartilage against enzymatic degradation and restore its lubrication properties during the early stages of osteoarthritis (OA). The copolymers feature a poly(glutamic acid) (PGA) backbone bearing hydroxybenzaldehyde (HBA) functions and cyclic poly(2-methyl-2-oxazoline) (PMOXA) side chains. PGA-PMOXA-HBA species chemisorb on the degraded tissue via Schiff bases and expose the biopassive and lubricious PMOXA cyclic grafts at the interface.

Nanoassemblies of Tissue-Reactive, Polyoxazoline Graft-Copolymers Restore the Lubrication Properties of Degraded Cartilage.

Osteoarthritis leads to an alteration in the composition of the synovial fluid, which is associated with an increase in friction and the progressive and irreversible destruction of the articular cartilage. In order to tackle this degenerative disease, there has been a growing interest in the medical field to establish effective, long-term treatments to restore cartilage lubrication after damage. Here we develop a series of graft-copolymers capable of assembling selectively on the degraded cartilage, resurfacing it, and restoring the lubricating properties of the native tissue.

Factor XIII Cross-Linked Hyaluronan Hydrogels for Cartilage Tissue Engineering.

In this study, transglutaminase-cross-linked hyaluronan (HA-TG) hydrogels are investigated for their potential to treat cartilage lesions. We show the hydrogels fulfill key requirements: they are simultaneously injectable, fast-gelling, biocompatible with encapsulated cells, mitogenic, chondroinductive, and form a stable and strongly adhesive bond to native cartilage. Human chondroprogenitors encapsulated in HA-TG gels simultaneously show good growth and chondrogenesis.

Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo.

The goal of this study was to evaluate human epiphyseal chondroprogenitor cells (ECPs) as a potential new cell source for cartilage regeneration. ECPs were compared to human bone marrow stromal cells (MSCs) and human adult articular chondrocytes (ACs) for their chondrogenic potential and phenotypic stability in vitro and in vivo. The cells were seeded in Optimaix-3D scaffolds at 5 × 10 cells/mm and gene expression, matrix production and mechanical properties were analysed up to 6 weeks.

Engineered Microtissues Formed by Schiff Base Crosslinking Restore the Chondrogenic Potential of Aged Mesenchymal Stem Cells.

A universal method for reproducibly directing stem cell differentiation remains a major challenge for clinical applications involving cell-based therapies. The standard approach for chondrogenic induction by micromass pellet culture is highly susceptible to interdonor variability. A novel method for the fabrication of condensation-like engineered microtissues (EMTs) that utilizes hydrophilic polysaccharides to induce cell aggregation is reported here.