A Pre-Clinical Animal Study for Zonal Articular Cartilage Regeneration Using Stratified Implantation of Microcarrier Expanded Zonal Chondrocytes.

Objective: The zonal properties of articular cartilage critically contribute to the mechanical support and lubrication of the tissue. Current treatments for articular cartilage have yet to regenerate this zonal architecture, thus compromising the functional efficacy of the repaired tissue and leading to tissue degeneration in the long term. In this study, the efficacy of zonal cartilage regeneration through bilayered implantation of expanded autologous zonal chondrocytes was investigated in a porcine chondral defect model.

Mesenchymal Stem Cell Exosomes Promote Functional Osteochondral Repair in a Clinically Relevant Porcine Model.

Background: Previous studies have reported the efficacy of human mesenchymal stem cell (MSC) exosomes for the repair of osteochondral defects in rats and rabbits. However, the safety and efficacy of MSC exosomes remain to be validated in a clinically relevant large animal model.

Purpose: To validate the safety and efficacy of human MSC exosomes for osteochondral repair in a clinically relevant micropig model.

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model.

Purpose: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model.

Methods: Critical-size osteochondral defects (4.5-mm diameter and 1.

Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform.

Background: Articular cartilage has a zonal architecture and biphasic mechanical properties. The recapitulation of surface lubrication properties with high compressibility of the deeper layers of articular cartilage during regeneration is essential in achieving long-term cartilage integrity. Current clinical approaches for cartilage repair, especially with the use of mesenchymal stem cells (MSCs), have yet to restore the hierarchically organized architecture of articular cartilage.

Improving the handling properties and long-term stability of polyelectrolyte complex by freeze-drying technique for low-dose bone morphogenetic protein 2 delivery.

A variety of controlled release carriers for bone morphogenetic protein 2 (BMP-2) delivery have been developed and tested in animal models. An alginate-based polyelectrolyte complex (PEC) for controlled release of low-dose BMP-2 has shown promising results in preclinical research. However, the poor handling properties and long-term stability of PEC need to be improved for translational applications.

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans.

Human mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes.

Synergistic Effect of NELL-1 and an Ultra-Low Dose of BMP-2 on Spinal Fusion.

Bone morphogenetic protein 2 (BMP-2) is widely used in spinal fusion but it can cause adverse effects such as ectopic bone and adipose tissue . Neural epidermal growth factor like-like molecule-1 (NELL-1) has been shown to suppress BMP-2-induced adverse effects. However, no optimum carriers that control both NELL-1 and BMP-2 releases to elicit long-term bioactivity have been developed.

Bone Regeneration by Controlled Release of Bone Morphogenetic Protein-2: A Rabbit Spinal Fusion Chamber Molecular Study.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) have led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion.

A Heparan Sulfate Device for the Regeneration of Osteochondral Defects.

Repairing damaged joint cartilage remains a significant challenge. Treatment involving microfracture, tissue grafting, or cell therapy provides some benefit, but seldom regenerates lost articular cartilage. Providing a point-of-care solution that is cell and tissue free has the potential to transform orthopedic treatment for such cases.

Characterization and application of size-sorted zonal chondrocytes for articular cartilage regeneration.

Current clinical approaches for articular cartilage repair have not been able to restore the tissue with zonal architecture, and its biomechanical and functional properties. Mimicking the zonal organization of articular cartilage in neo-tissue by implanting zonal chondrocyte subpopulations in multilayer construct could enhance the functionality of the graft, engineering of stratified tissue has not yet been realized due to lack of efficient and specific zonal chondrocyte isolation protocol. We show that by using a spiral microchannel device, the superficial, middle and deep zone chondrocytes can be separated based on cell size, and enriched from full thickness porcine cartilage in a high-throughput, label-free manner.

Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model.

Current surgical techniques for osteochondral injuries in young active patients are inadequate clinically. Novel strategies in tissue engineering are continuously explored in this area. Despite numerous animal studies that have shown encouraging results, very few large-scale clinical trials have been done to address this area of interest.

Oligo[poly(ethylene glycol)fumarate] hydrogel enhances osteochondral repair in porcine femoral condyle defects.

Background: Management of osteochondritis dissecans remains a challenge. Use of oligo[poly(ethylene glycol)fumarate] (OPF) hydrogel scaffold alone has been reported in osteochondral defect repair in small animal models. However, preclinical evaluation of usage of this scaffold alone as a treatment strategy is limited.