Background/Purpose: Because of a poor self-healing ability, joint cartilage undergoes progressive degradation in the course of aging or following traumatic injuries. One promising therapeutic approach is the use of mesenchymal stem cells (MSC), which have the potential to differentiate into chondrocytes. However, anchorage of MSC to the sites of injury and their differentiation in situ require combining cells with a biomaterial releasing a differentiation factor such as TGFβ3. Our objective was to design and test a new scaffold to support chondrogenic differentiation.

Methods:

Microspheres were formed using an acidic type I collagen solution and perfluorated oil, stabilized by a surfactant. Spherical microparticles of fibrillar collagen were obtained through a sol-gel transition induced in aqueous droplets in contact with ammonia vapors. Microspheres were impregnated with TGFβ3 and release of this factor was measured using a reporter gene assay. Impregnated microspheres were combined with human MSC and cultivated in vitro or subcutaneously injected into immunodeficient mice. Expression of chondrocyte markers was monitored by RT-qPCR and immunohistochemistry.

Results:

Microspheres are constituted by a gel of striated collagen fibrils and are 300±67 μm in diameter. Fibrils occupy ca. 5% of the total volume, forming an entangled network with pores of 1-10 μm. After MSC adhesion onto the microspheres and in vitro culture for 21 days, they differentiate into chondrocytes expressing the specific markers, such as collagen type II variant B and aggrecan. The type I collagen matrix is progressively degraded and replaced by the cartilaginous matrix. In vivo, MSC form a tissue histologically resembling cartilage which stain positive for collagen II and aggrecan.

Conclusion:

The biomaterial described here is promising for cartilage engineering. Future improvements aim at obtaining microspheres of smaller and more homogenous sizes, which will facilitate their injection; covalently linking the TGFβ3 to the microspheres to prevent its dispersal in the organism.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/collagen-based-microspheres-delivering-tgf-%ce%b23-for-mesenchymal-stem-cell-differentiation-an-innovative-strategy-for-cartilage-engineering/