Tissue Eng Part A. 2015 Feb;21(3-4):716-28. doi: 10.1089/ten.TEA.2014.0133.

Effect of the physicochemical properties of pure or chitosan-coated poly(L-lactic acid)scaffolds on the chondrogenic differentiation of mesenchymal stem cells from osteoarthritic patients.

Magalhães J, Lebourg M, Deplaine H, Gómez Ribelles JL, Blanco FJ.

Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) , Spain .

 

Abstract

Due to the attractive properties of poly(L-lactic acid) (PLLA) and chitosan (CHT) for tissue engineering applications, this study is aimed at analyzing the chondrogenic potential of human bone marrow-derived mesenchymal stem cells (BM-MSCs) derived from osteoarthritic (OA) patients, in pure or CHT-coated PLLA, using different coating methodologies. Although PLLA scaffolds coated in one-step (PLLA-CHT1) yielded CHT smooth pellicles filling the PLLA macropores, a two-step strategy resulted in a CHT fiber-like thin coating covering PLLA pore walls (PLLA-CHT2). Both strategies led to the incorporation of similar content of CHT and a two-fold increase in the scaffold’s water uptake capacity, providing elastic moduli values comparable to the ones found for human articular cartilage. After confirming OA-derived BM-MSCs, metabolic activity in the scaffolds, the chondrogenic potential was tested at 30 and 60 days, in a chondrogenic differentiation medium. PLLA scaffolds improved the chondrogenic differentiation of BM-MSCs, regarding cell pellet conventional culture and presented a typical cartilage zonal distribution, although was not able to revert a terminal differentiation. In PLLA-CHT1, on a short term, a rather heterogeneous tissue was formed, with confined areas of either slower cell infiltration or a faster maturation, with enhanced chondrogenic phenotype. In PLLA-CHT2, a similar tissue to PLLA was obtained, albeit on the long term, these scaffolds helped to maintain a hyaline-like phenotype and prevented the advance of the hypertrophic process. These results demonstrate the importance of the scaffolds microenvironment on the cellular events of chondrogenesis.

PMID: 25297938

 

Supplement:

Advances in the osteoarthritis (OA) field are emerging, such as a new standardization of the OA definition, the discovery of new targets for disease modifying drugs, or the market authorization of the first genetic test for OA predisposition. (1,2) These will clearly have an impact on the development of strategies that can effectively target this disease in its earlier stages, but for the time being no pharmacological nor clinical treatment is totally effective in detaining OA progression and in most cases the end result is a prosthetic replacement with all the economic and social burdens associated.

Tissue engineering (TE) strategies using combined synthetic and natural origin biomaterials and mesenchymal stem cells (MSCs) are becoming frequent, as classical TE strategies can not circumvent the development of a transient cartilage tissue during chondrogenesis, instead of promoting a proper arrest of a stable hyaline-like phenotype. Also, these have been mainly focused on the formation of a homogenous tissue with bulk properties similar to cartilage, instead of recreating the heterogenous zonal architecture of a normal adult cartilage tissue. (3)

In this study we have focused on the combination of an FDA-approved biomaterial poly(L-lactic acid) (PLLA) with incorporated chitosan (CHT) as a hydrogel- or fiber-like coating (Figure 1), in order to create microenvironments to control MSCs differentiation. Through their comparison with a pure-PLLA scaffold we were able to demonstrate the significance of tailoring cell-cell and cell-matrix interactions, between MSCs and their local microenvironment, as an integral part of signaling control of cell attachment, proliferation and differentiation. (4)

Our results suggest that MSCs derived from OA patients can undergo different degrees of chondrogenesis in distinct areas of the scaffolds depending on the local composition. PLLA allows MSCs chondrogenesis with the incipient formation of a hypertrophic tissue. CHT-coated scaffolds are able to promote a phenotype arrest, on the short-term (30 days) by the hydrogel-like environment (PLLA-CHT1) and on the long-term (60 days) by the fiber-like enviroment (PLLA-CHT2). In addition we have confirmed the synthesis of a protein characteristic of the superficial zone (lubricin), indicating the ability of these scaffolds to promote specific phenotypes that could culminate in the different zones of cartilage. We are currently performing more studies in order to understand the molecular mechanims and transduction signals involved in the chondrogenic process of MSCs derived from OA patients when exposed to different 3D microenvironments.

Supplement_Magalhaes et al 2015

Figure 1. Chitosan distribution on PLLA scaffolds: as hydrogel-like (PLLA-CHT1) or fiber-like (PLLA-CHT2) coatings.

 

References:   

  1. Kraus VB, Blanco FJ, Englund M, Karsdal MA, Lohmander LS 2015 Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis and Cartilage 23:1233-1241.
  2. Blanco FJ, Ruiz Romero C 2013 New targets for disease modifying osteoarthritis drugs; chondrogenesis and Runx1. Ann Rheum Dis 72:631-4.
  3. Johnstone B, Alini M, Cuchiriani M, Dodge GR, Eglin D, Guilak G, Madry H, Mata A, Mauck RL, Semino CE, Stoddart MJ 2013 Tissue Engineering for Cartilage Repair – The State of the Art. European Cells and Materials 25:248-267
  4. Magalhães J, Lebourg M, Deplaine H, Gómez Ribelles JL, Blanco FJ 2015 Effect of the physicochemical properties of pure or chitosan-coated poly(L-lactid acid) scaffolds on the chondrogenic differentiation of mesenchymal stem cells from osteoarthritic patients. Tissue Engineering Part A 21:716-28.

 

Acknowledgements

This work was supported by CIBER-BBN and the Galician Network of Biomaterials (R2014/033). CIBER-BBN is a national initiative of ISCIII.

 

 

 

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