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Open Access Research article

Response of human chondrocytes and mesenchymal stromal cells to a decellularized human dermis

Gianluca Giavaresi12*, Elena Bondioli3, Davide Melandri3, Roberto Giardino2, Matilde Tschon12, Paola Torricelli12, Giovanna Cenacchi4, Roberto Rotini5, Alessandro Castagna6, Francesca Veronesi1, Stefania Pagani12 and Milena Fini12

Author affiliations

1 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute IRCCS, Bologna, Italy

2 RIT Department, Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy

3 Burn Intensive Care Unit and “Regione Emilia Romagna” Skin Bank, Bufalini Hospital, Cesena, Italy

4 Department of Biomedical and Neuromotor Sciences, Saint Orsola Malpighi Hospital, Bologna, Italy

5 Shoulder and Elbow Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy

6 Shoulder Surgery, Istituto Clinico Humanitas IRCCS, Milan, Italy

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Citation and License

BMC Musculoskeletal Disorders 2013, 14:12  doi:10.1186/1471-2474-14-12

Published: 7 January 2013

Abstract

Background

Although progress has been made in the treatment of articular cartilage lesions, they are still a major challenge because current techniques do not provide satisfactory long-term outcomes. Tissue engineering and the use of functional biomaterials might be an alternative regenerative strategy and fulfill clinical needs. Decellularized extracellular matrices have generated interest as functional biologic scaffolds, but there are few studies on cartilage regeneration. The aim of this study was to evaluate in vitro the biological influence of a newly developed decellularized human dermal extracellular matrix on two human primary cultures.

Methods

Normal human articular chondrocytes (NHAC-kn) and human mesenchymal stromal cells (hMSC) from healthy donors were seeded in polystyrene wells as controls (CTR), and on decellularized human dermis batches (HDM_derm) for 7 and 14 days. Cellular proliferation and differentiation, and anabolic and catabolic synthetic activity were quantified at each experimental time. Histology and scanning electron microscopy were used to evaluate morphology and ultrastructure.

Results

Both cell cultures had a similar proliferation rate that increased significantly (p < 0.0005) at 14 days. In comparison with CTR, at 14 days NHAC-kn enhanced procollagen type II (CPII, p < 0.05) and aggrecan synthesis (p < 0.0005), whereas hMSC significantly enhanced aggrecan synthesis (p < 0.0005) and transforming growth factor-beta1 release (TGF-β1, p < 0.0005) at both experimental times. Neither inflammatory stimulus nor catabolic activity induction was observed. By comparing data of the two primary cells, NHAC-kn synthesized significantly more CPII than did hMSC at both experimental times (p < 0.005), whereas hMSC synthesized more aggrecan at 7 days (p < 0.005) and TGF-β1 at both experimental times than did NHAC-kn (p < 0.005).

Conclusions

The results obtained showed that in in vitro conditions HDM_derm behaves as a suitable scaffold for the growth of both well-differentiated chondrocytes and undifferentiated mesenchymal cells, thus ensuring a biocompatible and bioactive substrate. Further studies are mandatory to test the use of HDM_derm with tissue engineering to assess its therapeutic and functional effectiveness in cartilage regeneration.

Keywords:
Articular chondrocytes; Mesenchymal bone marrow stromal cells; Decellularized dermis; Bioactivity; In vitro study; Cartilage tissue engineering