Combinatorial scaffold morphologies for zonal articular cartilage engineering

J.A.M Steele,S.D Mccullen,A Callanan,H Autefage,M.A Accardi,D Dini,M.M Stevens

doi:10.1016/j.actbio.2013.12.030

J.A.M Steele, S.D Mccullen + Show 5 more

Open Access

https://doi.org/10.1016/j.actbio.2013.12.030

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Abstract

Articular cartilage lesions are a particular challenge for regenerative medicine strategies as cartilage function stems from a complex depth-dependent organization. Tissue engineering scaffolds that vary in morphology and function offer a template for zone-specific cartilage extracellular matrix (ECM) production and mechanical properties. We fabricated multi-zone cartilage scaffolds by the electrostatic deposition of polymer microfibres onto particulate-templated scaffolds produced with 0.03 or 1.0mm3 porogens. The scaffolds allowed ample space for chondrocyte ECM production within the bulk while also mimicking the structural organization and functional interface of cartilage’s superficial zone. Addition of aligned fibre membranes enhanced the mechanical and surface properties of particulate-templated scaffolds. Zonal analysis of scaffolds demonstrated region-specific variations in chondrocyte number, sulfated GAG-rich ECM, and chondrocytic gene expression. Specifically, smaller porogens (0.03mm3) yielded significantly higher sGAG accumulation and aggrecan gene expression. Our results demonstrate that bilayered scaffolds mimic some key structural characteristics of native cartilage, support in vitro cartilage formation, and have superior features to homogeneous particulate-templated scaffolds. We propose that these scaffolds offer promise for regenerative medicine strategies to repair articular cartilage lesions.

Highlights

Osteoarthritis is the predominant form of arthritis and remains a leading cause of disability [1]
Cartilage tissue engineering has emerged as a treatment method for articular cartilage lesions and this approach has employed a variety of scaffold materials which act as a carrier of and delivery vehicle for autologous chondrocytes and/or progenitor cells capable of cartilage formation [3,4,5]
Our results demonstrate that the electrostatic deposition of fibres with aligned orientation onto particulate-templated foams produces scaffolds which mimic key mechanical and functional characteristics of native cartilage and are able to support in vitro cartilage formation, indicating their promise in regenerative medicine strategies to repair articular cartilage lesions

Summary

Introduction

Osteoarthritis is the predominant form of arthritis and remains a leading cause of disability [1]. Cartilage tissue engineering has emerged as a treatment method for articular cartilage lesions and this approach has employed a variety of scaffold materials which act as a carrier of and delivery vehicle for autologous chondrocytes and/or progenitor cells capable of cartilage formation [3,4,5]. The cartilage portion of the osteochondral gradient can be simplified into two main regions: the superficial zone which exhibits a high tensile strength and low coefficient of friction to maintain smooth articulation; and a dense ECM region rich in proteoglycan molecules which contribute to the compressive mechanical

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