Nanotechnology biomimetic cartilage regenerative scaffolds

Abstract

Cartilage has a limited regenerative capacity. Faced with the clinical challenge of reconstruction of cartilage defects, the field of cartilage engineering has evolved. This article reviews current concepts and strategies in cartilage engineering with an emphasis on the application of nanotechnology in the production of biomimetic cartilage regenerative scaffolds. The structural architecture and composition of the cartilage extracellular matrix and the evolution of tissue engineering concepts and scaffold technology over the last two decades are outlined. Current advances in biomimetic techniques to produce nanoscaled fibrous scaffolds, together with innovative methods to improve scaffold biofunctionality with bioactive cues are highlighted. To date, the majority of research into cartilage regeneration has been focused on articular cartilage due to the high prevalence of large joint osteoarthritis in an increasingly aging population. Nevertheless, the principles and advances are applicable to cartilage engineering for plastic and reconstructive surgery.

Keywords: Biomimetics; Cartilage; Guided tissue regeneration; Nanotechnology; Tissue scaffolds.

Fig. 1

Human hyaline cartilage extracellular matrix structural architecture These are scanning electron microscopy (SEM) images of a section of human hyaline cartilage. (A) A lacuna surrounded by a dense collagen framework. (B) A high resolution image of cartilage extracellular matrix and collagen fibres. These SEM images of native human hyaline cartilage were fixed in 2.5% glutaraldehyde, followed by step-wise dehydration and sputtered gold coating.

Fig. 2

Pioneering tissue engineered skin and cartilage constructs (A) Gross appearance of Integra, (B) Scanning electron microscopy image of the type I collagen-chondroitin sulphate scaffold component of Integra (Permission granted by Integra LifeSciences Corp., Plainsboro, NJ, USA). (C) Human ear-shaped PLA-coated PGA scaffold seeded with bovine articular chondrocytes and implanted into the dorsum of an athymic nude mouse (BBC Photo Library), (D) Scanning electron microscopy of the cell-scaffold construct prior to implantation. Note the micron-sized PGA fibres. Scale bar=50 µm (Reprinted from Cao et al. Plast Reconstr Surg 1997;100:297-302, with permission from Lippincott Williams and Wilkins [27]). (E) Pre-implanted segment of tissue-engineered allogeneic airway, which was decellularised and reseeded with the recipient's bronchial epithelial cells and mesenchymal stem cell-derived chondrocytes (Reprinted from Macchiarini et al. Lancet 2008:372;2023-30, with permission from Elsevier [29]).

Fig. 3

Impact of scaffold architecture on cell behaviour Scaffold architecture influences cell binding, hence also cell behaviour and function. This figure illustrates the way in which nanoscaled fibrous scaffolds provide an environment for cells which better resemble the fibrous extracellular matrix of cartilage (Reprinted from Stevens and George. Science 2005;310:1135-8, with permission from AAAS [30]).

Fig. 4

Self-assembly of peptides to form nanofibres This is an example of a self-assembled peptide used in a study of wound healing. A single peptide, approximately 6 nanometres, is shown. Thousands of peptides self-assemble to form a single nanofibre; trillions of peptides or billions of nanofibres form the scaffold (scale bars=0.5 µm) (Reprinted from Schneider et al. PLoS One 2008;3:e1410 [43]).

Fig. 5

Formation of PLLA scaffolds with phase-separation Scanning electron microscopy images of poly(L-lactide) (PLLA) scaffolds produced using the phase-separation technique. (A) 500×, (B) 20,000× magnification (scale bars are 50 µm and 1 µm, respectively) (Reprinted from Ma and Zhang. J Biomed Mater Res 1999;46:60-72, with permission from John Wiley & Sons, Inc. [46]).

Fig. 6

Schematic representation of a typical electrospinning system The polymer solution is delivered, at a constant rate, to the tip of the charged spinneret. Electrospinning is initiated from the Taylor cone (depicted top right) when the charge overcomes the forces of surface tension. The electrospun fibres are then collected on the grounded targe (Image courtesy of Dr. Julian George, Imperial College London).

Fig. 7

The ability to mimic nature with electrospinning This is a comparison between the structural architecture of native human hyaline cartilage (A) and electrospun poly(L-lactide) (PLLA) scaffold (B). The fibrous PLLA scaffold was electrospun at a concentration of 3.0% w/w, 10 kV, at a rate of polymer solution delivery of 0.4 mL/hr and target distance of 10 cm.