BACKGROUND: To overcome the potential drawbacks of a short half-life and dose-related adverse effects of using active transforming growth factor-beta 1 for cartilage engineering, a cell-mediated latent growth factor activation strategy was developed incorporating latent transforming growth factor-beta1 (LTGF) into an electrospun poly(L-lactide) scaffold. METHODS: The electrospun scaffold was surface modified with NH3 plasma and biofunctionalised with LTGF to produce both random and orientated biofunctionalised electrospun scaffolds. Scaffold surface chemical analysis and growth factor bioavailability assays were performed. In vitro biocompatibility and human nasal chondrocyte gene expression with these biofunctionalised electrospun scaffold templates were assessed. In vivo chondrogenic activity and chondrocyte gene expression were evaluated in athymic rats. RESULTS: Chemical analysis demonstrated that LTGF anchored to the scaffolds was available for enzymatic, chemical and cell activation. The biofunctionalised scaffolds were non-toxic. Gene expression suggested chondrocyte re-differentiation after 14 days in culture. By 6 weeks, the implanted biofunctionalised scaffolds had induced highly passaged chondrocytes to re-express Col2A1 and produce type II collagen. CONCLUSIONS: We have demonstrated a proof of concept for cell-mediated activation of anchored growth factors using a novel biofunctionalised scaffold in cartilage engineering. This presents a platform for development of protein delivery systems and for tissue engineering.
Biological Availability ; Biomimetics ; Cartilage* ; Chondrocytes ; Gene Expression ; Guided Tissue Regeneration ; Half-Life ; Humans* ; Intercellular Signaling Peptides and Proteins ; Plasma ; Polyesters ; Tissue Engineering ; Tissue Scaffolds ; Transforming Growth Factor beta1

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.
Aging ; Biomimetics* ; Cartilage* ; Cartilage, Articular ; Cues ; Extracellular Matrix ; Guided Tissue Regeneration ; Joints ; Nanotechnology* ; Osteoarthritis ; Prevalence ; Regeneration ; Tissue Engineering ; Tissue Scaffolds