Bioreattori per la stimolazione meccanica nell'ingegneria tissutale cartilaginea

Cartilaginous tissue is a highly specialized connective tissue of the musculoskeletal system, characterized by a unique architecture that ensures the proper biomechanical functionality of the joints. Thanks to its composition and high elasticity, cartilage is able to resist to significant mechanical stresses, absorbing and distributing loads during movement and protecting the articular surfaces. However, the avascular nature of cartilage and the limited proliferative activity of chondrocytes give this tissue a poor self-regenerative capacity. Cartilage injuries, in fact, that are often the cause of chronic pain and reduced mobility, represent a clinical issue that remains difficult to address through conventional therapies. In this context, tissue engineering represents a promising approach for cartilage regeneration. By exploiting the techniques of regenerative medicine, it aims to recreate in vitro or in vivo a transplantable tissue capable of replacing the damaged one, through the combination of specific cells, biomaterials, and biochemical and biomechanical signals. Bioreactors, in particular, play a fundamental role in this field, as they allow the cultivation of constructs under controlled physiological conditions, reproducing the various mechanical stimuli to which chondrocytes are subjected during normal joint movement. Through the application of compressive forces, shear stresses, or hydrostatic pressure, these systems promote chondrogenic differentiation. Over the years, several types of bioreactors have been developed for the mechanical stimulation of cartilage, including spinner flasks, rotating wall vessels, perfusion bioreactors, and systems based on compression or hydrostatic pressure. Each system presents specific advantages and limitations in terms of loading parameters, nutrient distribution, and stimulus delivery, but all represent essential tools for improving cartilage tissue engineering strategies.

Nell’ingegneria tissutale della cartilagine, i bioreattori rappresentano strumenti fondamentali per ricreare in vitro l’ambiente fisiologico a cui il tessuto è normalmente sottoposto in vivo. La cartilagine articolare, infatti, non è solo regolata da fattori biochimici, ma anche da stimoli meccanici derivanti dal carico articolare, come compressione, taglio e flusso di liquido interstiziale. Tali stimoli influenzano profondamente il comportamento dei condrociti e delle cellule staminali mesenchimali, modulandone la proliferazione, la differenziazione e la sintesi di matrice extracellulare. I bioreattori meccanici permettono di applicare in modo controllato forze dinamiche ai costrutti tissutali tridimensionali, simulando le condizioni fisiologiche articolari. Tecnologie basate su compressione dinamica, stimolazione di taglio da flusso o tensione ciclica hanno dimostrato di promuovere la deposizione di collagene di tipo II e proteoglicani, favorendo lo sviluppo di un tessuto cartilagineo con proprietà biochimiche e biomeccaniche più simili a quelle del tessuto nativo