Multi-Biofabrication Of paTient-specific tIssues fOr regeneration of kNee meniscus (CEEC Individual - J. Costa)

Organ shortage and transplantation needs have led to congestion in healthcare systems resulting in a huge socioeconomic impact. Musculoskeletal (MSK) disorders directly affect the locomotor system and are characterized by pain and reduced physical function. The sustainable development goals (SDGs) and the Decade of Healthy Ageing 2020–2030 provides an auspicious opportunity to intensify global awareness on MSK health. Knee meniscus is vital for knee function. More than 0.4 million surgeries are performed on meniscus per year in Europe. Globally approximately 18% of women and 10% of men aged 60 years and above suffer from symptomatic injuries in meniscus and 75%-95% of the patients with knee osteoarthritis have a meniscus lesion. The current most used
treatments include menisectomy and meniscus repair, have high re-operation rates, need long periods of rehabilitation and lead to early osteoarthritic changes in the knee. Tissue Engineering has been revolutionizing the development of functional tissues, making them great alternatives to achieve a better, faster and effective worldwide patient care. However, the pursuit for a clinical relevant biomimetic implant is still a big challenge.
Therefore, the combination of 3D printing with high-resolution imaging techniques can be a powerful tool to closely mimic the meniscus. Combination of 3D printing with patient’s own cells can provide endless possibilities to
fabricate “on-demand” implants. Thus, this proposal aims to develop high-tech laboratory-generated tissues using a multi-biofabrication system capable to reproduce the hierarchical structure of the knee meniscus. Different inks
will be fine-tuned to achieve the ideal biomaterial combination targeting the mechanical/biofunctional performance of the native tissue. Silk fibroin and cellulose-based materials will be used in a combinatorial approach of 3D printing using a coaxial strategy to address the mechanical performance. Ceramics will be added to the implant horns zone to promote osseointegration and implant fixation. Then, decellularized human placenta extracellular matrix (dECM) powders will be combined with fibrin, growth factors and squalamine to develop cellladen bioinks aiming to: (1) promote in situ stem cell differentiation and (2) reproduce the vascularized hierarchical structure of knee meniscus. The goal is to obtain a mimetic meniscus with a signaling gradient to reproduce the
native tissue cell spatial distribution as well as the peripheral vascular region and the avascular inner zone. Lastly, 3D print patient-specific implants that will be subsequently pre-maturated in bioreactors and will be tested in vitro and in vivo. Therefore, the ultimate goal is to develop “on demand” knee meniscus tissues, with biomimetic mechanical and biological properties, capable of being promptly translated into the clinical setting for a faster, better and total recovery of meniscus disorders.