Nanoenabled Immunomodulatory Scaffolds for Cartilage Tissue Engineering

Figure 1: Researchers Daniela Pereira de Vasconcelos and Catarina Leite Pereira have developed 3D matrices empowered with nanomaterials loaded with an anti-inflammatory pharmaceutical (Nanonenabled Col-PLA scaffold) capable of promoting chondrogenesis as well as modulating the inflammatory response in order to overcome the current limitations of strategies used in cartilaginous tissue engineering. 

Our team in i3S, within the RESTORE Project, has developed a material that can promote the formation and development of cartilaginous tissue and, at the same time, stop the inflammatory process associated with osteoarthritis, a disabling disease that affects almost 600 million people worldwide. The results, which open the door to new therapies for cartilage regeneration, were recently published in the journal Advanced Functional Materials.

Osteoarthritis (OA) is a disabling disease that affects 7.6 percent of the world’s population and represents a considerable burden on patients and society due to its prevalence and economic cost. Conventional therapies administered systemically can block inflammation, but they do not prevent the process of cartilage tissue degeneration and the progression of the disease. As cartilage, unlike bone, cannot self-regenerate, there is a growing need to develop approaches that are effective in this function.

In order to overcome the limitations of traditional therapies used in regenerative medicine, the i3S team decided to improve a biodegradable 3D matrix, already tested and approved in veterinary medicine, to be used in humans, through the incorporation of nanomaterials loaded with ibuprofen, a drug for the treatment of pain, fever and inflammation.

According to Daniela Pereira Vasconcelos, one of the first authors of the article, «the use of 3D matrices is the most promising means to regenerate cartilage, since it provides a physical and chemical environment favorable to the survival and differentiation of cartilage cells, the so-called chondrocytes». Once implanted in the lesion, she adds, “this 3D matrix serves as a ‘home’ for cartilage cells and promotes their proliferation until the formation of new cartilage tissue”.

To test the efficacy of this matrix, explains Daniela Pereira de Vasconcelos, “we used cartilage cells from patients undergoing total hip and/or knee arthroplasty and cultured them in these 3D structures nanocapacitated with ibuprofen, called Nanoenabled Col-PLA scaffold”. With this procedure, says the researcher, “we found that these cartilage cells were able to reduce the inflammatory process and restore the production of extracellular matrix, that is, restore the cartilage tissue”. The team then tested the inflammatory response to the products secreted by cartilage cells in contact with this 3D matrix, in an animal model and found that there is a reduction in the recruitment of immune cells and inflammatory mediators with an important role in OA. 

This study, underlines Catarina Leite Pereira, who shares the first authorship of the article, «demonstrates that the 3D model developed has the ability to promote the development of cartilage, as well as modulate the inflammatory response, overcoming the limitations of traditional therapies used in regenerative medicine».

With this work, the i3S researchers add, “we try to overcome two of the main challenges in cartilage tissue engineering: integrating appropriate biological and mechanical properties into a 3D structure and modulating the host response to the 3D structure, recruiting cells capable of promoting regeneration and/or modulating the interaction with immune cells that can lead to rejection of the structure and/or an exacerbated inflammatory response”.

Figure 2: Cultured and differentiated human chondrocytes in the nanocapitated 3D matrix “Nanoenabled Col-PLA scaffold”. Cells isolated from patients undergoing total hip or knee arthroplasty at the Centro Hospitalar Universitário de São João. The collection of samples was approved by the ethics committee of the Centro Hospitalar Universitário de São João and after the patients signed an informed consent.

This work was carried out within the scope of the European project RESTORE, coordinated by the researcher Meriem Lamghari, group leader of the i3S Neuro Skeletal Circuits, and which includes four other partners: the Nanomedicines & Translational Drug Delivery group, from i3S, the Department of Biotechnology and Nanomedicine SINTEF Industry, from Norway, the Institute of Orthopedic Research and Biomechanics, University of Ulm,  from Germany and Askel Healthcare Ltd, from Finland.