Development of immune-informed biomaterials- working at the interface of science disciplines

Development of immune-informed biomaterials- working at the interface of science disciplines

Background

I am a 3rd year PhD student in Trinity College Dublin and my project is very much an interdisciplinary one. I’m very lucky to get to work between two great labs, Dr. Aisling Dunne’s Molecular Immunology lab and Professor Danny Kelly’s Musculoskeletal engineering lab. My research focuses on osteoarthritis which involves damage to both the upper protective layer of cartilage and underlying bone. Unfortunately, the only real function restoring treatment option for patients is to undergo a total joint replacement surgery. However, the materials currently used in these orthopaedic implants are highly potent drivers of inflammation and often these implants loosen and fail due to the inflammation at the bone-implant interface. Motivated by the limitations associated with current orthopaedic implants, many investigators are working to develop biologic tissue engineered scaffolds aimed at directly repairing and regenerating bone and cartilage tissues rather than replacing whole joints. As with metal/ceramic based prostheses, successful integration is dependent on appropriate host immune responses

What do I work on?

My research project involves assessing the immune response to various types of implant materials for use in orthopaedic devices and also for bone tissue regeneration applications. One particular immune cell type that we’re interested in is the macrophage, as it’s plastic phenotype has been shown to be an important aspect of the ‘biomaterial-scaffold immune microenvironment’ post-implantation. For example, classically activated M1 macrophages are required to initiate a foreign body response which is necessary for early post-implantation wound healing while their eventual transition to alternatively activated/anti-inflammatory M2 macrophages is required to prevent fibrous capsule formation and chronic inflammation. However a prolonged presence of M1 macrophages at the implant site leads to scar tissue formation and poor tissue quality. With this in mind, my work specifically aims to characterise the macrophage phenotype to various types of biomaterials and establish whether the secretome of these macrophages can influence the differentiation capacity of mesenchymal stem cells (MSCs) into new bone tissue. Culture of both macrophages and MSCs with various biomaterials has allowed us to identify certain cytokines and growth factors that drive osteogenesis, i.e., the formation new bone. This work demonstrates how the immune response can modulate stem cell regenerative capacity and emphasises the importance of integrating control of the host immune microenvironment into regenerative strategies. Such studies allow for optimisation of biomaterials on the bench prior to clinical trials and furthermore, may act as a predictor of success for implanted devices.

Why I love working on an interdisciplinary project?

The most exciting research is happening at the interface of the disciplines.There’s very much a creative side to science research and I believe interdisciplinary work like this project allows you to explore it. This kind of interdisciplinary research allows you to apply the fundamental skills and knowledge from one single science discipline to a new and exciting field. This project, which brings together two research themes, immunology and bioengineering is a clear example of how the merging of two disciplines is proving to be a major success. This work will contribute to the design of next generation immune-informed biomaterials with maximum tissue regeneration capacity but minimal inflammatory potential. This will undoubtedly improve the future of orthopaedic implants and scaffolds for bone and cartilage defects. This project with the ultimate goal of contributing to the development of novel commercially viable next generation biomaterial scaffolds.

10th Jul 2020 Olwyn Mahon

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