Engineering immunomodulatory materials for regenerative medicine

Current biomedical and tissue engineering strategies aim to provide technologies capable of improving or restoring the function of damaged or diseased tissues with functional and site-appropriate neo-tissue. Biomaterials have played a central role in the implantable medical device industry and have improved the lives of millions of people worldwide. However, biomaterials are foreign bodies, thus adverse immune reactions to biomaterials represents a fundamental challenge which can impact and reduce the quality of life for patients. These adverse reactions are often seen to interfere with healing, leading to immediate acute outcomes such as immense pain, excessive inflammation, tissue destruction, or even isolation and rejection of medical devices. The lack of detailed understanding of biomaterial-immune system interactions, resulting in significant pathological changes in the microenvironment, is a major barrier to developing effective biomaterial-based therapies and tissue engineering approaches.

Recently, it has been recognized that the most important determinant of successful clinical outcomes is the host response to the biomaterial, i.e., the immune-mediated tissue reaction to the presence of the foreign body. Biomaterials that have favourable immunomodulatory properties can shift the default response to a foreign body implant (i.e., scar tissue formation or fibrous encapsulation) towards one of tissue integration and functional remodelling.

Designing materials to modulate the immune response requires an understanding of the role of the immune system in normal physiologic processes including wound repair, development, and tissue homeostasis as well as an understanding of the immune system contribution to tissue remodelling through crosstalk with resident stem/progenitor cells. Hydrogels (highly hydrated polymeric matrices) are promising materials for immunomodulatory application in regenerative medicine due to their unique physicochemical properties (e.g., drug loading capacity, biocompatibility, and biodegradability). Within this highly interdisciplinary project, new biomaterials that can mitigate the foreign-body response and promote tissue regeneration will be developed by exploring natural and synthetic materials.

The standard in vitro testing protocols for assessing novel biomaterials generally follow the International Organisation of Standardisation (ISO) protocols for the biological evaluation of medical devices. However, a recent European multicentre analysis of biomaterial assessments concluded that in vitro evaluations of biomaterials are not suitable to predict in vivo acceptance and highlights the role for improving current in vitro assessment protocols and developing more relevant in vitro assays. Attempts to repair and engineer new tissues requires a well-established toolkit of methods to test and evaluate the immune response to these materials. For this, the proposed research will develop innovative approaches and solutions that enable to validate the broader biomaterials interactions, their regenerative potential and ability to control the immune response with the standardised tests. Specific objectives include:
O1. To develop a new toolkit of methods to test and evaluate the immune response of materials to standardise methods required.
O2. To develop tailored immunomodulatory biomaterials and approaches to direct immune response and environments in tissue regeneration. The physicochemical and biological properties (e.g., in vitro cell viability, ECM production, inflammatory response) of designed biomaterials will be assessed by exploiting the developed toolkit of methods to establish their immunomodulatory potential for regenerative medicine applications.
O3 To process developed immunomodulatory materials using 3D bioprinting to promote immune tolerance, and to assess the potential of manufactured structures for regenerative medicine applications by using the standardised toolkit of methods.