In this interview, Matteo Santin (University of Brighton) discusses the development of biomaterials for regenerative medicine.
Please introduce yourself and your institution
I am Professor of Tissue Regeneration at the University of Brighton (UK). I am Director of the Centre for Regenerative Medicine and Devices (CRMD) and Academic Lead for Healthy Futures, the university framework to develop and implement a strategy for research and enterprise in the field of health at the University of Brighton. I received my first degree in Biology at the University of Naples (Italy) where I also achieved my PhD in Biomaterials. I achieved a second PhD in Biomedical Sciences at the University of Brighton (UK) where I worked from 1994 to 1996 before coming back as post-doc in 1998. I have been research fellow at the Italian CNR and at the University of Turin (Italy).
The CRMD hosts 20 academics and three research fellows with a mission to develop novel biomimetic biomaterial technology platforms suitable for regenerative medicine applications, medical devices and theranostics in clinical, sport science and rehabilitation arenas. Our academics have expertise ranging from cell and molecular biology, material science and engineering, mathematical modelling, sport science, and rehabilitation and podiatry. We have clinicians with expertise in neurodegenerative, muscle-skeletal and cardiovascular diseases, and our research priorities are in these three topics, as well as in wound healing and diabetes.
What interests you in biomaterials?
As biologist I have always been interested in the interactions between biomaterial surfaces and biochemical and cellular components of our tissues, and how the understanding of these interactions could inform the synthesis of biomimetic biomaterials at the nanoscale.
What are the differences between natural biomaterials and synthetic biomaterials? What tissues are they best suited for supporting?
The difference between natural and synthetic biomaterials is fundamentally in the compromise between complexity, industrial feasibility and clinical reliability. In general natural biomaterials can be relatively inexpensive and offer a closer mimicking of the natural tissues, but they bear limitations in terms of batch-to-batch reproducibility and potential risk of transmittable diseases.
Synthetic biomaterials are relatively inexpensive only if we consider the three classical categories polymers, metal and ceramics, but they can become very expensive if more complex biomimetic biomaterials are synthesized and engineered at scaled up level. The advantage of the synthetic biomaterials is their batch-to-batch reproducibility that reflects upon their clinical safety and more consistent performance. In my view, natural biomaterials are best suited for wound healing applications, while synthetic biomaterials are suited for implants.
What techniques and technologies do you utilize to produce these biomaterials?
Throughout the years my research in biomaterials has acquired its distinct character for the study and development of two natural biomaterials: silk fibroin and soybean-based biomaterials. We were the first to publish a systematic study on the inflammatory response to silk fibroin and demonstrated that the engineering of its protein secondary structure could change the inflammatory response to the material.
The soybean-based biomaterials have been developed using de-fatted soya flour as raw material. This differs from other research groups who focused their attention on the protein fraction of the soya only. The benefit of our approach is that we can retain the carbohydrate fraction of the soya as well as its phytoestrogens, the isoflavones, which we have demonstrated to be anti-inflammatory, and stimulators of stem cell and tissue cell differentiation. We can engineer these materials by thermosetting to produce blocks and rubbery films or, through extraction procedures, to obtain hydrogels. The intellectual property of these biomaterials are now under CE mark validation process for wound dressings by Meillian Medical Technology (Suzhou, China).
My research in synthetic biomaterials has covered many types of polymers, ceramics and metals, but the distinctive character is given by the synthesis of hyperbranched biocompetent peptides to be used as surface functionalization molecules, mimicking various components of the extracellular matrix for soft and hard tissue regeneration. My spin out company, Tissue Click Ltd, has commercialized a novel class of substrates based on these biomimetic biomaterials for the in vitro culturing of many types of cells, including stem cells, iPSCs and vascularized organoids. The commercial name of these products is PhenoDrives and they can be used as a coating of plasticware in cell biology research, ensuring the fine control of cell phenotypes and the organization of cells in 3D tissue-like structures even in a 2D culture conditions. The same biomaterials are now under development as bio-inks for 3D printing.
What are the challenges in ensuring biomaterials are suitable to support the growth of tissue?
Our experience of over 27 years has convinced us that the control of the inevitable protein adsorption on the surface of implants is impossible to achieve. Hence, the promotion of tissue growth at the surface of the medical implant or tissue engineering construct needs to be pursued through the presentation of specific bioligands that, we know, control cell adhesion and activate intracellular pathways involved in cell proliferation and differentiation.
What is the future of regenerative medicine?
We are at the dawn of something really exciting. The ex-vivo transfection of cells and their re-implantation in the body has clearly been showing its potential in the cure of complex and life-threatening clinical conditions. The transplantation of mesenchymal stem cells has shown its potential in osteoarticular defect regenerations. Pancreatic islet transplantation is a concrete alternative to whole pancreas transplantation. iPSCs could soon expand the potential of regenerating any type of tissue solving the bioethical issues related to the use of embryonic stem cells.
However, we need to provide safe and highly performing biomaterials supporting the isolation, selection and culturing/manipulation of the cells as well as shuttles/scaffolds enabling their transplantation procedure and integration in the target tissues. To this end, we need to think about ways to develop synthetic biomimetic biomaterials capable of biospecific recognition of cells and target tissues. The former property will control the cell phenotype and the latter will enhance their tissue-specificity while enhancing grafting potential and retention time in the targeted anatomical area.