SciTech Europa Quarterly looks at recent research in the fields of biomaterials science and tissue engineering
A range of factors can lead to the damage and degeneration of tissue in the body, and treatment to repair, replace, or stimulate tissue regeneration can therefore be required. Biomaterials science and tissue engineering (TE) is the application of engineering methods to create either environments or materials which facilitate in vitro or in vivo cell or tissue growth and function. In the field, a significant amount of research focuses on biomedical materials with innovative chemical, physical or mechanical properties, alongside materials for a varied range of medical applications and interventions.
TE is an approach to regenerating damaged tissue by combining cells from the body with highly porous scaffold biomaterials, acting as templates for the regeneration of tissue, guiding growth of new tissue, and new technologies such as additive manufacturing are helping the field to develop.
For instance, in 2016 a new study published in the journal 3D Printing and Additive Manufacturing described the development of a novel hybrid polymer suitable for producing 3D-printed scaffolds on which living cells can be seeded to create engineered tissues.
The ability to use these hybrid polymer spools with easy-to-operate, commercial 3D printers has huge potential in applications such as tissue engineering to repair complex bone defects.
The researchers – Lucas Albrecht, Stephen Sawyer, and Pranav Soman, from Syracuse University, USA – produced polycaprolactone-based polymers and fabricated scaffolds using a Makerbot 3D Fused Deposition Modelling printer. To overcome the challenges associated with creating composite polymer spools, the authors incorporated living cells mixed with gelatine hydrogels into the scaffolds, achieving high levels of cell survival.
Biomaterials science and tissue engineering are growing very quickly, something evinced by the fact that the diverse breakthroughs and developments taking place have been recently compiled in special editions of a well-respected journal in the field: Tissue Engineering (Parts A, B, and C).
The first special collection of articles were published in Parts A and B and were compiled by Guest Editors Dr Megan Killian (University of Delaware, USA) and Dr Anne Gingery (Mayo Clinic, USA), who collected a diverse group of scientific articles by leading researchers who are using novel approaches to tissue engineering to develop treatments for musculoskeletal disorders.
Included here was an article by Dr Robby Bowles from the University of Utah, USA and his co-authors who have used CRISPR/Cas-9-based technology for epigenomic editing to produce cells from the chronic inflammation caused by musculoskeletal diseases. In their research, the team were able to demonstrate the ability to reduce the expression of genes that code for inflammatory cytokine receptors in adipose-derived stem cells grown in culture. They reported their findings in the article entitled ‘CRISPR-Based Epigenome Editing of Cytokine Receptors for the Promotion of Cell Survival and Tissue Deposition in Inflammatory Environments.’
A study entitled ‘In Vitro Generated Intervertebral Discs: Towards Engineering Tissue Integration,’ was also described in the publication, with authors Dr J Paul Santerre and Dr Rita Kandel, from the University of Toronto (Canada) and their co-authors outlining the development of a two-step process for engineering a biological intervertebral disc implant and demonstrating mechanically stable integration in a cow model. Working toward creating a replacement for degenerated intervertebral discs, a major cause of chronic neck and low back pain, the researchers explained how they are pursuing an approach in which they use tissue engineering to create the individual components of the disc and then combine them together in a co-culture system.
The journal also includes an article from Stephanie Bryant (from the University of Colorado, USA) who examined the degradation behaviour of enzyme-sensitive hydrogels, which have shown promise as cell delivery vehicles for cartilage tissue engineering. Her article (entitled ‘Understanding the Spatiotemporal Degradation Behavior of Aggrecanase-Sensitive Poly(ethylene glycol) Hydrogels for use in Cartilage Tissue Engineering’) explains how her team combined experimental studies and computational approaches to evaluate and model changes in hydrogel density and growth of extracellular matrix over time and how these affected the clustering and other properties of bovine chondrocytes.
The importance of animal models
In Part C, the special edition – compiled by guest editors Dr Jorge Piedrahita (North Carolina State University College of Veterinary Medicine, USA) and J Koudy Williams from Wake Forest School of Medicine (USA) – was dedicated to showcasing recent research into the latest research on using animal models in regenerative medicine research.
According to the journal, ‘Novel approaches to tissue engineering and regenerative medicine are first evaluated and optimized in animal models before making the leap to clinical testing in human subjects. For many of these innovative new techniques and materials to succeed and advance to the clinic, the selection of an appropriate animal model and design of the experiments to gauge performance and outcomes can determine whether a particular approach, and the field in general, continue to move forward.’
As such, the special edition included an article from Dr F Cumhur Öner et al., from the University Medical Center Utrecht, Delft University of Technology, and Utrecht University, the Netherlands, on ‘Inflammation-Induced Osteogenesis in a Rabbit Tibia Model’. Here, the authors explained how they had examined the inflammatory responses to bacterial infection that can promote bone formation, showing that the inflammatory response caused by exposure to Staphylococcus aureus antigens, in the absence of bacterial infection, could stimulate bone growth and might be a useful strategy in bone regenerative medicine.
Another article entitled ‘Rise of the Pigs: Utilization of the Porcine Model to Study Musculoskeletal Biomechanics and Tissue Engineering During Skeletal Growth’ saw Dr Matthew Fisher and co-authors describe the unique opportunities and challenges for using pigs as translational models in the development of musculoskeletal regenerative medicine approaches. In particular, the researchers describe the advantages porcine models offer for studying biomechanics.
The article entitled ‘Warning About the Use of Critical-Size Defects for the Translational Study of Bone Repair: Analysis of a Sheep Tibial Model’ saw Dr Johan Lammens and co-authors from various Belgian institutions caution that techniques for repairing large bone defects developed in the laboratory will only ultimately be successful in humans if the preclinical studies are performed in a reliable animal model using a bone defect of sufficient size created by following well-defined methods.
Co-Editor-in-Chief of Tissue Engineering Part C Dr John A. Jansen, Professor and Head, Department of Biomaterials at Radboud University Medical Center, the Netherlands, commented: “This special issue emphasises not only the need for appropriate animal models to increase our understanding and knowledge, but also for the final clinical application of regenerative medicine-based products.”
As these examples show, work in these fields is not only in abundance but is also providing novel advances as well as commenting on future needs for these disciplines moving forwards.
Croes Michiel, Boot Willemijn, Kruyt Moyo C., Weinans Harrie, Pouran Behdad, van der Helm Yvonne J.M., Gawlitta Debby, Vogely H. Charles, Alblas Jacqueline, Dhert Wouter J.A., and Öner F. Cumhur. Tissue Engineering Part C: Methods. August 2017
Farhang Niloofar, Brunger Jonathan M., Stover Joshua D., Thakore Pratiksha I., Lawrence Brandon, Guilak Farshid, Gersbach Charles A., Setton Lori A., and Bowles Robby D..Tissue Engineering Part A. February 2017