Ayesha Al-Sabah

Transforming healthcare through regenerative medicine

Regenerative medicine therapies, underpinned by the core principles of rejuvenation, regeneration and replacement, are shifting the paradigm in healthcare from symptomatic treatment in the 20th century to curative treatment in the 21st century. By addressing the reasons behind the rapid expansion of regenerative medicine research and presenting an overview of current clinical trials, we explore the potential of regenerative medicine to reshape modern healthcare.

3D bioprinting for reconstructive surgery: Principles, applications and challenges

Despite the increasing laboratory research in the growing field of 3D bioprinting, there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures are discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery. If successful, this platform technology has the potential to biomanufacture autologous tissue for reconstruction, obviating the need for donor sites or immunosuppression. The biological, technological and regulatory challenges are highlighted, with strategies to overcome these challenges by using an integrated approach from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery.

Skin tissue engineering using 3D bioprinting: An evolving research field

BACKGROUND Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin. METHODS We conducted a literature review using PubMed, EMBASE and Web of Science for studies on skin 3D bioprinting between 2009 and 2016, evaluating the bioprinting technique, cell source, scaffold type and in vitro and in vivo outcomes. RESULTS We outline the evolution of biological skin replacements, principles of bioprinting and how they apply to the skin tissue engineering field, potential clinical applications as well the current limitations and future avenues for research. Of the studies analysed, the most common types of bioinks consisted of keratinocytes and fibroblasts combined with collagen, although stem cells are gaining increasing recognition. Laser assisted deposition was the most common printing modality, although ink-jet and pneumatic extrusion have also been tested. Bioprinted skin promoted accelerated wound healing, was able to mimic stratified epidermis but not the thick, elastic, vascular dermis. CONCLUSIONS Although 3D bioprinting shows promise in engineering skin, evidenced by large collective investments from the cosmetic industry, the research is still in its infancy. The resolution, vascularity, optimal cell and scaffold combinations and cost of bioprinted skin are hurdles that need to be overcome before the clinical applicability can be realised. Small scale 3D skin tissue models for cosmetics, drug and toxicity testing as well as tumour modelling are likely to be translated first before we see this technology used in reconstructive surgery patients.

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions.

3D bioprinting cartilage

Abstract The heterogeneity in approaches for cartilage tissue engineering indicates that we do not yet have a long-lasting durable solution. Autologous tissue continues to be the mainstay for cartilaginous reconstruction in the head and neck and synthetic implants for treatment of articular cartilage disease. This chapter outlines cartilage development and morphology as the basis for how bioprinting may offer significant advantages over traditional tissue engineering techniques. Optimal cell sources, bioinks and bioprinting techniques are discussed, together with a summary of the current studies on cartilage bioprinting with their structural integrity and cell viability outcomes. Many challenges still exist before this technology can be utilized in a clinical setting. Namely demonstrating cell survival, safe proliferation, and differentiation under long-term physiological conditions, where complex constructs are subject to loading forces experienced by native cartilage.

The clinical need for 3D printed tissue in reconstructive surgery

Abstract The form and function of the human body is maintained through a network of connective tissues, such as bone, cartilage, muscle, skin and nerves. Defects in any of these tissue types can evoke presentation to clinical practice, and may require surgical reconstruction. Surgical reconstruction is often fraught with complications and donor site morbidity, much of which could be alleviated through the development of tissue bioprinting technologies.

Cell preparation for 3D bioprinting

Abstract 3D bioprinting has revolutionized the field of tissue engineering. However, 3D bioprinting constructs requires an immense number of cells. Consequently, cellular expansion is one of the initial steps of the bioprinting process. The growth and expansion of cells is known to give rise to a multitude of issues that includes dedifferentiation, genomic instability, contamination, and cell senescence. This chapter will discuss the techniques used to assess these issues in culture and how to optimize and maintain cells for cell expansion.

Characterization of pulp derived nanocellulose hydrogels using AVAP® technology

Bioinspiration from hierarchical structures found in natural environments has heralded a new age of advanced functional materials. Nanocellulose has received significant attention due to the demand for high-performance materials with tailored mechanical, physical and biological properties. In this study, nanocellulose fibrils, nanocrystals and a novel mixture of fibrils and nanocrystals (blend) were prepared from softwood biomass using the AVAP® biorefinery technology. These materials were characterized using transmission and scanning electron microscopy, and atomic force microscopy. This analysis revealed a nano- and microarchitecture with extensive porosity. Notable differences included the nanocrystals exhibiting a compact packing of nanorods with reduced porosity. The NC blend exhibited porous fibrillar networks with interconnecting compact nanorods. Fourier transform infrared spectroscopy and X-ray diffraction confirmed a pure cellulose I structure. Thermal studies highlighted the excellent stability of all three NC materials with the nanocrystals having the highest decomposition temperature. Surface charge analysis revealed stable colloid suspensions. Rheological studies highlighted a dominance of elasticity in all variants, with the NC blend being more rigid than the NC fibrils and nanocrystals, indicating a double network hydrogel structure. Given these properties, it is thought that these materials show great potential in (bio)nanomaterial applications where careful control of microarchitecture, surface topography and porosity are required.