Translation of 3D bioprinting into medical practice: learning from related fields to focus our efforts

Translation of 3D bioprinting into medical practice: learning from related fields to focus our effort

Results from an exploratory study to identify the factors that contribute to success for UK medical device small- and medium-sized enterprises

This paper reports the results from an exploratory study that sets out to identify and compare the strategic approaches and patterns of business practice employed by 14 UK small- and medium-sized enterprises to achieve success in the medical device sector of the health-care industry. An interview-based survey was used to construct individual case studies of the medical device technology (MDT) companies. A cross-case analysis was performed to search for patterns and themes that cut across these individual cases. Exploratory results revealed the heterogeneity of MDT companies and the distinctive features of the MDT innovation process that emphasize the importance of a strategic approach for achieving milestones in the product development and exploitation process and for creating value for the company and its stakeholders. Recognizing the heterogeneity of MDT companies, these exploratory findings call for further investigation to understand better the influence of components of the MDT innovation process on the commercialization life cycle and value trajectory. This is required to assist start-up or spin-out MDT companies in the UK and worldwide to navigate the critical transitions that determine access to financial and consumer markets and enhance the potential to build a successful business. This will be important not only for bioscience-based companies but also for engineering-based companies aiming to convert their activities into medical devices and the health- and social-care market

Processing of collagen gels to create in vitro cell growth matrix without damage to the collagen native structure

This preliminary work explores a technique for processing collagen gels to provide a structured matrix support for cell growth and other tissue engineering applications without using cyto-toxic photo-initiators. Collagen gels can be structured by techniques similar to those of rapid manufacturing and retain the fibril structure of native collagen. Incorporation of alpha-modified minimal essential medium (MEM) in the collagen solution improved the rate of gelation in a cell-friendly way. Local gelation of a collagen solution formulated with alpha-modified MEM can be achieved by exposure to radiation from a remote incandescent lamp source indicating that it may be possible to prepare structured gels by lithographically based rapid manufacturing processes. Exposure of the alpha-modified MEM collagen solution to the radiation also increased the thickness of the collagen fibrils formed during the gelation process to create a more structured gel. Methyl blue staining, scanning electron microscope (SEM), and differential scanning calorimetry (DSC) experiments confirmed the collagen was not denatured, i.e. the native structure of collagen was retained

Scanning the horizon for high value-add manufacturing science: Accelerating manufacturing readiness for the next generation of disruptive, high-value curative cell therapeutics

Since the Regenerative Medicine sector entered the second phase of its development (RegenMed 2.0) more than a decade ago, there is increasing recognition that current technology innovation trajectories will drive the next translational phase towards the production of disruptive, high value curative cell and gene based regenerative medicines. In this short report, a long lens look within the pluripotent stem cell therapeutic space, both embryonic and induced, is used to gain early insights on where critical technology and manufacturing challenges may emerge. The report offers a future perspective on the development and innovation that will be needed within manufacturing science to add value in the production and commercialisation of the next generation of advanced cell therapies and precision medicines

Reliability assessment of a digital electronic board assembly using the physics-of-failure approach: a case study

An independent study has been carried out to assess the extent to which the physics-of-failure (PoF) technique can help in reliability enhancement and assessment of electronic assemblies. In particular, a specific case study has been conducted on a real, digital electronic board assembly with known failure modes. Results from the study include the simulation of substrate and component temperatures based on the knowledge of component power dissipation, board assembly materials and cooling methods of the board assembly. The fundamental frequencies and dynamic displacements of the board were computed from the vibration models. The thermal and vibration results were then used to model the damage accumulation at solder joints of the components to accurately predict failure trends and failure sites. These results are compared with field failure data and results from other computer aided engineering (CAE) tools

Overcoming the translational challenges of the effective administration and delivery of cells

Of the few cell-based therapies widely available today the most mature are the treatment of blood-borne cancers and wound healing. The routes of administration for these applications are well understood and a great deal of research has resolved the many biological, pharmacological and engineering challenges associated with the delivery of cells by these methods. These delivery methods are only suitable for a small proportion of the possible cell therapies. Many other treatments under development for illnesses that affect organs – such as diabetes, dermatological conditions and degenerative diseases – require more complex tools and methods to ensure cells are efficiently and effectively delivered to structures such as the pancreas, skin and brain. Injuries to musculoskeletal tissues such as cartilage, intra-vertebral disc and bone may be more easily accessed; however, they present different challenges, as the delivery methods must not reduce the long-term mechanical function of the tissue the treatment is attempting to repair. Oversights can occur due to the reliance on existing and often unsuitable pre-clinical models for delivery and experimental methods and data that cannot be readily translated into the clinic. Different cell types and their behaviours will also lead to complications, so too will engineering challenges such as dosing accuracy, delivery to the appropriate site, engraftment and cell viability after shear and thermal stresses. The delivery method and device used should be considered a crucial part of the cell therapy as a whole. Many companies in regenerative medicine have designed their own delivery device often in series, not in parallel, with the development of their product. As more treatments get closer to clinic many more different devices will be required, thus presenting opportunities for those who understand the generic delivery challenges in the field

Determinants of clinician adoption of regenerative therapies in the UK and Canada: an ophthalmology perspective

The determinants of adoption of regenerative medicine therapies are currently poorly understood. This study aims to draw comparison between the UK and Canada in terms of factors likely to affect healthcare adoption of future regenerative therapies in ophthalmology. Conducting semi-structured interviews with senior ophthalmologists in the UK and Canada, their perceptions of factors either enabling or limiting adoption were recorded and analyzed. A number of key concepts were extracted from the interview data, perceived by stakeholders to contribute to adoption. The core factors developed in this work will be of use to those looking to understand the opportunities and risks involved in securing clinician adoption in both the UK and Canada

Design modification and optimisation of the perfusion system of a tri-axial bioreactor for tissue engineering

A systematic design of experiments (DOE) approach was used to optimize the perfusion process of a tri-axial bioreactor designed for translational tissue engineering exploiting mechanical stimuli and mechanotransduction. Four controllable design parameters affecting the perfusion process were identified in a cause–effect diagram as potential improvement opportunities. A screening process was used to separate out the factors that have the largest impact from the insignificant ones. DOE was employed to find the settings of the platen design, return tubing configuration and the elevation difference that minimise the load on the pump and variation in the perfusion process and improve the controllability of the perfusion pressures within the prescribed limits. DOE was very effective for gaining increased knowledge of the perfusion process and optimizing the process for improved functionality. It is hypothesized that the optimized perfusion system will result in improved biological performance and consistency

Quantification of biological variation in blood-based therapy – a summary of a meta-analysis to inform manufacturing in the clinic

Background and Objectives Biological raw materials, the basis for cellular therapies such as stem cells, have a significantly greater degree of complexity than their traditional pharmaceutical counterparts. This can be attributed to the inherent variation of its source – human beings. Currently, cell therapies are made in small, ad hoc batches, but larger scale production is a prerequisite to meeting future demand and will require a quality-by-design approach to manufacturing that will be designed around, or be robust to this variation. Quantification of variation will require understanding of the current baseline and stratification of its sources. Materials and Methods Haematopoietic stem cell therapy was chosen as a case study to explore this variation, and a PRISMA-guided (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) systematic meta-analysis was carried out for a number of predetermined cell measurements. Results From this data set, it appears that the extent of variation in therapeutic dose (in terms of transplanted total nucleated cells and CD34+ cells per kilogram) for HSCT is between one and four orders of magnitude of the median. Conclusions This is tolerated under the practice of medicine but would be unmanageable from a biomanufacturing perspective and raises concerns about comparable levels of efficacy and treatment. A number of sources that will contribute towards this variation are also reported, as is the direction of travel for 4 greater clarity of the scale of this challenge

Investigating UK Biobank blood metrics variation to inform cell therapy manufacturing process control [poster]

Investigating UK Biobank blood metrics variation to inform cell therapy manufacturing process control [poster