20-Bio-B5 Rehabilitation Engineering · May 2013
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
Paper format: National Exams, May 2013 — 04-Bio-B5 Cell and Tissue Engineering (the exam's own header). Three hours, open book, any Casio/Sharp non-communicating calculator. Six questions of equal value (20 marks each, 120 marks printed); five constitute a complete paper and only the first five appearing in the answer book are marked (100 marks total). All six are solved here, because this set is a study resource rather than an examination script. Every question is essay/descriptive (design, regulatory, and mechanistic reasoning in tissue engineering) with no numerical data to compute — the marking-scheme arithmetic is the only concrete number in the paper.
Reference texts (the books an open-book candidate should have on the desk for this subject):
Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.
Moving a novel cell-adhesive peptide from a laboratory discovery to a patented artificial-liver product raises issues in four linked domains — biological, engineering/design, regulatory, and commercial/IP — and a credible presentation to the board has to address all four, since a technically excellent construct that cannot be manufactured, approved, or defended as intellectual property will never reach a patient.
The liver performs an enormous range of functions (albumin and clotting-factor synthesis, ammonia detoxification via the urea cycle, drug/xenobiotic metabolism via cytochrome P450 enzymes, bile production, glucose homeostasis), and no single cell type or device yet reproduces all of them. The team must decide on a cell source: primary human hepatocytes (functionally ideal but scarce, donor-dependent, and rapidly de-differentiate in standard culture), immortalized hepatocyte cell lines (expandable but with reduced or altered metabolic function), xenogeneic cells such as porcine hepatocytes (abundant but carrying zoonotic-transmission and immunogenicity risk), or stem-cell-derived hepatocyte-like cells (a promising but not yet fully mature source in 2013). Whichever source is chosen, maintaining hepatocyte phenotype and polarity in vitro is a central biological challenge — hepatocytes rapidly lose cytochrome P450 activity and characteristic bile-canalicular polarity when cultured on standard tissue-culture plastic, so the peptide's cell-adhesive chemistry must be shown to preserve (or ideally promote) differentiated function, not just attachment. The team also needs to characterize whether the novel peptide supports the specific integrin/adhesion-receptor profile hepatocytes actually use, since a generic cell-adhesive peptide (e.g., a bare RGD sequence) may support attachment of many cell types non-specifically without preserving liver-specific function.
An artificial liver construct needs a scaffold or matrix that presents the peptide at a density and geometry the cells can use, with adequate mass-transfer design: the liver is one of the most metabolically active and highly perfused organs in the body, so any bioreactor or implanted construct must supply oxygen and nutrients and remove metabolic waste at a rate that avoids a hypoxic, non-functional core — this typically drives the choice toward a perfused hollow-fibre or micro-channel bioreactor architecture rather than a simple static scaffold. The team must also decide on the device concept: an extracorporeal bioartificial liver (blood or plasma perfused through a hepatocyte-loaded cartridge, used as a bridge-to-transplant) versus an implantable construct, each with very different engineering constraints (extracorporeal devices need only bridge liver function for days to weeks and can use non-human or immortalized cells behind a filtration barrier; an implantable, permanent construct needs long-term vascular integration and a cell source the host will not reject). Scale-up is a further engineering issue — a functional human liver contains roughly 1011 hepatocytes, so the construct's cell mass, oxygenation capacity, and perfusion architecture must be engineered to approach a clinically meaningful fraction of that functional mass.
Because the peptide and any scaffold material will be in direct, sustained contact with cells and (for an implantable or blood-contacting device) with the patient, a full ISO 10993 biocompatibility program (cytotoxicity, sensitization, and, for blood-contacting or implantable use, haemocompatibility and chronic implantation studies) is required before clinical use. If xenogeneic cells are used, additional regulatory scrutiny around zoonosis risk and immune barrier design applies. In Canada, the finished product would move through the Health Canada medical device (or combination product/cell-therapy) pathway depending on its final mode of action — a distinction the team needs early, since it determines the entire preclinical and clinical evidence package (see Question 5).
For patenting specifically, the team should assess: novelty and freedom to operate — is a peptide with generic cell-adhesive activity distinguishable from existing RGD-type adhesion peptides already claimed by others, or is the liver-specific application (and any liver-selective adhesion sequence/receptor targeting) the genuinely novel, defensible claim; claim scope — should the patent claim the peptide composition, the scaffold/device incorporating it, the method of use for liver applications, or all three, since narrow claims are easier to grant but easier to design around; and competitive landscape — existing extracorporeal liver-support technologies (e.g., the MARS albumin dialysis system, ELAD) define the commercial bar the new construct must clear. The board also needs a realistic development timeline and cost estimate spanning cell-source qualification, scaffold/device engineering, preclinical biocompatibility and efficacy studies, and the regulatory submission, before a "recommendation for patenting and future development" can responsibly be made.
The presentation should recommend proceeding with patent filing on the peptide's liver-specific adhesive/functional-preservation properties (the most defensible and specific claim) while flagging that a full development program — cell-source selection, bioreactor/scaffold engineering for adequate mass transfer, a biocompatibility and regulatory strategy, and a competitive freedom-to-operate analysis — must run in parallel before a marketable product exists; patenting alone secures the invention but does not resolve any of the biological or engineering feasibility questions above.
