Date of Award
PhD (Doctor of Philosophy)
A short commentary, not exceeding one thousand words, indicating how each publication contributes to the total corpus of the candidate’s research
The majority of bioengineering papers deal with bone, the detection of microdamage within it, its remodelling and adaptation in health and disease and its behaviour as a material in both theory and practice. The exception (B21) involves mechanical testing of vascular tissue. Paper B1 introduces a new fluorescence-aided technique for quantifying fuchsin-stained microdamage in bone, which was featured on the cover of the Journal o f Anatomy. Paper B4 describes a series of fluorescent agents used, for the first time, to label crack propagation and relate crack growth to changes in the material properties o f bone. Both papers arose from my MD thesis. The fluorescence technique was also used to study microdamage (B6) and Haversian systems (B11) in three dimensions. My first PhD student improved the sequential labelling technique (B8) and applied it to fatigue testing of compact bone (B13). Histological microcrack data confirmed our theoretical predictions (B2) and provided valuable experimental data (B3). Indeed, there was a consistent interplay between theory (B7, B9, B12) and practice (B14). As well as affecting the material properties of dead bone, we showed that microdamage is normally found in living bone, where it acts as a stimulus for bone remodelling. Ulnar osteotomy caused increased loading on the sheep radius and an initial increase in microdamage which activated osteoclasts to remove and then osteoblasts to replace the damaged bone (BIO). Fluorochrome-labelled secondary osteons were chosen for the cover of the Journal o f Anatomy.. Surface adaptation, bone density and surface strain changes were described in paper B17 and both papers were taken from my PhD thesis. The theory and practice of microdamage-driven bone remodelling were summarised in B5, B 15 with a third Journal o f Anatomy cover, and B16.
The challenge was now to quantify microdamage in vivo. Histological measurements of microdamage are destructive and so of limited clinical application, so our aim was to develop a dye which would selectively label microdamage and be detected both noninvasively, using radiological techniques, and histologically, to provide validation. A chemist colleague and I co-supervised a PhD student who tested a range of fluorescent photoinduiced electron transfer (PET) chemosensors (B18). This initially yielded sensors for zinc (B19) and cadmium (B22, B24, B42). A reappraisal of the surface chemistry of microcracks (B32) led to the development of novel computer tomography contrast agents (B38), which are suitable for research studies (B44), but the radiation dose involved precludes their clinical use.
Having shown that microdamage activates remodelling, its mechanism warranted study. We theorised that damage to osteocyte cell processes might be involved (B20, B31) and studied short crack growth in bone specimens (B29, B35) and tissue culture (B41), concluding that upregulation of RANKL stimulates osteoclast activity. Our mechanical and biological theories and experimental findings are summarised in B39, B40, B46 and in our Nature Materials paper, B45. We have also described microdamage and bone remodelling around orthodontic implants (B23, B27), the interaction of cracks with microstructural features in bone (B25, B30, B34, B43), and a new embedding medium for sectioning bone (B36). The genetic and morpholological effects of underloading bone were studied in a hindlimb suspension model (B37) and bone mechanobiology reviewed in B26, B28 and B33. Ovariectomy was used as a model of post-menopausal osteopaenia and osteoporosis to study its effect in increasing bone turnover (B52) which in affects microcrack behaviour (B50) and the biomechanical properties of bone (B49, B51, B53). A recent series of papers (B47, B48, B54, B55) explains engineering principles and practice to a medical audience.
Case studies of renal adenocarcinoma (SA1), seal finger (SA3), nose replantation (SA4), inguinal appendicitis (SA5) and sacral Richter hernia (SA6) emphasise the importance of anatomy as the basis of surgical intervention. Larger numbers of cadaveric specimens were studied to describe the tendinous interruption in semitendinosus, important in the location of hamstring injuries (SA2), and the distribution of the mental nerve, important in the siting of biopsies (SA12). New surgical techniques for K-wiring (SA10), hip arthroplasty (SA11) and laparoscopic surgery (SA14) were investigated. My MSc study on carotid blood flow and CNS cell damage was the source of three publications, SA7, SA9 and SA15. One paper assessed our teaching methods (SA8), my professorial inaugural lecture outlined how I would like to combine teaching and research in our Department (SA13) and a chapter in the definitive reference text for ear, nose and throat surgeons, describes the development of the head and neck regions from Carnegie embryonic stages to the clinical presentation of abnormalities (SA16).
HISTORY OF SCIENCE & MEDICINE
The first history paper (HI) describes the Northumberland Museum in RCSI and its relationship with both anatomical teaching and the Smithsonian Institution. The other seven papers are biographical, featuring Denis Burkitt (H2), three eponymous Irish surgeons, Colles (H6), Smith (H7) and Bennett (H8), and three biomechanicians. The Wolff paper (H4) is taken from my PhD, the Haughton paper (H3) describes the father of Irish biomechanics and the MacConaill paper (H5) its greatest Irish exponent in the 20th century.
The first Editorial (El) describes a forum to provide engineering solutions to medical audiences, while the second (E2) announces its establishment as a new section of the Royal Academy o f Medicine in Ireland. The interaction of medicine and engineering on a European scale is the subject of E4, while E7 describes a new series of papers in Technology & Health Care explaining engineering theory and practice to a medical audience. Three editorials are from special issues of journals which covered two symposia on microdamage, hosted by the Anatomical Society o f Great Britain and Ireland in Dresden (E3) and by the European Society o f Biomechanics in ‘Den Bosch (E5), and one on tissue engineering, hosted by the European Society for Engineering and Medicine in Prague (E6).
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Lee TC. Anatomists and geometers : a selection from the published work. [D.Sc Thesis]. Dublin: Royal College of Surgeons in Ireland; 2009.