Browsing by Author "Bezuidenhout, Martin Botha"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Additive manufacturing enabled drug delivery features for titanium-based total hip replacement cementless femoral stems
    (Stellenbosch : Stellenbosch University, 2015-03) Bezuidenhout, Martin Botha; Dimitrov, D. M.; Dicks, Leon Milner Theodore; Van der Merwe, A. F.; Stellenbosch University. Faculty of Engineering. Dept. of Industrial Engineering.
    ENGLISH ABSTRACT: Bacterial colonisation and biofilm formation onto total hip replacement femoral stems remain a serious complication detrimental to the success of total hip arthroplasty. Current treatment procedures are accompanied by a heavy financial burden and morbidity for the patient while failing to guarantee a successful outcome with no reinfection. In fact, infection rates after revision surgeries are typically higher than those for primary hip arthroplasties. This study investigates conceptual drug delivery channels to be incorporated within cementless femoral stems by applying additive manufacturing as enabler technology. Drug delivery from these features is aimed at both prophylaxis and treatment of infection, with the latter emphasising the concept of creating a reinforceable antimicrobial depot inside the implant. The novelty lies in facilitating the administration of multiple drug dosages from within the implant instead of the once-off implant-based release strategies currently employed. Samples containing internal channels were designed based on analogies to drug delivery studies reporting on the commercial antibiotic loaded bone cement, Palacos R+G loaded with gentamicin. These samples were manufactured by LaserCUSING® from Ti-6Al-4V ELI powder. For prophylactic proof of concept, testing the channels were filled with Palacos R+G and challenged with two clinical isolates of Staphylococcus aureus in a bacterial growth inhibition study. Gentamicin-susceptible S.aureus Xen 36 was prevented from colonising for a minimum of 72 hours, whereas gentamicin resistant S.aureus Xen 31 reached the material within 24 h, signifying the importance of drug selection according to pathogen. Hence, a solution of vancomycin in phosphate buffered saline pH 7.4 was used during in vitro reservoir release testing. Three dosage injections were made into each of six samples during a cumulative incubation period of 100 h. A biocompatible 5,000 Da molecular weight cut off polyethersulfone nanoporous membrane was employed as release rate-controlling device. Released vancomycin was quantified with reversed phase high performance liquid chromatography. The resulting release profile was characterised by means of the Korsmeyer-and-Peppas model for diffusion based drug delivery. Constraint diffusion was identified as the mechanism controlling release, implying interplay between Fickian diffusion and polymer relaxation for effecting vancomycin release from within the reservoir. The concept created in this study provides a basis towards the development of full scale intelligent implants with multiple dose in situ drug delivery capabilities. Implants incorporating this concept could aid in the perpetual struggle against infection by providing a new strategy for delivery of high level antibiotics directly to the site of infection.
  • Thumbnail Image
    Item
    Laser powder bed fusion-centred approach to enable local drug delivery from a cementless hip stem
    (Stellenbosch : Stellenbosch University, 2021-03) Bezuidenhout, Martin Botha; Damm, Oliver; Sacks, Natasha; Dicks, Leon Milner Theodore; Stellenbosch University. Faculty of Engineering. Dept. of Industrial Engineering.
    ENGLISH ABSTRACT: Periprosthetic joint infection (PJI) resulting from colonisation of implant surfaces by pathogenic bacteria and subsequent biofilm formation is a devastating complication following total hip arthroplasty. It significantly reduces a patient’s quality of life and, in severe cases, can result in amputation or mortality. Treatment of PJI is associated with a substantial burden on healthcare and economic resources. The importance of research towards innovations in PJI prevention and treatment is emphasised. Local delivery of antimicrobial drugs is an effective approach to prevent and treat PJI as it enables high local drug concentrations while avoiding systemic side effects. Current practice is considered sub-optimal and appreciable research exists on the improvement of local drug delivery strategies. For cementless hip stems the focus tends to be on coatings and conditioning of the external implant surface. A significant research gap exists between external and internal drug delivery strategies where ‘internal’ refers to the incorporation of reservoir structures within the implant. Therefore, a prototype strategy utilising the internal volume of a cementless stem for a reservoir from which an antimicrobial drug can be delivered directly to the implant surface was investigated. The challenge of fabricating a cementless hip stem with intricate internal geometries can be effectively addressed through metal additive manufacturing (MAM). Industry is steadily incorporating MAM into process chains as the main production technology for the fabrication of high-value functional components. Laser powder bed fusion (LPBF) was applied in this study as MAM technology to fabricate a Ti6Al4V ELI demonstrator cementless hip stem with local drug delivery functionality. This required an interdisciplinary approach, for which a problem solving framework has been synthesised to aid in process chain development from an LPBF-centred perspective. The overall problem was decomposed into integrated partial and single problems which were systematically investigated through literature study and experimentation. An LPBF-centred solution was developed for the direct integration of permeable structures in a dense part using an in-process assembly method. Different levels of porosity were induced into permeable thin walls according to a systematically identified window for ranges of the process parameters, laser power and scanning speed. This resulted in tailorable release profiles for the model antibiotic vancomycin from an aqueous formulation. Released vancomycin retained its antibiotic efficacy against Staphylococcus aureus Xen 36 (methicillin sensitive) and Staphylococcus aureus Xen 31 (methicillin resistant), representing two of the most frequent pathogens in PJI. Solutions for single problems were recomposed for integrated solutions to partial problems, and subsequently for an overall prototype solution. The overall solution cementless hip stem prototype effectively prevented surface colonisation by Staphylococcus aureus Xen 31, confirming the efficacy of the developed local drug delivery strategy. These results were used to inductively refine the LPBF-centred interdisciplinary problem solving framework. The original contribution of the research corresponds to the experimentation and framework development phases respectively. This involves the systematic investigation of LPBF to enable local drug delivery and an LPBF-centred approach for interdisciplinary problem solving. Lastly, it contributes to the advancement of LPBF by demonstrating the application efficacy of the prototype solution.