Can platelet rich plasma improve bone healing? - An in vitro and in vivo investigation into the use of platelet rich plasma to augment bone regeneration

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Copyright: Malhotra, Angad
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Abstract
Introduction: The management of bone defects continues to present surgical challenges, and alternatives to autograft remain sought after. Upon activation, platelets release an array of growth factors which regulate and contribute to healing. Therefore, combining platelet rich plasma (PRP) with synthetic bone graft substitutes has the potential to reduce the reliance on autograft. Currently, the use of PRP is controversial. The progression of PRP is hindered by the absence of robust pre-clinical investigations, which has led to conflicting outcomes on its efficacy within the literature. This thesis investigates the potential of PRP for bone augmentation in an older age sheep model. Specifically, PRP dose is controlled to provide clearer indications for its clinical use. Methods: Clinical application of bovine thrombin is avoided, yet, many animal studies report outcomes with its use as a PRP activator. The first study investigates ovine PRP activation methods in vitro, and confirms a relevant alternative to bovine thrombin for use in the animal study. Such pre-clinical animal studies require appropriate characterisation of the model to ensure treatment outcomes are judged appropriately. Therefore, the second study develops and characterises an aged ovine multi-site bone defect model suitable for the aims of this thesis. The final study assembles the knowledge gained from the preceding chapters, and investigates the use of PRP at varying doses when combined with a biphasic calcium phosphate to treat critical size bone defects. Results: Autologous thrombin-activated PRP stimulated new bone formation within the bone defect with a dose dependant response. When the PRP was combined with a biphasic calcium phosphate, new bone formation within the defect was significantly greater than if the calcium phosphate was used on its own, demonstrating the benefit of PRP in a pre-clinical setting. Additionally, the role of other PRP constituents is revealed. In particular, the potential benefit of fibrinogen in the PRP. Overall, the PRP appeared to share chemotactic and mitogenic cell signalling functions similar to that of autograft at four weeks. However, the autograft displayed a more immediate healing response compared to PRP. Conclusion: PRP induces new bone formation at four weeks in aged sheep with a dose dependant response. Relevance: Clinical investigations of PRP are impeded by conflicting indications for its use. If a biphasic calcium phosphate is used to treat bone defects, the addition of an autologous thrombin-activated 3-fold PRP, mixed at a 1cc:1mL ratio, can improve the early bone defect healing response.
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Author(s)
Malhotra, Angad
Supervisor(s)
Walsh, William
Pelletier, Matthew
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Publication Year
2013
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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