Regenerating bone following osteosarcoma tumour resection in a post-chemotherapy treated bone defect

Overview

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Standard treatment involves surgical resection of the tumour combined with systemic chemotherapy. While most patients undergo limb-sparing surgery to avoid amputation, this often results in significant morbidity and lifelong complications. These complications stem from the creation of large bone defects, poor healing outcomes, the need for revision surgeries, and long-term prosthetic failure

There is a critical clinical need for regenerative strategies that restore bone integrity and function following tumour resection, particularly in paediatric patients where long-term success depends on restoring bone that can grow and remodel over time. This project aims to regenerate, rather than replace lost bone using scaffold-guided techniques that support vascularised, mechanically functional tissue capable of integrating with the individuals own bone over their lifetime.

In this project, we will harness the body’s innate regenerative capacity by implementing a clinically relevant induced membrane technique, adapted to a preclinical rat model. This approach creates a pro-regenerative environment that promotes bone formation and integration. Importantly, this model will be applied in the context of chemotherapy-treated bone defects, enabling evaluation of how prior treatment impacts regenerative capacity. Our team has developed advanced in vivo models using highly immunocompromised rats, enabling the evaluation of scaffold-based regenerative therapies in settings that closely mimic the clinical challenges of osteosarcoma surgery.

Research activities

The objective of this project is to evaluate scaffold-guided bone regeneration following osteosarcoma resection using bioengineered constructs in an orthotopic rat model. In this project, you will:

• perform critical-sized bone defect surgeries following tumour resection in immunocompromised rats
• fabricate and implant 3D printed scaffolds, including drug-eluting and cell-free biomaterials
• use preclinical imaging (µCT, X-ray) to assess bone regeneration over time
• collect and analyse tissue for biomechanical testing, histology, immunohistochemistry, and molecular assays
• investigate the influence of chemotherapy (systemic and local) on bone healing capacity.

Approaches and learning opportunities offered include:

• surgical modelling of limb-sparing resection in a rat orthotopic bone tumour model
• fabrication and application of 3D printed scaffolds for bone regeneration
• preclinical imaging using µCT and X-ray to assess bone healing longitudinally
• biomechanical testing, tissue processing, histology, and immunohistochemistry to assess the quality of regenerated bone
• quantitative assays for regenerative outcomes (e.g. ELISA, RNA-seq).

Outcomes

This project contributes to the development of scaffold-guided bone regeneration strategies that aim to improve functional outcomes following osteosarcoma resection in paediatric patients.

Skills and experience

Ideal eligible candidates should:

• have previous PC2 laboratory and small animal handling experience
• have previous experience with cell culture, in vivo studies and common bioassays
• be interested in tissue engineering, orthopaedic surgery, and regenerative medicine
• demonstrate strong written and verbal communication skills
• be self-motivated, with the ability to plan and prioritise workloads to meet deadlines
• be capable of critical thinking and able to undertake complex problem-solving activities
• be able to work in a multidisciplinary team environment.

Scholarships

You may be eligible to apply for a research scholarship.

Explore our research scholarships

Keywords

• osteosarcoma
• bone regeneration
• tissue engineering
• preclinical models
• scaffold-guided healing
• chemotherapy
• hydrogels
• preclinical imaging
• regenerative medicine

Contact

Contact Dr Jacqui McGovern for more information.