Local drug delivery to prevent osteosarcoma recurrence and metastasis

Overview

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Despite aggressive treatment involving multi-agent chemotherapy and wide surgical resection, survival outcomes remain poor, with five year survival as low as 13% for patients with metastatic or recurrent disease. Current treatment relies heavily on systemic chemotherapy, which is associated with significant toxicity and long-term side effects, including cardiotoxicity, nephrotoxicity, and impaired growth and fertility. Local recurrence occurs in up to 30% of patients after surgical resection, often leading to further metastasis and treatment failure. There is a critical need for new therapeutic approaches that improve local tumour control without increasing systemic toxicity.

Our team has developed a local chemotherapy delivery system that uses drug-eluting hydrogels embedded within bioengineered bone scaffolds to release chemotherapeutics directly into the surgical site. This approach aims to prevent local tumour regrowth, reduce metastatic spread, and improve quality of life. This project involves testing the novel drug eluting systems in a humanised orthotopic OS model using highly immunocompromised rats, enabling clinically relevant evaluation of treatment efficacy in a tissue-engineered bone environment.

Research activities

The objective of this project is to develop and evaluate a local chemotherapy delivery system using drug-loaded hydrogels embedded within bioengineered bone scaffolds to prevent osteosarcoma recurrence and metastasis following tumour resection.

In this project, you will gain practical experience and a strong foundation in:

• designing and fabricating tissue-engineered bone constructs using 3D printing and cell culture
• performing rodent orthopaedic tumour surgery and local defect bridging
• developing and characterising drug-loaded hydrogels (e.g. drug release assays, mechanical testing)
• conducting preclinical imaging (µCT, X-ray, bioluminescence) to monitor tumour growth and treatment response
• histological and immunohistochemical analysis of tumour progression and treatment efficacy.

Approaches and learning opportunities offered include:

• design and fabrication of 3D printed scaffolds for local drug delivery
• hydrogel formulation, drug loading, and release characterisation (e.g. fluorescence assays, HPLC)
• cell culture (primary and cell line), cell-based assays, immunofluorescence, and image analysis
• small animal surgery for orthotopic tumour implantation and defect repair
• preclinical imaging (bioluminescence, µCT, X-ray) to monitor tumour growth and treatment response
• histological and immunohistochemical assessment of tumour, bone, and tissue responses
• analysis of treatment efficacy, local recurrence, and metastatic progression in vivo.

Outcomes

This project will contribute to the development of safer, more effective local chemotherapy strategies to prevent osteosarcoma recurrence and metastasis and reduce treatment-related morbidity.

Skills and experience

Ideal eligible candidates should:

• have previous PC2 laboratory experience
• have previous experience with cell culture, in vivo studies and common bioassays
• be interested in tumour biology, drug delivery and preclinical models
• 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.

Keywords

• osteosarcoma
• local drug delivery
• chemotherapy
• hydrogels
• tissue engineering
• in vivo models
• preclinical imaging
• regenerative medicine

Contact

Contact Dr Jacqui McGovern for more information.