Prof. Dr. Tunku Kamarul Zaman Bin Tunku Zainol Abidin
Professor
Faculty of Medicine
Universiti Malaya
tkzrea@um.edu.my

NO	NAME	PROJECT TITLE	RESEARCH DOMAIN (SUB DOMAIN)
1	Prof. Dr. Tunku Kamarul Zaman Bin Tunku Zainol Abidin	A Study To Determine The Role Of Multi-modal Cellular Supplementary Support Approach In Treating Cartilage Diseases Using Focal Cartilage Disease Model In Rabbit Models.	Clinical and Health Sciences (Basic Medical Sciences)
2	Assoc. Prof. Dr Ardiyansyah Bin Syahrom	Predicting The Involvement Of Subchondral Bone Degenerative Process In Cartilage Disease Progression Using Advanced Conversion Pre-clinical Imaging Modality Approach.	Technology and Engineering (Material and Polymer)
3	Assoc. Prof. Dr. Hanumantha Rao Balaji Raghavendran	Understanding The Potential Of 3d/fibrous Scaffolds In The Differentiation Of Human Bone Marrow Concentrate And Mechanism Of Interaction Between Cell And Extracellular Matrix For Tissue Engineering Application	Pure and Applied Science (Materials Science)
4	Assoc. Prof. Dr. Nahrizul Adib Kadri	Establishing Microcellular Biomechanical Alterations In Cartilage Tissue That May Be Associated With The Cartilage Diseases In Vivo.	Clinical and Health Sciences (Basic Medical Sciences)

3 years (01 December 2016 – 30 November 2019)

Musculoskeletal diseases are one of four chronic diseases commonly presented in urban-dwelling older people in Malaysia. Although not life-threatening, articular cartilage injury and degeneration are considered to be the leading causes of disability and pose a huge financial burden on any individual or existing health system. The replacement or regeneration of damaged or diseased articular cartilage with functional tissue is the main objective in performing cartilage repair. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. One such new therapeutic strategy that brings promise to patients suffering from damaged cartilage is Mesenchymal stromal cells (MSCs) and Bone marrow concentrates (BMCs). Our previous research work has shown that protocols based on the delivery of stem cells introduced in patients, showed encouraging results in treating articular cartilage lesions (focal defects, osteoarthritis). Possible improvements may reside in the use of biological supplements including Hyaluronic acid (HA), Platelet rich concentrate (PRC) and chondroitin sulfate (CS) along with MSCs and BMCs. However, no single strategy is able to provide surgeons with the best result for long-term successful outcomes. As such, the development of novel techniques and optimization of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. Therefore, the present study aims to examine the effects of BMMSCs, BMCs with the combination of Chondroitin Sulfate (CS)-Hyaluronic acid (HA), CS-Platelet rich concentrate (PRC), HA-PRC in treating focal cartilage defect in rabbit model using study designs modeled from our previously completed research works.

1. To establish the superior effects of multimodal treatment strategies in the restoration of cartilage disease in animal models as suggested from our previous extensive studies conducted in our research laboratory and consortium.
2. To establish the role and influence of subchondral bone involvement in the disease process and its relationship to cartilage disease progression. This in turn would help develop an approach to prevent future progression of the disease by correcting the disease at the subchondral level and not address the cartilage tissue only.
3. To investigate changes to the tissue micro-biomechanics and cellular-molecular mechanical influences with potentially elucidating the mechanotransduction process disruption during the progress of cartilage disease. This would help establish a potentially new disease pathway and thus allow the development of novel treatment strategies.
4. Using objective 3 as the premise for the presence of mechanical influence in cartilage homeostasis, the development of the appropriate biomaterials to replace existing loss in cartilage-bone will be suggested as part of this program. Biomaterials to be suggested for this study will be based on the success of our previously reported biomaterial development in vitro, which needs to be further assessed in compliance with international standards in healthcare delivery including FDA and EMA.

1. Talent:
   • 1 PHD
     1. Rufaidah Othman (Graduated)
   
   


2. Publication:
   
   • Article in Indexed Journals
     1. Biomineralization, Mechanical, Antibacterial and Biological Investigation of Larnite and Rankinite Bioceramics (2020) - Web of Science, Q1
     2. Assessing The Potential Of Bone Marrow Concentrate For Cartilage Repair And Regeneration In Animal Models : A Systematic Review (2021) - Web of Science
     3. Fluid Structure Interaction (FSI) Modeling of Bone Marrow through Trabecular Bone Structure under Compression (2021) - Web of Science
     4. Influence of Bone Marrow Characteristic and Trabecular Bone Morphology on Bone Remodelling Process with FSI Approach (2021) - Web of Science
     5. Effect of Chitosan Nanoparticle-Loaded Thymus serpyllum on Hydrogen Peroxide-Induced Bone Marrow Stromal Cell Damage (2019) - ISI
     6. A systematic review on peripheral blood mesenchymal stem cells: A potential cell therapy for cartilage repair (2019) - SCOPUS
   • Conference Proceedings
     1. Combined effect of bone marrow concentrate and platelet rich plasma in treating focal cartilage defect (2019)
     2. Regenerative Repair of Articular Cartilage Defect in Osteoarthritis Rabbit Model using Non-Mobilized Peripheral Blood-Derived Mesenchymal Stem Cells and PlateletRich Plasma (2018)

• FEA has positively impacted on the extent of cartilage repair and regeneration. Varying the loading conditions in the FEA has provided novel insights on the biomechanics of the newly formed cartilage tissue.
• New Fibrous/3D composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment.
• Submission for new product registration under NPRA can be made by submitting the dossier for combination products.
• On approval from National Stem Cell Research and Ethics Subcommittee (NSCERT) the cell therapy products can be progressed to phase I and phase II clinical trials.
• In-house prepared biomaterials can be submitted for MDA application after completing the in vivo proof of concept study and clinical trials.
• Successful outcome of cartilage repair using platelet rich plasma has progressed to its usage in patients with osteoarthritis. Nearly 100 patients were treated with platelet rich plasma with favorable outcomes.