Research Projects
Mechanoresponsive stem cells and immune cells in bone regeneration

Severe orthopaedic conditions like limb deformities, nonunions, and large segmental bone defects cause significant disability and socioeconomic burden. Distraction osteogenesis (DO), pioneered by the Ilizarov technique, provides an effective graft-free approach for large bone defects by applying controlled mechanical tension to stimulate endogenous regeneration. DO offers benefits including shorter hospitalization and lower costs. However, prolonged consolidation times and complications such as nonunion and infection remain major challenges. Understanding mechanoresponsive mechanisms in regenerating tissues during DO could lead to strategies that accelerate healing and reduce complications.

Our research targets key players in the DO regenerate: periosteum-derived stem cells (PSCs) and macrophages. Lineage tracing shows PSCs dominate bone formation in defect healing. In a periosteum-depleted DO model, PSCs  rather than bone marrow derived mesenchymal stem cells (BMSCs) restore robust regeneration. We are elucidating specific mechanoresponsive pathways driving PSC-mediated osteogenesis.

Macrophages transition from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes critical for repair. Our findings reveal mechanical cues during DO promote M2 polarization via the Integrin-SRC-STAT6 pathway. Single-cell RNA-seq further identified a mechanoresponsive macrophage subpopulation that enhances regeneration. Ongoing studies investigate metabolic reprogramming and epigenetic changes in these cells.

Professor S Lin, Department of Orthopaedics and Traumatology

Dr. Sien Lin is an Assistant Professor in the Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU). Dr. Lin obtained his PhD in the Chinese University of Hong Kong (CUHK) after attaining his medical degrees, then pursued his postdoctoral training in CUHK and Stanford University. After working as a Research Assistant Professor over 4 years in CUHK, Dr. Lin joined HKU in September 2025. Dr. Lin is passionate about the research and development (R & D) of regenerative strategies for challenging skeletal disorders. His recent work focuses on mechanoresponsive skeletal tissue regeneration, crosstalk between bone and distal organs, and skeletal stem cell for tissue regeneration. He has published over 100 publications in peer-reviewed journals including Nature Communications, Science Advances, Bone Research, Advanced Science, etc (H index 40). His research is funded by the General Research Fund (GRF) of Research Grant Council (RGC) Hong Kong, National Natural Science Foundation of China (NSFC), NSFC-RGC joint research scheme, Innovation and Technology Fund (ITF) and Heath and Medical Research Fund (HMRF). Dr. Lin serves as an editorial board member of Journal of Orthopaedic Translation (JCR Q1) and World Journal of Orthopedics (JCR Q2). Dr. Lin also serves as a lifetime member of the International Chinese Musculoskeletal Research Society (ICMRS), and Member of Tissue Engineering and Regenerative Medicine International Society (TERMIS) and Association of Rehabilitation Medicine. He was appointed as an adjunct professor of Orthopaedic Surgery in the Affiliated Hospital of Guangdong Medical University, China. Dr. Lin was a recipient of the TERMIS Student and Young Investigator Award, Best Poster awarded by ICMRS or Orthopaedic Research Society (ORS), and Bronze Medal of the Asia Exhibition of Innovations and Inventions. Dr. Lin serves as a grant reviewer for UK Research and Innovation (UKRI), British Medical Research Council (MRC), Dutch Research Council (NWO), and NSFC.  In addition, he also actively serves as a reviewer for over 20 journals.

Biography
HKU Scholars Hub
Lab Homepage
ORCID
sienlin@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.