Precision Orthopaedics and Innovative Technologies (POINT)

Introduction

This theme, Precision Orthopaedics and Innovative Technologies (POINT), consists of different programs:

Laboratory for Orthopaedic Advanced Technology Research

Research Team

Prof. YUNG Shu-hang, Patrick (ORCID)	Prof. LAW Sheung-wai	Prof. WONG Man-yeung, Ronald (ORCID)
Prof. CHEUNG Wing-hoi, Louis (ORCID)	Prof. CHUI Chun-sing, Elvis (ORCID)

Research Background

Research direction of this team is to develop advanced technology for diagnosis, treatment or prevention of orthopaedic diseases. Artificial intelligence (AI), robotics, augmented reality (AR) will be applied to develop cutting-edge devices or facilities targeting to facilitate early diagnosis, improved and more precise surgery procedures or treatment, as well as effective prevention of various orthopaedic diseases, which would ultimately achieve precision medicine. This team is composed of multidisciplinary experts, including orthopaedic surgeons, biomedical engineers and scientists to collectively develop advanced technologies to solve orthopaedic problems. This joint force expects to translate their research work into products to benefit patients suffering from musculoskeletal disorders and to achieve healthy ageing for the senior citizens.

Research Direction

Fig 1. Passive active robot for orthopaedic surgery HybriDot

Fig 2. AR assisted pedical screw insertion module for orthopaedic surgery training

Fig 3. Intra-operative planning - AR navigation system

Fig 4. Deep learning based prosthesis loosening detection

Fig 5. Artificial intelligence assisted orthopaedic surgery planning system

Fig 6. Semi-automatic 3D spine bracing designing system

Current On-going Projects

Completed Projects

Patents

Awards

Fig 7. Certificates from the 48th International Exhibition of Inventions of Geneva in 2023.

Selected Publications

Innovative Orthopaedic Biomaterial and Drug Translational Research

Research Team

Program Director	Program Co-Directors
Prof. QIN Ling (ORCID)	Dr. TANG Ning	Prof. YUNG Shu-hang, Patrick (ORCID)

Team Members (Photo taken in Jan 2025)

Overview of our roadmap for translational research, from establishing clinical indications to preclinical assessments, clinical trials, regulatory approval, and realization of our research outcome in clinical applications of our Class III medical implants, devices, and drugs

Research Background

Population aging is a global challenge. Ageing is associated with many musculoskeletal problems, including primary or secondary osteoporosis (OP), osteoarthritis (OA), and chronic tendon-bone insertion (TBI) disorder or injury, which often lead to bone fractures, joint deformity, and disability. These costs impose a huge socioeconomic and healthcare burden on the patient, family, healthcare system, and society in Hong Kong and worldwide. Therefore, there is an urgent need for further development or improvement of orthopaedic implants/devices, drugs/supplements to prevent or treat musculoskeletal disorders, and accelerate musculoskeletal regeneration. The World Health Organization (WHO) designated 2000-2010 as the Bone Joint Decade and has subsequently extended it to 2020, which implies musculoskeletal diseases are a big challenge for our modern yet aging society.

Our research focuses on the development of orthopaedic implants/devices with innovative biomaterial or hybrid systems and medical drugs/nutrition supplements for orthopaedic diseases or injuries, such as osteoporosis, osteoporotic fractures, and osteonecrosis. By integrating medical science, life science, material science, pharmacological science, imaging technology, and biomechanics, we identify potential solutions for clinical problems. Then, we collaborate with our industrial partner to transform our research into medical products that benefit patients. The feedback from patients and clinicians would refine future R&D and improve the quality of innovative products.

Research Directions

Biodegradable and Bioactive Metallic Orthopaedic Implants

Fig 1.1. Hybrid implant for fracture fixation. Schematic diagram of the hybrid system after surgery. The Mg plug is close to the fracture site. The released Mg ions would be distributed to the surrounding tissue and promote fracture healing. (a) CAD model of modified IM nail; (b) The prototype of the hybrid IM nailing system with insertion of Mg plug; (c) The fabricated Mg plug.

Our innovative and patented biodegradable implants made of pure magnesium (Mg) or its alloys have demonstrated initial stable fixation ability and regeneration in challenging orthopaedic conditions, including treatment of osteoporotic fractures, osteonecrosis, and bone-tendon insertion (TBI) repair. Our collaborators from both academia and industry provide platforms for realizing our proof-of-concept implants for our collective efforts in clinical translation and bedside applications. Our preclinical and clinical research and published work serve as key references for regulatory bodies, such as the US FDA and Chinese FDA, for establishing ISO standards and guidelines for developing biodegradable metallic implants.

Professor Ling Qin focuses on the R&D of innovative orthopaedic implants and drugs or supplements for the prevention and treatment of skeletal disorders and injuries with limited healing potential, including patients with impaired healing capacity, large bone defects, and healing at different tissue types such as the bone-tendon/bone-cartilage interface. He has been developing innovative biomedical and tissue engineering products, clinical indication-oriented treatment regimens and protocols that utilize stem cells, bioactive and biodegradable materials (e.g., biodegradable Magnesium), endogenous and exogenous growth factors, and external biophysical stimuli to enhance musculoskeletal tissue regeneration. The goal of his research is to facilitate not only anatomical but more importantly also functional restoration to achieve early rehabilitation and reduce disease-associated morbidity and mortality.

Being multidisciplinary in nature, Professor Qin and his team collaborate with local and international engineers and material scientists for developing innovative biomaterials and drugs, such as redesigning the current commercially available implant to incorporate Mg-based components. Recently, we have tested different Mg-based alloys and have applied different coatings to prevent the rapid degradation. One innovative approach is that we have modified current commercially available implants to incorporate Mg-based components to enhance bone healing. This hybrid implant, with both conventional titanium metal and Mg components, can deliver Mg to fracture sites and also has great potential in facilitating and enhancing fracture healing, which could accelerate an early initiation of mobility and rehabilitation of patients with fractures.

Recently, with collective efforts and endeavors, Professor Qin's R&D program has secured significant R&D and scientific competitive grants, including the Areas of Excellence Scheme (AoE/M-402/20), Theme-based Research Scheme (T13-402/17-N), and Collaborative Research Fund (C4028-14G, C4026-17W), which are three of the most competitive grants schemes given by the Research Grant Council of the Hong Kong Special Administrative Region. Our team in CUHK has been dedicating our efforts to innovation and R&D of the biodegradable magnesium (Mg)-based implants to develop desirable novel medical implants for avoiding or overcoming the above-mentioned drawbacks. Moreover, as shown in our recent Nature Medicine and Materials Today articles, to promote fracture healing and bone regeneration via the special osteo-promotive property of the Mg implants, which are partially through the nerve system and the calcitonin gene-related peptide (CGRP) in the challenging osteoporotic and bisphosphonate-associated atypical femoral fractures. Our innovative R&D has also received global attention, including an Innovation feature or Research Highlights by Nature in 2018 and Science in 2022. We have successfully designed and developed many novel Mg-based implants for a number of orthopaedic indications, including various fractures and bone defects at different skeletal sites, as well as anterior cruciate ligament (ACL) reconstruction, protected with the USA and PRC patents and recognized with Geneva Invention awards. We verified their function and efficacy by using the well-established animal models and disclosed the mechanism via the cellular and molecular experiments, especially the cutting-edge single-cell sequencing and analysis platform to identify the key genes responsible for the effect of the biodegradable Mg-based implants that lay down a solid foundation for designing our biodegradable implants to facilitate and accelerate bone regeneration and fracture healing.

Fig 1.2. Schematic diagram showing diffusion of implant-derived Mg2+ across the bone toward the periosteum that is innervated by DRG sensory neurons and enriched with PDSCs undergoing osteogenic differentiation into new bone (top). Inset (shown enlarged at bottom), the released Mg2+ enters DRG neurons via Mg2+ transporters or channels (i.e., MAGT1 and TRPM7) and promotes CGRP-vesicles accumulation and exocytosis. The DRG-released CGRP, in turn, activates the CGRP receptor (consisting of CALCRL and RAMP1) in PDSCs, which triggers phosphorylation of CREB1 via cAMP and promotes the expression of genes contributing to osteogenic differentiation. [Zhang Y et al., Nat Med. 2016 Oct;22(10):1160–9.]

Fig 1.3. Mg-based interference screws can promote the formation of the mineralized fibrous tissue at the tendon-bone interface via increasing the migration ability, adhesion capability, and osteogenic differentiation potential of bone marrow stem cells [Wang J et al. Acta Biomater. 2017 Nov;63:393–410.]

Osteopromotive Agents for the Treatment of Osteoporosis and Osteonecrosis

Icaritin, a phytoestrogen with a similar function and structure to estrogen, is extracted from the Epidemii herb. Our previous studies demonstrated the beneficial effect of icaritin on osteoporotic bone in both animals and humans.

Fig 2.1. 3D micro-CT image of trabecular bone in proximal tibia of mice. Mice with ovariectomy (OVX) were established as an osteoporotic model (OVX-1). Icaritin was given as treatment one month after surgery (ICT-1).

Since the oral bioavailability of icaritin is low (around 10%-17% reported by previous studies) and the retention time in blood circulation is relatively short, a bone-targeting liposome delivery system was developed. This delivery system has been reported in our previous study published in Nature Medicine and Biomaterials (Zhang G et al. Nat Med. 2012 Feb;18(2):307–14; Huang L et al. Biomaterials. 2018 Nov;182:58–71.).

Fig 2.2 The targeting delivery system with icaritin. A: The bilayer liposome structure under TEM. B: Icaritin delivery system under SEM. C: Schematic diagram of our bone-targeting delivery system

Fig 2.3. Tissue distribution after labeled liposome-icaritin and (Asp)8-liposome-icaritin ex vivo. A fluorescence-labeled delivery system with or without a targeting peptide was injected into mice. Organs have been harvested at different time points and scanned with an IVIS fluorescence detector.

Fig 2.4. Icaritin in the bone-targeting delivery system prevents bone loss in OVX mice. Ex vivo micro-CT quantification of the bone mineral density (BMD) and 3D trabecular architecture at proximal tibia in groups with or without ovariectomy surgery (OVX) and treated with administration of different treatments including oral administration of estradiol (E2) and intravenous injection of targeting delivery system (AP8+Lip), delivery system with icaritin (Lip+ICT) and targeting delivery system with icaritin (AP8+Lip+ICT).

Fig 2.5. Icaritin regulates adipogenesis through the Akt-GSK-3β/β-catenin signaling pathway. Icaritin promotes the phosphorylation of Akt, and phosphorylated Akt can further phosphorylate GSK-3β, thus inhibiting the combination of the β-catenin destruction complex. Therefore, β-catenin accumulates in the cytoplasm and then transfers into nuclei to activate the downstream of β-catenin signaling pathway to further promote osteogenesis and inhibit adipogenesis of BMSCs.

Research Impacts

Patents

Fig 3.1 Patents certificates.

Awards

Fig 3.2. Certificates from the International Exhibition of Inventions.

Fig 3.3. Program director Professor Ling QIN (2nd from right) was showing Ms. Carrie LAM (Previous Chief Executive of Hong Kong, 3rd from right) Professor Rocky TUAN (Previous Vice Chancellor of CUHK, 3rd from the left) and Professor Chunli BAI (Previous President of the Chinese Academy of Sciences, 2nd from left) the innovative biodegradable Magnesium-based orthopaedic implants (Nov 8, 2018).

10 Selected and Representative Publications from a Total of over 500 SCI Papers

Prof. Qin’s team has focused on the discovery of innovative biomaterials with a focus on R&D of Mg-based medical implants for 15 years, with fruitful outputs. There are 10528 academic publications in Web of Science with the topic Mg for Bone from January 2015 to March 2025, and according to the citation numbers, 5 of the top 10 are from Prof. Qin’s team (No. 1, 2, 3, 4, and 10). This indicates the profound international recognition of academic achievements.

Funding Support (recent 5 years)

Bone Tumor Team

Introduction

The Bone Tumor Team in the Department of Orthopaedics and Traumatology and focuses on both basic science and clinical research in the field. In the past 22 years, they have developed a niche area investigating the etiology and pathogenesis of Giant Cell Tumor of Bone (GCTB), and over 90 peer-reviewed journal articles have been published.

Dr. WONG Kwok-chuen

Research Background and Direction

GCTB is a nonmalignant, primary bone tumor which contributes about 20% of all skeletal neoplasms in Chinese population. It is typically found at the epiphyseal ends of long bones & its prime radiological characteristic is the presence of large expansile osteolytic lesions. GCTB is well known for its potential to recur following treatment, local recurrence rates of 18% to 50% have been reported.

In basic research, they have investigated the molecular events of histogenesis and biological behavior of GCTB, and the transcriptional regulation of RANKL promoter in this tumor. Moreover, they have also studied the molecular mechanisms for different drugs applying on GCTB treatments, such as nitrogen-containing bisphosphonates, prenyl transferase inhibitors, and denosumab. Recently, differential gene expression of the neoplastic GCTB stromal cells have been studied with the Next Generation Sequencing technique.

In clinical studies, they have done the pioneering work on computer assisted tumor surgery, to establish a unique computer-assisted workflow in musculoskeletal tumor surgery. In addition, they have used tumor prostheses in limb salvage surgery for patients with bone tumors and surgical techniques to insert complex custom tumor prostheses, to develop the Asian modification of tumor prostheses for Chinese population. They have received a number of both local and international awards in this field.

On-going Research / Projects

Research Impacts

Awards

Press Releases, News Articles

Selected Publications