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

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)	Prof. CHOW Ho-kiu, Dick (ORCID)

Team Members (Photo taken in Jan 2018)

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 huge socioeconomic and healthcare burden to 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 orthopaedics implants/devices with innovative biomaterial or hybrid systems and medical drugs/nutrition supplements for orthopaedics diseases or injuries, such as osteoporosis, osteoporotic fractures, osteonecrosis. By integrating medical science, life science, material science, pharmacological science, imaging technology, and biomechanics, we identify the potential solutions for clinical problems. Then, we collaborate with our industrial partner to transform our research into medical products that benefits 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 orthopaedics conditions, including treatment of osteoporotic fracture, 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 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 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-orientated 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 to redesign the current commercially available implant to incorporate with Mg-based components. Recently, we have tested different Mg-based alloys and have applied different coating 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 also have 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 Theme-based Research Scheme (T13-402/17-N) and Collaborative Research Fund (C4028-14G, C4026-17W), which are two of the most competitive grants schemes given by the Research Grant Council of the Hong Kong Special Administrative Region. The approval of these two milestone research funds acknowledges the scientific and translational value of Professor Qin's research and its high potential of application in the clinical setting – "Seeking biodegradable metals for clinical use" as highlighted in Scientific Feature of Nature in May 2018.
(https://www.nature.com/articles/d42473-018-00028-w)

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 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 animal and human.

Fig 2.1. 3D micro-CT image of trabecular bone in proximal tibia of mice. Mice with ovariectomy (OVX) were established as 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. Fluorescence labeled delivery system with or without targeting peptide was injected in mice. Organs have been harvested at different time points and scanned with 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 ar- chitecture 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 Akt-GSK-3β/β-catenin signaling pathway. Icaritin promotes the phosphorylation of Akt, phosphorylated Akt can further phosphorylate GSK-3β thus inhibit combination of the β-catenin destruction complex. Therefore, β-catenin accumulates in 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 of Geneva in 2015, 2016, and 2018.

Fig 3.3. Program director Professor Ling QIN (2nd from right) is showing Ms. Carrie LAM (Chief Executive of Hong Kong, 3rd from right) Professor Rocky TUAN (Vice Chancellor of CUHK, 3rd from the left) and Professor Chunli BAI (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 324 SCI Papers

Publication and Citation of Professor Ling QIN's group documented in Web of Science since joining CUHK in 1994, with a total of 324 SCI papers, 7435 citations, and 23 citations per publication (updated on December 18, 2018).

Funding Support (recent 5 years)

Bone Tumor Team

Introduction

Professor Shekhar-Madhukar KUMTA leads 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, Professor Kumta and his research staff 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.

Prof. KUMTA Shekhar Madhukar (ORCID)	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, Prof. Kumta has investigated the molecular events of histogenesis and biological behavior of GCTB, and the transcriptional regulation of RANKL promoter in this tumor. Moreover, he has 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, he and his colleague, Dr. KC Wong 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