RESEARCH

TENDON/LIGAMENT TE

The restoration of ruptured Anterior Cruciate Ligaments (ACL) is an important field for orthopaedic research. If left untreated, ruptured ACLs will deteriorate into serious degenerative joint diseases.  In view of the clinical needs, a novel tissue interface augmentation (TIA) device, which consist of a hybrid silk knit sheath with porous silk sponge and hydroxapatite nanoparticles has been developed to be used in conjunction with the use of tendon autografts. Concurrently, a 3D printable Tissue Interface Augmentation (TIA) device is being designed and developed for its future application in ACL reconstruction surgery; as a graft sleeve which helps in the promotion of osteointegration at the bone-tendon-graft interface within the bone tunnel.

BONE-LIGAMENT INTERFACE TE

Ligament-to-bone interface is a complex multiphase structure which consists of ligament, uncalcified and calcified fibrocartilage and bone. After injuries, there is no regeneration of interface and tissue engineering approaches using ligament grafts are not able to reconstruct the complex structural and cellular composition of native interface. This results in poor integration into bone tissue and poor mechanical stability, leading to graft failure eventually.  The aim of this area of work is to develop a bone-ligament-bone graft with a native-like fibrocartilage interface.  A tri-segmental hybrid scaffold of both knitted silk and silk sponge with regional deposition of hydroxyapatite (HA) was developed.  Following this previous study, an integrated silk fibroin based composite scaffold embedded with growth factor loaded gelation microspheres was also fabricated.

BONE-CARTILAGE INTERFACE TE

The generation of whole osteochondral constructs with a physiological tissue structure is a challenge. We started with the investigation and development of several co-culture models which uses silk fibroin sponge and RADA self-peptide hybrid scaffolds with chondrogenic rabbit BMSCs (rBMSCs) to generate osteochondral interface and the multilayered osteochondral tissue in vitro. Thereafter, a 3D-3D osteogenic/chondrogenic co-culture model was developed and results indicated that the cell-cell interactions between chondrogenic and osteogenic BMSCs induced the formation of the osteochondral interface. To further investigate the possibility of using pre-differentiated BMSCs to generate a whole osteochondral construct, a static two-chambered co-culture well and three-chambered bioreactor were designed.  Lastly, a bioreactor providing 3 different kinds of medium (i.e. chondrogenic, osteogenic and hypertrophic chondrogenic) was fabricated.

INTERVERTEBRAL DISC (IVD) TE

Low back pain is a major socioeconomic burden on the healthcare system worldwide and is estimated to grow at an annual compound rate of >20%. Traditional treatment strategies such as spinal fusion are not reliable and cause instability at adjacent levels of the intervertebral column. In recent years, technologies such as artificial disc replacement are promising due to its ability to restore degree of motion while preventing future adjacent segment related abnormalities and surgeries. However, several long term studies of such total disc replacements have showed that the approach is still marred by complications from wear and tear debris from the artificial joint and adjacent segment degeneration. Tissue engineering a functional disc replacement hence offers a promising new treatment modality in this regard.  We developed a structurally robust de novo IVD by mimicking the osmotic turgidity relationship between the native NP and annulus fibrosus (AF) through a three-pronged approach of using topographical cues, chemical induction and mechanical stimulus. A combination of silk-based laminates in the form of nanomats was used to recapitulate the circumferentially oriented multi-ply lamellae architecture of native AF while a novel silk/PVA cryogel forms the NP component.  To further assess the functionality of the tissue-engineered de novo disc construct in an in vivo environment, the de novo disc was implanted at one of the exposed disc space at the C5/C6 caudal level of the spinal columns of athymic rats. In the next phase of the project, we will develop this de novo disc construct technology for clinical applications and subsequently look into the area of bone-disc interface and integrate it with the current disc design.

CARDIAC PATCH TE

Myocardial infarctions or heart attacks result to the death of cardiac tissue due to its high sensitivity to oxygen.  Dead heart tissue is often replaced by scar tissue after and this decreases the heart's functionality.  As cardiovascular diseases remains one of the leading causes of death worldwide and with limited clinical success of cellular strategies and the higher risks in genetic therapies, the possibility of using cardiac tissue engineering to surgically restore heart function remains to be noteworthy of investigation.  We aim to develop a cardiac patch that delivers biochemical cues to promote tissue regeneration by loading a unidirectionally-frozen silk/gelatin scaffold with VEGF.  In addition to this, we are looking into developing conductive cardiac patches that will further promote the integration of the cardiac patch to the native tissue.

BIOREACTOR/PEMF FOR BONE TE

Bone tissue engineering has become a potential solution to unmet clinical needs for treatment of critical size bone defects. Moreover, biophysical stimulations have been shown to promote the development of bone grafts in vitro and in vivo. In particularly, the application of pulsed electromagnetic field (PEMF) stimulation has been demonstrated to promote healing of non-union fractures in patients. To study the effects of PEMF stimulation on tissue engineered bone constructs, we built and characterized a PEMF stimulation apparatus.

IN VITRO 3D TUMOR MODEL

Anticancer drug discovery has been hampered by the lack of reliable preclinical models, which routinely use cells grown in two-dimensional (2D) culture systems. However, many of the characteristics of cells in 2D culture do not translate into the findings in animal xenografts. Three-dimensional (3D) growth may be responsible for some of these changes and models using cells grown in 3D may form a reproducible and more representative step in tumoricidal validation prior to animal implantation or even human testing.  We used a tissue engineering approach to develop an in vitro 3D tumour model with replicated tumour microenvironment (i.e. physiological pressure, oxygen, and pH levels) for drug sensitivity studies through the use of a perfusion bioreactor.