Therapeutically Relevant Scaffolds: Scaffolds and biomatrices that designed to be therapeutically relevant hold great promise in tissue regeneration. This is possible either by the internal or by the external modulation. Intrinsically, tuning chemical and physical properties, tethering active moieties and matching stiffness are the proper strategies. On the other hand, therapeutic drugs and growth factors can be combined with the matrices to deliver into target sites in a controllable, sustainable, and sequential manner, to control the complex repair and regeneration processes, such as anti-inflammation, angiogenesis, cell mitosis, migration, and differentiation. Therapeutic cues thus need to be considered relevant to target tissues and range control from molecular and ionic levels to morphological and geometrical parameters.
Nanobiomaterials for Delivery System: Nanomaterials impart unique properties compared to their microscopic/macroscopic counterparts. Our group has been interested in developing a range of biocompatible nanomaterials in nanoparticulates, nanotubes and nanofibers that can have significant impacts on cell behaviors. Furthermore, controlling the nanotopology of the nanomaterials allows for the effective loading and intracellular delivery of therapeutic molecules, including chemical drugs, proteins and genes, targeting diseases and regenerative functions. Besides their delivery capability, we can tune their physical and chemical composition to obtain multifunctional properties including electrical, magnetic and optical properties in order to extend their applications and improve therapeutic and diagnostic efficacy. Among the different forms developed are carbon nanotubes, magnetic nanoparticles, mesoporous silica nanotubes/particles, calcium phosphates, and their nanohybrids with stimuli- responsive/specific tethering biopolymers
3D Tissue Engineering: Providing matrix cues for stem cells to properly anchor, proliferate and differentiate is a key aspect for tissue engineering. Our group has been focused on developing a wide range of matrixes using biopolymers, bioactive inorganics as well as their combinations to obtain optimized physico-chemical and mechanical properties in order to mimic the tissues that need to regenerate, such as nerve, muscle, bone and dental tissues. 3D culture methods involving perfusion system, spinner flask culture, and dynamic mechanical culture are also proper to achieve ex vivo tissue engineered constructs that can be native tissue equivalents. Co-culture of cells such as mesenchymal stem cells with endothelial cells is another stimulating strategy to engineer complex tissue structure with fully vascularized. Our group has been exploring novel 3D tissue engineering methodologies for the successful regeneration of target tissues, including bone, cartilage, nerve, muscle and dental tissues.
Stem Cell Fate Control: Controlling the fate of pluripotent (iPSCs and ESCs) and multipotent stem cells (MSCs) including the maintenance of self-renewal and the stimulation into specific lineage cells such as neurogenic, osteogenic, odontogenic and chondrogenic cells, is explored through the use of matrix and delivery cues. A wide variety of substrates, such as nano-structured matrixes, surface tethered/functionalized scaffolds, and 3D hydrogels among others are currently being tested. In combination with the inductive substrates, external stimuli may also dictate the fate of stem cells.
In Vivo Animal Models
We develop animal models to prove our hypothesis and to study in vivo phenomena of the developed biomaterials, manipulated cells and tissue-engineered constructs. Most studies are in rodent (rat and nude mouse) and some are in rabbit, beagle dog, and porcine, targeting diseases and damaged tissues in neuro-musculo-skeletal systems. Below are details developed thus far in ITREN, and more are under development.
- Bone models: calvarium critical-sized defect, alveolar bone critical-sized defect, vertical bone augmentation, bone fracture model for large bone defects
- Cartilage defect model for hydrogel-cell
- Tendon repair models: patellar tendon, Achilles tendon
- Bone-cartilage model for hydrogel implant
- Bone-ligament model
- Periodontal ligament defect model
- Tooth extraction model
- Dentin regeneration model
- Skeletal muscle defect models
- Aorta blood vessel model for tissue engineered BV
- Spinal cord injury model for neural regeneration (with JK Hyun’s group)
- Sciatic nerve model for nerve conduits (with JK Hyun’s group)
- Temporomandibular joint model for osteoarthritis disease treatment
- Osteoporosis model (ovariectomy) for bone disease treatment