Research

RESEARCH AREA 1: Immuno-modulatory biomaterials

Objective: Probing the effects of material characteristics on molecular and cellular immuno-modulation of host response.

Host immune response to implanted biomaterials, which constitute major components of medical devices, drug delivery systems and tissue-engineered scaffolds, is important for their clinical success. Favorable response facilitates host-device integration while adverse reaction can lead to compromised function, device failure and medical complications. Probing the roles of molecular and cellular immune components in the complex interplay between implanted materials and the immune system constitutes a major aspect of our research. Moving forwards, the immediate next step for this research direction is to deepen our insight into material-induced host immune response, particularly the influence of controlled physiochemical characteristics of material formulation and patterning on the recruitment and activation of adaptive immune cells. Our long-term vision for this research direction is to leverage the fundamental understanding of relationship between material characteristics and immune response to enable rational selection and design of clinically relevant biomaterials.

Molecular and cellular events occuring after surgical implantation of a medical devices

RESEARCH AREA 2: Inflammation-responsive drug delivery

Objective : Rational design of in vivo protease-activated drug delivery systems for
management of chronic inflammatory diseases

A dynamic balance between multiple interacting molecular and cellular components of the immune system maintains healthy physiological conditions. However, disturbance of this balance often results in pathological states, which are associated with altered expression of specific immune biomarkers. Specifically, chronic inflammatory diseases are associated with recurring inflammation which requires treatment with anti-inflammatory therapeutic to restore immune homeostasis. However, clinically accepted treatment paradigm to mitigate excessive inflammation relies on systemic administration or extended release formulation often fail to account for the temporal dynamics of the biological microenvironment, resulting in excessive dosage and suboptimal duration of drug administration and subsequent harmful side effects. Therefore, our research centers on designing novel drug delivery systems that harness disease-specific immunological signals, particularly proteases, in pathological states to program the release of therapeutics for effective restoration of physiological balance in chronic inflammatory diseases. Our long-term motivation and vision for this research thrust is (1) expanding the versatility of these responsive platforms for a range of therapeutics including both small molecule and larger peptides/proteins and (2) evaluate the clinical relevance of this platform for management of specific indications such as chronic wounds and arthritis.

Inflammation-responsive drug delivery

RESEARCH AREA 3: Immuno-isolated cellular therapeutics

Objective : Rational design of geometrically tailored, immuno-protected microtissues for enhanced viability of cellular therapeutics

Transplantation of cellular therapeutics holds great promise as a long-term therapy to replace diminished pancreatic insulin production and improve glucose regulation to potentially benefit more than 500M diabetic patients worldwide. Encapsulation of these therapeutic cells in immuno-isolating hydrogels prior to transplantation protects them from host immunological attack without the needs for immunosuppressants which are often associated with adverse side effects. Nonetheless, hypoxia-induced death of transplanted cells, which occurs due to the absence of native supporting blood vessels for active oxygen transport, results in the release of cellular debris which has been postulated to increase immunological attack and fibrotic response against the remaining therapeutic cells resulting in ultimate graft failure. To address this challenge of hypoxic cell death, our team pioneers the design of novel tissue engineering strategies that improve survival of transplanted therapeutic microtissues by (1) directed assembly of microtissues into non-spheroidal geometry to facilitate passive oxygen diffusion to center of microtissues and (2) positioning these microtissues in controlled distribution to minimize their aggregation. Looking ahead, we aim to translate this platform into clinically relevant therapies by integrating stem cell technology with advanced automated microfabrication techniques, paving the way for scalable and effective treatments.

Immuno-isolation and implantation of geometrically tailored, therapeutic microtissues