Current Research Projects
1. Targeted nano-thermotherapy for the resolution of biofilm infection in chronic wounds
Clinical data from human non-healing chronic wounds has shown that biofilm formation is correlated with the onset of wound chronicity, which can lead to prolonged hospitalization and amputation. Current approaches for the treatment of wound infections include the application of topical or systemic antibiotic treatments along with wound debridement, drainage, and surgical intervention. However, a critical challenge in treatment of biofilm infection is that they are often antibiotic resistant and readily evade innate immune attack. There is an urgent need for a new strategy that can successfully target biofilms in the management of non-healing chronic wounds. To address this challenge, our lab is developing a non-invasive, antimicrobial, magnetic thermotherapy platform in which a high-frequency alternating magnetic field (AMF) is used to rapidly heat magnetic nanoparticles (MNPs) that are bound to a bacterial pathogen. In our recent work (Kim et al. Annals Biomed Eng., 41:598-609, 2013), we demonstrated that targeted MNP hyperthermia can be used as a non-invasive antimicrobial therapeutic for management and accelerated healing of wound infection. Our lab is currently engaged in a research to simultaneously target multiple Gram + and Gram - bacterial species. The long-term goal of this study is to provide preclinical validation of magnetic nanoparticle thermotherapy that cooperates with the innate immune response, works synergistically with conventional antibiotic treatment, is effective in the treatment of polymicrobial biofilm infection with both Gram + and Gram - bacterial species, and ensures safety of the technology.
2. Targeting macrophage phenotype for immunomodulation and wound healing in diabetic wounds.
Diabetic wounds are characterized by a chronic inflammatory state manifested by imbalances in pro- and anti-inflammatory cytokines. A large body of evidences support that diabetic wounds are associated with macrophage dysfunction, including persistent trafficking of M1-like macrophages, which might act as a key source of inflammation that leads to persistent neutrophils trafficking and their excessive activation. Although mesenchymal stem cells (MSCs) have been recognized to have therapeutic potentials in the repair of tissue injuries, a persistent pro-inflammatory M1 environment at the inflamed tissue could significantly diminish functional abilities of MSCs. However, the nature of the complex interplay between these two cell types and how these interactions influence the ability for MSC mediated tissue regeneration in diabetic wounds are not well understood. Our approach is to selectively direct and promote an anti-inflammatory and tissue reparative M2 response to tissue injury, which may potentially change regeneration paradigms in diabetic wounds by modulating aberrant inflammatory responses. In addition, this strategy may improve MSC-based therapy by providing a better understanding of crosstalk between macrophage and MSC.
3. Mesenchymal stem cell-encapsulated microspheres for tissue engineering
Despite promising potential of MSCs for tissue regeneration, major challenge in MSC-based therapy has been associated with poor cell survival and low levels of cell integration into host tissue following transplantation. Upon implantation, donor cells are immediately exposed to pro-inflammatory microenvironment of the injury site, which could significantly decrease the viability of exogenously implanted donor cells. Although the use of biomaterial scaffolds for encapsulating cells have been reported as an effective approach for cell delivery, it still necessitates the development of novel cell carrier that not only is biocompatible and biodegradable, but also can confer stable attachment and integration into host tissue. Our lab is developing and utilizing gelatin based microspheres as an injectable carrier of mesenchymal stem cells for tissue engineering applications, which not only is injectable, biodegradable and biocompatible, but also can provide a protective diffusional barrier against pro-inflammatory mediators in the environment.