Cathal J. Kearney

Bio: Cathal J. Kearney is an academic researcher from Royal College of Surgeons in Ireland. The author has contributed to research in topics: Tissue engineering & Drug delivery. The author has an hindex of 19, co-authored 43 publications receiving 1961 citations. Previous affiliations of Cathal J. Kearney include VA Boston Healthcare System & Massachusetts Institute of Technology.

Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy

Abstract: Biological systems are exquisitely sensitive to the location and timing of physiologic cues and drugs. This spatiotemporal sensitivity presents opportunities for developing new therapeutic approaches. Polymer-based delivery systems are used extensively for attaining localized, sustained release of bioactive molecules. However, these devices typically are designed to achieve a constant rate of release. We hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels. We demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides. Parallel in vitro studies demonstrated that the concept of applying temporally short, high-dose “bursts” of drug exposure could be applied to enhance the toxicity of mitoxantrone toward breast cancer cells. We thus used the hydrogel system in vivo to treat xenograft tumors with mitoxantrone, and found that daily ultrasound-stimulated drug release substantially reduced tumor growth compared with sustained drug release alone. This approach of digital drug release likely will be applicable to a broad variety of polymers and bioactive molecules, and is a potentially useful tool for studying how the timing of factor delivery controls cell fate in vivo.

Macroscale delivery systems for molecular and cellular payloads

Abstract: Macroscale drug delivery (MDD) devices are engineered to exert spatiotemporal control over the presentation of a wide range of bioactive agents, including small molecules, proteins and cells. In contrast to systemically delivered drugs, MDD systems act as a depot of drug localized to the treatment site, which can increase drug effectiveness while reducing side effects and confer protection to labile drugs. In this Review, we highlight the key advantages of MDD systems, describe their mechanisms of spatiotemporal control and provide guidelines for the selection of carrier materials. We also discuss the combination of MDD technologies with classic medical devices to create multifunctional MDD devices that improve integration with host tissue, and the use of MDD technology in tissue-engineering strategies to direct cell behaviour. As our ever-expanding knowledge of human biology and disease provides new therapeutic targets that require precise control over their application, the importance of MDD devices in medicine is expected to increase.

Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions

Abstract: Osteomyelitis is an inflammatory bone disease that is caused by an infecting microorganism and leads to progressive bone destruction and loss The most common causative species are the usually commensal staphylococci, with Staphylococcus aureus and Staphylococcus epidermidis responsible for the majority of cases Staphylococcal infections are becoming an increasing global concern, partially due to the resistance mechanisms developed by staphylococci to evade the host immune system and antibiotic treatment In addition to the ability of staphylococci to withstand treatment, surgical intervention in an effort to remove necrotic and infected bone further exacerbates patient impairment Despite the advances in current health care, osteomyelitis is now a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients This review aims to provide information about staphylococcus-induced bone infection, covering the clinical presentation and diagnosis of osteomyelitis, pathophysiology and complications of osteomyelitis, and future avenues that are being explored to treat osteomyelitis

Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype.

Abstract: Diabetic foot ulceration is a major complication of diabetes Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds

Cancer nanomedicine: progress, challenges and opportunities.

Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Designing hydrogels for controlled drug delivery.

Abstract: Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.