(6z) Regenerative Bandages for Enhanced Healing in Diabetic Wounds

During the last several decades, biomaterials have emerged as a platform for creating solutions to various biological impairments and disease states. Within this field, a number of materials have been developed to deliver therapeutics to specific sites in the body and improve the health of patients. Unfortunately, many of the current strategies lack specificity, require repeated administration, suffer from non-compliance in patients, and have severe side effects. As such, there is a clear need in this field to develop materials and fabrication techniques that can deliver therapeutics effectively and with minimum side effects. During my PhD, I focused on using the electrohydrodynamic co-jetting process to develop a set of tools for the fabrication of carrier systems in which the physical and chemical properties could be pre-programmed for specific applications. Such properties include both physical parameters (size, shape, surface charge, and porosity) and chemical parameters (rate of degradation or stimuli-responsive erosion, design of surface groups for inclusion of targeting and stealth moieties, and encapsulation of therapeutics and their controlled release kinetics). Using this toolbox, I fabricated carriers for several applications including cancer therapy, cochlear delivery, cardiovascular therapy, and Alzheimer therapy. Specifically, I was able to establish controlled and on-demand release kinetics of various therapeutics, demonstrate control over the size of multifunctional particles, and create orthogonal patches on the surface of particles for the inclusion of targeting and stealth moieties. Using these techniques, I’ve demonstrated the circulation of PEG-ylated nanoparticles in mice, and the persistence and viability of particles for cochlear delivery in guinea pigs.

As a post-doctoral fellow, I have expanded my knowledge in the biomaterial field by working with a new set of materials, and more importantly, have gained hands-on experience in a more biologically driven environment. My focus has been on the development of immunotherapies for the treatment of wounds in diabetic patients, especially diabetic foot ulcers (DFUs). In the US alone, 29 million individuals suffer from diabetes, approximately 15% of whom will likely develop DFUs. Patients suffering from DFU’s can have significant life impairments, including amputated lower extremities. While a number of methods have been developed for wound healing in recent times, most are not applicable for DFUs since the pathophysiology in diabetic patients is different than in healthy individuals. A significant aspect of this difference lies in the impaired wound healing cascade observed in diabetic patients, where the inflammatory phase of the wound healing process is elongated and the healing phase is delayed and, at times, not observed. An important player in the healing cascade are polarized macrophages that can both orchestrate the inflammatory and healing phases (M1 and M2 macrophages, respectively). Our hypothesize is that increasing the number of macrophages at the wound site and redirecting the local macrophages to a more pro-healing state can enhance healing in diabetic wounds. Our approach to enhance wound healing is two-fold: (i) the isolation, polarization, and delivery of pro-healing macrophages to the wounds using hydrogel bandages; and (ii) the release of factors from hydrogel bandages to first recruit, then polarize macrophages to the pro-healing state at the wound site. Thus far, we’ve been able to establish that the delivery of pro-healing macrophages to wounds in a type 2 diabetic murine model can enhance their wound healing, and we have examined the various factors released by these cells by testing and analyzing their conditioned media. Furthermore, the encapsulation of various factors in the hydrogel bandages and their pro-longed release has been established. Using these bandages, we’ve been able to recruit macrophages to the wound site and are currently working on polarizing them to the pro-healing state to determine their effectiveness in enhancing wound healing in diabetic patients. Such bandage systems can potentially provide significant improvement in the lives of diabetic patients by employing their immune system to directly address their impaired healing mechanism. As an independent researcher, I plan to continue my work at the interface of material science and medicine by developing unique solutions to complex biological challenges.

Post-Doctoral Research:

Post-doctoral work: “Regenerative Bandages for Enhanced Healing in Diabetic Wounds” under the guidance of Professor David Mooney at Harvard University.

PhD Dissertation:

Thesis work: “Multifunctional Drug Carriers with Programmable Properties” under the guidance of Professor Joerg Lahann at University of Michigan.

Successful Proposals & Fellowships:

T32 Organ Design & Engineering Post-Doctoral Training Program (ODET) 2016-2018

T32 Tissue Engineering and Regeneration Training Grant (TEAM) Fellowship 2011-2013

Selected Publications:

1. Rahmani, D. J. Mooney, “Tissue Engineered Wound Dressings for Diabetic Foot Ulcers”. In Editors: A. Veves, J. M. Guirini, R. J. Guzman, The Diabetic Foot – Medical and Surgical Management, 4^th Edition. 2018, Springer.
2. Rahmani, S. Ashraf, R. Hartmann, A. F. Dishman, M. V. Zyuzin, et. al., “Engineering of Nanoparticle Size via Electrohydrodynamic Jetting”, Bioengineering & Translational Medicine, 2016, 1, 82-93.
3. Rahmani, A. M. Ross, T. H. Park, H. Durmaz, A. F. Dishman, et. al., “Dual Release Carriers for Cochlear Delivery”, Adv. Healthc. Mater., 2016, 7 (18), 9744-9751.
4. Rahmani, C. H. Villa, A. F. Dishman, M. E. Grabowski, D. Pan, et. al., “Long Circulating Janus Nanoparticles Made by Electrohydrodynamic Co-Jetting for Systemic Drug Delivery Applications”, J. Drug Targeting, 2015, 23 (7-8), 750-758.
5. Rahmani, J. Lahann, “Recent Progress with Multicompartmental Nanoparticles”, MRS Bull., 2014, 39 (03), 251-257. The article was an invited review and received the cover.
6. Rahmani, S. Saha, H. Durmaz, A. Donini, A. C Misra, et. al., “Chemically Orthogonal Three-Patch Microparticles”, Angew. Chem. Int. Ed., 2014, 53, 2332-2338. The article was reviewed as one of the top 10% of manuscripts submitted to Angewandte Chemie, Int. Ed., and was also displayed as the communication section’s cover piece.
7. Rahmani, T.-H. Park, A. F. Dishman, J. Lahann, “Multimodal Delivery of Irinotecan from Microparticles with Two Distinct Compartments”, J. Control. Release, 2013, 172, 239-245.
8. J. Lee*, J. Yoon*, S. Rahmani, S. Hwang, S. Bhaskar, et. al., “Spontaneous Shape Reconfiguration in Multicompartmental Microcylinders”, Proc. Nat. Acad. Sci., 2012, 109 (40), 16057-16062.

Teaching Interests:

Teaching Interests:

I am interested in teaching Biomedical Engineering and Chemical Engineering courses at the undergraduate and graduate levels, especially in the areas of biomaterials, mechanics, bio-reactions, and cell & tissue engineering. My background is in Biomedical Engineering and I have experience teaching in Chemical Engineering and feel comfortable teaching in both areas.

Teaching Experience:

During my PhD, I was a graduate student instructor for the Chemical Engineering 230: Introduction to Materials and Energy Balances course, which had over 230 students. I was responsible for preparing and teaching three discussion sections each week (90 students); holding several office hours during the week; grading exams, quizzes, and projects; helping with the organization of the course; and managing interactions with students with disabilities.

Mentoring Experience:

Over the course of my PhD and post-doctoral training, I have had the opportunity to mentor over 17 students (graduate, undergraduate, and high school students). My students have come from different academic backgrounds and we have kept in touch as they have moved on to various industry and academic positions. I have tremendously enjoyed the experience and look forward to continuing mentoring as a faculty member.