A5065868161- Pancreatic function and diabetes
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Diabetes Management and Research
- Tissue Engineering and Regenerative Medicine
- Electrospun Nanofibers in Biomedical Applications
- Immune Cell Function and Interaction
- Genetics and Neurodevelopmental Disorders
- Mesenchymal stem cell research
- 3D Printing in Biomedical Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Hydrogels: synthesis, properties, applications
- Xenotransplantation and immune response
- Innovative Microfluidic and Catalytic Techniques Innovation
- Neuroendocrine Tumor Research Advances
- RNA Interference and Gene Delivery
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pancreatic and Hepatic Oncology Research
- Organ and Tissue Transplantation Research
- Pluripotent Stem Cells Research
- T-cell and B-cell Immunology
Georgia Institute of Technology
2018-2024
University of Michigan
2023-2024
University of Florida
2017-2021
University of Miami
2012-2017
A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results dying or dysfunctional portions graft. The development methods to increase oxygen availability within tissue-engineered particularly during early engraftment period, would serve allay hypoxia-induced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial form polydimethylsiloxane...
Local biomaterial-mediated delivery of PD-L1 induces alloislet graft survival and function in a murine model type 1 diabetes.
Islet transplantation to treat insulin-dependent diabetes is greatly limited by the need for maintenance immunosuppression. We report a strategy through which cotransplantation of allogeneic islets and streptavidin (SA)–FasL–presenting microgels omentum under transient rapamycin monotherapy resulted in robust glycemic control, sustained C-peptide levels, graft survival diabetic nonhuman primates >6 months. Surgical extraction prompt hyperglycemia. In contrast, animals receiving without...
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of more than 50%, progressive graft dysfunction over time, and precludes recovery grafts should there be serious complications such as development teratomas with that are stem cell-derived (SC-islets). omentum features attractive extrahepatic alternative site for clinical islet transplantation. We explore in which allogeneic transplanted onto omentum, is bioengineered a plasma-thrombin biodegradable...
Abstract For cell therapies, the subcutaneous space is an attractive transplant site due to its large surface area and accessibility for implantation, monitoring, biopsy, retrieval. However, poor vascularization has catalyzed research induce blood vessel formation within enhance revascularization survival. Most studies focus on of rodents, which does not recapitulate important anatomical features responses humans. Herein, we evaluate biomaterial‐driven in porcine space. Additionally, report...
Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies chemistries have been implemented, yet manipulation degradability its effect on in vivo tissue responses remains underexplored. Here, authors report a facile method to synthesize microgels crosslinked ester-containing junctions afford tunable degradation kinetics....
Allogeneic islet transplantation is limited by adverse effects of chronic immunosuppression used to control rejection. The programmed cell death 1 pathway as an important immune checkpoint has the potential obviate need for immunosuppression. We generated oligomeric form ligand chimeric with core streptavidin (SA-PDL1) that inhibited T effector response alloantigens and converted conventional cells into CD4+Foxp3+ regulatory cells. SA-PDL1 protein was effectively displayed on surface...
Abstract Thiol–norbornene (thiol–ene) photoclickable poly(ethylene glycol) (PEG) hydrogels are a versatile biomaterial for cell encapsulation, drug delivery, and regenerative medicine. Numerous in vitro studies with these 4‐arm ester‐linked PEG‐norbornene (PEG‐4eNB) demonstrate robust cytocompatibility ability to retain long‐term integrity nondegradable crosslinkers. However, when transplanted vivo into the subcutaneous or intraperitoneal space, PEG‐4eNB crosslinkers rapidly degrade within...
Abstract Translation of transplanted alginate‐encapsulated pancreatic islets to treat type 1 diabetes has been hindered by inconsistent long‐term efficacy. This loss graft function can be partially attributed islet dysfunction associated with the destruction extracellular matrix (ECM) interactions during isolation process as well immunosuppression‐associated side effects. study aims at recapitulating islet‐ECM direct functionalization alginate ECM‐derived peptides RGD, LRE, YIGSR, PDGEA, and...
Type 1 diabetes (T1D), an autoimmune disorder in which the insulin-producing β-cells islets of Langerhans pancreas are destroyed, afflicts over 1.6 million Americans. Although pancreatic islet transplantation has shown promise treating T1D, continuous use required immunosuppression regimens limits clinical as it poses significant adverse effects on graft recipients and does not achieve consistent long-term survival with 50%-70% maintaining insulin independence at 5 years. T cells play a key...
Immune checkpoint signaling, such as programmed cell death protein-1 (PD-1), is a key target for immunotherapy due to its role in dampening immune responses. PD-1 signaling T cells regulated by complex physicochemical and mechanical cues. However, how these forces are integrated with biochemical responses remains poorly understood. Our previous work demonstrated that the use of an immobilizing polyethylene glycol (PEG) linker on synthetic microgels presentation chimeric form PD-L1, SA-PD-L1,...
Biomaterial systems such as hydrogels enable localized delivery and postinjection modulation of cellular therapies in a wide array contexts. Biomaterials adjuvants have been an active area investigation, but the study functionalized biomaterials supporting immunosuppressive cell for tolerogenic applications is still nascent. Here, we developed 4-arm poly(ethylene-glycol)-maleimide (PEG-4MAL) hydrogel with interleukin-10 (IL-10) to improve local efficacy therapy against autoimmune disease....
Introduction and Objective Allogenic islet transplantation is an important therapeutic approach for the treatment of Type 1 Diabetes (T1D). However, graft rejection initiated perpetuated by pathogenic T effector (Teff) cells presents a major barrier. One that has proven successful promoting tolerance shifting cell balance away from induction Teff towards generation protective regulatory (Treg) cells. PD-1/PD-L1 immune checkpoint pathway plays role in Treg with demonstrated clinical efficacy...
Abstract Allogenic islet transplantation is an effective therapy for type 1 diabetes in the clinic. Sustained graft survival requires chronic immunosuppression that has adverse effects. Islet rejection initiated and perpetuated by T effector cells (Teffs). Teffs upregulate Fas death receptor on their surface undergo apoptosis following engagement with FasL. Therefore, FasL potential as immunomodulator to establish immune tolerance grafts eliminate alloreactive Teffs. This study used PEG...
Introduction and Objective Type 1 diabetes (T1D) is a chronic condition in which patients produce little to no insulin due the progressive loss of betacells. While disease can be managed via external delivery, still experience high incidence mortality development debilitating comorbidities. Islet transplantation has emerged as potential strategy restore patient’s glycemic control, yet long-term rejection need for immunosuppression present major barrier. Herein, we engineered synthetic...