Whitaker Biomedical Engineering Institute

Baltimore, MD, United States

Whitaker Biomedical Engineering Institute

Baltimore, MD, United States
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Nyland J.F.,University of South Carolina | Jiang X.,Johns Hopkins University | Jiang X.,Whitaker Biomedical Engineering Institute | Mao H.Q.,Johns Hopkins University | Mao H.Q.,Whitaker Biomedical Engineering Institute
Current Molecular Medicine | Year: 2013

Malaria sexual stage and mosquito transmission-blocking vaccines (SSM-TBV) have recently gained prominence as a necessary tool for malaria eradication. SSM-TBVs are unique in that, with the exception of parasite gametocyte antigens, they primarily target parasite or mosquito midgut surface antigens expressed only inside the mosquito. As such, the primary perceived limitation of SSM-TBVs is that the absence of natural boosting following immunization will limit its efficacy, since the antigens are never presented to the human immune system. An ideal, safe SSM-TBV formulation must overcome this limitation. We provide a focused evaluation of relevant nano-/microparticle technologies that can be applied toward the development of leading SSM-TBV candidates, and data from a proof-of-concept study demonstrating that a single inoculation and controlled release of antigen in mice, can elicit long-lasting protective antibody titers. We conclude by identifying the remaining critical gaps in knowledge and opportunities for moving SSM-TBVs to the field. ©2013 Bentham Science Publishers.


Tammia M.,Johns Hopkins University | Martin R.,Johns Hopkins University | Mao H.-Q.,Johns Hopkins University | Mao H.-Q.,Whitaker Biomedical Engineering Institute
Current Opinion in Biotechnology | Year: 2011

Limitations in current nerve regeneration techniques have stimulated the development of various approaches to mimic the extrinsic cues available in the natural nerve regeneration environment. Biomaterials approaches modulate the microenvironment of a regenerating nerve through tailored presentation of signaling molecules, creating physical and biochemical guidance cues to direct axonal regrowth across nerve lesion sites. Cell-based approaches center on increasing the neurotrophic support, adhesion guidance and myelination capacity of Schwann cells and other alternative cell types to enhance nerve regrowth and functional recovery. Recent advances in presenting directional guidance cues in nerve guidance conduits and improving the regenerative outcomes of cell delivery provide inspirations to engineering the next generation of nerve repair solutions. © 2011 Elsevier Ltd.


Jiang X.,Johns Hopkins University | Jiang X.,Whitaker Biomedical Engineering Institute | Qu W.,Northwestern University | Ren Y.,Johns Hopkins University | And 4 more authors.
Advanced Materials | Year: 2013

DNA-containing micellar nanoparticles with distinctly different and highly uniform morphologies are prepared via condensation of plasmid DNA with a block copolymer of polyethylene glycol and a polycation in solvents of different polarity. Molecular dynamics simulations explain the underlying mechanism. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


News Article | October 25, 2016
Site: www.cemag.us

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial infections related to total joint replacement surgery. A report on the study, published in Proceedings of the National Academy of Sciences, was conducted on the rodents’ knee joints, but, the researchers say, the technology would have “broad applicability” in the use of orthopedic prostheses, such as hip and knee total joint replacements, as well pacemakers, stents and other implantable medical devices. In contrast to other coatings in development, the researchers report the new material can release multiple antibiotics in a strategically timed way for an optimal effect. “We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws and plates to pacemakers, implantable defibrillators and dental hardware,” says co-senior study author Lloyd S. Miller, M.D., Ph.D., an associate professor of dermatology and orthopedic surgery at the Johns Hopkins University School of Medicine. Surgeons and biomedical engineers have for years looked for better ways —including antibiotic coatings — to reduce the risk of infections that are a known complication of implanting artificial hip, knee, and shoulder joints. Every year in the U.S., an estimated 1 to 2 percent of the more than 1 million hip and knee replacement surgeries are followed by infections linked to the formation of biofilms — layers of bacteria that adhere to a surface, forming a dense, impenetrable matrix of proteins, sugars and DNA. Immediately after surgery, an acute infection causes swelling and redness that can often be treated with intravenous antibiotics. But in some people, low-grade chronic infections can last for months, causing bone loss that leads to implant loosening and ultimately failure of the new prosthesis. These infections are very difficult to treat and, in many cases of chronic infection, prostheses must be removed and patients placed on long courses of antibiotics before a new prosthesis can be implanted. The cost per patient often exceeds $100,000 to treat a biofilm-associated prosthesis infection, Miller says. Major downsides to existing options for local antibiotic delivery, such as antibiotic-loaded cement, beads, spacers or powder, during the implantation of medical devices are that they can typically only deliver one antibiotic at a time and the release rate is not well-controlled. To develop a better approach that addresses those problems, Miller teamed up with Hai-Quan Mao, Ph.D., a professor of materials science and engineering at the Johns Hopkins University Whiting School of Engineering, and a member of the Institute for NanoBioTechnology, Whitaker Biomedical Engineering Institute and Translational Tissue Engineering Center. Over three years, the team focused on designing a thin, biodegradable plastic coating that could release multiple antibiotics at desired rates. This coating is composed of a nanofiber mesh embedded in a thin film; both components are made of polymers used for degradable sutures. To test the technology’s ability to prevent infection, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with one of three other antibiotics: vancomycin, daptomycin, or linezolid. “Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance,” says Miller. The coatings released vancomycin, daptomycin or linezolid for seven to 14 days and rifampin over three to five days. “We were able to deploy two antibiotics against potential infection while ensuring rifampin was never present as a single agent,” Miller says. The team then used each combination to coat titanium Kirschner wires — a type of pin used in orthopedic surgery to fix bone in place after wrist fractures — inserted them into the knee joints of anesthetized mice and introduced a strain of Staphylococcus aureus, a bacterium that commonly causes biofilm-associated infections in orthopedic surgeries. The bacteria were engineered to give off light, allowing the researchers to noninvasively track infection over time. Miller says that after 14 days of infection in mice that received an antibiotic-free coating on the pins, all of the mice had abundant bacteria in the infected tissue around the knee joint, and 80 percent had bacteria on the surface of the implant. In contrast, after the same time period in mice that received pins with either linezolid-rifampin or daptomycin-rifampin coating, none of the mice had detectable bacteria either on the implants or in the surrounding tissue. “We were able to completely eradicate infection with this coating,” says Miller. “Most other approaches only decrease the number of bacteria but don’t generally or reliably prevent infections.” After the two-week test, each of the rodents’ joints and adjacent bones were removed for further study. Miller and Mao found that not only had infection been prevented, but the bone loss often seen near infected joints — which creates the prosthetic loosening in patients — had also been completely avoided in animals that received pins with the antibiotic-loaded coating. Miller emphasized that further research is needed to test the efficacy and safety of the coating in humans, and in sorting out which patients would best benefit from the coating — people with a previous prosthesis joint infection receiving a new replacement joint, for example. The polymers they used to generate the nanofiber coating have already been used in many approved devices by the U.S. Food and Drug Administration, such as degradable sutures, bone plates, and drug delivery systems. In addition to Miller and Mao, the study’s authors are Alyssa Ashbaugh, Xuesong Jiang, Jesse Zheng, Andrew Tsai, Woo-Shin Kim, John Thompson, Robert Miller, Jonathan Shahbazian, Yu Wang, Carly Dillen, Alvaro Ordonez, Yong Chang, Sanjay Jain, Lynne Jones, and Robert Sterling of The Johns Hopkins University. Funding for this work was provided by a Nexus Award from the Johns Hopkins Institute for Clinical and Translational Research, which has been funded by the National Center for Advancing Translational Sciences and the National Institutes of Health Roadmap for Medical Research.


News Article | October 25, 2016
Site: www.rdmag.com

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial infections related to total joint replacement surgery. A report on the study, published online the week of Oct. 24 in Proceedings of the National Academy of Sciences, was conducted on the rodents' knee joints, but, the researchers say, the technology would have "broad applicability" in the use of orthopaedic prostheses, such as hip and knee total joint replacements, as well pacemakers, stents and other implantable medical devices. In contrast to other coatings in development, the researchers report the new material can release multiple antibiotics in a strategically timed way for an optimal effect. "We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws and plates to pacemakers, implantable defibrillators and dental hardware," says co-senior study author Lloyd S. Miller, M.D., Ph.D., an associate professor of dermatology and orthopaedic surgery at the Johns Hopkins University School of Medicine. Surgeons and biomedical engineers have for years looked for better ways --including antibiotic coatings -- to reduce the risk of infections that are a known complication of implanting artificial hip, knee and shoulder joints. Every year in the U.S., an estimated 1 to 2 percent of the more than 1 million hip and knee replacement surgeries are followed by infections linked to the formation of biofilms -- layers of bacteria that adhere to a surface, forming a dense, impenetrable matrix of proteins, sugars and DNA. Immediately after surgery, an acute infection causes swelling and redness that can often be treated with intravenous antibiotics. But in some people, low-grade chronic infections can last for months, causing bone loss that leads to implant loosening and ultimately failure of the new prosthesis. These infections are very difficult to treat and, in many cases of chronic infection, prostheses must be removed and patients placed on long courses of antibiotics before a new prosthesis can be implanted. The cost per patient often exceeds $100,000 to treat a biofilm-associated prosthesis infection, Miller says. Major downsides to existing options for local antibiotic delivery, such as antibiotic-loaded cement, beads, spacers or powder, during the implantation of medical devices are that they can typically only deliver one antibiotic at a time and the release rate is not well-controlled. To develop a better approach that addresses those problems, Miller teamed up with Hai-Quan Mao, Ph.D., a professor of materials science and engineering at the Johns Hopkins University Whiting School of Engineering, and a member of the Institute for NanoBioTechnology, Whitaker Biomedical Engineering Institute and Translational Tissue Engineering Center. Over three years, the team focused on designing a thin, biodegradable plastic coating that could release multiple antibiotics at desired rates. This coating is composed of a nanofiber mesh embedded in a thin film; both components are made of polymers used for degradable sutures. To test the technology's ability to prevent infection, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with one of three other antibiotics: vancomycin, daptomycin or linezolid. "Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance," says Miller. The coatings released vancomycin, daptomycin or linezolid for seven to 14 days and rifampin over three to five days. "We were able to deploy two antibiotics against potential infection while ensuring rifampin was never present as a single agent," Miller says. The team then used each combination to coat titanium Kirschner wires -- a type of pin used in orthopaedic surgery to fix bone in place after wrist fractures -- inserted them into the knee joints of anesthetized mice and introduced a strain of Staphylococcus aureus, a bacterium that commonly causes biofilm-associated infections in orthopaedic surgeries. The bacteria were engineered to give off light, allowing the researchers to noninvasively track infection over time. Miller says that after 14 days of infection in mice that received an antibiotic-free coating on the pins, all of the mice had abundant bacteria in the infected tissue around the knee joint, and 80 percent had bacteria on the surface of the implant. In contrast, after the same time period in mice that received pins with either linezolid-rifampin or daptomycin-rifampin coating, none of the mice had detectable bacteria either on the implants or in the surrounding tissue. "We were able to completely eradicate infection with this coating," says Miller. "Most other approaches only decrease the number of bacteria but don't generally or reliably prevent infections." After the two-week test, each of the rodents' joints and adjacent bones were removed for further study. Miller and Mao found that not only had infection been prevented, but the bone loss often seen near infected joints -- which creates the prosthetic loosening in patients -- had also been completely avoided in animals that received pins with the antibiotic-loaded coating. Miller emphasized that further research is needed to test the efficacy and safety of the coating in humans, and in sorting out which patients would best benefit from the coating -- people with a previous prosthesis joint infection receiving a new replacement joint, for example. The polymers they used to generate the nanofiber coating have already been used in many approved devices by the U.S. Food and Drug Administration, such as degradable sutures, bone plates and drug delivery systems.


Wall B.D.,Johns Hopkins University | Diegelmann S.R.,Johns Hopkins University | Zhang S.,Johns Hopkins University | Dawidczyk T.J.,Johns Hopkins University | And 5 more authors.
Advanced Materials | Year: 2011

A facile technique is reported to prepare globally aligned arrays of self-assembled peptide nanostructures within macroscopic hydrogels starting from a solution of peptide molecules with embedded π-conjugated oligomers. The alignment of the π-stacked conduits within these macrostructures is verified with polarized optical microscopy and leads to anisotropic photophysical and electrical properties. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Jiang X.,Johns Hopkins University | Jiang X.,Translational Tissue Engineering Center | Christopherson G.T.,Johns Hopkins University | Mao H.-Q.,Johns Hopkins University | And 2 more authors.
Interface Focus | Year: 2011

Previous studies have shown that substrate surface chemistry and topography exhibit significant impact on haematopoietic progenitor cell adhesion, proliferation and differentiation. In the present study, the effect of surface amine density and structure of grafted polymer chains on the adhesion and expansion of haematopoietic progenitor cells was investigated. Cryopreserved human umbilical cord blood CD133 + cells were expanded in cytokine-supplemented medium on ethylenediamine (EDA)- or 2-aminoethyl methacrylate hydrochloride (AEMA)-grafted polyethersulphone (PES) nanofibre scaffolds for 10 days. Although the percentage of CD34 + cells among the expanded cells increased with the surface amine density, the maximum fold expansion of CD34 + cells was obtained at a moderate amine density of 20-80 nmol cm -2.When comparing nanofibre matrices with similar amine densities, but prepared with two different methods, cells cultured on the AEMA-grafted PES nanofibre matrix showed lower fold expansion in terms of total cell number (300+84 fold) and CD34{thorn} cell number (68+19-fold) in comparison with those cultured on EDA-grafted nanofibres (787+84-fold and 185+84-fold, respectively). These results indicate that the surface amine density and the conjugate structure are important determinants for the preservation of CD34 surface marker and expansion efficiency of CD34 + cells. © 2011 The Royal Society.


Khalifian S.,Johns Hopkins University | Sarhane K.A.,Johns Hopkins University | Tammia M.,Johns Hopkins University | Ibrahim Z.,Johns Hopkins University | And 6 more authors.
Archivum Immunologiae et Therapiae Experimentalis | Year: 2015

Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cellbased therapies have been postulated and tested in preclinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues forregenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patientspecific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across ‘‘gaps’’ in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration. © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2014.


Patil R.R.,Johns Hopkins University | Yu J.,Johns Hopkins University | Banerjee S.R.,Johns Hopkins University | Ren Y.,Johns Hopkins University | And 7 more authors.
Molecular Therapy | Year: 2011

Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with 111 In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles. © 2011 The American Society of Gene & Cell Therapy.


Jiang H.,Whitaker Biomedical Engineering Institute | Sun S.X.,Whitaker Biomedical Engineering Institute
Soft Matter | Year: 2012

A combination of cell wall growth and cytoskeletal protein action gives rise to the observed bacterial cell shape. Aside from the common rod-like and spherical shapes, bacterial cells can also adopt curved or helical geometries. To understand how curvature in bacteria is developed or maintained, we examine how Caulobacter crescentus obtains its crescent-like shape. Caulobacter cells with or without the cytoskeletal bundle crescentin, an intermediate filament-like protein, exhibit two distinct growth modes, curvature maintenance that preserves the radius of curvature and curvature relaxation that straightens the cell (Fig. 1). Using a proposed mechanochemical model, we show that bending and twisting of the crescentin bundle can influence the stress distribution in the cell wall, and lead to the growth of curved cells. In contrast, after crescentin bundle is disrupted, originally curved cells will slowly relax towards a straight rod over time. The model is able to quantitatively capture experimentally observed curvature dynamics. Furthermore, we show that the shape anisotropy of the cross-section of a curved cell is never greater than 4%, even in the presence of crescentin. © 2012 The Royal Society of Chemistry.

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