Visiting research scientist, Northeastern University
Infection resistant, injectable cryogels suitable for drug delivery, regenerative therapy
Regenerative medicine has revolutionized medicine. But is associated with introduction of foreign material into the body, which is prone to attachment, colonization and infection by bacterial pathogens. There are many hospital borne pathogens which have developed resistance to existing antibiotics. If in case the patient catches such infection, it is likely pose severe threat. So in this scenario it is imperative to make the insertion material resistant to bacterial infection. In this direction, we are trying to attach HHC-36 to cryogel, HHC-36 is a kind of antimicrobial peptide which is strongly effective against strains of multidrug-resistant P. aeruginosa, methicillin-resistant Staphylococcus aureus, and a few other ‘superbugs. Hydrogels are a class of highly hydrated polymeric materials used in the biomedical field due to their unique properties such as high water content, softness, flexibility, and biocompatibility. Recently, we have developed mechanically robust and syringe-injectable biomimetic cryogels. These cryogels form a new class of polymeric hydrogels with unique properties including large and interconnected pores, mechanical robustness, and injectability with shape memory properties. We are trying out 2 complimentary approaches for attachment of HHC-36 to cryogel. First approach is to chemically attach the HHC-36 to cryogel so that initially it will kill the bacteria which come in direct contact and then over the time as cryogel degrades, HHC-36 will become free and will be released into the surrounding to kill the pathogens. The second approach is to physically entrap the HHC-36 withing cryogel such that it can diffuse out of the cryogel. Injectable antimicrobial cryogel scaffolds show great potential in tissue engineering as they can overcome two main challenges faced by gel implants, namely: biomaterial associated infections and suitable three-dimensional microarchitectural features for guided tissue regeneration and biointegration.
Abstract: Prevention of post-surgery infection and promotion of bio-integration are the key factors to achieve long-term success in orthopaedic implants. Localized delivery of antibiotics and bioactive molecules by the implant surface serves as a promising approach towards these goals. However, previously reported methods for surface functionalization of the titanium (Ti) alloy implants to load bioactive ingredients suffer from time-consuming complex processes and lack of long-term stability. Here, we present the design and characterization of an adhesive, osteoconductive, and antimicrobial hydrogel coating for Ti implants. To form the multifunctional hydrogels, a photocrosslinkable gelatin-based hydrogel was modified with catechol motifs to enhance adhesion to Ti surfaces and thus promote coating stability. To induce antimicrobial and osteoconductive properties, a short cationic antimicrobial peptide (AMP) and synthetic silicate nanoparticles (SNs) were introduced into the hydrogel formulation. The controlled release of AMP loaded in the hydrogel demonstrated excellent antimicrobial activity to prevent biofilm formation. Moreover, the addition of SNs to the hydrogel formulation showed enhanced osteogenesis when cultured with human mesenchymal stem cells, suggesting the potential to promote new bone formation in the surrounding tissues. Considering the unique features of our implant hydrogel coating including high adhesion, antimicrobial capability, and the ability to induce osteogenesis, it is believed that our design provides a useful alternative method for bone implant surface modification and functionalization.
Pub.: 01 Feb '17, Pinned: 03 Jul '17
Abstract: Cationic antimicrobial peptides are promising sources for novel therapeutic agents against multi-drug-resistant bacteria. HHC-36 (KRWWKWWRR) is a simple but effective antimicrobial peptide with similar or superior activity compared with several conventional antibiotics. In this biophysical study, unique conformational properties of this peptide and some of its analogs as well as its interaction with lipid membranes are investigated in detail. Circular dichroism (CD) and molecular dynamics modeling studies of HHC-36 in different environments reveal a dynamic amphipathic structure composed of competing turn conformations with free energies lower than that of the unfolded state, implying a strong influence of tryptophan interactions in formation of the turns. CD spectra and gel electrophoresis also show strong evidence of self-association of this peptide in aqueous milieu and interaction with both neutrally and negatively charged lipid membrane systems. Isothermal titration calorimetry and acrylamide fluorescence quenching experiments emphasize the preference of HHC-36 for negatively charged vesicles. In addition, dye leakage experiments suggest that this peptide functions through a surface-associated mechanism with weak lytic activity against bacterial model membranes.
Pub.: 08 Nov '13, Pinned: 03 Jul '17
Abstract: Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.
Pub.: 23 Nov '15, Pinned: 30 Jun '17
Abstract: Authors: Jianyu Li ; David J. Mooney Article URL: http://feeds.nature.com/~r/natrevmats/rss/current/~3/ZkgvFqtf4O0/natrevmats201671 Citation: Nature Reviews Materials, Published online: 18 October 2016; doi:10.1038/natrevmats.2016.71 Publication Date: 2016-10-18 Journal: Nature Reviews Materials
Pub.: 18 Oct '16, Pinned: 30 Jun '17
Abstract: Injectable biomaterials are increasingly being explored to minimize risks and complications associated with surgical implantation. We describe a strategy for delivery via conventional needle-syringe injection of large preformed macroporous scaffolds with well-defined properties. Injectable 3D scaffolds, in the form of elastic sponge-like matrices, were prepared by environmentally friendly cryotropic gelation of a naturally sourced polymer. Cryogels with shape-memory properties may be molded to a variety of shapes and sizes, and may be optionally loaded with therapeutic agents or cells. These scaffolds have the capability to withstand reversible deformations at over 90% strain level, and a rapid volumetric recovery allows the structurally defined scaffolds to be injected through a small-bore needle with nearly complete geometric restoration once delivered. These gels demonstrated long-term release of biomolecules in vivo. Furthermore, cryogels impregnated with bioluminescent reporter cells provided enhanced survival, higher local retention, and extended engraftment of transplanted cells at the injection site compared with a standard injection technique. These injectable scaffolds show great promise for various biomedical applications, including cell therapies.
Pub.: 15 Nov '12, Pinned: 30 Jun '17