Translational Biomaterials Research Laboratory

We are investigating the efficacy of non-leaching, highly-bactericidal polymer coatings to combat the spread of infectious diseases due to contaminated surfaces. Specifically, we have synthesized polyurethanes containing quaternary ammoniums immobilized within the polymer backbone, resulting in a potent and non-leaching bactericidal polymer that works by physically compromising the bacterial cell wall/membrane rather than targeting bacterial functions or growth processes. This polymer is optimized for rendering surfaces permanently bactericidal without using traditional antibiotics.

Currently antimicrobial surgical drapes are used to prevent infections. However, this approach has many disadvantages; such as long preparation times, drape detachment from skin, and allergens present in drapes. We are designing an antimicrobial polymer to improve on this surgical drape design, employing charged polymers to target negatively charged bacterial membranes.​​​​

Cardiac tissue regeneration

After a myocardial infarction, many patients develop decreased heart function due to damaged cardiac tissue. To this end, we are investigating the use of a polymer growth factor delivery system to reduce tissue death and increase angiogenesis following myocardial infarction. This unique polymer system will possess sulfonate groups that will interact with growth factors to release the growth factor slowly and constantly over a longer period of time to increase therapeutic outcome. In addition, this polymer will possess reverse thermal gelling properties that would allow for injection of the polymer directly into the infarct site. We anticipate that the unique properties of this polymer will improve the effects of growth factors on damaged heart tissue.

Figure:  SEM of RTG microstructure (top left), vial tilt test at room temperture and physiological temperture demonstrating fast, stable gel formation (bottom left), and in-vitro 3D cell culture demonstrating growth of cardiomyocytes within the gelled polymer (right) (Brisa Peña, Valentina Martinelli, Mark Jeong, Susanna Bosi, Romano Lapasin, Matthew R. G. Taylor, Carlin S. Long, Robin Shandas, Daewon Park, and Luisa Mestroni Biomacromolecules 2016 17 (5), 1593-1601 DOI: 10.1021/acs.biomac.5b01734​).

Guided neurite growth

Functional nerve recovery from severe neuropathies presenst a major technical challenge. Large (>3 cm) injuries to the peripheral nervous system or central nervous system require a finely tuned environment to encourage myelination of surviving neurons and promote new neurite extension. A peptide-modified electrospun biomimetic polymer has demonstrated the ability to direct and promote neurite outgrowth, and we are currently investigating its use in vivo.

​​Figure: SEM image of the structure of the electrospun polymer, including the guidance channels for peripheal nerve regeneration (top left), Electrospun nerve conduit implanted into the sciatic nerve after rat sciatic nerve injury model (top right), immunohistochemical stain for axon extensions (red) and Schwann cells (green) within the electrospun scaffold 8 weeks after implantation into a rat sciatic nerve injury model (Biomimetic Nerve Guidance Conduit Containing Intraluminal Microchannels with Aligned Nanofibers Markedly Facilitates in Nerve Regeneration .David J. Lee, Arjun Fontaine, Xianzhong Meng, and Daewon Park ACS Biomaterials Science & Engineering 2016 2 (8), 1403-1410 DOI: 10.1021/acsbiomaterials.6b00344​)

A Biomimetic Reverse Thermal Gel for Retinal Ganglion Cells

Glaucoma, among other optic neuropathies, leads to the neurodegeneration of retinal ganglion cells (RGCs), the projection neurons located in the retina with axons extending through the optic nerve. These cells play a crucial role in sight by transmitting visual information from the bipolar, amacrine, and interplexiform cells of the retina to the visual cortex of the brain. It was previously believed that RGCs, like many central nervous system neurons, do not possess the ability to regenerate following injury or death. However, it is now known that the limited regeneration of axonal regrowth of these cells is possible but inhibited because of the injured microenvironment (myelin-associated molecules), scar formation, and lack of passage across a lesion. Therefore, the regenerative capacity of RGCs may be stimulated by creating an alternate extracellular microenvironment that will instead activate RGC growth, maintain RGC viability, and counteract the inhibitory signals of the injured nerve. To alter the fate of damaged RGCs, the cells must be encapsulated in a growth permissive microenvironment, protected from the diseased environment, presented with cell binding molecules, and exposed to appropriate mechanical properties to induce and cue growth. We have developed an injectable biomimetic threedimensional (3D) scaffold with mechanical and morphological properties similar to those of native retinal tissue.

Figure: RGCs cultured in biomimetic RTG for 3, 5, adn 7 days. Blue: DAPI, Red: Brn3a (a marker for RGCs), and Green: Beta-Tubulin (a marker for axons) (A Self-Assembling Injectable Biomimetic Microenvironment Encourages Retinal Ganglion Cell Axon Extension in Vitro Melissa R. Laughter, David A. Ammar, James R. Bardill, Brisa Pena, Malik Y. Kahook, David J. Lee, and Daewon Park ACS Applied Materials & Interfaces 2016 8 (32), 20540-20548 DOI: 10.1021/acsami.6b04679​)

A Biomimetic Polymer Patch for Myelomeningocele

Myelomeningocele (MMC) is the most common congential birth defect of the central nervous system, resulting in lifelong neurological and functional deficits. Currently, an in-utero surgical repair of MMC covers/patches the defect, resulting in a significant 50% reduction in post natal ventriculoperitoneal shunting. However, this invasive surgery is complicated by risks of morbidity to the mother and infant. The surgery is also limited by a 22-25 week gestational age criteria. A reverse thermal gel (RTG) poses a unique solution to patch MMC. A RTG exists as an aqueous solution at room temperature and forms a fast forming gel when injected by needle into physiologic temperatures/specimens. This approach could allow for a minimally invasive and earlier gestational age application of a patch for MMC.

Figure: Small needle application of a RTG to patch a mouse MMC defect (A. I. Marwan, S. M. Williams, J. R. Bardill, J.

Ocular drug delivery

Delivery of drugs to the eye is a challenging endeavor due to the myriad anatomical and physiological barriers preventing intraocular absorption of molecules that either contact the anterior surfaces of the eye or are present in the bloodstream. Topical administration—the workhorse of ophthalmic drug delivery—suffers from numerous drawbacks including poor intraocular bioavailability, excessive systemic absorption, need for frequent re-administration and a reliance on patient adherence for therapeutic efficacy, among others. To overcome these limitations, researchers have explored various controlled release drug delivery systems with the ultimate goal of sustaining consistent, localized drug levels at the target tissue thereby maximizing therapeutic efficacy and minimizing unintended adverse effects. Among the options explored, in situ-gelling polymeric systems may hold the most promise due to their ability to be administered directly at the target site by a minimally-invasive injection and to form a stable physical gel while conforming to the specific anatomy of that space. To date, clinical application of such systems has been hindered by their limited ability to sustain long-term delivery of drugs. To overcome this limitation, we developed a system comprising a reverse thermal gel encapsulating drug-loaded polymeric micelles as a combined system for the sustained local delivery of poorly soluble drugs.

Figure: TEM imaging of PEG-PSH-PEG core-shell micelle structure and histological sections of retinas injected with micelles or PBS (far left column). Minimal inflammation was observed after 3 days (middle column) and 14 days (far right column). (D) lens, (E) vitreous humor, retina (F), choroid (G), and sclera (H) (Famili, A., Kahook, M. Y. and Park, D. (2014), A Combined Micelle and Poly(Serinol Hexamethylene Urea)-Co-Poly(N-Isopropylacrylamide) Reverse Thermal Gel as an Injectable Ocular Drug Delivery System. Macromol. Biosci., 14: 1719–1729. doi:10.1002/mabi.201400250​).