Research in the Joy lab is guided by critical biomedical and engineering needs. We address those needs with comprehensive and translatable solutions based on tailored biomaterials and advanced polymers.
Functional Polymer Synthesis
WOUND HEALING AND SKIN REGENERATION
Addressing non-healing wounds is a challenging proposition as it requires addressing several underlying physiological conditions. Due to the increase in obesity, diabetes and trauma there is an increasing need to provide creative solutions for the non-healing wounds. Wounds are classified as acute or chronic wounds. Acute wounds are tissue injuries such as from trauma or burns that heal completely with minimal scarring within a short period of time. Chronic wounds are those that do not heal even after long periods. These wounds have an underlying defect in the physiological condition, such as occurs in patients with diabetes or persistent infections. In these patients there is often an incorrect balance of the expression levels of different cytokines and cells in the wound area.
Wound healing or repair in adults is evolutionarily designed to be a rapid process to prevent tissue infection and to enable the rapid functionality of tissues. This often results in a fibrous scar at the site of injury. On the other hand, fetal wounds repair without scaring and this is essentially a regenerative process. (Fig. 1). Optimum healing of wounds is a dynamic process that involves the orchestrated action of numerous soluble factors, cell types and the extracellular matrix. The stages of normal adult wound healing include coagulation, inflammation, and formation of granulation tissue, remodeling and scarring.
In order to bring forth translatable approaches to non-healing wounds, the underlying physiological challenges need to be addressed. The Joy Lab is bringing a multi-pronged approach to this challenging issue. We bring forth solutions that decrease or eliminate bacterial contamination of the wound area, and design polymeric devices that serve as hosts for cells involved in the granulation and remodeling process. In addition, we design devices or approaches that can deliver therapeutics and growth factors in a controlled manner so as to promote the progression of the wound healing cascade. In several instances of skin grafting or regeneration, there is a need to adhere tissues in wet environments and we have designed tissue adhesives with good performance in a physiological environment. There are also instances where adhesive dressings are stuck on too well and removal of the adhesive bandages causes tissue damage. To address this challenge, we have designed solutions for the easy removal of adhesive bandages.
Antimicrobial Polyesters, Polyurethanes and Poly(ester urethane)s
Even a casual observer of the news will have noticed the numerous reports of microbial resistance to even the last defense antimicrobial therapeutics. The current lack of antibiotics to address rapidly evolving pathogens is indication that we have come full circle from the time when penicillin was first developed and shown to dramatically increase human lifespans over the past century. Due to the low return on investment on antibiotic development and the careless use of antibiotics in modern life, we have reached the point where non-traditional antimicrobials is becoming a viable option.
There is a critical need for novel antimicrobials in several settings, such as in supplementing the decreasing options of small molecule therapeutics; antimicrobial surfaces and coatings in hospitals and on medical devices; protecting agricultural and food products; and in preventing or decreasing the bacterial load in wounds so as that the wound can transition from an inflammatory stage to the healing stage.
The Joy Lab develops antimicrobial polyesters, polyurethanes and poly(ester urethane)s based on the design features seen in antimicrobial peptides (host defense peptides). These polymers are designed for several applications, such as addressing wound bacterial infections and creating antibacterial and antibiofilm coatings on surfaces and in medical devices such as urinary and in-dwelling catheters. The challenge in all these approaches is to maximize antibacterial efficiency while minimizing mammalian cell toxicity.
Technical personnel on the project: Apoorva Vishwakarma, Chinnapatch Tantisuwanno
Collaborators: Hazel A. Barton (Univ. Akron, Biology)
Funding from the National Science Foundation (NSF) for the development of functionalized polyesters and polyurethanes is gratefully acknowledged. This funding was crucial in allowing us to develop these platforms of pendant functionalized polymers. We are happy to provide these diverse sets of polymers to collaborators for various applications.
Functionalized 3D printed scaffolds and electrospun mats
The promise of 3D printed devices and scaffolds in tissue engineering is that such devices can be personalized to provide ideal mechanical and biological needs. There are several approaches being employed for fabrication of such devices such as fused deposition modelling, stereolithographic printing and ink-jet printing. A critical need in this area is the lack of polymers that can be printed at low temperatures and without any solvent or additives. We deliver solutions for this need by designing low modulus functionalized polyesters that can be printed at ambient temperatures and can be incorporated with bioactives that promote the biological pathways being targeted. Following fabrication of the printed scaffolds, they are converted to elastomeric solids by external or internal stimuli to fix the structures. The chemical diversity of the functionalized polyester scaffolds enables tailoring the printed scaffolds for the biological need with appropriate chemical functionality, peptides, growth factors or ligands.
Technical personnel on the project: Tanmay Jain, Qianhui Liu, Yen-Ming Tseng, Xinhao Liu
Collaborators: Jae-Won Choi (Univ. Akron, Mechanical Engineering); Irada Isayeva (US FDA); John Fisher (Univ. Maryland)
Funding from NSF-Food and Drug Administration (FDA) Scholar in Residence Program is gratefully acknowledged for this work.
Tissue Adhesives / Wet Adhesives
Adhesion of an adhesive to a substrate involves the maximizing both the adhesive interactions between the substrate and adhesive and the cohesive interactions in the bulk of the adhesive material. Therefore, an adhesive has to address the opposing forces of forming good contact with the substrate and having bulk mechanical strength. In addition, in a biological environment, addition of any organic solvent to the adhesive to increase its contact with the substrate is not an ideal option. Tissue adhesives that are too hydrophilic will not make good contact with the substrate and those that make contact due to, or after a chemical reaction, are likely to cause tissue inflammation or damage. In the Joy Lab we have developed tissue adhesives that have remarkable adhesion in wet environments due to their ability to maximize both adhesive and cohesive interactions and by their ability to displace the water layers that are intimately associated with a hydrophilic surface. Our studies have shown that these polyester adhesives have better performance than commercial protein-based adhesives and are degradable and non-toxic. These adhesives have applications are tissue adhesives for wound dressings, skin grafts, dental applications and in engineering applications for underwater adhesives.
Technical personnel on the project: Amal Narayanan, Josh Menefee
Collaborators: Ali Dhinojwala (Univ. Akron, Polymer Science)
Funding from NSF is gratefully acknowledged for this work.
Controlled Release of growth factors and therapeutics
The release of growth factors or small molecule therapeutics in a controlled or sustained manner enables presenting an optimum concentration of the therapeutic for the biological need. In addition, controlled release decreases the overall cost of treatment and promotes patient compliance. We are addressing the diverse needs for controlled release of therapeutics and growth factors in wound healing and other physiological conditions by providing tailored polymeric devices or vehicles. In the wound healing area, our lab designs 3D printed scaffolds or electrospun mats with encapsulated antimicrobials. In addition, we also design polymers tethered or encapsulated with growth factors. We have designed a platform of thermoresponsive polyesters for the encapsulation and controlled release of protein therapeutics and growth factors. We are tailoring this platform for delivering VEGF and PDGF, which are key players in the wound healing cascade. The Joy Lab also designs polymeric devices for extended release of oral therapeutics, anti-opioid and pain therapeutics.
Technical personnel on the project: Megan Cruz, Nicholas Nun, Tanmay Jain, Mangaldeep Kundu, Wenbo Ma
Collaborators: Nic Leipzig (Univ. Akron, Chemical Engineering)
PROTEIN-POLYMER INTERACTIONS / OLIGONUCLEOTIDE-POLYMER INTERACTIONS
Protein-protein and nucleotide-protein interactions make up the bulk of life processes. Evolution has perfected these interactions and the fidelity of such interactions over our lifetimes has enabled DNA to be transcribed to RNA, which in turn are translated to proteins. Interactions between the translated proteins provide the information necessary for proper functioning of our tissues and organs. Key studies of protein-protein interactions and nucleotide-protein interactions have deepened our understanding and appreciation of the key pathways in functioning and non-functioning cells and has provided a means to intervene in the underlying causes of certain diseases.
We are inspired by these fundamental studies and are designing functionalized polyesters and polyurethanes that can mimic such interactions with the expectation that understanding the design principles of such interactions will enable us to design custom polymers for the inhibition or enhancement of protein-protein and/or nucleotide-protein interactions.
Through this effort we design stimuli responsive polyesters for the inhibition or encapsulation of proteins based on evaluating specific protein-polymer interactions uncovered through NMR, calorimetric and thermal analyses. These thermoresponsive polyesters are designed to be soluble at low temperatures (~5-15C) and undergo a phase transition to a coacervated phase at temperatures close to body tempertaures (~25-37C). We have designed a diverse family of such pendant functionalized polyesters and by choosing the identity of the pendant groups, the transition temperature (Tcp or cloud point) can be precisely tuned to the desired temperature. We have shown that such thermoresponsive polyesters are biodegradable, are non-toxic and can be encapsulated with small molecules and proteins. For example, a thermoresponsive polyester was designed to have a Tcp below room temperature and specifically encapsulate BSA with high efficiency by tailoring the pendant functional groups. A similar approach is being taken to encapsulate growth factors that promote the wound healing cascade.
We are also designing polyesters that can specifically interact with intracellular and extracellular proteins. There are several applications for which this approach will have far reaching impact. Currently we are designing such polyesters for optimizing the extraction and release of proteins obtained from human touch samples for an IARPA project between UA, GE Global Research Center and George Washington University.
Technical personnel on the project: Megan Cruz, Mangaldeep Kundu
Collaborators: Thomas Leeper (Kennesaw State Univ.); Brian Davis (GE Global Research Center); Akos Vertes (George Washington Univ.)
Photoresponsive polymers are useful for several applications. Photochemistry can be used to modulate the physical and chemical properties of polymers. We have designed polyesters, polycarbonates and polyurethanes incorporating alkoxyphenacyl or coumarin units. Irradiation at appropriate wavelengths enable cleavage of the polymers into oligomeric chains, or crosslinking of the polymers into networks. Such responsive polymers can be used to fabricate patterned surfaces or to release encapsulate molecules.
We are currently designing photoresponsive polymers for efficient retrieval and release of trace DNA samples. This is critical problem as in many situations as the efficient collection of the few DNA molecules at the site oftentimes results in poor release for downstream analysis protocols. Similarly, we are using our photoresponsive platform for the optimizing the protocols for trace protein extraction and downstream analysis.
Technical personnel on the project: Nicholas Nun, Yen-Ming Tseng
Collaborators: Arunkumar Natarajan, John Nelson (GE Global Research Center); Johnson & Johnson
Funding from the National Institute of Justice and Johnson & Johnson is gratefully acknowledged.
OPIOIDS AND FORENSICS
Countering the opioid epidemic
Opioid addiction and the collateral damage from addiction to psychoactive compounds has plunged several US communities into a severe crisis resulting from loss of lives, livelihood and dignity. Addiction to opioids devastates families and places an incredible economic and mental burden on survivors and their families. Ohio is one of the states that have been brutally affected by this crisis. Solutions to the epidemic should be multipronged but scientists have a critical role to play in providing lasting solutions to the opioid epidemic. Our lab has risen to the challenge and provides solutions that addresses several key challenges that the epidemic presents.
We address the tremendous stress and potential safety that first responders are under when called upon to treat opioid overdose victims or arrest opioid trafficking suspects. Media reports describe frequent incidences where very small quantities of substances such as carfetanil has cost the lives of officers called upon to rescue overdose victims. Currently there is no easy to use, low-cost technology that allows an officer to quickly detect the presence of psychoactive substances on an object or surface. The drug-detecting kits available are designed for prosecutorial or analysis purposes and not necessarily for ease of use. Although the drug-detecting kits are used by first responders, these are cumbersome to use in a high-stress environment. A technology that enables the first responder to quickly obtain a yes/no answer to determine the presence of a psychoactive substance is a critical need. We are working on developing polymer substrates that quickly and reliably detect the presence of a controlled substance. A first responder can simply wipe the suspect or surface with the polymer mat and a color change will indicate the presence of a controlled substance.
In other approaches we are designing matrices that provide a sustained delivery of opioids and this approach prevents the abuse of opioids. We are also designing antagonists to counter drug overdoses.
Technical personnel on the project: Tanmay Jain, Nicholas Nun, Amal Narayanan
Current methods that have been developed for trace analysis of DNA obtained from crime scene samples allows unambiguous correlation of the obtained sample to the perpetrator. However, oftentimes the DNA that can be obtained from a sample is too small to enable confident analysis and prosecution. A complicating factor is that the substrates used for collection of DNA is not good at release of the collected sample. In collaboration with GE Global Research Center and funding from the National Institutes of Justice, we have developed photoresponsive polymers that collect the DNA and efficiently release the trace DNA upon irradiation with light that does not affect the integrity of the DNA.
On a related front, we are working with collaborators at GE Global Research Center and George Washington University for trace proteomic analysis from human touch samples. Oftentimes, cells left at sites do not have enough DNA for contributor analysis. We are working on an alternative method for collection of proteins obtained from trace samples for contributor analysis. The Joy Lab is designing polymers for the efficient collection and downstream analysis of proteins obtained from such trace samples.
Technical personnel on the project: Nicholas Nun, Francis Dang, Mangaldeep Kundu, Megan Cruz
Collaborators: Brian Davis, John Nelson (GE Global Research Center)
Funding from the National Institute of Justice and the Intelligence Advanced Research Program Activity (IARPA) is gratefully acknowledged.