Rebecca McMahon - Academia.edu (original) (raw)

Papers by Rebecca McMahon

Wounds : a compendium of clinical research and practice, 2020

INTRODUCTION Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differ... more INTRODUCTION Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing. OBJECTIVE In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro. MATERIALS AND METHODS The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results. RESULTS Synergy is defined as the interaction of components to produce a combined effect g...

Journal of Drug Delivery Science and Technology, 2020

Pain control following thermal injury remains a significant clinical challenge from the initial p... more Pain control following thermal injury remains a significant clinical challenge from the initial point of care through rehabilitation. Although standard analgesics provide some relief, there is a critical need to better modulate burn pain while minimizing the undesirable side effects associated with current systemic pain treatments. To that end, we developed a novel reverse microemulsion (RmE) that encapsulated the polar and ionic analgesics nordihydroguaiaretic acid (NDGA) and ketoconazole with 10-20% efficiency and could deliver the analgesics into bioartificial tissues. When RmE-analgesic formulations were incorporated into a liquid bandagelike amphiphilic acrylate polymer, the analgesics were released slowly over 24 hours. Incorporation into the amphiphilic acrylate polymer slowed analgesic release from the RmE and the majority of the analgesics remained in the topically-applied residual polymer layer. Both the RmE and the polymer-RmE formulations induced significant reductions in post-burn pain for at least 48 h. Altogether, these data suggest a RmE loaded with NDGA and ketoconazole can act as a novel long-acting and topical method for reducing thermal hyperalgesia and mechanical allodynia nociceptive responses.

Journal of Biomedical Materials Research Part A, 2016

The current work investigates the potential of cell layer-electrospun mesh constructs as coronary... more The current work investigates the potential of cell layer-electrospun mesh constructs as coronary artery bypass grafts. These cell-mesh constructs were generated by first culturing a confluent layer of 10T½ smooth muscle progenitor cells on a high strength electrospun mesh with uniaxially aligned fibers. Cell-laden mesh sheets were then wrapped around a cylindrical mandrel such that the mesh fibers were aligned circumferentially. The resulting multi-layered constructs were then cultured for 4 wks in media supplemented with TGF-β1 and ascorbic acid to support 10T½ differentiation toward a smooth muscle cell-like fate as well as to support elastin and collagen production. The underlying hypothesis of this work was that extracellular matrix (ECM) deposited by the cell layers would act as an adhesive agent between the individual mesh layers, providing strength to the construct as well as a source for structural elasticity at low strains. In addition, the structural anisotropy of the mesh would inherently guide desired circumferential cell and ECM alignment. Results demonstrate that the cell-mesh constructs exhibited a J-shaped circumferential stress-strain response similar to that of native coronary artery, while also displaying acceptable tensile strength. Furthermore, associated 10T½ cells and deposited collagen fibers showed a high degree of circumferential alignment.

Wound Management & Prevention

Biofilms are believed to be a source of chronic inflammation in non-healing wounds. PURPOSE: In t... more Biofilms are believed to be a source of chronic inflammation in non-healing wounds. PURPOSE: In this study, the pre-clinical anti-biofilm efficacy of several wound cleansers was examined using the Calgary minimum biofilm eradication concentration (MBEC) and ex vivo porcine dermal explant (PDE) models on Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans biofilms. METHODS: A surfactant-based cleanser and antimicrobial-based cleansers containing ionic silver, hypochlorous acid (HOCl), sodium hypochlorite (NaOCl), and polyhexamethylene biguanide (PHMB) were tested on the MBEC model biofilms with a 10-minute application time. Select cleansers were then tested on the mature PDE biofilms with 10-minute applications followed by the application of cleanser-soaked gauze. The PDE model was further expanded to include single and daily applications of the cleansers to mimic daily and 72-hour dressing changes. RESULTS: In the MBEC model, PHMB- and HO...

There are more than 150,000 anterior cruciate ligament reconstructions each year with the goal of... more There are more than 150,000 anterior cruciate ligament reconstructions each year with the goal of recovering the balance between knee stability and mobility. As many as 25% of these procedures will end in joint instability that can cause further damage. The risk of developing degenerative joint disease (DJD) increases in patients with previous knee injury, resulting in a higher instance of total knee arthroplasty (TKA). There are more than 400,000 TKA procedures each year, but the waiting lists for this surgery shows that many more patients are hoping to undergo this procedure. TKA provides improved knee function and pain relief for patients suffering from DJD. Although this procedure is considered successful, as younger patients undergo this treatment, the long-term performance must be improved. Major mechanisms of failure include component loosening from stress-shielding, poor integration of the implant with native tissue, and ion release from the implant. TiNb alloys are more biocompatible than currently used alloys, such as NiTi, and have mechanical properties closer to bone, so they would reduce the instance of stress shielding. TiNb can be made porous for better integration with the native bone and has superior corrosion resistance than NiTi. Engineered ligaments have generally failed to achieve mechanical properties sufficiently similar to their native counterparts, but also lack the osteochondral interface critical to the transfer of load between ligament and bone. The osteochondral interface could be incorporated through a gradient of inorganic content toward the bony insertion ends of the ligament graft, as we showed that in increase of inorganic content resulted in

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012

Bone is a nanocomposite composed of organic (mainly collagen) and inorganic (nanocrystalline hydr... more Bone is a nanocomposite composed of organic (mainly collagen) and inorganic (nanocrystalline hydroxyapatite) components, with a hierarchical structure ranging from nano- to macroscale. Its functions include providing mechanical support and transmitting physio-chemical and mechano-chemical cues. Clinical repair and reconstruction of bone defects has been conducted using autologous and allogeneic tissues and alloplastic materials, with functional limitations. The design and development of biomaterial scaffolds that will replace the form and function of native tissue while promoting regeneration without necrosis or scar formation is a challenging area of research. Nanomaterials and nanocomposites are promising platforms to recapitulate the organization of natural extracellular matrix for the fabrication of functional bone tissues because nanostructure provides a closer approximation to native bone architecture. Nanostructured scaffolds provide structural support for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. Unique properties of nanomaterials, such as increased wettability and surface area, lead to increased protein adsorption when compared with conventional biomaterials. Cell-scaffold interactions at the cell-material nanointerface may be mediated by integrin-triggered signaling pathways that affect cell behavior. The materials selection and processing techniques can affect the chemical, physical, mechanical, and cellular recognition properties of biomaterials. In this article, we focused on reviewing current fabrication techniques for nanomaterials and nanocomposites, their cell interaction properties and their application in bone tissue engineering and regeneration.

Regenerative Biomaterials, 2016

Providing improved health care for wound, burn and surgical patients is a major goal for enhancin... more Providing improved health care for wound, burn and surgical patients is a major goal for enhancing patient well-being, in addition to reducing the high cost of current health care treatment. The introduction of new and novel biomaterials and biomedical devices is anticipated to have a profound effect on the future improvement of many deleterious health issues. This publication will discuss the development of novel non-stinging liquid adhesive bandages in healthcare applications developed by Rochal Industries. The scientists/engineers at Rochal have participated in commercializing products in the field of ophthalmology, including rigid gas permeable contact lenses, soft hydrogel contact lenses, silicone hydrogel contact lenses, contact lens care solutions and cleaners, intraocular lens materials, intraocular controlled drug delivery, topical/intraocular anesthesia, and in the field of wound care, as non-stinging, spray-on liquid bandages to protect skin from moisture and body fluids and medical adhesive-related skin injuries. Current areas of entrepreneurial activity at Rochal Industries pertain to the development of new classes of biomaterials for wound healing, primarily in regard to microbial infection, chronic wound care, burn injuries and surgical procedures, with emphasis on innovation in product creation, which include cell-compatible substrates/scaffolds for wound healing, antimicrobial materials for opportunistic pathogens and biofilm reduction, necrotic wound debridement, scar remediation, treatment of diabetic ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and adjuvants for skin tissue substitutes.

Over the past decade, tissue engineered vascular grafts (TEVGs) have emerged as potential replace... more Over the past decade, tissue engineered vascular grafts (TEVGs) have emerged as potential replacements for small diameter blood vessels. Recent literature indicates that scaffold modulus critically influences smooth muscle cell (SMC) behavior under static culture conditions. Thus, a number of studies are currently being performed to optimize the modulus of TEVGs scaffolds so as to elicit desired cell ECM deposition prior to implantation. However, little work has been done to determine whether scaffold modulus is a significant regulator of cell response under physiological (dynamic culture) conditions. The present study was designed to evaluate the influence of scaffold modulus relative to applied mechanical strain on SMC extracellular matrix deposition and phenotype. Tubular scaffolds of distinct moduli (60 kPa and 300 kPa) but with similar mesh sizes and bioactivity levels were prepared using diacrylate derivatized poly(ethylene glycol) (PEGDA). For each scaffold modulus group, two...

Tissue Engineering Part C: Methods, 2011

The aim of the present study was to investigate the potential of hydrogel-electrospun mesh hybrid... more The aim of the present study was to investigate the potential of hydrogel-electrospun mesh hybrid scaffolds as coronary artery bypass grafts. The circumferential mechanical properties of blood vessels modulate a broad range of phenomena, including vessel stress and mass transport, which, in turn, have a critical impact on cardiovascular function. Thus, coronary artery bypass grafts should mimic key features of the nonlinear stress-strain behavior characteristic of coronary arteries. In native arteries, this J-shaped circumferential stress-strain curve arises primarily from initial load transfer to low stiffness elastic fibers followed by progressive recruitment and tensing of higher stiffness arterial collagen fibers. This nonlinear mechanical response is difficult to achieve with a single-component scaffold while simultaneously meeting the suture retention strength and tensile strength requirements of an implantable graft. For instance, although electrospun scaffolds have a number of advantages for arterial tissue engineering, including relatively high tensile strengths, tubular mesh constructs formed by conventional electrospinning methods do not generally display biphasic stress-strain curves. In the present work, we demonstrate that a multicomponent scaffold comprised of polyurethane electrospun mesh layers (intended to mimic the role of arterial collagen fibers) bonded together by a fibrin hydrogel matrix (designed to mimic the role of arterial elastic fibers) results in a composite construct which retains the high tensile strength and suture retention strength of electrospun mesh but which displays a J-shaped mechanical response similar to that of native coronary artery. Moreover, we show that these hybrid constructs support cell infiltration and extracellular matrix accumulation following 12-day exposure to continuous cyclic distension.

Journal of Biomedical Materials Research Part A, 2010

Ligament graft failure frequently results from poor integration of the replacement tissue with as... more Ligament graft failure frequently results from poor integration of the replacement tissue with associated bone. Thus, the ability to regenerate the bone-ligament osteochondral interface would be advantageous in ligament reconstruction. At the osteochondral interface, the tissue transitions from a bone-like matrix to fibrocartilage. Therefore, a scaffold which promotes a spatially regulated transition in cell behavior from osteoblast-like to chondrocyte-like would be desirable. Previous research indicates that addition of inorganic components to organic scaffolds can enhance the deposition of bone-like matrix by associated osteoblasts. We therefore reasoned that a gradient in the inorganic content of a hybrid inorganic-organic scaffold may induce an osteochondral-like transition in cell phenotype and matrix production. To test this hypothesis, hydrogels were prepared from poly(ethylene glycol) (PEG) and star poly(dimethylsiloxane) (PDMS star). As anticipated, both the matrix deposition and phenotype of encapsulated osteoblasts varied with scaffold inorganic content, although the directionality of this modulation was contrary to expectation. Specifically, osteoblasts appeared to transdifferentiate into chondrocyte-like cells with increasing scaffold inorganic content, as indicated by increased chondroitin sulfate and collagen type II production and by upregulation of sox9, a transcription factor associated with chondrocytic differentiation. Furthermore, the deposition of bone-like matrix (collagen type I, calcium phosphate, and osteocalcin) decreased with increasing PDMS star content. The resistance of the PDMS star-PEG scaffolds to protein adsorption and/or the changes in gel modulus/mesh structure accompanying PDMS star incorporation may underlie the unexpected increase in chondrocytic phenotype with increasing inorganic content. Combined, the present results indicate that PDMS star-PEG hybrid gels may prove promising for osteochondral regeneration.

Annals of Biomedical Engineering, 2010

A major roadblock in the development of tissue engineered vascular grafts (TEVGs) is achieving co... more A major roadblock in the development of tissue engineered vascular grafts (TEVGs) is achieving construct endothelialization that is stable under physiological stresses. The aim of the current study was to validate an approach for generating a mechanically stable layer of endothelial cells (ECs) in the lumen of TEVGs. To accomplish this goal, a unique method was developed to fabricate a thin EC layer using poly(ethylene glycol) diacrylate (PEGDA) as an intercellular "cementing" agent. This EC layer was subsequently bonded to the lumen of a tubular scaffold to generate a bi-layered construct. The viability of bovine aortic endothelial cells (BAECs) through the "cementing" process was assessed. "Cemented" EC layer expression of desired phenotypic markers (AcLDL uptake, VE-cadherin, eNOS, PECAM-1) as well as of injury-associated markers (E-selectin, SM22alpha) was also examined. These studies indicated that the "cementing" process allowed ECs to maintain high viability and expression of mature EC markers while not significantly stimulating primary injury pathways. Finally, the stability of the "cemented" EC layers under abrupt application of high shear pulsatile flow (approximately 11 dyn/cm(2), P (avg) approximately 95 mmHg, DeltaP approximately 20 mmHg) was evaluated and compared to that of conventionally "seeded" EC layers. Whereas the "cemented" ECs remained fully intact following 48 h of pulsatile flow, the "seeded" EC layers delaminated after less than 1 h of flow. Furthermore, the ability to extend this approach to degradable PEGDA "cements" permissive of cell elongation was demonstrated. Combined, these results validate an approach for fabricating bi-layered TEVGs with stable endothelialization.

Acta Biomaterialia, 2012

Nickel-titanium (NiTi) shape memory alloys (SMAs) are commonly used in a range of biomedical appl... more Nickel-titanium (NiTi) shape memory alloys (SMAs) are commonly used in a range of biomedical applications. However, concerns exist regarding their use in certain biomedical scenarios due to the known toxicity of Ni and conflicting reports of NiTi corrosion resistance, particularly under dynamic loading. Titanium-niobium (TiNb) SMAs have recently been proposed as an alternative to NiTi SMAs due to the biocompatibility of both constituents, the ability of both Ti and Nb to form protective surface oxides, and their superior workability. However, several properties critical to the use of TiNb SMAs in biomedical applications have not been systematically explored in comparison with NiTi SMAs. These properties include cytocompatibility, corrosion resistance, and alterations in alloy surface composition in response to prolonged exposure to physiological solutions. Therefore, the goal of the present work was to comparatively investigate these aspects of NiTi (49.2 at.% Ti) and TiNb (26 at.% Nb) SMAs. The results from the current studies indicate that TiNb SMAs are less cytotoxic than NiTi SMAs, at least under static culture conditions. This increased TiNb cytocompatibility was correlated with reduced ion release as well as with increased corrosion resistance according to potentio-dynamic tests. Measurements of the surface composition of samples exposed to cell culture medium further supported the reduced ion release observed from TiNb relative to NiTi SMAs. Alloy composition depth profiles also suggested the formation of calcium phosphate deposits within the surface oxide layers of medium-exposed NiTi but not of TiNb. Collectively, the present results indicate that TiNb SMAs may be promising alternatives to NiTi for certain biomedical applications.

Biotechnology and Bioengineering, 2009

A number of treatments are being investigated for vocal fold (VF) scar, including designer implan... more A number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high Mw HA (HA(HMW)), intermediate Mw HA (HA(IMW)), or the control polysaccharide, alginate, and cultured for 7 and 21 days. HA(HMW) promoted sustained increases in active ERK1/2 relative to HA(IMW). Furthermore, VFFs in HA(IMW) gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in HA(HMW) and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to HA(IMW) relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior.

Wounds : a compendium of clinical research and practice, 2020

INTRODUCTION Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differ... more INTRODUCTION Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing. OBJECTIVE In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro. MATERIALS AND METHODS The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results. RESULTS Synergy is defined as the interaction of components to produce a combined effect g...

Journal of Drug Delivery Science and Technology, 2020

Pain control following thermal injury remains a significant clinical challenge from the initial p... more Pain control following thermal injury remains a significant clinical challenge from the initial point of care through rehabilitation. Although standard analgesics provide some relief, there is a critical need to better modulate burn pain while minimizing the undesirable side effects associated with current systemic pain treatments. To that end, we developed a novel reverse microemulsion (RmE) that encapsulated the polar and ionic analgesics nordihydroguaiaretic acid (NDGA) and ketoconazole with 10-20% efficiency and could deliver the analgesics into bioartificial tissues. When RmE-analgesic formulations were incorporated into a liquid bandagelike amphiphilic acrylate polymer, the analgesics were released slowly over 24 hours. Incorporation into the amphiphilic acrylate polymer slowed analgesic release from the RmE and the majority of the analgesics remained in the topically-applied residual polymer layer. Both the RmE and the polymer-RmE formulations induced significant reductions in post-burn pain for at least 48 h. Altogether, these data suggest a RmE loaded with NDGA and ketoconazole can act as a novel long-acting and topical method for reducing thermal hyperalgesia and mechanical allodynia nociceptive responses.

Journal of Biomedical Materials Research Part A, 2016

The current work investigates the potential of cell layer-electrospun mesh constructs as coronary... more The current work investigates the potential of cell layer-electrospun mesh constructs as coronary artery bypass grafts. These cell-mesh constructs were generated by first culturing a confluent layer of 10T½ smooth muscle progenitor cells on a high strength electrospun mesh with uniaxially aligned fibers. Cell-laden mesh sheets were then wrapped around a cylindrical mandrel such that the mesh fibers were aligned circumferentially. The resulting multi-layered constructs were then cultured for 4 wks in media supplemented with TGF-β1 and ascorbic acid to support 10T½ differentiation toward a smooth muscle cell-like fate as well as to support elastin and collagen production. The underlying hypothesis of this work was that extracellular matrix (ECM) deposited by the cell layers would act as an adhesive agent between the individual mesh layers, providing strength to the construct as well as a source for structural elasticity at low strains. In addition, the structural anisotropy of the mesh would inherently guide desired circumferential cell and ECM alignment. Results demonstrate that the cell-mesh constructs exhibited a J-shaped circumferential stress-strain response similar to that of native coronary artery, while also displaying acceptable tensile strength. Furthermore, associated 10T½ cells and deposited collagen fibers showed a high degree of circumferential alignment.

Wound Management & Prevention

Biofilms are believed to be a source of chronic inflammation in non-healing wounds. PURPOSE: In t... more Biofilms are believed to be a source of chronic inflammation in non-healing wounds. PURPOSE: In this study, the pre-clinical anti-biofilm efficacy of several wound cleansers was examined using the Calgary minimum biofilm eradication concentration (MBEC) and ex vivo porcine dermal explant (PDE) models on Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans biofilms. METHODS: A surfactant-based cleanser and antimicrobial-based cleansers containing ionic silver, hypochlorous acid (HOCl), sodium hypochlorite (NaOCl), and polyhexamethylene biguanide (PHMB) were tested on the MBEC model biofilms with a 10-minute application time. Select cleansers were then tested on the mature PDE biofilms with 10-minute applications followed by the application of cleanser-soaked gauze. The PDE model was further expanded to include single and daily applications of the cleansers to mimic daily and 72-hour dressing changes. RESULTS: In the MBEC model, PHMB- and HO...

There are more than 150,000 anterior cruciate ligament reconstructions each year with the goal of... more There are more than 150,000 anterior cruciate ligament reconstructions each year with the goal of recovering the balance between knee stability and mobility. As many as 25% of these procedures will end in joint instability that can cause further damage. The risk of developing degenerative joint disease (DJD) increases in patients with previous knee injury, resulting in a higher instance of total knee arthroplasty (TKA). There are more than 400,000 TKA procedures each year, but the waiting lists for this surgery shows that many more patients are hoping to undergo this procedure. TKA provides improved knee function and pain relief for patients suffering from DJD. Although this procedure is considered successful, as younger patients undergo this treatment, the long-term performance must be improved. Major mechanisms of failure include component loosening from stress-shielding, poor integration of the implant with native tissue, and ion release from the implant. TiNb alloys are more biocompatible than currently used alloys, such as NiTi, and have mechanical properties closer to bone, so they would reduce the instance of stress shielding. TiNb can be made porous for better integration with the native bone and has superior corrosion resistance than NiTi. Engineered ligaments have generally failed to achieve mechanical properties sufficiently similar to their native counterparts, but also lack the osteochondral interface critical to the transfer of load between ligament and bone. The osteochondral interface could be incorporated through a gradient of inorganic content toward the bony insertion ends of the ligament graft, as we showed that in increase of inorganic content resulted in

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012

Bone is a nanocomposite composed of organic (mainly collagen) and inorganic (nanocrystalline hydr... more Bone is a nanocomposite composed of organic (mainly collagen) and inorganic (nanocrystalline hydroxyapatite) components, with a hierarchical structure ranging from nano- to macroscale. Its functions include providing mechanical support and transmitting physio-chemical and mechano-chemical cues. Clinical repair and reconstruction of bone defects has been conducted using autologous and allogeneic tissues and alloplastic materials, with functional limitations. The design and development of biomaterial scaffolds that will replace the form and function of native tissue while promoting regeneration without necrosis or scar formation is a challenging area of research. Nanomaterials and nanocomposites are promising platforms to recapitulate the organization of natural extracellular matrix for the fabrication of functional bone tissues because nanostructure provides a closer approximation to native bone architecture. Nanostructured scaffolds provide structural support for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. Unique properties of nanomaterials, such as increased wettability and surface area, lead to increased protein adsorption when compared with conventional biomaterials. Cell-scaffold interactions at the cell-material nanointerface may be mediated by integrin-triggered signaling pathways that affect cell behavior. The materials selection and processing techniques can affect the chemical, physical, mechanical, and cellular recognition properties of biomaterials. In this article, we focused on reviewing current fabrication techniques for nanomaterials and nanocomposites, their cell interaction properties and their application in bone tissue engineering and regeneration.

Regenerative Biomaterials, 2016

Providing improved health care for wound, burn and surgical patients is a major goal for enhancin... more Providing improved health care for wound, burn and surgical patients is a major goal for enhancing patient well-being, in addition to reducing the high cost of current health care treatment. The introduction of new and novel biomaterials and biomedical devices is anticipated to have a profound effect on the future improvement of many deleterious health issues. This publication will discuss the development of novel non-stinging liquid adhesive bandages in healthcare applications developed by Rochal Industries. The scientists/engineers at Rochal have participated in commercializing products in the field of ophthalmology, including rigid gas permeable contact lenses, soft hydrogel contact lenses, silicone hydrogel contact lenses, contact lens care solutions and cleaners, intraocular lens materials, intraocular controlled drug delivery, topical/intraocular anesthesia, and in the field of wound care, as non-stinging, spray-on liquid bandages to protect skin from moisture and body fluids and medical adhesive-related skin injuries. Current areas of entrepreneurial activity at Rochal Industries pertain to the development of new classes of biomaterials for wound healing, primarily in regard to microbial infection, chronic wound care, burn injuries and surgical procedures, with emphasis on innovation in product creation, which include cell-compatible substrates/scaffolds for wound healing, antimicrobial materials for opportunistic pathogens and biofilm reduction, necrotic wound debridement, scar remediation, treatment of diabetic ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and adjuvants for skin tissue substitutes.

Over the past decade, tissue engineered vascular grafts (TEVGs) have emerged as potential replace... more Over the past decade, tissue engineered vascular grafts (TEVGs) have emerged as potential replacements for small diameter blood vessels. Recent literature indicates that scaffold modulus critically influences smooth muscle cell (SMC) behavior under static culture conditions. Thus, a number of studies are currently being performed to optimize the modulus of TEVGs scaffolds so as to elicit desired cell ECM deposition prior to implantation. However, little work has been done to determine whether scaffold modulus is a significant regulator of cell response under physiological (dynamic culture) conditions. The present study was designed to evaluate the influence of scaffold modulus relative to applied mechanical strain on SMC extracellular matrix deposition and phenotype. Tubular scaffolds of distinct moduli (60 kPa and 300 kPa) but with similar mesh sizes and bioactivity levels were prepared using diacrylate derivatized poly(ethylene glycol) (PEGDA). For each scaffold modulus group, two...

Tissue Engineering Part C: Methods, 2011

The aim of the present study was to investigate the potential of hydrogel-electrospun mesh hybrid... more The aim of the present study was to investigate the potential of hydrogel-electrospun mesh hybrid scaffolds as coronary artery bypass grafts. The circumferential mechanical properties of blood vessels modulate a broad range of phenomena, including vessel stress and mass transport, which, in turn, have a critical impact on cardiovascular function. Thus, coronary artery bypass grafts should mimic key features of the nonlinear stress-strain behavior characteristic of coronary arteries. In native arteries, this J-shaped circumferential stress-strain curve arises primarily from initial load transfer to low stiffness elastic fibers followed by progressive recruitment and tensing of higher stiffness arterial collagen fibers. This nonlinear mechanical response is difficult to achieve with a single-component scaffold while simultaneously meeting the suture retention strength and tensile strength requirements of an implantable graft. For instance, although electrospun scaffolds have a number of advantages for arterial tissue engineering, including relatively high tensile strengths, tubular mesh constructs formed by conventional electrospinning methods do not generally display biphasic stress-strain curves. In the present work, we demonstrate that a multicomponent scaffold comprised of polyurethane electrospun mesh layers (intended to mimic the role of arterial collagen fibers) bonded together by a fibrin hydrogel matrix (designed to mimic the role of arterial elastic fibers) results in a composite construct which retains the high tensile strength and suture retention strength of electrospun mesh but which displays a J-shaped mechanical response similar to that of native coronary artery. Moreover, we show that these hybrid constructs support cell infiltration and extracellular matrix accumulation following 12-day exposure to continuous cyclic distension.

Journal of Biomedical Materials Research Part A, 2010

Ligament graft failure frequently results from poor integration of the replacement tissue with as... more Ligament graft failure frequently results from poor integration of the replacement tissue with associated bone. Thus, the ability to regenerate the bone-ligament osteochondral interface would be advantageous in ligament reconstruction. At the osteochondral interface, the tissue transitions from a bone-like matrix to fibrocartilage. Therefore, a scaffold which promotes a spatially regulated transition in cell behavior from osteoblast-like to chondrocyte-like would be desirable. Previous research indicates that addition of inorganic components to organic scaffolds can enhance the deposition of bone-like matrix by associated osteoblasts. We therefore reasoned that a gradient in the inorganic content of a hybrid inorganic-organic scaffold may induce an osteochondral-like transition in cell phenotype and matrix production. To test this hypothesis, hydrogels were prepared from poly(ethylene glycol) (PEG) and star poly(dimethylsiloxane) (PDMS star). As anticipated, both the matrix deposition and phenotype of encapsulated osteoblasts varied with scaffold inorganic content, although the directionality of this modulation was contrary to expectation. Specifically, osteoblasts appeared to transdifferentiate into chondrocyte-like cells with increasing scaffold inorganic content, as indicated by increased chondroitin sulfate and collagen type II production and by upregulation of sox9, a transcription factor associated with chondrocytic differentiation. Furthermore, the deposition of bone-like matrix (collagen type I, calcium phosphate, and osteocalcin) decreased with increasing PDMS star content. The resistance of the PDMS star-PEG scaffolds to protein adsorption and/or the changes in gel modulus/mesh structure accompanying PDMS star incorporation may underlie the unexpected increase in chondrocytic phenotype with increasing inorganic content. Combined, the present results indicate that PDMS star-PEG hybrid gels may prove promising for osteochondral regeneration.

Annals of Biomedical Engineering, 2010

A major roadblock in the development of tissue engineered vascular grafts (TEVGs) is achieving co... more A major roadblock in the development of tissue engineered vascular grafts (TEVGs) is achieving construct endothelialization that is stable under physiological stresses. The aim of the current study was to validate an approach for generating a mechanically stable layer of endothelial cells (ECs) in the lumen of TEVGs. To accomplish this goal, a unique method was developed to fabricate a thin EC layer using poly(ethylene glycol) diacrylate (PEGDA) as an intercellular "cementing" agent. This EC layer was subsequently bonded to the lumen of a tubular scaffold to generate a bi-layered construct. The viability of bovine aortic endothelial cells (BAECs) through the "cementing" process was assessed. "Cemented" EC layer expression of desired phenotypic markers (AcLDL uptake, VE-cadherin, eNOS, PECAM-1) as well as of injury-associated markers (E-selectin, SM22alpha) was also examined. These studies indicated that the "cementing" process allowed ECs to maintain high viability and expression of mature EC markers while not significantly stimulating primary injury pathways. Finally, the stability of the "cemented" EC layers under abrupt application of high shear pulsatile flow (approximately 11 dyn/cm(2), P (avg) approximately 95 mmHg, DeltaP approximately 20 mmHg) was evaluated and compared to that of conventionally "seeded" EC layers. Whereas the "cemented" ECs remained fully intact following 48 h of pulsatile flow, the "seeded" EC layers delaminated after less than 1 h of flow. Furthermore, the ability to extend this approach to degradable PEGDA "cements" permissive of cell elongation was demonstrated. Combined, these results validate an approach for fabricating bi-layered TEVGs with stable endothelialization.

Acta Biomaterialia, 2012

Nickel-titanium (NiTi) shape memory alloys (SMAs) are commonly used in a range of biomedical appl... more Nickel-titanium (NiTi) shape memory alloys (SMAs) are commonly used in a range of biomedical applications. However, concerns exist regarding their use in certain biomedical scenarios due to the known toxicity of Ni and conflicting reports of NiTi corrosion resistance, particularly under dynamic loading. Titanium-niobium (TiNb) SMAs have recently been proposed as an alternative to NiTi SMAs due to the biocompatibility of both constituents, the ability of both Ti and Nb to form protective surface oxides, and their superior workability. However, several properties critical to the use of TiNb SMAs in biomedical applications have not been systematically explored in comparison with NiTi SMAs. These properties include cytocompatibility, corrosion resistance, and alterations in alloy surface composition in response to prolonged exposure to physiological solutions. Therefore, the goal of the present work was to comparatively investigate these aspects of NiTi (49.2 at.% Ti) and TiNb (26 at.% Nb) SMAs. The results from the current studies indicate that TiNb SMAs are less cytotoxic than NiTi SMAs, at least under static culture conditions. This increased TiNb cytocompatibility was correlated with reduced ion release as well as with increased corrosion resistance according to potentio-dynamic tests. Measurements of the surface composition of samples exposed to cell culture medium further supported the reduced ion release observed from TiNb relative to NiTi SMAs. Alloy composition depth profiles also suggested the formation of calcium phosphate deposits within the surface oxide layers of medium-exposed NiTi but not of TiNb. Collectively, the present results indicate that TiNb SMAs may be promising alternatives to NiTi for certain biomedical applications.

Biotechnology and Bioengineering, 2009

A number of treatments are being investigated for vocal fold (VF) scar, including designer implan... more A number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high Mw HA (HA(HMW)), intermediate Mw HA (HA(IMW)), or the control polysaccharide, alginate, and cultured for 7 and 21 days. HA(HMW) promoted sustained increases in active ERK1/2 relative to HA(IMW). Furthermore, VFFs in HA(IMW) gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in HA(HMW) and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to HA(IMW) relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior.