Rural patients' access to mobile phones and willingness to receive mobile phone-based pharmacy and other health technology services: a pilot study.

OBJECTIVE: This pilot study explores the patient-centered demand for mobile phone-based health (mobile health [m-health]) services in the rural United States by documenting rural patients' access to mobile phones and patients' willingness to receive m-health services. SUBJECTS AND METHODS: An anonymous institutional review board-approved survey was completed by patients visiting two rural pharmacies in Nebraska from August to October 2011. Patients who volunteered to complete the survey provided their demographic data, disease state information, health status, mobile phone access, and willingness to receive (in terms of using and giving time to) m-health services. RESULTS: The majority of the 24 survey respondents were 19-40 years old (52%), female (88%), married (63%), with excellent to very good health status (63%), with no comorbidities (83%), with ≤$100 monthly medication expenses (80%), with private insurance (78%), living within 5 miles of their pharmacy (71%), and reporting that m-health services are important to them (75%; 12/16). Approximately 95%, 81%, 73%, and 55% of respondents reported access to a mobile phone, voice mails, text messaging, and mobile phone applications, respectively. Of the respondents, 65%, 57%, 52%, and 48% were willing to receive prerecorded messages for appointment reminders from the doctor, disease information, medication use/self-care information, and symptom monitoring information, respectively. In total, 70%, 63%, 61%, 54%, and 50% were willing to receive prerecorded messages from the pharmacist containing contact requests, new/refill prescription reminders, information on medication problems, reviewing/monitoring of medication use, and medication self-management/preventive screenings/immunizations, respectively. Of 44% (7/16) respondents willing to give time for m-health services, 83% were willing to give 15 min, and 17% were willing to give 30 min every month. CONCLUSIONS: By demonstrating rural patients' demand for m-health (including pharmacy) services, this is one of the first pilot studies showing rural patients have access to mobile phones and may be willing to use and give time to m-health services. Further research is needed on delivery and coordination of transitions in patient-centered care in the United States with m-health services.

Deformation responses of a physically cross-linked high molecular weight elastin-like protein polymer.

Recombinant protein polymers were synthesized and examined under various loading conditions to assess the mechanical stability and deformation responses of physically cross-linked, hydrated, protein polymer networks designed as triblock copolymers with central elastomeric and flanking plastic-like blocks. Uniaxial stress-strain properties, creep and stress relaxation behavior, as well as the effect of various mechanical preconditioning protocols on these responses were characterized. Significantly, we demonstrate for the first time that ABA triblock protein copolymers when redesigned with substantially larger endblock segments can withstand significantly greater loads. Furthermore, the presence of three distinct phases of deformation behavior was revealed upon subjecting physically cross-linked protein networks to step and cyclic loading protocols in which the magnitude of the imposed stress was incrementally increased over time. We speculate that these phases correspond to the stretch of polypeptide bonds, the conformational changes of polypeptide chains, and the disruption of physical cross-links. The capacity to select a genetically engineered protein polymer that is suitable for its intended application requires an appreciation of its viscoelastic characteristics and the capacity of both molecular structure and conditioning protocols to influence these properties.

The effect of a recombinant elastin-mimetic coating of an ePTFE prosthesis on acute thrombogenicity in a baboon arteriovenous shunt.

A recombinant elastin-mimetic triblock protein polymer with an inverse transition temperature (approximately 20 degrees C) was used to impregnate small-diameter (4 mm i.d.) expanded polytetrafluoroethylene (ePTFE) vascular grafts. Scanning electron microscopy confirmed that initial elastin impregnation of the graft followed by further multilayer coating with elastin films filled in the fibril and node structure of the luminal surface of the ePTFE graft and was macroscopically smooth. Elastin protein polymer impregnation reduced the advancing contact angle of the luminal surface to 43 degrees, which was comparable to the advancing contact angle of 47 degrees for a cast elastin film. Attenuated total reflection infrared spectroscopy and Coomassie blue staining revealed little discernable change in the protein surface film after 24 h of shear at 500 s(-1) and 37 degrees C. Excellent short-term blood-contacting properties as determined by minimal fibrin and platelet deposition were demonstrated using a baboon extracorporeal femoral arteriovenous shunt model. The results of this study demonstrate the applicability of an elastin-mimetic triblock protein polymer as a non-thrombogenic coating or as a component of a tissue-engineered composite.

Cell behavior on a CCN1 functionalized elastin-mimetic protein polymer.

We report the design of an elastin-mimetic triblock copolymer with the ability to guide endothelial cell adhesion, spreading, and migration while maintaining the elastomeric properties of the protein polymer. The V2 ligand sequence from matricellular protein CCN1 (cysteine-rich 61, CYR61) was multimerized and cloned into elastin polymer LysB10, creating LysB10.V2. Cell adhesion studies demonstrated that a LysB10.V2 surface density of at least 40 pmol/cm(2) was required to elicit cell attachment. Peptide blocking studies confirmed V2 specific engagement with integrin receptor α(v)ß(3) (P < 0.05) and we observed the formation of actin stress fiber networks and vinculin clustering, characteristic of focal adhesion assembly. Haptotatic migration assays demonstrated the ability of LysB10.V2 surfaces to stimulate migration of endothelial cells (P < 0.05). Significantly, we illustrated the ability of LysB10.V2 to support a quiescent endothelium. The CCN1 molecule functions to support many key biological processes necessary for tissue repair and thus presents a promising target for bioengineering applications. Collectively, our results demonstrate the potential to harness CCN1 specific function in the design of new scaffold materials for applications in regenerative medicine.

Long-term biostability of self-assembling protein polymers in the absence of covalent crosslinking.

Unless chemically crosslinked, matrix proteins, such as collagen or silk, display a limited lifetime in vivo with significant degradation observed over a period of weeks. Likewise, amphiphilic peptides, lipopeptides, or glycolipids that self-assemble through hydrophobic interactions to form thin films, fiber networks, or vesicles do not demonstrate in vivo biostability beyond a few days. We report herein that a self-assembling, recombinant elastin-mimetic triblock copolymer elicited minimal inflammatory response and displayed robust in vivo stability for periods exceeding 1 year, in the absence of either chemical or ionic crosslinking. Specifically, neither a significant inflammatory response nor calcification was observed upon implantation of test materials into the peritoneal cavity or subcutaneous space of a mouse model. Moreover, serial quantitative magnetic resonance imaging, evaluation of pre- and post-explant ultrastructure by cryo-high resolution scanning electron microscopy, and an examination of implant mechanical responses revealed substantial preservation of form, material architecture, and biomechanical properties, providing convincing evidence of a non-chemically or ionically crosslinked protein polymer system that exhibits long-term stability in vivo.

Expression of a recombinant elastin-like protein in pichia pastoris.

The translation of highly repetitive gene sequences is often associated with reduced levels of protein expression and may be prone to mutational events. In this report, we describe a modified concatemerization strategy to construct a gene with enhanced sequence diversity that encodes a highly repetitive elastin-like protein polymer for expression in Pichia pastoris. Specifically, degenerate oligonucleotides were used to create a monomer library, which after concatemerization yielded a genetically nonrepetitive DNA sequence that encoded identical pentapeptide repeat sequences. By limiting genetic repetition, the risk of genetic deletions, rearrangements, or premature termination errors during protein synthesis is minimized.

Elastin-mimetic protein polymers capable of physical and chemical crosslinking.

We report the synthesis of a new class of recombinant elastin-mimetic triblock copolymer capable of both physical and chemical crosslinking. These investigations were motivated by a desire to capture features unique to both physical and chemical crosslinking schemes so as to exert optimal control over a wide range of potential properties afforded by protein-based multiblock materials. We postulated that by chemically locking a multiblock protein assembly in place, functional responses that are linked to specific domain structures and morphologies may be preserved over a broader range of loading conditions that would otherwise disrupt microphase structure solely stabilized by physical crosslinking. Specifically, elastic modulus was enhanced and creep strain reduced through the addition of chemical crosslinking sites. Additionally, we have demonstrated excellent in vivo biocompatibility of glutaraldehyde treated multiblock systems.

A permanent change in protein mechanical responses can be produced by thermally-induced microdomain mixing.

Electrospinning was employed to fabricate 3-D fiber networks from a recombinant amphiphilic elastin-mimetic tri-block protein polymer and the effects of moderate thermal conditioning (60 degrees C, 4 h) on network mechanical responses investigated. Significantly, while cryo-high resolution scanning electron microscopy (cryo-HRSEM) revealed that the macroscopic and microscopic morphology of the network structure was unchanged, solid-state (1)H-NMR spectroscopy demonstrated enhanced interphase mixing of hydrophobic and hydrophilic blocks. Significantly, thermal annealing triggered permanent changes in network swelling behavior (28.75 +/- 2.80 non-annealed vs. 13.55 +/- 1.39 annealed; P < 0.05) and uniaxial mechanical responses, including Young's modulus (0.170 +/- 0.010 MPa non-annealed vs. 0.366 +/- 0.05 MPa annealed; P < 0.05) and ultimate tensile strength (0.079 +/- 0.008 MPa vs. 0.119 +/- 0.015 MPa; P < 0.05). To our knowledge, these investigations are the first to note that mechanical responses of protein polymers can be permanently altered through a temperature-induced change in microphase mixing.

Micelle density regulated by a reversible switch of protein secondary structure.

Protein secondary structures may exhibit reversible transitions that occur in an abrupt and controllable manner. In this report, we demonstrate that such transitions may be utilized in the design of a "smart" protein micellar system, in which a stimulus-induced change in protein structure triggers a rapid change in micelle compacticity and size. Specifically, recombinant DNA methods were used to prepare a protein triblock copolymer containing a central hydrophilic block and two hydrophobic end blocks derived from elastin-mimetic peptide sequences. Below the copolymer inverse transition temperature (T(t)), dilute solutions of this amphiphilic protein formed monodispersed micelles in a narrow range of R(H) of approximately 100 nm. When the the temperature was raised above T(t), an abrupt increase in micelle internal density was observed with a concomitant reduction in micelle size. This reversible change in micelle compacticity was triggered by helix-to-sheet protein folding transition. Significantly, these protein polymer-based micelles, which are rapidly responsive to environmental stimuli, establish a new mechanism for the design of controlled drug delivery vehicles.