Engineering Adhesion to Thermoresponsive Substrates: Effect of Polymer Composition on Liquid–Liquid–Solid Wetting

Adhesion control in liquid–liquid–solid systems represents a challenge for applications ranging from self-cleaning to biocompatibility of engineered materials. By using responsive polymer chemistry and molecular self-assembly, adhesion at solid/liquid interfaces can be achieved and modulated by external stimuli. Here, we utilize thermosensitive polymeric materials based on random copolymers of di­(ethylene glycol) methyl ether methacrylate (<i>x</i> = MEO₂MA) and oligo­(ethylene glycol) methyl ether methacrylate (<i>y</i> = OEGMA), that is, P­(MEO₂MA_<i>x</i>-<i>co</i>-OEGMA_<i>y</i>), to investigate the role of hydrophobicity on the phenomenon of adhesion. The copolymer ratio (<i>x</i>/<i>y</i>) dictates macromolecular changes enabling control of the hydrophilic-to-lipophilic balance (HBL) of the polymer brushes through external triggers such as ionic strength and temperature. We discuss the HBL of the thermobrushes in terms of the surface energy of the substrate by measuring the contact angle at water–decane–P­(MEO₂MA_<i>x</i>-<i>co</i>-OEGMA_<i>y</i>) brush contact line as a function of polymer composition and temperature. Solid supported polyelectrolyte layers grafted with P­(MEO₂MA_<i>x</i>-<i>co</i>-OEGMA_<i>y</i>) display a transition in the wettability that is related to the lower critical solution temperature of the polymer brushes. Using experimental observation of the hydrophilic to hydrophobic transition by the contact angle, we extract the underlying energetics associated with liquid–liquid–solid adhesion as a function of the copolymer ratio. The change in cellular attachment on P­(MEO₂MA_<i>x</i>-<i>co</i>-OEGMA_<i>y</i>) substrates of variable (<i>x</i>/<i>y</i>) composition demonstrates the subtle role of compositional tuning on the ability to control liquid–liquid–solid adhesion in biological applications

Optimizing the alignment of thermoresponsive poly(N-isopropyl acrylamide) electrospun nanofibers for tissue engineering applications: A factorial design of experiments approach.

Thermoresponsive polymers, such as poly(N-isopropyl acrylamide) (PNIPAM), have been identified and used as cell culture substrates, taking advantage of the polymer's lower critical solution temperature (LCST) to mechanically harvest cells. This technology bypasses the use of biochemical enzymes that cleave important cell-cell and cell-matrix interactions. In this study, the process of electrospinning is used to fabricate and characterize aligned PNIPAM nanofiber scaffolds that are biocompatible and thermoresponsive. Nanofiber scaffolds produced by electrospinning possess a 3D architecture that mimics native extracellular matrix, providing physical and chemical cues to drive cell function and phenotype. We present a factorial design of experiments (DOE) approach to systematically determine the effects of different electrospinning process parameters on PNIPAM nanofiber diameter and alignment. Results show that high molecular weight PNIPAM can be successfully electrospun into both random and uniaxially aligned nanofiber mats with similar fiber diameters by simply altering the speed of the rotating mandrel collector from 10,000 to 33,000 RPM. PNIPAM nanofibers were crosslinked with OpePOSS, which was verified using FTIR. The mechanical properties of the scaffolds were characterized using dynamic mechanical analysis, revealing an order of magnitude difference in storage modulus (MPa) between cured and uncured samples. In summary, cross-linked PNIPAM nanofiber scaffolds were determined to be stable in aqueous culture, biocompatible, and thermoresponsive, enabling their use in diverse cell culture applications

Harnessing systems biology approaches to engineer functional microvascular networks

This is a copy of an article published in Tissue Engineering Part B. © 2010 Mary Ann Liebert, Inc.; Tissue Engineering Part B is available online at: http://online.liebertpub.comDOI: 10.1089/ten.teb.2009.0611Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery

FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects

The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P1 and S1P3 significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P3 promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Proper spatial and temporal regulation of microvascular remodeling is critical to the formation of functional vascular networks, spanning the various arterial, venous, capillary, and collateral vessel systems. Recently, our group has demonstrated that sustained release of sphingosine 1-phosphate (S1P) from biodegradable polymers promotes microvascular network growth and arteriolar expansion. In this study, we employed S1P receptor-specific compounds to activate and antagonize different combinations of S1P receptors to elucidate those receptors most critical for promotion of pharmacologically induced microvascular network growth. We show that S1P1 and S1P3 receptors act synergistically to enhance functional network formation via increased functional length density, arteriolar diameter expansion, and increased vascular branching in the dorsal skinfold window chamber model. FTY720, a potent activator of S1P1 and S1P3, promoted a 107% and 153% increase in length density 3 and 7 days after implantation, respectively. It also increased arteriolar diameters by 60% and 85% 3 and 7 days after implantation. FTY720-stimulated branching in venules significantly more than unloaded poly(D, L-lactic-co-glycolic acid). When implanted on the mouse spinotrapezius muscle, FTY720 stimulated an arteriogenic response characterized by increased tortuosity and collateralization of branching microvascular networks. Our results demonstrate the effectiveness of S1P1 and S1P3 receptor-selective agonists (such as FTY720) in promoting microvascular growth for tissue engineering applications

Determinants of behavioral and psychological symptoms of dementia: A scoping review of the evidence

BackgroundBehavioral and psychological symptoms of dementia (BPSD) are prevalent in people with neurodegenerative diseases.PurposeIn this scoping review the Kales, Gitlin and Lykestos framework is used to answer the question: What high quality evidence exists for the patient, caregiver and environmental determinants of five specific BPSD: aggression, agitation, apathy, depression and psychosis?MethodAn a priori review protocol was developed; 692 of 6013 articles retrieved in the search were deemed eligible for review. Gough's Weight of Evidence Framework and the Cochrane Collaboration's tool for assessing risk of bias were used. The findings from 56 high quality/low bias articles are summarized.DiscussionEach symptom had its own set of determinants, but many were common across several symptoms: neurodegeneration, type of dementia, severity of cognitive impairments, and declining functional abilities, and to a lesser extent, caregiver burden and communication.ConclusionResearch and policy implications are relevant to the National Plan to Address Alzheimer's Disease

Laminin Nanofiber Meshes That Mimic Morphological Properties and Bioactivity of Basement Membranes

The basement membrane protein, laminin I, has been used broadly as a planar two-dimensional film or in a three-dimensional form as a reconstituted basement membrane gel such as Matrigel to support cellular attachment, growth, and differentiation in vitro. In basement membranes in vivo, laminin exhibits a fibrillar morphology, highlighting the electrospinning process as an ideal method to recreate such fibrous substrates in vitro. Electrospinning was employed to fabricate meshes of murine laminin I nanofibers (LNFs) with fiber size, geometry, and porosity of authentic basement membranes. Purified laminin I was solubilized and electrospun in parametric studies of fiber diameters as a function of polymer solution concentration, collecting distance, and flow rate. Resulting fiber diameters ranged from 90 to 300 nm with mesh morphologies containing beads. Unlike previously described nanofibers (NFs) synthesized from proteins such as collagen, meshes of LNFs retain their structural features when wetted and do not require fixation by chemical crosslinking, which often destroys cell attachment and other biological activity. The LNF meshes maintained their geometry for at least 2 days in culture without chemical crosslinking. PC12 cells extended neurites without nerve growth factor stimulation on LNF substrates. Additionally, LNFs significantly enhance both the rate and quantity of attachment of human adipose stem cells (ASCs) compared to laminin films. ASCs were viable and maintained attachment to LNF meshes in serum-free media for at least 3 days in culture and extended neurite-like processes after 24 h in serum-free media conditions without media additives to induce differentiation. LNF meshes are a novel substrate for cell studies in vitro, whose properties may be an excellent scaffold material for delivering cells in tissue engineering applications in vivo