Cell transplantation is a promising therapy for myriad of debilitating diseases; however, current delivery protocols using direct injection result in poor cell viability. We demonstrate that during the actual process, mechanical membrane disruption results significant acute loss viability at clinically relevant rates. As strategy to protect cells from these damaging forces, we hypothesize encapsulation within hydrogels specific properties will significantly improve use controlled vitro model...

Short peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials-an attractive approach neural tissue engineering. Here, we report a new class of short, five-residue that form hydrogels with nanofiber structures. Using rheology and spectroscopy, describe how sequence variations, pH, concentration alter the mechanical properties our pentapeptide hydrogels. We find this seven unmodified forms...

The design of bioactive materials allows tailored studies probing cell–biomaterial interactions, however, relatively few have examined the effects ligand density and material stiffness on neurite growth in three-dimensions. Elastin-like proteins (ELPs) been designed with modular structural regions to enable systematic characterization parameters within three-dimensional (3-D) materials. To promote out-growth better understand common biomaterial neuronal cultures we here focused cell-adhesive...

Native tissues provide cells with complex, three-dimensional (3D) environments comprised of hydrated networks extracellular matrix proteins and sugars. By mimicking the dimensionality native tissue while deconstructing effects environmental parameters, protein-based hydrogels serve as attractive, in vitro platforms to investigate cell–matrix interactions. For cell encapsulation, process hydrogel formation through physical or covalent cross-linking must be mild compatible. While many chemical...

Neural progenitor cells (NPCs) are a promising cell source to repair damaged nervous tissue. However, expansion of therapeutically relevant numbers NPCs and their efficient differentiation into desired mature types remains challenge. Material-based strategies, including culture within 3D hydrogels, have the potential overcome these current limitations. An ideal material would enable both NPC subsequent single platform. It has recently been demonstrated that cell-mediated remodeling hydrogels...

Poly(ethylene glycol) or PEG-based hydrogels provide a useful methodology for tissue engineering and the controlled-release of drugs within central nervous system (CNS). To be successful, local neuroinflammatory response to an implant must well understood. Toward this end, focus was examine localized recruitment activation microglia astrocytes following implantation in brain. Because they are clinical relevance may impact brain differently, with different mass loss profiles were examined. At...

Neural precursor cells (NPCs) are a renewable cell source that may be useful for neural transplant therapies. Their expansion and differentiation potential have traditionally been explored by culturing them on stiff tissue culture polystyrene. Here we describe advantages of an alternative system: bio-inert poly(ethylene glycol) (PEG) hydrogels. Specifically this work reports the effect macromer weight percent has metabolic apoptotic activity, proliferation, cellular composition mixed...

Degradable polymers have been used successfully in a wide variety of peripheral applications from tissue regeneration to drug delivery. These induce little inflammatory response and appear be well accepted by the host environment. Their use brain, for neural reconstruction or delivery, also could advantageous treating neurodegenerative disorders. Because brain has unique immune response, polymer that is compatible body may not so brain. In present study, polyethylene glycol (PEG)-based...

Biomaterials prepared from polyesters of lactic acid and glycolic acid, or a mixture the two, degrade in presence water into naturally occurring metabolites, acid. While degradation product that is released biomaterials well tolerated by body, can influence metabolic function cells; it serve as an energy substrate for cells, has been shown to have antioxidant properties. Neural precursor cell population considerable interest source cells neural tissue regeneration strategies, generate high...

Abstract Tailored delivery of neurotrophic factors (NFs) is a critical challenge that continues to inhibit strategies for guidance axonal growth in vivo . Of particular importance the ability recreate innervation distant brain regions by transplant tissue, instance rebuilding nigrostriatal track, one focus Parkinson's disease research. Many have utilized polymer drug target NF release space and time, but combinatorial approaches are needed deliver multiple NFs at relevant therapeutic times...

Hydrogels that degrade at different rates were prepared by copolymerizing slowly degrading macromer poly(ethylene glycol) (PEG) dimethacrylate with a faster poly(lactic acid)-b-PEG-b-poly(lactic acid) dimethacrylate. A clinically relevant population of neural cells composed differentiated neurons and multipotent precursor was cultured within hydrogels. Within 2 h after encapsulation, metabolic activity higher in hydrogels increasing levels degradable content. This improvement accompanied...

The lack of regenerative solutions for demyelination within the central nervous system motivates development strategies to expand and drive bioactivity cells, including oligodendrocyte progenitor cells (OPCs), that ultimately give rise myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel study effects microenvironmental mechanical properties on behavior OPCs. We tuned stiffness hydrogels match brain tissue (storage modulus 200–2000 Pa) studied metabolic activity,...

Stereocomplexation, or specific interactions among complementary stereoregular macromolecules, is burgeoning as an increasingly impactful design tool, exerting exquisite control of material structure and properties. Since stereocomplexation polymers produces remarkable transformations in mechanics, morphology, degradation, we sought to leverage tune these properties peptide-based biomaterials. We found that blending the pentapeptides l- d-KYFIL triggers dual mechanical morphological from...

Oligodendrocytes in the central nervous system (CNS) are responsible for generating myelin, an electrically insulating layer around neuronal axons. When myelin is damaged, neurons incapable of sustaining normal communications, which can manifest patients as pain and loss mobility vision. A plethora research has used biomaterials to promote regeneration, but despite wide implications a disrupted sheath, very little known about how biomaterial environments impact proliferation oligodendrocyte...

Coacervates have enormous potential due to their diverse functional properties supporting a wide number of applications in personal care products, pharmaceuticals, and food processing. Normally, separation coacervate phases is induced by changes pH, ionic strength, and/or polyelectrolyte concentration. This study investigates the microphase complex formation two natural polyelectrolytes, elastin-like polypeptides (ELPs) hyaluronic acid (HA), as simple models for biological coacervates. These...

Novel methods to endow cell-responsiveness into hydrogels are explored and successful work is summarized.

Low cell survival after syringe injection hampers the success of preclinical and clinical transplantation trials. During injection, cells experience mechanical forces that lead to cell-membrane disruption decreased viability. To improve survival, we designed rapidly assembling pentapeptides for injectable delivery (RAPID) hydrogels shear-thin, protect from extensional flow, form fibers, provide properties similar native tissue. We found 1.5 wt % RAPID mitigate damaging effects resulting in...

Biomaterial hydrogels are made by cross-linking either natural materials, which exhibit inherent bioactivity but suffer from batch-to-batch variations, or synthetic have a well-defined chemical structure usually require modification to bioactivity. Recombinant engineered proteins bridge the divide between and materials because incorporate bioactive domains within biopolymer backbone amino acid sequence. elastin-like (ELPs) modeled native tropoelastin ELPs composed of repeating VPGxG...

The density of integrin-binding ligands in an extracellular matrix (ECM) is known to regulate cell migration speed by imposing a balance traction forces between the leading and trailing edges cell, but effect cell-adhesive on neurite chemoattraction not well understood. A platform presented here that combines gradient-generating microfluidic devices with 3D protein-engineered hydrogels study RGD ligand pathfinding from chick dorsal root ganglia-derived spheroids. Spheroids are encapsulated...