Abstract:Amino acid-based poly(ester urea)s (PEU) are high modulus, resorbable polymers with many potential uses, including the surgical repair of bone defects. In vitro and in vivo studies have previously shown that phenylalanine-based PEUs have nontoxic hydrolytic byproducts and tunable degradation times. Phenylalanine PEUs (poly(1-PHE-6)) have been further modified by tethering osteogenic growth peptide (OGP) to tyrosine-based monomer subunits. These OGP-tethered PEUs have been fabricated into porous scaffolds and c… Show more
“…In summary, we were able to manipulate HUVECs to attract or repel in response to different bioactive molecules and different spatial patterns. These examples add growing body of research illustrating the potential of ways to immobilize bioactive molecules to mimicry and study in vivo signaling that including sequestered growth factors [22], [23], [24], [25], [26], [27], [28], and cell-cell mimicry [12], [29] and multivalent signals [30], [31].Fig. 9 EphrinB2-Fc gradient repel HUVECs.…”
Bioactive signals play many important roles on cell function and behavior. In most biological studies, soluble biochemical cues such as growth factors or cytokines are added directly into the media to maintain and/or manipulate cell activities in vitro. However, these methods cannot accurately mimic certain in vivo biological signaling motifs, which are often immobilized to extracellular matrix and also display spatial gradients that are critical for tissue morphology. Besides biochemical cues, biophysical properties such as substrate stiffness can influence cell behavior but is not easy to manipulate under conventional cell culturing practices. Recent development in photocrosslinkable hydrogels provides new tools that allow precise control of spatial biochemical and biophysical cues for biological applications, but doing so requires a comprehensive study on various hydrogel photochemistry kinetics to allow thorough photocrosslink reaction while maintain protein bioactivities at the same time. In this paper, we studied several photochemistry reactions and evaluate key photochemical parameters, such as photoinitiators and ultra-violet (UV) exposure times, to understand their unique contributions to undesired protein damage and cell death. Our data illustrates the retention of protein function and minimize of cell health during photoreactions requires careful selection of photoinitiator type and concentration, and UV exposure times. We also developed a robust method based on thiol-norbornene chemistry for independent control of hydrogel stiffness and spatial bioactive patterns. Overall, we highlight a class of bioactive hydrogels to stiffness control and site specific immobilized bioactive proteins/peptides for the study of cellular behavior such as cellular attraction, repulsion and stem cell fate.
“…In summary, we were able to manipulate HUVECs to attract or repel in response to different bioactive molecules and different spatial patterns. These examples add growing body of research illustrating the potential of ways to immobilize bioactive molecules to mimicry and study in vivo signaling that including sequestered growth factors [22], [23], [24], [25], [26], [27], [28], and cell-cell mimicry [12], [29] and multivalent signals [30], [31].Fig. 9 EphrinB2-Fc gradient repel HUVECs.…”
Bioactive signals play many important roles on cell function and behavior. In most biological studies, soluble biochemical cues such as growth factors or cytokines are added directly into the media to maintain and/or manipulate cell activities in vitro. However, these methods cannot accurately mimic certain in vivo biological signaling motifs, which are often immobilized to extracellular matrix and also display spatial gradients that are critical for tissue morphology. Besides biochemical cues, biophysical properties such as substrate stiffness can influence cell behavior but is not easy to manipulate under conventional cell culturing practices. Recent development in photocrosslinkable hydrogels provides new tools that allow precise control of spatial biochemical and biophysical cues for biological applications, but doing so requires a comprehensive study on various hydrogel photochemistry kinetics to allow thorough photocrosslink reaction while maintain protein bioactivities at the same time. In this paper, we studied several photochemistry reactions and evaluate key photochemical parameters, such as photoinitiators and ultra-violet (UV) exposure times, to understand their unique contributions to undesired protein damage and cell death. Our data illustrates the retention of protein function and minimize of cell health during photoreactions requires careful selection of photoinitiator type and concentration, and UV exposure times. We also developed a robust method based on thiol-norbornene chemistry for independent control of hydrogel stiffness and spatial bioactive patterns. Overall, we highlight a class of bioactive hydrogels to stiffness control and site specific immobilized bioactive proteins/peptides for the study of cellular behavior such as cellular attraction, repulsion and stem cell fate.
“…As reported, most of the serum OGP is noncovalently bound to OGPBPs. Gavish et al [44] suggested a potential role of the α2 - Macroglobulin (α2M) in this process, as recently outlined in Policastro and Becker [45]. α2M is a major serum multifunctional protein that binds several regulatory polypeptides [46] and has been found in two conformations: a primary circulating form, referred to as the “native” form, and another one as the “activated” form.…”
Section: Literature Reviewmentioning
confidence: 99%
“…Policastro et al [45] successfully developed non-functionalized and functionalized phenylalanine-based poly(ester urea) porous scaffolds with various pore sizes. The phenylalanine PEUs (poly(1-Phe-6)) were modified by tethering osteogenic growth peptide (OGP) to tyrosine-based monomer subunits.…”
Bone regeneration is a process that involves several molecular mediators, such as growth factors, which directly affect the proliferation, migration and differentiation of bone-related cells. The osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP(10–14) have been shown to stimulate the proliferation, differentiation, alkaline phosphatase activity and matrix mineralization of osteoblastic lineage cells. However, the exact molecular mechanisms that promote osteoblastic proliferation and differentiation are not completely understood. This review presents the main chemical characteristics of OGP and/or OGP(10–14), and also discusses the potential molecular pathways induced by these growth factors to promote proliferation and differentiation of osteoblasts. Furthermore, since these peptides have been extensively investigated for bone tissue engineering, the clinical applications of these peptides for bone regeneration are discussed.
“…As was emphasized above, after the biodegradation of the AABB polymers very little or no local acidity causing inflammation is built up [39,40]. Therefore, these polymers are especially promising for constructing biodegradable micro and nanoscaled devices used as containers for drug delivery to tissues that are highly sensitive to acidic media.…”
Abstract:A systematic study of fabricating nanoparticles (NPs) by cost-effective polymer deposition/solvent displacement (nanoprecipitation) method has been carried out. Five amino acid based biodegradable (AABB) ester polymers (four neutral and one cationic), four organic solvents miscible with water, and eight surfactants were tested for the fabrication of the goal NPs. Depending on the nature of the AABB polymers, organic solvents and surfactants, as well as on the fabrication conditions, the size (Mean Particle Diameter) of the NPs could be tuned within 42 ÷ 398 nm, the zeta-potential within 12.5 ÷ +28 mV. The stability (resuspendability) of the NPs upon storage (at room temperature and refrigerated) was tested as well. In Vitro biocompatibility study of the NPs was performed with four different stable cell lines: A549, HeLa (human); RAW264.7, Hepa 1-6 (murine). Comparing the NPs parameters, their stability upon storage, and the data of biological examinations the best were found: As the AABB polymer, a poly(ester amide) composed of L-leucine, 1,6-hexanediol and sebacic acid-8L6, as a solvent (organic phase-DMSO), and as a surfactant, Tween 20.
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