Tissue geometry drives deterministic organoid patterning Gjorevski, N; Nikolaev, M; Brown, T E ...
Science (American Association for the Advancement of Science),
2022-Jan-07, 2022-01-07, 20220107, Volume:
375, Issue:
6576
Journal Article
Peer reviewed
Open access
Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they ...self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.
Poly(ethylene glycol) (PEG) hydrogels were investigated as encapsulation matrices for osteoblasts to assess their applicability in promoting bone tissue engineering. Non-adhesive hydrogels were ...modified with adhesive Arg-Gly-Asp (RGD) peptide sequences to facilitate the adhesion, spreading, and, consequently, cytoskeletal organization of rat calvarial osteoblasts. When attached to hydrogel surfaces, the density and area of osteoblasts attached were dramatically different between modified and unmodified hydrogels. A concentration dependence of RGD groups was observed, with increased osteoblast attachment and spreading with higher RGD concentrations, and cytoskeleton organization was seen with only the highest peptide density. A majority of the osteoblasts survived the photoencapsulation process when gels were formed with 10% macromer, but a decrease in osteoblast viability of ∼25% and 38% was seen after 1 day of in vitro culture when the macromer concentration was increased to 20 and 30
wt%, respectively. There was no statistical difference in cell viability when peptides were added to the network. Finally, mineral deposits were seen in all hydrogels after 4 weeks of in vitro culture, but a significant increase in mineralization was observed upon introduction of adhesive peptides throughout the network.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Poly(ethylene glycol) hydrogels were synthesized with pendant peptide functionalities to examine the influence of synergistic peptide sequences on osteoblast adhesion, spreading, and function. ...Specifically, acrylated monomers were prepared that contained the peptide sequence, Arg–Gly Asp (RGD), as well as monomers with RGD plus its synergy site, Pro–His–Ser–Arg–Asn (PHSRN), linked via a polyglycine sequence to recapitulate the native spacing of fibronectin. The colocalized RGD–PHSRN sequence improved osteoblast adhesion, spreading, and focal contact formation when compared to RGD alone. In addition, proliferation, metabolic activity, and levels of alkaline phosphatase production, a common marker for osteoblast function, were statistically higher for the colocalized peptide sequences at 1 day, 1 week, and 2 weeks, when compared to control surfaces. Interestingly, increases were not observed in all areas of cell function, as extracellular matrix (ECM) production was the lowest on gels functionalized with the colocalized peptide sequence. This result was attributed to strong receptor–ligand interactions initiating signal transduction cascades that down-regulate ECM production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Polyethylene glycol (PEG) hydrogels are widely used in a variety of biomedical applications, including matrices for controlled release of biomolecules and scaffolds for regenerative medicine. The ...design, fabrication, and characterization of PEG hydrogels rely on the understanding of fundamental gelation kinetics as well as the purpose of the application. This review article will focus on different polymerization mechanisms of PEG-based hydrogels and the importance of these biocompatible hydrogels in regenerative medicine applications. Furthermore, the design criteria that are important in maintaining the availability and stability of the biomolecules as well as the mechanisms for loading of biomolecules within PEG hydrogels will also be discussed. Finally, we overview and provide a perspective on some of the emerging novel design and applications of PEG hydrogel systems, including the spatiotemporal-controlled delivery of biomolecules, hybrid hydrogels, and PEG hydrogels designed for controlled stem cell differentiation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Degradable thiol-acrylate photopolymers are a new class of biomaterials capable of rapidly polymerizing under physiological conditions upon exposure to UV light, with or without added ...photoinitiators, and to depths exceeding 10
cm. These materials are formed in situ, and the versatility of their chemistry affords a high degree of control over the final material properties. For example, variations in monomer mole fractions directly affect the final network molecular structure, varying the time required to achieve complete mass loss from 25 to 100 days, the molecular weight distributions of the degradation products, and the swelling ratios and compressive moduli throughout degradation. Additionally, varying the mole fraction of multifunctional thiol monomer in the initial reaction mixture controls the concentration of reactive sites in the network available for post-polymerization modification of the polymer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
The thickness of human articular cartilage has been reported to vary from less than 0.5 up to 7
mm. Hence, tissue engineered cartilage scaffolds should be able to span the thickness of native ...cartilage to fill defects of all shapes and sizes. In this study, we demonstrate the potential for using photopolymerization technology to encapsulate chondrocytes in poly(ethylene oxide) hydrogels, which vary in thickness from 2 to 8
mm. Chondrocytes, encapsulated in an 8
mm thick, photocrosslinked hydrogel and cultured in vitro for 6 weeks, remained viable and produced cartilaginous tissue throughout the construct comparable to a 2
mm thick gel as seen both histologically and biochemically. In addition, the total collagen and glycosaminoglycan contents per wet weight of the 8
mm thick cell-polymer construct were 0.13±0.01 and 0.25±0.03%, respectively, and did not vary significantly as a function of spatial position in the construct. The histological evidence and the biochemical content were similar in all constructs of varying thickness. The results suggest that photocrosslinked hydrogels are promising scaffolds for tissue engineering cartilage as cell viability is readily maintained; uniform cell seeding is easy to achieve; and the biochemical content of the extracellular matrix is not compromised as the scaffold thickness is increased from 2 to 8
mm.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Craniofacial injuries require a variety of different cell types to repopulate areas of bone, cartilage, tendon, and fat. Mesenchymal stem cells (MSCs) provide a multipotent cell source for tissue ...engineering of this area, particularly when the cells are delivered via a 3D hydrogel environment. MSC differentiation into cartilage, bone, and fat has been investigated through a variety of techniques, some of which include the use of synthetic hydrogel scaffolds, integration of extracellular matrix components and other natural gel chemistries, microparticle delivery of growth factors, simultaneous mechanical stimulation, and the delivery of microRNA. This review aims to summarize the most recent studies involving the synthesis and application of 3D hydrogels to induce the differentiation of encapsulated MSCs and their subsequent matrix production.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Progress in material design for biomedical applications Tibbitt, Mark W; Christopher B. Rodell; Jason A. Burdick ...
Proceedings of the National Academy of Sciences - PNAS,
11/2015, Volume:
112, Issue:
47
Journal Article
Peer reviewed
Open access
Biomaterials that interface with biological systems are used to deliver drugs safely and efficiently; to prevent, detect, and treat disease; to assist the body as it heals; and to engineer functional ...tissues outside of the body for organ replacement. The field has evolved beyond selecting materials that were originally designed for other applications with a primary focus on properties that enabled restoration of function and mitigation of acute pathology. Biomaterials are now designed rationally with controlled structure and dynamic functionality to integrate with biological complexity and perform tailored, high-level functions in the body. The transition has been from permissive to promoting biomaterials that are no longer bioinert but bioactive. This perspective surveys recent developments in the field of polymeric and soft biomaterials with a specific emphasis on advances in nano- to macroscale control, static to dynamic functionality, and biocomplex materials.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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