Biodegradable, <i>in Situ</i>-Forming Cell-Laden Hydrogel Composites of Hydroxyapatite Nanoparticles for Bone Regeneration

Watson, Brendan M.; Vo, Tiffany N.; Engel, Paul S.; Mikos, Antonios G.

doi:10.1021/acs.iecr.5b01388

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…Little red staining was observed due to interfering autofluorescence from the degrading composite gel, a phenomenon which has been observed in hydrogels of similar composition. [18, 27] More viable cells were qualitatively observed at the last timepoint with a high seeding density.…”

Section: Resultsmentioning

confidence: 99%

Effects of cellular parameters on thein vitroosteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels

Tabata

Mikos

2016

Journal of Biomaterials Science, Polymer Edition

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This work investigated the effects of cellular encapsulation density and differentiation stage on the osteogenic capacity of injectable, dual physically and chemically gelling hydrogels comprised of thermogelling macromers and polyamidoamine crosslinkers. Undifferentiated and osteogenically predifferentiated mesenchymal stem cells (MSCs) were encapsulated within 20 wt% composite hydrogels with gelatin microparticles at densities of 6 or 15 million cells/mL. We hypothesized that a high encapsulation density and predifferentiation would promote increased cellular interaction and accelerate osteogenesis, leading to enhanced osteogenic potential in vitro. Hydrogels were able to maintain the viability of the encapsulated cells over a period of 28 days, with the high encapsulation density and predifferentiation group possessing the highest DNA content at all timepoints. Early alkaline phosphatase activity and mineralization were promoted by encapsulation density, whereas this effect by predifferentiation was only observed in the low seeding density groups. Both parameters only demonstrated short-lived effects when examined independently, but jointly led to greater levels of alkaline phosphatase activity and mineralization. The combined effects suggest that there may be optimal encapsulation densities and differentiation periods that need to be investigated to improve MSCs for biomaterials-based therapeutics in bone tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Effects of cellular parameters on thein vitroosteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels

Tabata

Mikos

2016

Journal of Biomaterials Science, Polymer Edition

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“…The hydrogel mineralization was supported by the combination of the encapsulated MSCs. This type of systems promotes and gives a very potential platform for the in situ forming nanocomposite hydrogels which simultaneously promote the cell delivery as well as mineralization which is the most important condition for craniofacial bone tissue engineering [81].…”

Section: Application Of Injectable Gels As On-demand Drug Release Sysmentioning

confidence: 99%

Bioresponsive Injectable Hydrogels for On-demand Drug Release and Tissue Engineering

Vashist

Alexis

Jayant

et al. 2017

CPD

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The emergence of injectable hydrogels as biomaterials has been a revolutionary breakthrough in the field of on-demand drug delivery and tissue engineering. The promising features of these systems include their biodegradability, biocompatibility, permeability, ease of the surgical implantation, and most importantly exhibit minimally invasiveness. These hydrogels have been explored as sustained and on-demand release carriers for the various bioactive agents, growth factors, live cells, various hydrophobic drugs and as extracellular matrices for tissue engineering. Present review is an attempt to highlight the recent systems explored for on-demand drug release and tissue engineering. It also gives an overview of the role of nanotechnology in the advancements of injectable hydrogels. The future prospects and challenges of these hydrogels have also been addressed.

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“…Driving osteogenic differentiation purely by the scaffold, and without the inclusion of exogenous factors is appealing. Inclusion of calcium phosphate or hydroxyapatite particles, or the formation of a composite with these, has been shown to facilitate mineralization and induce osteogenic differentiation [77]. Wu et al [78] created inorganic polyphosphate chain-functionalized hyaluronic acid hydrogels.…”

Section: Osteoinductive Moietiesmentioning

confidence: 99%

Engineering Approaches for Understanding Osteogenesis: Hydrogels as Synthetic Bone Microenvironments

Shapiro

Oyen

2016

Horm Metab Res

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The microenvironment, which can be considered the sum of all the components and conditions surrounding a particular cell, is critical to moderating cellular behavior. In bone, interactions with the microenvironment can influence osteogenic differentiation, and subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs, can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic polymer networks, are popularly used for cell culture constructs due to their substantial water content and their ability to be tailored for specific applications. As synthetic microenvironments, a level of control can be exerted on the hydrogel structure and material properties, such that individual contributions from the scaffold on cellular behavior can be observed. Both biochemical and mechanical stimuli have been shown to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive ligands, include osteoinductive moieties, vary mechanical properties, and be subject to external mechanical stimulation, all of which have been shown to affect osteogenic differentiation. Following "bottom-up" fabrication methods, levels of complexity can be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic bone microenvironments to observe both individual and synergistic effects from biochemical and mechanical signals on osteogenic differentiation. Ultimately, a better understanding of how material properties can influence cellular behavior will better inform design of tissue engineering scaffolds, not just for studying cell behavior, but also for regenerative medicine purposes.

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Biodegradable, in Situ-Forming Cell-Laden Hydrogel Composites of Hydroxyapatite Nanoparticles for Bone Regeneration

Cited by 12 publications

References 15 publications

Effects of cellular parameters on thein vitroosteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels

Effects of cellular parameters on thein vitroosteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels

Bioresponsive Injectable Hydrogels for On-demand Drug Release and Tissue Engineering

Engineering Approaches for Understanding Osteogenesis: Hydrogels as Synthetic Bone Microenvironments

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