Dataset Information

Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.

ABSTRACT: Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene hydrogel is functionalized with thiolated transforming growth factor (TGF-?1) and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated with a smaller population of mesenchymal stem cells, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. The co-encapsulated cells cleave the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly degraded materials show significantly increased glycosaminoglycan and collagen deposition over just 14 d of culture, while maintaining high levels of viability and producing a more widely-distributed matrix. These results indicate the potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications.

SUBMITTER: Sridhar BV

PROVIDER: S-EPMC4487633 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.

Sridhar Balaji V BV Brock John L JL Silver Jason S JS Leight Jennifer L JL Randolph Mark A MA Anseth Kristi S KS

Advanced healthcare materials 20150121 5

Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match th ...[more]

PMID: 25607633

Similar Datasets

Project description:UnlabelledPhotopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE.Statement of significanceDesigning synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an increase in mechanical properties. Nondestructive assays based on mechanical and ultrasonic properties were also investigated using a novel instrument and found to correlate with matrix deposition and evolution. In sum, this study presents a new hydrogel platform combined with nondestructive assessments, which together have potential for in vitro cartilage tissue engineering.

Project description:SignificanceArticular cartilage exhibits a zonal architecture, comprising three distinct zones: superficial, middle, and deep. Collagen fibers, being the main solid constituent of articular cartilage, exhibit unique angular and size distribution in articular cartilage zones. There is a gap in knowledge on how the unique properties of collagen fibers across articular cartilage zones affect the scattering properties of the tissue.AimThis study hypothesizes that the structural properties of articular cartilage zones affect its scattering parameters. We provide scattering coefficient and scattering anisotropy factor of articular cartilage zones in the spectral band of 400 to 1400 nm. We enumerate the differences and similarities of the scattering properties of articular cartilage zones and provide reasoning for these observations.ApproachWe utilized collimated transmittance and integrating sphere measurements to estimate the scattering coefficients of bovine articular cartilage zones and bulk tissue. We used the relationship between the scattering coefficients to estimate the scattering anisotropy factor. Polarized light microscopy was applied to estimate the depth-wise angular distribution of collagen fibers in bovine articular cartilage.ResultsWe report that the Rayleigh scatterers contribution to the scattering coefficients, the intensity of the light scattered by the Rayleigh and Mie scatterers, and the angular distribution of collagen fibers across tissue depth are the key parameters that affect the scattering properties of articular cartilage zones and bulk tissue. Our results indicate that in the short visible region, the superficial and middle zones of articular cartilage affect the scattering properties of the tissue, whereas in the far visible and near-infrared regions, the articular cartilage deep zone determines articular cartilage scattering properties.ConclusionThis study provides scattering properties of articular cartilage zones. Such findings support future research to utilize optical simulation to estimate the penetration depth, depth-origin, and pathlength of light in articular cartilage for optical diagnosis of the tissue.

Project description:Cartilage tissue engineering strategies often rely on hydrogels with fixed covalent crosslinks for chondrocyte encapsulation, yet the resulting material properties are largely elastic and can impede matrix deposition. To address this limitation, hydrazone crosslinked poly(ethylene glycol) hydrogels were formulated to achieve tunable viscoelastic properties and to study how chondrocyte proliferation and matrix deposition vary with the time-dependent material properties of covalent adaptable networks. Hydrazone equilibrium differences were leveraged to produce average stress relaxation times from hours (4.01 × 103 s) to months (2.78 × 106 s) by varying the percentage of alkyl-hydrazone (aHz) and benzyl-hydrazone (bHz) crosslinks. Swelling behavior and degradation associated with adaptability were characterized to quantify temporal network changes that can influence the behavior of encapsulated chondrocytes. After four weeks, mass swelling ratios varied from 36 ± 3 to 17 ± 0.4 and polymer retention ranged from 46 ± 4% to 92 ± 5%, with higher aHz content leading to loss of network connectivity with time. Hydrogels were formulated near the Flory-Stockmayer bHz percolation threshold (17% bHz) to investigate chondrocyte response to distinct levels of covalent architecture adaptability. Four weeks post-encapsulation, formulations with average relaxation times of 3 days (2.6 × 105s) revealed increased cellularity and an interconnected articular cartilage-specific matrix. Chondrocytes embedded in this adaptable formulation (22% bHz) deposited 190 ± 30% more collagen and 140 ± 20% more sulfated glycosaminoglycans compared to the 100% bHz control, which constrained matrix deposition to pericellular space. Collectively, these findings indicate that incorporating highly adaptable aHz crosslinks enhanced regenerative outcomes. However, connected networks containing more stable bHz bonds were required to achieve the highest quality neocartilaginous tissue. STATEMENT OF SIGNIFICANCE: Covalently crosslinked hydrogels provide robust mechanical support for cartilage tissue engineering applications in articulating joints. However, these materials traditionally demonstrate purely elastic responses to deformation despite the dynamic viscoelastic properties of native cartilage tissue. Here, we present hydrazone poly(ethylene glycol) hydrogels with tunable viscoelastic properties and study covalent adaptable networks for cartilage tissue engineering. Using hydrazone equilibrium and Flory-Stockmayer theory we identified average relaxation times leading to enhanced regenerative outcomes and showed that extracellular matrix deposition was biphasic as a function of the hydrazone covalent adaptability. We also showed that the incorporation of highly adaptable covalent crosslinks could improve cellularity of neotissue, but that a percolating network of more stable bonds was required to maintain scaffold integrity and form the highest quality neocartilaginous tissue.

Dataset Information

Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.

Publications

Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets