Using chondroitin sulfate to improve the viability and biosynthesis of chondrocytes encapsulated in interpenetrating network (IPN) hydrogels of agarose and poly(ethylene glycol) diacrylate

Ingavle, Ganesh; Dormer, Nathan H.; Gehrke, Stevin H.; Detamore, Michael S.

doi:10.1007/s10856-011-4499-9

Cited by 49 publications

(59 citation statements)

References 45 publications

(42 reference statements)

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“…Moreover, DVC consistently outperformed all TGF-b 3 -exposed groups in aggrecan and collagen II gene expression, which may present significant advantages in cost and regulatory approval of chondroinductive strategies for cartilage regeneration because of eliminating the need for costly growth factors. 41 Certainly, future work will need to address improving the mechanical properties of these networks, whereby choosing a higher mechanically performing hydrogel, such as an interpenetrating network hydrogel, [42][43][44][45][46] could be considered. In addition, overall matrix production will need to be addressed, where in vivo studies will be paramount because immunogenicity as well as how biomechanical stimulation of DCC and DVC may affect chondroinductivity and therefore, hyaline-like cartilage regeneration can be tested.…”

Section: Discussionmentioning

confidence: 99%

Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

Beck

Barragan

Libeer

et al. 2016

Tissue Engineering Part A

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Hydrogel precursors are liquid solutions that are prone to leaking after surgical placement. This problem was overcome by incorporating either decellularized cartilage (DCC) or devitalized cartilage (DVC) microparticles into traditional photocrosslinkable hydrogel precursors in an effort to achieve a paste-like hydrogel precursor. DCC and DVC were selected specifically for their potential to induce chondrogenesis of stem cells, given that materials that are chondroinductive on their own without growth factors are a revolutionary goal in orthopedic medicine. We hypothesized that DVC, lacking the additional chemical processing steps in DCC to remove cell content, would lead to a more chondroinductive hydrogel with rat bone marrow-derived mesenchymal stem cells. Hydrogels composed of methacrylated hyaluronic acid (MeHA) and either DCC or DVC microparticles were tested with and without exposure to transforming growth factor (TGF)-b 3 over a 6 week culture period, where swelling, mechanical analysis, and gene expression were observed. For collagen II, Sox-9, and aggrecan expression, MeHA precursors containing DVC consistently outperformed the DCC-containing groups, even when the DCC groups were exposed to TGF-b 3 . DVC consistently outperformed all TGF-b 3 -exposed groups in aggrecan and collagen II gene expression as well. In addition, when the same concentrations of MeHA with DCC or DVC microparticles were evaluated for yield stress, the yield stress with the DVC microparticles was 2.7 times greater. Furthermore, the only MeHA-containing group that exhibited shape retention was the group containing DVC microparticles. DVC appeared to be superior to DCC in both chondroinductivity and rheological performance of hydrogel precursors, and therefore DVC microparticles may hold translational potential for cartilage regeneration.

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Section: Discussionmentioning

confidence: 99%

Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

Beck

Barragan

Libeer

et al. 2016

Tissue Engineering Part A

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“…Instead, a 'raw materials' approach was taken whereby natural materials are leveraged both as building blocks to be incorporated into regenerating tissue and as signaling molecules to elicit desirable responses from infiltrating cells [40]. Our previous studies have demonstrated favorable cell responses to chondroitin sulfate [20,[41][42], and β-TCP is a well-known building block for bone regeneration, which is more easily integrated into regenerating bone than the hydroxyapatite we have used in our previous microsphere-based scaffold studies [10,35,43].…”

Section: Discussionmentioning

confidence: 99%

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

et al. 2015

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Background:The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture.

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“…A rigid, brittle network interpenetrated with a softer, more ductile network is theorised to serve as the key to enhanced mechanical performance in composite IPN gels. In addition, Ingavle et al [11][12][13][14] recently applied 2-hydroxyethyl agarose-poly(ethylene glycol) diacrylate (PEG-DA) IPN hydrogels to cartilage tissue engineering and showed that it was possible to encapsulate viable cells and provide a significant improvement in mechanical performance relative to the two constituent hydrogels. Previous studies of 2-hydroxyethyl agarose/PEG-DA IPNs showed improvement in mechanical performance compared to both single networks, but it can be further improved by increasing the concentration of either first or second network and the molecular weight (MW) of PEG-DA while still maintaining cell performance.…”

Section: -10mentioning

confidence: 99%

Biomineralised interpenetrating network hydrogels for bone tissue engineering

Ingavle

Avadhanam

Zheng

et al. 2016

Bioinspired, Biomimetic and Nanobiomaterials

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Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but their use is limited by inadequate mechanical strength and poor biocompatibility. In this study, to better mimic the mineral component and the mechanical strength of natural bone, two biocompatible materials, 2-hydroxyethyl agarose and poly (ethylene glycol) diacrylate, were combined with nanocrystalline hydroxyapatite (nHAp)-coated poly(lactic-co-glycolic acid) (PLGA) microspheres. A novel composite interpenetrating network (IPN) hydrogel scaffold was created to investigate its mechanical and osteoconductive performance for bone tissue engineering-related applications.The inclusion of nHAp-coated PLGA microspheres in an IPN hydrogel led to an increase in compressive modulus.In the absence of nHAp-coated microspheres, cell viability dropped to 59·1% at 3 weeks post-encapsulation.However, by incorporating nHAp-coated microspheres, cell viability improved to 80·6%. The capacity of composite IPN hydrogels to promote bone formation in cell culture was assessed. In the presence of mineralised microspheres, a composite IPN gel showed a significant increase in alkaline phosphatase activity and calcium (Ca) deposition following 3 weeks of incubation when compared with plain IPNs. This technology may be also applied to other cellbased applications where the improved mechanical integrity and osteoconductivity of cell-containing IPN hydrogels may be used to mimic bone tissue replacement.

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Using chondroitin sulfate to improve the viability and biosynthesis of chondrocytes encapsulated in interpenetrating network (IPN) hydrogels of agarose and poly(ethylene glycol) diacrylate

Cited by 49 publications

References 45 publications

Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

Biomineralised interpenetrating network hydrogels for bone tissue engineering

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