Fabrication of Cell-Laden Macroporous Biodegradable Hydrogels with Tunable Porosities and Pore Sizes

Wang, Limin; Lu, Shuaiyao; Lam, Johnny; Kasper, F. Kurtis; Mikos, Antonios G.

doi:10.1089/ten.tec.2014.0224

Cited by 21 publications

(21 citation statements)

References 53 publications

(65 reference statements)

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“…76 Recently, Wang et al proposed uncrosslinked gelatin microspheres as porogen agent. Gelatin microsphere can be incorporated in the hydrogel at room temperature but they dissolve in non-cytotoxic products at 37°C, allowing to control porosity and pore size in cell-laden hydrogels without affecting cell viability.…”

Section: Hydrogels: Suitable Micro-environments For Btementioning

confidence: 99%

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

et al. 2017

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Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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Section: Hydrogels: Suitable Micro-environments For Btementioning

confidence: 99%

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

et al. 2017

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“…16, 31 To prepare the OPF precursor solution, 50 mg of OPF and 25 mg of PEG-diacrylate (3,400 Da, Laysan Bio) were dissolved in 112.5 μL PBS and set at room temperature for 45 min to eliminate air bubbles. 23 μL each of radical initiators, 0.3 M ammonium persulfate (APS) and 0.3 M N,N,N’,N’-tetramethylethylenediamine (TEMED), were then mixed into the polymer solution and vortexed.…”

Section: Methodsmentioning

confidence: 99%

“…The concentrations of APS and TEMED used were expected to have minimal cytotoxic effects and allow for high viability of encapsulated cells in OPF-based hydrogels following fabrication. 10, 31 After 30 seconds, 100 μL PBS or cell suspension (6 × 10 6 MSCs) were added followed by the MSC-GMPs or blank GMPs, respectively. The solution was mixed carefully to create a homogenous distribution of GMPs and to avoid the formation of bubbles.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite

Lee

Lam

et al. 2016

Ann Biomed Eng

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Due to the lack of cell-adhesive moieties in traditional synthetic hydrogels, the present work investigated the use of degradable gelatin microparticles (GMPs) as temporary adherent substrates for anchorage-dependent mesenchymal stem cells (MSCs). MSCs were seeded onto GMPs of varying crosslinking densities and sizes to investigate their role on influencing MSC differentiation and aggregation. The MSC-seeded GMPs were then encapsulated in poly(ethylene glycol)-based hydrogels and cultured in serum-free, growth factor-free osteochondral medium. Non-seeded MSCs co-encapsulated with GMPs in the hydrogels were used as a control for comparison. Over the course of 35 days, MSC-seeded GMPs exhibited more cell-cell contacts, greater chondrogenic potential, and a down-regulation of osteogenic markers compared to the controls. Although the factors of GMP crosslinking and size had nominal influence on MSC differentiation and aggregation, GMPs demonstrate potential as an adherent-substrate for improving cell delivery from hydrogel scaffold by facilitating cell-cell contacts and improving MSC differentiation.

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“…Inspired by the porogen leaching method used to fabricate conventional scaffolds [18] , recent studies have explored the use of degradable hydrogels as porogens to introduce macroporosity in situ, such as gelatin hydrogels that undergo a gel-sol transition below 37 °C [54] and alginate hydrogels crosslinked by Ca 2+ that are cleared by calcium chelators (e.g. EDTA).…”

Section: New Strategies To Overcome Challenges Associated With Currenmentioning

confidence: 99%

“…[54c] Degradable hydrogels are also used, such as hydrogels formed from oxidized alginate that undergo rapid hydrolytic degradation [55] and hyaluronic acid hydrogels that are degraded by hyaluronidase. [54c] Using these cell-compatible porogen leaching methods, cells and micron-sized porogens can be loaded into the hydrogels and injected. Macroporosity is introduced after ‘leaching’ of the porogens post-transplantation.…”

Section: New Strategies To Overcome Challenges Associated With Currenmentioning

confidence: 99%

Recent Progress in Developing Injectable Matrices for Enhancing Cell Delivery and Tissue Regeneration

Tong

Yang

2017

Adv Healthcare Materials

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Biomaterials are key factors in regenerative medicine. Matrices used for cell delivery are especially important, as they provide support to transplanted cells that is essential for promoting cell survival, retention, and desirable phenotypes. Injectable matrices have become promising and attractive due to their minimum invasiveness and ease of use. Conventional injectable matrices mostly use hydrogel precursor solutions that form solid, cell-laden hydrogel scaffolds in situ. However, these materials are associated with challenges in biocompatibility, shear-induced cell death, lack of control over cellular phenotype, lack of macroporosity and remodeling, and relatively weak mechanical strength. This Progress Report provides a brief overview of recent progress in developing injectable matrices to overcome the limitations of conventional in situ hydrogels. Biocompatible chemistry and shear-thinning hydrogels have been introduced to promote cell survival and retention. Emerging investigations of the effects of matrix properties on cellular function in 3D provide important guidelines for promoting desirable cellular phenotypes. Moreover, several novel approaches are combining injectability with macroporosity to achieve macroporous, injectable matrices for cell delivery.

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Fabrication of Cell-Laden Macroporous Biodegradable Hydrogels with Tunable Porosities and Pore Sizes

Cited by 21 publications

References 53 publications

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite

Recent Progress in Developing Injectable Matrices for Enhancing Cell Delivery and Tissue Regeneration

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