Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

Lee, Soah; Tong, Xinming; Yang, Fan

doi:10.1039/c5bm00256g

Cited by 81 publications

(59 citation statements)

References 29 publications

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“…To solve this problem, PEGTA was chosen to enhance mechanical property and stabilize the crosslinked matrix. Moreover, the increased branching of PEG molecules could further result in an improvement in the biomolecule diffusivity and pore size that would support better cell growth than linear PEG [48]. Multilayered coaxial nozzles consisting of two or three needles assembled concentrically were successfully fabricated for direct extrusion of perfusable tubes with consistent or varying diameters (Fig.…”

Section: Resultsmentioning

confidence: 99%

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

et al. 2016

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Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(-ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also have significant potentials in engineering large-scale vascularized tissue constructs towards applications in organ transplantation and repair.

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Section: Resultsmentioning

confidence: 99%

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

et al. 2016

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“…In addition, thiol–ene PEG hydrogels exhibit high cytocompatibility, precise spatiotemporal control of gelation, tunable degradation, and versatile modulation of biophysical and biochemical properties. The versatility of these hydrogels is demonstrated through extensive applications, ranging from protein and drug delivery, cartilage development, osteogenic differentiation, endothelial tubulogenesis, brain tumor models, synthetic matrix mimics, 2D culture substrates, and islet and cell encapsulation . However, these applications have been exclusively conducted in vitro, yielding little insight into the in vivo behavior of these hydrogels.…”

mentioning

confidence: 99%

Linkage Groups within Thiol–Ene Photoclickable PEG Hydrogels Control In Vivo Stability

Hunckler

Medina

Coronel

et al. 2019

Adv Healthcare Materials

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step-growth photopolymerization based on the orthogonal reaction between thiol and norbornene has emerged as an attractive strategy for many biomedical applications. [7,8] These step-growth photoinitiated (thiol-ene) hydrogels have shown great promise in 2D and 3D cell culture and organoid development, due, in part, to the low radical concentration and physiological pH required for crosslinking. [9] In addition, thiol-ene PEG hydrogels exhibit high cytocompatibility, precise spatiotemporal control of gelation, tunable degradation, and versatile modulation of biophysical and biochemical properties. The versatility of these hydrogels is demonstrated through extensive applications, ranging from protein and drug delivery, [10][11][12][13][14][15][16][17] cartilage development, [18,19] osteogenic differentiation, [20,21] endothelial tubulogenesis, [22] brain tumor models, [23] synthetic matrix mimics, [8,[24][25][26][27][28][29][30][31][32] 2D culture substrates, [33][34][35] and islet and cell encapsulation. [36][37][38][39][40][41][42][43] However, these applications have been exclusively conducted in vitro, yielding little insight into the in vivo behavior of these hydrogels. Our initial exploratory studies with these widely used 4-arm, ester-linked, thiol-ene PEG (PEG-4eNB) hydrogels implanted into the intraperitoneal space of mice unexpectedly showed that the hydrogels undergo rapid degradation in vivo ( Figure S1, Supporting Information). Hypothesizing that the poor in vivo stability may result from the hydrolysis of the ester linkage between the PEG backbone and norbornene functional end group, we replaced this connection with a more hydrolytically stable amide linkage. Here, we describe the characterization and implementation of 4-arm, amide-linked, thiol-ene PEG (PEG-4aNB) hydrogels that retain long-term stability in both in vitro and in vivo environments. We demonstrate rapid (<24 h) in vivo degradation of PEG-4eNB and gradual (>35 days) in vitro degradation. Conversely, PEG-4aNB retains long-term in vitro and in vivo stability while maintaining high cytocompatibility, and this material can be utilized as an appropriate replacement in many biomedical applications.The ester linkage in PEG hydrogels has been reported to be hydrolytically labile over the course of many weeks in cell culture. [44] This feature has been exploited further by introducing ester-containing poly(caprolactone) linkage groups to accelerate in vitro degradation of PEG hydrogels to within a Thiol-norbornene (thiol-ene) photoclickable poly(ethylene glycol) (PEG) hydrogels are a versatile biomaterial for cell encapsulation, drug delivery, and regenerative medicine. Numerous in vitro studies with these 4-arm ester-linked PEG-norbornene (PEG-4eNB) hydrogels demonstrate robust cytocompatibility and ability to retain long-term integrity with nondegradable crosslinkers. However, when transplanted in vivo into the subcutaneous or intraperitoneal space, these PEG-4eNB hydrogels with nondegradable crosslinkers rapidly degrade within 24 h. This char...

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“…For TEHV applications, PEG hydrogels are commonly fabricated by crosslinking PEGDA with exposure to UV or white light in the presence of their respective photoinitiators: 2‐hydroxy‐4′‐(2‐hydroxyethoxy)‐2‐methylpropiophenone (Irgacure 2925) for UV light, and triethanolamine, Eosin Y, and N ‐vinyl pyrrolidone for white light . PEGDA undergoes a rapid and random free radical propagation and termination, known as chain‐growth polymerization . This polymerization method results in a heterogeneous polymer network.…”

Section: Application Of Biomaterials To Heart Valve Tissue Engineeringmentioning

confidence: 99%

Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches

Nachlas

Davis

2017

Adv Healthcare Materials

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Tissue engineered heart valves (TEHVs) have the potential to address the shortcomings of current implants through the combination of cells and bioactive biomaterials that promote growth and proper mechanical function in physiological conditions. The ideal TEHV should be anti-thrombogenic, biocompatible, durable, and resistant to calcification, and should exhibit a physiological hemodynamic profile. In addition, TEHVs may possess the capability to integrate and grow with somatic growth, eliminating the need for multiple surgeries children must undergo. Thus, this review assesses clinically available heart valve prostheses, outlines the design criteria for developing a heart valve, and evaluates three types of biomaterials (decellularized, natural, and synthetic) for tissue engineering heart valves. While significant progress has been made in biomaterials and fabrication techniques, a viable tissue engineered heart valve has yet to be translated into a clinical product. Thus, current strategies and future perspectives are also discussed to facilitate the development of new approaches and considerations for heart valve tissue engineering.

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Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

Cited by 81 publications

References 29 publications

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

Linkage Groups within Thiol–Ene Photoclickable PEG Hydrogels Control In Vivo Stability

Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches

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