Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing

Sivaraj, Dharshan; Chen, Kellen; Chattopadhyay, Arhana; Henn, Dominic; Wu, Wanling; Noishiki, Chikage; Magbual, Noah J.; Mittal, Smiti; Mermin-Bunnell, Alana M.; Bonham, Clark A.; Trotsyuk, Artem A.; Barrera, Janos A.; Padmanabhan, Jagannath; Januszyk, Michael; Gurtner, Geoffrey C.

doi:10.3389/fbioe.2021.660145

Cited by 74 publications

(61 citation statements)

References 128 publications

(204 reference statements)

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“…Since our numerical model enables the investigation of tensile stress as well as elastic coefficient for different fibrinogen concentrations, calculated elastic coefficients of fibrin clots with specific fibrinogen concentrations based on blood samples would provide additional bioengineering insights in the diagnosis of thromboembolism. While nonlinear mechanical properties of fibrin clots can be useful in bioengineering applications not only in wound repair but also drug delivery, cell delivery, cell differentiation, tissue engineering and patterning [ 59 , 64 , 65 ]. Our numerical model will gain insights into their designs, in terms of mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation

Takeishi

Shigematsu

Enosaki

et al. 2021

J. R. Soc. Interface.

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Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. It is theorized that the mechanical effect of the fibrin clot is caused by the polymeric protofibrils between crosslinks, or to their dynamics on a nanoscale order. Despite a number of studies, however, it is still unknown, how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. A mesoscopic framework would be useful to tackle this multi-scale problem, but it has not yet been established. We thus propose a minimal mesoscopic model for protofibrils based on Brownian dynamics, and performed numerical simulations of protofibril aggregation. We also performed stretch tests of polymeric protofibrils to quantify the elasticity of fibrin clots. Our model results successfully captured the conformational properties of aggregated protofibrils, e.g., strain-hardening response. Furthermore, the results suggest that the bending stiffness of individual protofibrils increases to resist extension.

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Section: Discussionmentioning

confidence: 99%

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation

Takeishi

Shigematsu

Enosaki

et al. 2021

J. R. Soc. Interface.

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“…Scaffold porosity is also responsible for facilitating cell survival and proliferation [ 129 ]. The extent of secretion of ECM also is enhanced by increasing porosity [ 128 , 130 ]. Tan et al incorporated different concentrations of starch-based nanospheres (SNs) (0.25 to 1.0 g/g of NIPAM) into the structure of thermoresponsive PNIPAm hydrogels (TPHs) [ 131 ].…”

Section: Tuning Scaffolding Propertiesmentioning

confidence: 99%

Tuning the Properties of PNIPAm-Based Hydrogel Scaffolds for Cartilage Tissue Engineering

Rana

Siegler

2021

Polymers

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Poly(N-isopropylacrylamide) (PNIPAm) is a three-dimensional (3D) crosslinked polymer that can interact with human cells and play an important role in the development of tissue morphogenesis in both in vitro and in vivo conditions. PNIPAm-based scaffolds possess many desirable structural and physical properties required for tissue regeneration, but insufficient mechanical strength, biocompatibility, and biomimicry for tissue development remain obstacles for their application in tissue engineering. The structural integrity and physical properties of the hydrogels depend on the crosslinks formed between polymer chains during synthesis. A variety of design variables including crosslinker content, the combination of natural and synthetic polymers, and solvent type have been explored over the past decade to develop PNIPAm-based scaffolds with optimized properties suitable for tissue engineering applications. These design parameters have been implemented to provide hydrogel scaffolds with dynamic and spatially patterned cues that mimic the biological environment and guide the required cellular functions for cartilage tissue regeneration. The current advances on tuning the properties of PNIPAm-based scaffolds were searched for on Google Scholar, PubMed, and Web of Science. This review provides a comprehensive overview of the scaffolding properties of PNIPAm-based hydrogels and the effects of synthesis-solvent and crosslinking density on tuning these properties. Finally, the challenges and perspectives of considering these two design variables for developing PNIPAm-based scaffolds are outlined.

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“…In addition, hydrogels are presented as an advantageous matrix for CAT immobilization preserving its three-dimensional structure. Hydrogels including gelatin and alginate have been disclosed as ideal physicochemical mimetic biological scaffolds that can be used as a delivery vehicle for wound healing, as they can maintain a moist environment, absorb wound exudates, and fight bacteria (Sivaraj et al 2021 ; Zhang et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant-biocompatible and stable catalase-based gelatin–alginate hydrogel scaffold with thermal wound healing capability: immobilization and delivery approach

et al. 2022

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Hydrogel-based matrix prepared using biopolymers is a new frontier of emerging platforms for enzyme immobilization for biomedical applications. Catalase (CAT) delivery can be effective in inhibiting reactive oxygen species (ROS)-mediated prolongation of the wound healing process. In this study, to improve CAT stability for effective application, gelatin(Gel)–alginate (Alg) biocompatible hydrogel (Gel–Alg), as immobilization support, was prepared using calcium chloride as an ionic cross-linker. High entrapment efficiency of 92% was obtained with 2% Gel and 1.5% Alg. Hydrogel immobilized CAT (CAT–Gel–Alg) showed a wide range of pH from 4 to 9 and temperature stability between 20 to 60 °C, compared to free CAT. CAT–Gel–Alg kinetic parameters revealed an increased Km (24.15 mM) and a decreased Vmax (1.39 µmol H2O2/mg protein min) × 104. CAT–Gel–Alg retained 52% of its original activity after 20 consecutive catalytic runs and displayed improved thermal stability with a higher t1/2 value (half-life of 100.43 vs. 46 min). In addition, 85% of the initial activity was maintained after 8 weeks’ storage at 4 °C. At 24 h after thermal injury, a statistically significant difference in lesion sizes between the treated group and the control group was reported. Finally, our findings suggest that the superior CAT–Gel–Alg stability and reusability are resonant features for efficient biomedical applications, and ROS scavenging by CAT in the post-burn phase offers protection for local treatment of burned tissues with encouraging wound healing kinetics.

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Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing

Cited by 74 publications

References 128 publications

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation

Tuning the Properties of PNIPAm-Based Hydrogel Scaffolds for Cartilage Tissue Engineering

Antioxidant-biocompatible and stable catalase-based gelatin–alginate hydrogel scaffold with thermal wound healing capability: immobilization and delivery approach

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