Injectable nanocomposite cryogels for versatile protein drug delivery

Koshy, Sandeep T.; Zhang, David; Grolman, Joshua M.; Stafford, Alexander; Mooney, David J.

doi:10.1016/j.actbio.2017.11.024

Cited by 140 publications

(102 citation statements)

References 34 publications

(46 reference statements)

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“…The Mooney group followed up with a similar hydrogel system in 2018 to deliver BDC peptide antigens to dendritic cells to induce regulatory T cells via two methods: i) encapsulated in PLG microparticles within the gel or ii) directly conjugated to the alginate gel . In the same year, the authors developed a photoclickable alginate gel containing laponite (a charged nanocomposite on which proteins can adsorb) for the prolonged release of cytokines, reducing burst release effects and extending their release over several weeks …”

Section: Macroscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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Section: Macroscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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“…Currently, the controlled release of proteins has been regarded as a key to maximize the therapeutic effect of growth factors. To generate a controlled release system, diverse kinds of hydrogels or cryogels were applied to protein delivery to increase immobilization and localization of proteins . Herein, we used heparin as one of the biomaterials of cryogels to support VEGF‐ADSCs offering enhanced captivity of VEGF through heparin's specific binding affinity to VEGF.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Effects of VEGF‐Overexpressed Human Adipose‐Derived Stem Cells with Whitlockite Reinforced Cryogel for Bone Regeneration

Kim

Lee

Kim

et al. 2019

Macromolecular Bioscience

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Bone is a vascularized tissue that is comprised of collagen fibers and calcium phosphate crystals such as hydroxyapatite (HAp) and whitlockite (WH). HAp and WH are known to elicit bone regeneration by stimulating osteoblast activities and osteogenic commitment of stem cells. In addition, vascular endothelial growth factor (VEGF) is shown to promote osteogenesis and angiogenesis which is considered as an essential process in bone repair by providing nutrients. In this study, VEGF-secreting human adipose-derived stem cells (VEGF-ADSCs) are developed by transducing ADSCs with VEGF-encoded lentivirus. Additionally, WH-reinforced gelatin/heparin cryogels (WH-C) are fabricated by loading WH into gelatin/heparin cryogels. VEGF-ADSC secrete tenfold more VEGF than ADSC and show increased VEGF secretion with cell growth. Also, incorporation of WH into cryogels provides a mineralized environment with ions secreted from WH. When the VEGF-ADSCs are seeded on WH-C, sustained release of VEGF is observed due to the specific affinity of VEGF to heparin. Finally, the synergistic effect of VEGF-ADSC and WH on osteogenesis is successfully confirmed by alkaline phosphatase and real-time polymerase chain reaction analysis. In vivo bone formation is demonstrated via implantation of VEGF-ADSC seeded WH-C into mouse calvarial bone defect model, resulted in enhanced bone development with the highest bone volume/total volume.

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“…Moreover, cryogels could be made using biopolymers with intrinsic antimicrobial activity, such as chitosan (Khan et al, 2019). Koshy et al (2018) demonstrated that injectable cryogel is able to incorporate and release various molecules to mediate their biological activities. Based on published data of the anti-inflammatory and prohealing properties of IL-10 and TGF-β as well as the angiogenic and regenerative properties of VEGF and FGF, these growth factors and cytokines (GF/C) were used in the current study.…”

Section: Introductionmentioning

confidence: 99%

Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration

Jimi

Jaguparov

Nurkesh

et al. 2020

Front. Bioeng. Biotechnol.

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Growth factors and cytokines that are secreted by cells play a crucial role in the complex physiological reaction to tissue injury. The ability to spatially and temporally control their actions to maximize regenerative benefits and minimize side effects will help accelerate wound healing and improve tissue regeneration. In this study, the sequential targeted delivery of growth factor/cytokine combinations with regulatory functions on inflammation and tissue regeneration was examined using an internal splint wound healing model. Four examined growth factors and cytokines were effectively incorporated into a novel chitosan-based cryogel, which offered a controlled and sustained release of all factors while maintaining their biological activities. The cryogels incorporated with inflammation modulatory factors (IL-10 and TGF-β) and with wound healing factors (VEGF and FGF) were placed on the wound surface on day 0 and day 3, respectively, after wound initiation. Although wound area gradually decreased in all groups over time, the area in the cryogel group with growth factor/cytokine combinations was significantly reduced starting on day 7 and reached about 10% on day 10, as compared to 60-65% in the control groups. Sequential delivery of inflammation modulatory and wound healing factors enhanced granulation tissue formation, as well as functional neovascularization, leading to regenerative epithelialization. Collectively, the chitosan-based cryogel can serve as a controlled release system for sequential delivery of several growth factors and cytokines to accelerate tissue repair and regeneration.

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Injectable nanocomposite cryogels for versatile protein drug delivery

Cited by 140 publications

References 34 publications

Materials for Immunotherapy

Materials for Immunotherapy

Osteogenic Effects of VEGF‐Overexpressed Human Adipose‐Derived Stem Cells with Whitlockite Reinforced Cryogel for Bone Regeneration

Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration

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