Impact of endotoxins in gelatine hydrogels on chondrogenic differentiation and inflammatory cytokine secretion<i>in vitro</i>

Groen, Wilhelmina M G A C; Utomo, Lizette; Castilho, Miguel; Gawlitta, Debby; Malda, Jos; Weeren, P. R. van; Levato, Riccardo; Korthagen, N.M.

doi:10.1101/2020.07.28.224451

Cited by 2 publications

(1 citation statement)

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“…While this exemplifies an elegant strategy to improve structural biomimicry in collagen/gelatin bioinks, researchers still struggle to meet regulatory constraints as these bioinks are still known to contain highly variable levels of endotoxins [141]. [115].…”

Section: Natural Materialsmentioning

confidence: 99%

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

et al. 2021

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Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.

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Section: Natural Materialsmentioning

confidence: 99%

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

et al. 2021

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The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

Korntner

Olijve³

et al. 2021

Biomolecules

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In the medical device sector, bloom index and residual endotoxins should be controlled, as they are crucial regulators of the device’s physicochemical and biological properties. It is also imperative to identify a suitable crosslinking method to increase mechanical integrity, without jeopardising cellular functions of gelatin-based devices. Herein, gelatin preparations with variable bloom index and endotoxin levels were used to fabricate non-crosslinked and polyethylene glycol succinimidyl glutarate crosslinked gelatin scaffolds, the physicochemical and biological properties of which were subsequently assessed. Gelatin preparations with low bloom index resulted in hydrogels with significantly (p < 0.05) lower compression stress, elastic modulus and resistance to enzymatic degradation, and significantly higher (p < 0.05) free amine content than gelatin preparations with high bloom index. Gelatin preparations with high endotoxin levels resulted in films that induced significantly (p < 0.05) higher macrophage clusters than gelatin preparations with low endotoxin level. Our data suggest that the bloom index modulates the physicochemical properties, and the endotoxin content regulates the biological response of gelatin biomaterials. Although polyethylene glycol succinimidyl glutarate crosslinking significantly (p < 0.05) increased compression stress, elastic modulus and resistance to enzymatic degradation, and significantly (p < 0.05) decreased free amine content, at the concentration used, it did not provide sufficient structural integrity to support cell culture. Therefore, the quest for the optimal gelatin crosslinker continues.

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Impact of endotoxins in gelatine hydrogels on chondrogenic differentiation and inflammatory cytokine secretionin vitro

Cited by 2 publications

References 61 publications

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

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