ArticleEuropean cells & materials2020
Crosslinker concentration controls TGFβ-3 release and annulus fibrosus cell apoptosis in genipin-crosslinked fibrin hydrogels.
Article in European cells & materials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- The Functional Role of Interface Tissue Engineering in Annulus Fibrosus Repair: Bridging Mechanisms of Hydrogel Integration with Regenerative Outcomes.ACS biomaterials science & engineering · 2020Pooled it
- Balancing biological and biomechanical performance in intervertebral disc repair: a systematic review of injectable cell delivery biomaterials.European cells & materials · 2020Pooled it
- A natural hydrogel complex improves intervertebral disc degeneration by correcting fatty acid metabolism and inhibiting nucleus pulposus cell pyroptosis.Materials today. Bio · 2024Article
- Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects.Gels (Basel, Switzerland) · 2024Review
- Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.JOR spine · 2023Article
- Hydrogel Coating Optimization to Augment Engineered Soft Tissue Mechanics in Tissue-Engineered Blood Vessels.Bioengineering (Basel, Switzerland) · 2023Article
- Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment.Frontiers in immunology · 2023Review
- Recent advances in the repair of degenerative intervertebral disc for preclinical applications.Frontiers in bioengineering and biotechnology · 2023Review
- Genipin-crosslinked fibrin seeded with oxidized alginate microbeads as a novel composite biomaterial strategy for intervertebral disc cell therapy.Biomaterials · 2022Article
- Putting the Pieces in Place: Mobilizing Cellular Players to Improve Annulus Fibrosus Repair.Tissue engineering. Part B, Reviews · 2021Review
- Bioadhesives for musculoskeletal tissue regeneration.Acta biomaterialia · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Back pain is a leading cause of global disability associated with intervertebral disc (IVD) pathologies. Discectomy alleviates disabling pain caused by IVD herniation without repairing annulus fibrosus (AF) defects, which can cause accelerated degeneration and recurrent pain. Biological therapies show promise for IVD repair but developing high-modulus biomaterials capable of providing biomechanical stabilisation and delivering biologics remains an unmet challenge. The present study identified critical factors and developed an optimal formulation to enhance the delivery of AF cells and transforming growth beta-3 (TGFβ-3) in genipin-crosslinked fibrin (FibGen) hydrogels. Part 1 showed that AF cells encapsulated in TGFβ-3-supplemented high-modulus FibGen synthesised little extracellular matrix (ECM) but could release TGFβ-3 at physiologically relevant levels. Part 2 showed that AF cells underwent apoptosis when encapsulated in FibGen, even after reducing fibrin concentration from 70 to 5 mg/mL. Mechanistic experiments, modifying genipin concentration and integrin binding site presence demonstrated that genipin crosslinking caused AF cell apoptosis by inhibiting cell-biomaterial binding. Adding integrin binding sites with fibronectin partially rescued apoptosis, indicating genipin also caused acute cytotoxicity. Part 3 showed that FibGen formulations with 1 mg/mL genipin had enhanced ECM synthesis when supplemented with fibronectin and TGFβ-3. In conclusion, FibGen could be used for delivering biologically active compounds and AF cells, provided that formulations supplied additional sites for cell-biomaterial binding and genipin concentrations were low. Results also highlighted a need for developing strategies that protect cells against acute crosslinker cytotoxicity to overcome challenges of engineering high-modulus cell carriers for musculoskeletal tissues that experience high mechanical demands.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.