Gelatin-Based Hydrogels for Peripheral Nerve Regeneration: A Multifunctional Vehicle for Cellular, Molecular, and Pharmacological Therapy
Abstract
1. Background
2. Gelatin Hydrogel Fabrication and Functionalization Techniques
3. Evaluation of Gelatin-Based Hydrogels for Peripheral Nerve Regeneration
3.1. Comparative Analysis of Gelatin-Based Hydrogels vs. Other Natural and Synthetic Hydrogels
3.2. Basic and Functionalized GelMA Hydrogels
3.3. Gelatin Hydrogels for Delivery of Drugs, Cells, and Growth Factors
3.4. Conductive and Piezoelectric Hydrogels
3.5. 3D Printed and Architecturally Tuned Conduits
3.6. Stem Cell-Based and Neural Network Systems
4. Future Directions
4.1. Translational Studies
4.2. Regulatory Considerations
5. The Evolving Role of Gelatin Hydrogels in Peripheral Nerve Repair
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BDNF | Brain-Derived Neurotrophic Factor |
BMS | Basso Mouse Scale |
BWT | Beam Walk Test |
CGRP | Calcitonin Gene-Related Peptide |
DLP | Digital Light Processing |
DRG | Dorsal Root Ganglia/Ganglion |
ECM | Extracellular Matrix |
ELISA | Enzyme-Linked Immunosorbent Assay |
EMG | Electromyography |
FKBPs | FK506-Binding Proteins |
FR | Functional Recovery |
GelMA | Gelatin Methacryloyl |
HA | Hyaluronic Acid |
IGF-1 | Insulin-Like Growth Factor 1 |
LAP | Lithium Phenyl-2,4,6-Trimethylbenzoylphosphinate |
MMP | Matrix Metalloproteinase |
MSCs | Mesenchymal Stem Cells |
MeTro | Methacrylated Tropoelastin |
NGCs | Nerve Guidance Conduits |
NGF | Nerve Growth Factor |
NIH | National Institutes of Health |
NSCs | Neural Stem Cells |
PCL | Polycaprolactone |
PEGDA | Polyethylene Glycol Diacrylate |
PI | Photoinitiators |
PNIs | Peripheral Nerve Injuries |
PVDF | Polyvinylidene Fluoride |
ROS | Reactive Oxygen Species |
SCI | Spinal Cord Injury |
SCs | Schwann Cells |
VEGF | Vascular Endothelial Growth Factor |
bFGF | Basic Fibroblast Growth Factor |
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Parameter | Gelatin-Based Hydrogel | Collagen-Based Hydrogel | Chitosan-Based Hydrogel | Alginate-Based Hydrogel | PEG-Based Hydrogel |
---|---|---|---|---|---|
Biocompatibility | High; supports cell adhesion via RGD motifs | Excellent; native ECM protein; supports Schwann cells | Good; may require deacetylation to reduce immune response | Moderate; lacks native adhesion motifs without modification | High; non-immunogenic synthetic polymer |
Biodegradability | Moderate; tunable via crosslinking (e.g., GelMA) | Rapid; enzymatic degradation | Moderate; adjustable via crosslinking | Fast; needs modification to delay degradation | Slow; highly stable unless modified |
Mechanical Strength | Tunable; enhanced with GelMA or composites | Low; requires reinforcement | Good; suitable mechanical integrity in blends | Soft; mechanically weak without reinforcement | Tunable; wide range achievable with crosslinkers |
Nerve Regeneration Efficiency | High; supports axonal growth and Schwann cell migration | High; proven in nerve guidance conduits | Moderate to high; effective especially in blends | Moderate; supports cell encapsulation, but limited axon guidance | Moderate; inert but functionalized PEG supports growth |
Inflammatory Response | Low; minimal immune reaction | Low; generally well tolerated | Variable; mild to moderate inflammation possible | Low; but lacks immunomodulatory cues | Very low; highly inert and non-immunogenic |
Drug/Growth Factor Delivery | Excellent; enables controlled delivery | Moderate; limited control over release kinetics | Good; functionalization improves loading | Poor; requires modification for sustained delivery | Excellent; ideal for controlled release systems |
Ease of Fabrication and Modification | High; GelMA is photo-crosslinkable, printable | Moderate; limited crosslinking options | High; easily functionalized and blendable | Moderate; ionically crosslinked, easy to gel | Very high; synthetic control allows precise tuning |
Clinical Translation Status | Preclinical; no clinical trials yet | Clinically used (e.g., Integra™) in soft tissue | Preclinical; some progress toward trials | Preclinical; limited nerve-specific applications | Used clinically in drug delivery; limited in nerve repair |
Study | Materials | Type | Model | Key Findings | Ref |
---|---|---|---|---|---|
Luo et al. | GelMA, bFGF, DPSCs | Photocrosslinked hydrogel | In vitro and 15-mm rat sciatic nerve model | Porous, bioactive, supports cell viability | [48] |
Sukhinich et al. | Gelatin + glutaraldehyde | Simple gelatin conduit | In vivo mouse sciatic nerve | Good regrowth, no muscle atrophy reversal | [49] |
Wu et al. | GelMA + SF-MA + DLP 3D printing | Prodrug nanoassemblies | 12 mm rat sciatic nerve | Autograft-level results, improved myelination | [43] |
Javidi et al. | Gelatin, PAG, ZnO, PCL/PVDF shell | Conductive, piezoelectric scaffold | PC12 cells | Enhanced neuronal differentiation | [61] |
Maeng et al. | GelMA + PEGDA | 3D-printed multi-channel | 10 mm rat sciatic model | Good motor/sensory recovery, minimal inflammation | [66] |
Zhang et al. | GelMA + HEAA + SCs | 3D-bioprinted microchannel | In vitro and in vivo | High SC viability, strong mechanics | [21] |
Zhang et al. | GM hydrogel + VEGF/NGF + chitin | Dual growth factor delivery | 16-week rat model | Enhanced axon growth, angiogenesis | [58] |
Lee et al. | PLCL + gelatin hydrogel + NGF | 3D-printed porous conduit | Rat sciatic nerve defect | High protein release, comparable to autografts | [64] |
Xu et al. | GelMA + VEGF165 | Injectable hydrogel | Crush injury rat model | Sustained VEGF, functional and angiogenic gains | [20] |
Li et al. | GelMA + CGRP | 405 nm UV-crosslinked | Diabetic mouse model | Improved wound healing and anti-inflammatory | [59] |
Krieghoff et al. | Gelatinous peptides + oligomers | 3D-printable, tunable | Preclinical in vitro | Customizable, aseptic printing | [65] |
Javanmardi | PA + Dex-Mp + HA | Injectable drug delivery | Rat crush injury model | Highest SFI, reduced vacuolation | [60] |
Neuman | GelMA and Gel-Amin | Ionically conductive hydrogel | In vitro DRG, SCs | Magnetic stimulation improves outcomes | [62] |
Sugiyama | MedGel + IGF-1 | Topical hydrogel | Facial nerve guinea pig model | 67% complete recovery | [70] |
Zhou | Gelatin hydrogel + Neural Stem Cells (NSCs) | Gelatin hydrogel conduit | 5 mm mouse sciatic nerve defect | NSCs promoted nerve repair; miR-7 inhibits NSC migration/proliferation via cdc42; overexpression worsened repair | [55] |
Aregueta-Robles | Gelatin hydrogel + NSCs | miR-7 functional model | In vivo nerve injury | Improved CMAPs, reversed by miR-7 | [57] |
Esaki | PVA-Tyr + sericin + gelatin | 3D co-culture hydrogel | In vitro PC12 and SCs | 3D neural networks, stiffness tuned | [56] |
Soucy et al. | GelMA + MeTro | Adhesive hydrogel | In vitro and ex vivo | Superior mechanical and adhesive properties | [45] |
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Viezuina, D.-M.; Musa, I.; Aldea, M.; Matache, I.-M.; Rotaru Zavaleanu, A.-D.; Gresita, A.; Veronica, S.; Mitran, S.I. Gelatin-Based Hydrogels for Peripheral Nerve Regeneration: A Multifunctional Vehicle for Cellular, Molecular, and Pharmacological Therapy. Gels 2025, 11, 490. https://doi.org/10.3390/gels11070490
Viezuina D-M, Musa I, Aldea M, Matache I-M, Rotaru Zavaleanu A-D, Gresita A, Veronica S, Mitran SI. Gelatin-Based Hydrogels for Peripheral Nerve Regeneration: A Multifunctional Vehicle for Cellular, Molecular, and Pharmacological Therapy. Gels. 2025; 11(7):490. https://doi.org/10.3390/gels11070490
Chicago/Turabian StyleViezuina, Denisa-Madalina, Irina Musa, Madalina Aldea, Irina-Mihaela Matache, Alexandra-Daniela Rotaru Zavaleanu, Andrei Gresita, Sfredel Veronica, and Smaranda Ioana Mitran. 2025. "Gelatin-Based Hydrogels for Peripheral Nerve Regeneration: A Multifunctional Vehicle for Cellular, Molecular, and Pharmacological Therapy" Gels 11, no. 7: 490. https://doi.org/10.3390/gels11070490
APA StyleViezuina, D.-M., Musa, I., Aldea, M., Matache, I.-M., Rotaru Zavaleanu, A.-D., Gresita, A., Veronica, S., & Mitran, S. I. (2025). Gelatin-Based Hydrogels for Peripheral Nerve Regeneration: A Multifunctional Vehicle for Cellular, Molecular, and Pharmacological Therapy. Gels, 11(7), 490. https://doi.org/10.3390/gels11070490