Application of Human Epineural Patch (hEP) as a Novel Strategy for Nerve Protection and Enhancement of Regeneration After Nerve Crush Injury
Abstract
1. Introduction
2. Materials and Methods
2.1. Experimental Animals
2.2. Human Epineural Patch Creation
2.3. Human Amniotic Membrane
2.4. Surgical Procedure
Postsurgical Supportive Treatment
2.5. Experimental Groups and Study Design
2.6. Functional Tests and Histomorphometric Analysis
2.6.1. Functional Motor Assessment by Toe-Spread Test
2.6.2. Functional Sensory Assessment with Pinprick Test
2.6.3. Macroscopic Assessment of the hEP and hAM at the Sciatic Nerve Injury Site
2.6.4. Assessment of Muscle Denervation Atrophy by Gastrocnemius Muscle Index
2.6.5. Histomorphometric Analysis
2.7. Assessment of Immune Responses
2.8. Statistical Analysis
3. Results Following Sciatic Nerve Crush Injury in a 6-Week Study
3.1. Toe-Spread Test
3.2. Pinprick Test
3.3. Gastrocnemius Muscle Index
3.4. Myelin Thickness
3.5. Fiber Diameter
3.6. Percentage of Myelinated Fibers
3.7. Axonal Density
3.8. GFAP Expression
3.9. Laminin B Expression
3.10. NGF Expression
3.11. S-100 Expression
3.12. VEGF Expression
3.13. vWF Expression
3.14. HLA-DR Expression
3.15. HLA-I Expression
4. Results Following Sciatic Nerve Crush Injury in a 12-Week Study
4.1. Toe-Spread Test
4.2. Pinprick Test
4.3. Gross Assessment
4.4. Gastrocnemius Muscle Index
4.5. Myelin Thickness
4.6. Fiber Diameter
4.7. Myelinated Fibers Percentage
4.8. Axonal Density
4.9. GFAP Expression
4.10. Laminin B Expression
4.11. NGF Expression
4.12. S-100 Expression
4.13. VEGF Expression
4.14. vWF Expression
4.15. HLA-DR Expression
4.16. HLA-I Expression
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AAALAC | American Association for the Accreditation of Laboratory Animal Care |
ACC | Animal Care Committee |
CTR | Crush/Transection/Repair |
GFAP | Glial Fibrillary Acidic Protein |
GMI | Gastrocnemius Muscle Index |
hAM | human Amniotic Membrane |
hEP | human Epineural Patch |
HLA-DR | Human Leukocyte Antigen—DR |
HLA-I | Human Leukocyte Antigen—Class I |
MTF | Musculoskeletal Transplant Foundation |
NGF | Nerve Growth Factor |
S-100 | S-100 Protein |
SEM | Standard Error of the Mean |
VEGF | Vascular Endothelial Growth Factor |
vWF | von Willebrand Factor |
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Experimental Group Number | Repair Method | Number of Athymic Nude Rats per Group |
---|---|---|
6 weeks study | ||
1 | no protective wrapping | n = 6 |
2 | hEP | n = 6 |
3 | hAM | n = 6 |
12 weeks study | ||
1 | no protective wrapping | n = 6 |
2 | hEP | n = 6 |
3 | hAM | n = 6 |
6 Weeks Study | ||||
---|---|---|---|---|
Parameter | Location | Control (Mean ± SEM) | hEP (Mean ± SEM) | hAM (Mean ± SEM) |
Myelin Thickness | ||||
(μm) | Proximal | 0.532 ± 0.016 | 0.571 ± 0.017 | 0.677 ± 0.018 **** |
Crush | 0.372 ± 0.009 | 0.326 ± 0.008 | 0.460 ± 0.018 **** | |
Distal | 0.334 ± 0.007 **** | 0.278 ± 0.008 | 0.320 ± 0.007 **** | |
% of Myelinated Fibers | ||||
(%) | Proximal | 84.711 ± 1.570 | 91.185 ± 0.628 *** | 89.454 ± 0.865 ** |
Crush | 86.509 ± 0.621 | 84.102 ± 0.666 | 86.991 ± 0.864 * | |
Distal | 84.637 ± 0.852 | 86.191 ± 0.588 ** | 82.970 ± 0.719 | |
Fiber Diameter | ||||
(μm) | Proximal | 11.770 ± 0.359 | 12.568 ± 0.213 | 12.006 ± 0.179 |
Crush | 8.029 ± 0.077 * | 8.577 ± 0.104 **** | 9.720 ± 0.190 **** | |
Distal | 8.196 ± 0.087 | 8.871 ± 0.117 **** | 8.246 ± 0.096 **** | |
Axonal Density | ||||
(axons/μm2) | Proximal | 28.722 ± 3.477 | 41.111 ± 2.021 ** | 39.000 ± 1.690 * |
Crush | 47.167 ± 2.306 | 60.556 ± 4.027 ** | 47.611 ± 2.432 | |
Distal | 44.389 ± 2.171 | 47.444 ± 2.173 | 48.222 ± 1.821 |
6-Week Study | |||
---|---|---|---|
Control | hEP | hAM | |
NEUROGENIC | |||
GFAP | |||
Crush | 2.333 ± 0.333 | 2.833 ± 0.167 | 1.583 ± 0.083 |
Distal | 1.500 ± 0.500 | 1.833 ± 0.601 | 0.583 ± 0.083 |
Laminin B | |||
Crush | 1.167 ± 0.167 | 1.167 ± 0.333 | 1.167 ± 0.167 |
Distal | 0.500 ± 0.000 | 1.500 ± 0.500 * | 0.333 ± 0.167 |
NGF | |||
Crush | 0.500 ± 0.289 | 1.250 ± 0.629 | 0.667 ± 0.167 |
Distal | 0.333 ± 0.167 | 1.833 ± 0.601 | 0.500 ± 0.289 |
S-100 | |||
Crush | 1.667 ± 0.167 | 1.833 ± 0.333 | 1.833 ± 0.333 |
Distal | 2.167 ± 0.167 | 2.500 ± 0.289 * | 1.167 ± 0.441 |
ANGIOGENIC | |||
VEGF | |||
Crush | 1.167 ± 0.441 | 1.833 ± 0.167 | 1.167 ± 0.441 |
Distal | 1.167 ± 0.167 | 1.833 ± 0.333 | 1.333 ± 0.167 |
wVF | |||
Crush | 1.167 ± 0.667 | 2.167 ± 0.167 * | 0.583 ± 0.083 |
Distal | 1.167 ± 0.167 | 2.500 ± 0.500 | 1.833 ± 0.167 |
IMMUNOGENIC | |||
HLA-DR | |||
Crush | 1.500 ± 0.289 | 0.833 ± 0.601 | 1.333 ± 0.441 |
Distal | 1.000 ± 0.289 | 0.833 ± 0.167 | 1.500 ± 0.500 |
HLA-I | |||
Crush | 1.400 ± 0.430 | 0.900 ± 0.187 | 1.000 ± 0.274 |
Distal | 1.700 ± 0.255 | 0.900 ± 0.292 | 1.500 ± 0.224 |
12 Weeks Study | ||||
---|---|---|---|---|
Parameter | Location | Control (Mean ± SEM) | hEP (Mean ± SEM) | hAM (Mean ± SEM) |
Myelin Thickness | ||||
(μm) | Proximal | 0.664 ± 0.030 | 0.641 ± 0.020 | 0.881 ± 0.037 **** |
Crush | 0.502 ± 0.023 **** | 0.294 ± 0.008 | 0.351 ± 0.010 **** | |
Distal | 0.421 ± 0.026 **** | 0.372 ± 0.012 *** | 0.274 ± 0.007 | |
% of Myelinated Fibers | ||||
(%) | Proximal | 89.582 ± 0.748 | 88.475 ± 1.607 | 92.128 ± 0.474 * |
Crush | 88.713 ± 0.656 | 89.784 ± 0.548 | 87.881 ± 0.664 | |
Distal | 88.479 ± 0.507 | 89.537 ± 0.431 * | 87.262 ± 0.665 | |
Fiber Diameter | ||||
(μm) | Proximal | 11.701 ± 0.166 | 14.142 ± 0.189 **** | 11.859 ± 0.176 |
Crush | 10.322 ± 0.151 **** | 7.677 ± 0.088 | 8.748 ± 0.086 **** | |
Distal | 8.409 ± 0.114 | 8.957 ± 0.093 *** | 8.574 ± 0.093 * | |
Axonal Density | ||||
(axons/μm2) | Proximal | 27.778 ± 2.535 | 40.222 ± 1.832 **** | 38.167 ± 1.172 ** |
Crush | 45.944 ± 3.845 | 56.056 ± 3.785 | 59.222 ± 2.697 * | |
Distal | 54.667 ± 2.974 | 59.333 ± 3.734 | 57.556 ± 3.781 |
12-Week Study | |||
---|---|---|---|
Control | hEP | hAM | |
NEUROGENIC | |||
GFAP | |||
Crush | 1.833 ± 0.601 * | 2.500 ± 0.289 | 0.750 ± 0.433 |
Distal | 1.667 ± 0.601 | 1.333 ± 0.167 | 0.333 ± 0.167 |
Laminin B | |||
Crush | 2.333 ± 0.333 | 2.000 ± 0.289 * | 0.583 ± 0.220 ** |
Distal | 1.167 ± 0.441 | 1.667 ± 0.333 | 0.750 ± 0.382 |
NGF | |||
Crush | 0.500 ± 0.289 | 1.750 ± 0.144 * | 0.667 ± 0.333 |
Distal | 0.667 ± 0.167 | 0.917 ± 0.300 | 0.167 ± 0.167 |
S-100 | |||
Crush | 1.667 ± 0.441 | 2.167 ± 0.167 | 1.667 ± 0.167 |
Distal | 1.333 ± 0.333 | 2.000 ± 0.289 * | 0.833 ± 0.167 |
ANGIOGENIC | |||
VEGF | |||
Crush | 2.333 ± 0.667 | 2.667 ± 0.167 | 2.000 ± 0.500 |
Distal | 1.500 ± 0.500 | 2.167 ± 0.601 | 1.833 ± 0.167 |
wVF | |||
Crush | 1.667 ± 0.601 | 2.167 ± 0.833 | 2.000 ± 0.500 |
Distal | 0.833 ± 0.333 | 1.500 ± 0.289 | 0.917 ± 0.546 |
IMMUNOGENIC | |||
HLA-DR | |||
Crush | 2.500 ± 0.289 * | 1.083 0.363 | 2.000 ± 0.577 |
Distal | 1.333 ± 0.333 | 0.833 ± 0.167 | 2.333 ± 0.333 * |
HLA-I | |||
Crush | 2.000 ± 0.289 * | 0.917 ± 0.300 * | 2.333 ± 0.333 * |
Distal | 0.917 ± 0.363 | 0.833 ± 0.167 | 0.667 ± 0.220 |
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Share and Cite
Kozlowska, K.; Radecka, W.; Brodowska, S.; Chambily, L.; Kuc, D.; Lopez, A.; Siemionow, M. Application of Human Epineural Patch (hEP) as a Novel Strategy for Nerve Protection and Enhancement of Regeneration After Nerve Crush Injury. Biomedicines 2025, 13, 1633. https://doi.org/10.3390/biomedicines13071633
Kozlowska K, Radecka W, Brodowska S, Chambily L, Kuc D, Lopez A, Siemionow M. Application of Human Epineural Patch (hEP) as a Novel Strategy for Nerve Protection and Enhancement of Regeneration After Nerve Crush Injury. Biomedicines. 2025; 13(7):1633. https://doi.org/10.3390/biomedicines13071633
Chicago/Turabian StyleKozlowska, Katarzyna, Weronika Radecka, Sonia Brodowska, Lucile Chambily, Dominika Kuc, Amber Lopez, and Maria Siemionow. 2025. "Application of Human Epineural Patch (hEP) as a Novel Strategy for Nerve Protection and Enhancement of Regeneration After Nerve Crush Injury" Biomedicines 13, no. 7: 1633. https://doi.org/10.3390/biomedicines13071633
APA StyleKozlowska, K., Radecka, W., Brodowska, S., Chambily, L., Kuc, D., Lopez, A., & Siemionow, M. (2025). Application of Human Epineural Patch (hEP) as a Novel Strategy for Nerve Protection and Enhancement of Regeneration After Nerve Crush Injury. Biomedicines, 13(7), 1633. https://doi.org/10.3390/biomedicines13071633