Application of collagen-based scaffolds for the treatment of spinal cord injuries in animal models. A literature update.

  • D. Zachariou
  • I. Vlamis
Keywords: Spinal Cord Injury, Animal Model, Collagen-Based Scaffold, Regenerative Medicine, Tissue Engineering


This review compiles newer bibliographical data with regards to the application of collagen scaffolds for the purposes of treatment of Spinal cord injury (SCI) in animal models. SCI is regarded as one of the most devastating central nervous system (CNS) injuries, exhibiting an alarmingly rising incidence rate, indirectly connected with the expansion of global economy. The consequences of SCI are multidimensional: SCI injuries may result in permanent voluntary motor disfunction and loss of sensation, while incurring heavy economic and psychological burden as part of the treatment. Thus, it is of great importance that effective and suitable SCI treatment strategies are developed. Collagen-based scaffolds application is one of the most promising methods of SCI treatment. They come in a variety of forms, including hydrogel, sponge or guidance conduit serving as an instrument to administer therapeutic drugs and proteins to the SCI site. A number of relevant studies have been carried out fairly recently, exclusively using carefully selected animals that resemble human pathophysiology and surgical outcomes, without incurring cost-related, ethical or regulatory limitations. In mouse, rat and canine models having mainly undergone transection and hemisection, the stump connection, along with transplanted cell differentiation, elimination of glial scar, increased neuronal growth, decreased collagen deposition, behavioural recovery, improved electrophysiology and enhanced axonal regeneration are evident.


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Author Biographies

D. Zachariou

3rd Orthopaedic Dept, National and Kapodistrian University of Athens, Greece

I. Vlamis

3rd Orthopaedic Dept, National and Kapodistrian University of Athens, Greece


1. Litowczenko J, Woźniak-Budych MJ, Staszak K et al. Milestones and current achievements in development of multifunctional bioscaffolds for medical application. Bioactive Materials. 2021;6(8):2412-38
2. Silva R., Singh R., Sarker B et al. Hydrogel matrices based on elastin and alginate for tissue engineering applications. Int. J. Biol. Macromol. 2018
3. Furlan JC, Craven BC, Massicotte EM et al. Fehlings MG. Early versus delayed surgical decompression of spinal cord after traumatic cervical spinal cord injury: a cost-utility analysis. World neurosurgery. 2016;88:166-74
4. Yeh JZ, Wang DH, Cherng JH et al. Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury. Polymers. 2020;12(10):2245
5. Quraishe S., Forbes L.H., Andrews M.R. The extracellular environment of the cns: Influence onplasticity, sprouting, and axonal regeneration after spinal cord injury. Neural Plast.2018;2018:2952386
6. Dias DO, Kim H, Holl D et al. Reducing pericyte-derived scarring promotes recovery after spinal cord injury. Cell. 2018;173:153-65
7. Xu B., Park D., Ohtake Y. et al. Role of CSPG receptor LAR phosphatase in restricting axon regeneration after CNS injury. Neurobiol. Dis.2015;73:36-48
8. Orr M.B., Gensel J.C. Spinal cord injury scarring and inflammation: Therapies targeting glial andinflammatory responses. Neurotherapeutics. 2018;15:541-53.
9. Wang N, Xiao Z, Zhao Y, et al. Collagen scaffold combined with human umbilical cord‐derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury. Journal of tissue engineering and regenerative medicine. 2018;12(2):e1154-63.
10. Chen X., Zhao Y., Li X. Et al. Functional Multichannel Poly(Propylene Fumarate)-Collagen Scaffold with Collagen-Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury. Adv. Healthc. Mater. 2018
11. Yao Q., Liu Y., Pan Y. Et al. One-pot porogen free method fabricated porous microsphere-aggregated 3D PCL scaffolds for bone tissue engineering. J. Biomed. Mater. Res. - Part B Appl. Biomater. 2020
12. Wang J., Zheng J., Zheng Q. et al. FGL-functionalized self-assembling nanofiber hydrogel as a scaffold for spinal cord-derived neural stem cells. Mater. Sci. Eng.C Mater. Biol. Appl. 2015;46:140-47.
13. Song R., Murphy M., Li C et al. Current development of biodegradable polymeric materials for biomedical applications. Drug Des. Devel. Ther. 2018
14. Breen BA, Kraskiewicz H, Ronan R et al. Therapeutic effect of neurotrophin-3 treatment in an injectable collagen scaffold following rat spinal cord hemisection injury. Acs Biomater Sci Eng. 2016;3:1287
15. Han S, Li X, Xiao Z, Dai J. Complete canine spinal cord transection model: a large animal model for the translational research of spinal cord regeneration. Science China Life Sciences. 2018;61(1):115-17
16. Xiao Z, Tang F, Tang J, et al. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients. Science China Life Sciences. 2016;59(7):647-55.
17. Xiao Z, Tang F, Zhao Y et al. Significant improvement of acute complete spinal cord injury patients diagnosed by a combined criterion implanted with neuroregen scaffolds and mesenchymal stem cells. Cell transplantation. 2018;27(6):907-15.
18. Zhao Y, Tang F, Xiao Z. et al. Clinical study of NeuroRegen scaffold combined with human mesenchymal stem cells for the repair of chronic complete spinal cord injury. Cell transplantation. 2017;26(5):891-900.
19. Li X, Han J, Zhao Y et al. Functionalized collagen scaffold neutralizing the myelin-inhibitory molecules promoted neurites outgrowth in vitro and facilitated spinal cord regeneration in vivo. ACS applied materials & interfaces. 2015;7(25):13960-71.
20. Li X, Han J, Zhao Y et al. Functionalized collagen scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration. Acta biomaterialia. 2016;30:233-45.
21. Li X, Zhao Y, Cheng S et al. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair. Biomaterials. 2017;137:73-86.
22. Li X, Fan C, Xiao Z et al. A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/β-catenin signaling for spinal cord injury repair, Biomaterials 2018, doi: 10.1016/j.biomaterials.2018.08.037.
23. Snider S, Cavalli A, Colombo F et al. A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury. J Biomed Mater Res Part B 2016:00B:000.
24. Sharif-Alhoseini M, Rahimi-Movaghar V. Animal models in traumatic spinal cord injury. Topics in Paraplegia. 2014:209-28.
25. Sugai K, Nishimura S, Kato‐Negishi M et al. Neural stem/progenitor cell‐laden microfibers promote transplant survival in a mouse transected spinal cord injury model. Journal of neuroscience research. 2015;93(12):1826-38.
26. Han S, Wang B, Jin W et al. The collagen scaffold with collagen binding BDNF enhances functional recovery by facilitating peripheral nerve infiltrating and ingrowth in canine complete spinal cord transection. Spinal cord. 2014;52(12):867-73.
27. Han S, Xiao Z, Li X et al. Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine. Science China Life Sciences. 2018;61(1):2-13.