Spinal cord tissue engineering via covalent interaction between biomaterials and cells

Sci. Adv., 2023 · DOI: 10.1126/sciadv.ade8829 · Published: February 8, 2023

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

The study explores the effects of covalent interactions between cells and biomaterials on cell behavior to promote neural regeneration after spinal cord injury (SCI). A combined strategy based on covalent conjugation between biomaterials and various cells was demonstrated. Metabolic azido-labeled human neural progenitor cells conjugated on dibenzocyclooctyne-modified collagen fibers significantly promoted cell adhesion, spreading, and differentiation compared with noncovalent adhesion. The combined application of covalent conjugation strategies in a rat SCI model boosted neural regeneration, suggesting that covalent interactions between cells and biomaterials have great potential for tissue regeneration.

Study Duration

Not specified

Participants

SD rats aged 6 to 8 weeks

Evidence Level

Not specified

Key Findings

1
Covalent conjugation (CC) between dibenzocyclooctyne-modified collagen fibers (DBCO-LACF) and azide-modified neural progenitor cells (NPCs) enhanced cell adhesion, retention, and induced cells to spread along the direction of fibers.
2
Targeted delivery of edaravone (Eda) via DBCO-modified lipid nanoparticles (Eda-Lips) to azide-labeled spinal cord (SC) tissues or transplanted azide-modified astrocytes attenuated oxidative stress at the SCI sites and promoted survival of exogenous NPCs.
3
Transplantation of engineered spinal cord–like transplant (Et-SCT) containing N3-labeled human astrocytes significantly promoted cell survival, axon regeneration, and angiogenesis after SCI.

Research Summary

The study introduces a strategy using click chemistry to enhance donor cell retention and survival on scaffolds, promoting neural regeneration post-SCI. The research combines DBCO-modified scaffolds with N3-modified donor cells, demonstrating improved neural stem cell adhesion, differentiation, and axon growth compared to non-covalent interactions. Following stem cell-biomaterial transplantation in SCI rats, ROS-scavenging Eda was loaded into DBCO-modified Lips to target N3-modified SC tissues or N3-modified exogenous implanted astrocytes, boosting Eda-Lips accumulation and improving donor cell retention and neural regeneration.

Practical Implications

Enhanced Cell Adhesion

Covalent conjugation can be used to improve cell adhesion to biomaterials for tissue engineering applications.

Targeted Drug Delivery

The click chemistry approach can be employed for targeted drug delivery to specific cells or tissues in vivo.

Neural Regeneration

The combined strategy can be used to promote neural regeneration after spinal cord injury.

Study Limitations

1
The number and proportion of surviving cells decreased at 60 dpi, which may be related to lymphocyte-mediated immune reaction, poor blood supply, non–ROS-dependent secondary inflammation, cytotoxic neural excitement, and other factors.
2
The methods currently reported are complex in operation, and in particular, metabolic labeling strategies for endogenous cells may encounter difficulties in clinical translation.
3
The therapeutic window for drug targeting based on metabolic labeling can only last 10 days.

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