In the wave of regenerative medicine, pluripotent stem cell therapy, with its huge application potential and continuous breakthroughs, has become a hot track in the global medical field. Recently, this field has witnessed frequent exciting advancements, opening up new paths for the treatment of intractable diseases and injecting strong impetus into the development of regenerative medicine, making the hope of conquering difficult and complicated conditions increasingly clear.

Recently, a research team led by Guebum Han, Nicolas S. Lavoie, Nandadevi Patil and others from the University of Minnesota published a breakthrough study in Advanced Healthcare Materials. They adopted a "three-in-one" innovative strategy, which involves using region-specific spinal cord neural precursor cells (sNPCs) derived from human induced pluripotent stem cells (IPscs) and combining multi-material 3D printing technology to construct spinal cord organoid scaffolds with microchannel structures, successfully achieving functional recovery after spinal cord injury in rat models. It has opened up a new path for the treatment of human spinal cord injuries.

The technical route of the team is:

STEP 1 Cell source

Human induced pluripotent stem cells (IPscs) were directed to differentiate into cervic-thoracic specific spinal neural progenitor cells (sNPCs), expressing location markers such as HOXA4/HOXC8 to ensure matching with the injured segments.

STEP 2 3D printing multi-material scaffolds

1) Material: Dual-network hydrogel - The outer layer is GelMA/ hyaluronic acid (high modulus, ≥50kPa, providing mechanical support); The inner layer is matrix adhesive/laminin (low modulus, ≈5kPa, conducive to cell adhesion).

2) Structure: Microchannel array (diameter 200µm, spacing 400µm), longitudinally through to simulate the spinal white matter conduction tract; Radial holes (with a diameter of 80µm) are designed at the intersection of the channels to promote oxygen/nutrient exchange.

3) Printing parameters: Multi-head digital light curing (DLP) printer, layer thickness 50µm, 405nm blue light 25 MW cm⁻², single-layer cross-linking completed within 2 seconds, cell survival rate >90%.

STEP 3 Cell Loading and Organoid formation

1) Mix sNPCs with Matrigel and neurotrophic factors to form bio-ink and print it into the channel at low temperature.

2) After 40 days of in vitro culture, a spinal organoid scaffold with multiple subtypes of neurons was formed.

STEP 4 Animal transplantation

Two organoid scaffolds (dorsal + ventral) were implanted into the 1.8 mm defect area of the rat T8/9 complete transection model.

Schematic diagram of 3D printed spinal cord organoid scaffolds transplanted into a rat model of transverse injury

STEP 5 Multi-dimensional evaluation

1) In vitro: Neuronal maturity and function were detected by IHC, RNA-seq and patch clamp.

2) In vivo: BBB score, motor evoked potential (MEPs), histological analysis, stent integration and neural network reconstruction.

The team plans to initiate a Phase I clinical trial in 2026 (IND application has been submitted), focusing on evaluating the safety of iPSC cell products, dose escalation, and the in vivo degradation kinetics of 3D-printed scaffolds.

Summary

This research integrates the cutting-edge achievements in materials science, stem cell technology and biomanufacturing, providing an innovative "structure-cell-function" trinity solution for the treatment of spinal cord injuries. It not only brings new hope to patients with spinal cord injuries, but also injects new impetus into the development of regenerative medicine in the field of neural repair, and is expected to drive greater breakthroughs in this field and lead to innovations in treatment plans for more intractable neurological diseases.