## 2 Discussion
### Effectiveness of Magnetic Nanoparticles in Enhanced Delivery of HCECs
This research paper concluded that magnetic HCECs showed superior performance compared to control HCECs guided solely by gravity, demonstrating that targeted magnetic guidance may enhance cell delivery and integration at the host corneal endothelium. While the studies mentioned demonstrate promising outcomes of MNPs in CE-CI, their short follow-up periods limit our understanding of the long-term implications of this technique. In a related investigation, [PERSON] et al. explored the long-term outcomes of transplanting cultured rabbit CECs (RCECs) [82]. Cultured RCECs were labelled with iron nanoparticles and transplanted into the anterior chamber of rabbits with corneal endothelial dysfunction induced by cryo-injury. A cryo-injury group with normal injection of RCECs and a cryo-injury group with no treatment injection were used as controls. At 24 h post-injection the corneal thickness was 1000 \(\upmu\)m in all groups and at 2 weeks the iron-RCEC-treated group had a mean corneal thickness of 492 \(\upmu\)m, whilst the cryo-only and the cryo-RCEC groups showed limited variability at 1016 \(\upmu\)m and 1004 \(\upmu\)m, respectively. Throughout the 12 months, corneal thickness in the iron-RCEC group remained around 400 \(\upmu\)m. Data in both control groups were unable to be collected from the second month onwards due to post-operative corneal oedema. Histological examination at 12 months post-operatively showed that in the iron-RCEC group, RCECs were found to completely cover Descenter's membrane across the entire cornea. Conversely, RCECs were only present in the periphery and midperiphery in both of the other groups, but not in the central region. The results showed that the magnetic attraction method facilitated the delivery and retention of the transplanted CECs to Descenter's membrane. The transplanted cells maintained high viability and functionality over the observation period, with evidence of CEC layer regeneration and improvement in corneal transparency. Consistent with the aforementioned study, there was no increase in IOP observed during the 12-month observation period, no migration of iron powder into ocular tissues, and no recorded ocular complications [81]. Although the study's focus on long-term results is promising, the study's limited sample size and follow-up duration may inhibit the generalisability of the findings. [PERSON] et al. 's study contributes to the existing literature on magnetic assisted CEC transplantation, providing a novel approach using injectable magnetic hyaluronic acid (HA) gel [83]. HA is a natural polysaccharide widely investigated in tissue engineering due to its adequate biocompatibility and clearance in the body [84]. Endogenous HA has been found to support the migration of epithelial cells and promote wound healing [84,85]. Recent studies focusing on the ability of HA hydrogels to aid in the delivery of corneal epithelial cells in the context of corneal regeneration have reported favourable outcomes, but its use in endothelial cell delivery is underexplored [85, 86, 87]. [PERSON] et al. incorporated superparamagnetic iron oxide nanoparticles into a HA gel matrix which was used to encapsulate donor HCECs. After the rabbit corneal endothelium injury model was established by mechanical destruction, the magnetic HA gel formulation with 100,000 CECs was then introduced into rabbit corneas and guided by an external neodymium magnetic to the target location [83]. The same injury model was used for the control group as well as the same concentration of MNPs and quantity of CECs; however, instead of HA gel, the magnetic formulation contained sterile phosphate-buffered saline (PBS). As the gel gradually degraded, HCECs were continuously released and delivered to the injured corneal endothelium. The quantity of HCECs delivered was higher in the HA gel group at each tested checkpoint compared to the control. The magnetic HA gel facilitated precise localisation of the transplanted cells whilst maintaining high cell viability.