## 2 Discussion
### Effectiveness of Magnetic Nanoparticles in Enhanced Delivery of HCECs
However, HCECs signals were not equally dispersed onto the corneal endothelium in fluorescent imaging. This inconsistency may be a result of irregular cellular distribution or a possible discrepancy between gel degradation and CEC release, which may result in HA gel degrading prior to the release and adhesion of all the cells. Furthermore, the injected HCECs demonstrated functional characteristics, including cell morphology and expression of endothelial markers, providing relevant insights into the functional integration of cells into the corneal endothelium, signalling a successful transplantation. The magnetic HA gel matrix ensured stable localisation and release of the cells in a controlled environment, which may be crucial for long-term graft survival and function. However, HA is used in ophthalmic surgery as a viscoelastic agent to raise IOP by increasing the volume of the aqueous humour, therefore avoiding anterior chamber collapse, and aiding in the manipulation of ocular structures [88; 89]. [PERSON] et al. did not investigate the effect of the HA gel formulation on IOP, which is a vital parameter to evaluate in the context of adverse events that could inform future safety practices. Nevertheless, this study underscores significant implications for future research by elucidating the potential versatility of an HA system platform, delineating its capability to integrate and enhance functionality through the incorporation of adhesion-promoting peptides, particularly ROCK inhibitors. \begin{table}
\begin{tabular}{p{128.0 pt} p{128.0 pt} p{128.0 pt}} \hline \hline  & **[PERSON] et al. [80]** & **[PERSON] et al. [81]** & **[PERSON] et al. [83]** \\ \hline Cell type & Cadaveric donor & Cadaveric donor primary & Donor CECs (origin not specified)—100,000 \\ \hline \multirow{4}{*}{Experimental Model} & \multirow{4}{*}{In vitro (contact lens model)} & Rabbit model (corneal endothelial dysfunction; endothelial cell or Descemet stripping) & Rabbit model (corneal endothelium injury by mechanical destruction) \\ \cline{3-3}  
Comparative analysis across these studies underscores the diverse methodologies and outcomes associated with MNP-assisted HCEC transplantation. [PERSON] et al. highlighted the logarithmic correlation between magnetic field strength and delivered HCEC density, emphasising the importance of nanoparticle concentration in optimising cell delivery efficiency [80]. [PERSON] et al. provided quantitative OCT data showing reduced corneal thickness and improved clarity following magnetic HCEC transplantation, corroborated by histological findings of preserved endothelial tight junctions and marker expression [81]. [PERSON] et al. extended these findings with long-term observations demonstrating sustained corneal transparency and cellular integration post-MNP-labelled RCEC transplantation, further supporting the therapeutic potential of MNPs in corneal endothelial regeneration [82]. [PERSON] et al. 's use of magnetic HA gel matrices highlighted controlled cell release dynamics and functional HCEC integration despite challenges in achieving uniform distribution [83]. These studies collectively underscore the potential of MNPs in enhancing targeted HCEC delivery and integration, while emphasising the need for continued research to address validate clinical applicability. Despite promising preclinical outcomes of magnetic HCEC transplants, significant scientific and clinical hurdles remain before widespread clinical adoption. These include ensuring the safety and biocompatibility of MNPs, optimising targeted delivery efficiency, and conducting rigorous clinical trials to thoroughly evaluate long-term safety and efficacy. Ongoing phase I human trials are assessing the safety and tolerance of single intracameral injections of magnetic HCECs in patients with corneal oedema, with or without endothelial brushing or Descent Stripping [90; 91].