Ocular Bioink as an Immunoregenerative Interface: An Open Proposal from the Clinical Frontier
Abstract
We propose a frontier application of bio-ink technologies in regenerative ophthalmology: the sequential use of bio-inks derived from autologous monocytes and adipose tissue, printed onto customized therapeutic lenses for patients with corneal erosion and various immunoinflammatory or infectious ocular surface conditions. This approach integrates localized immunomodulation and structural regeneration, offering a non-invasive, autologous pathway that could control viral reactivations (such as Varicella Zoster Virus), increase antigen-presenting cell (APC) exposure, trigger a localized immune response, and support tissue healing to prevent irregular astigmatism and permanent visual impairment.
Clinical Context
Corneal erosion caused by inflammatory, infectious, or immune-mediated etiologies presents a chronic clinical challenge, requiring a balance of anatomical precision, biocompatibility, and reduced immunological risk.
In patients with a history of inflammatory or viral ocular conditions (e.g., VZV), the ocular surface becomes vulnerable to immune-mediated damage, chronic inflammation, and cicatricial alteration.
Scleral or therapeutic lenses, originally developed for keratoconus, allow for continuous physical intervention without requiring invasive grafts, serving as biofunctional platforms for printed therapies.
Future Directions and Preclinical Validation
To reinforce feasibility, the following steps are proposed:
Suggested preclinical model: validation in an immunocompetent murine model with application of printed lens (Phase 1 and 2) on induced corneal erosion. Evaluation would include fluorescein staining, epithelial histology, and local immune activation markers.
Current limitations: the avascular nature of the cornea may require additional support for bio-ink survival; co-formulation with stabilizing factors such as type I collagen and slow-release hydrogels is suggested.
Relevant clinical precedents: previous studies demonstrate the use of autologous SVF in ocular surface regeneration, as well as CD14⁺ monocytes as local inflammation modulators (ref. PubMed ID: 28678923; 31245688).
Recommended visualization: a schematic figure of the therapeutic lens is advised, illustrating the two printed phases (initial immunomodulation and subsequent regeneration) and its interface with the eroded cornea.
Technology Proposal
Immunomodulatory bio-ink sourcing:
Monocyte-enriched bio-ink can be obtained via ultracentrifugation of a patient’s blood sample (~20 minutes). This process isolates the immune cell-rich fraction, which can be used directly as the active component in the immunomodulatory phase.
Adipose-derived regenerative bio-ink sourcing:
Autologous adipose tissue may be harvested under local or general anesthesia, depending on clinical condition and patient tolerance. Only small volumes are required. Standard SVF or mesenchymal stem cell isolation techniques can be used. To provide structural support and improve integration with the ocular surface, the bio-ink may be formulated with hyaluronic acid and collagen, creating a matrix compatible with corneal regeneration.
Phase 1 – Immunomodulation and APC stimulation:
Monocyte-derived autologous bio-ink applied to a personalized therapeutic lens. This phase aims to:
Control local infections or viral reactivations
Enhance exposure to antigen-presenting cells (APCs)
Regulate the ocular inflammatory microenvironment
Activate M2-like pro-regenerative immune profiles
Phase 2 – Structural regeneration:
Autologous adipose-derived bio-ink (e.g., SVF) or autologous stem cells printed sequentially onto the same lens after environment stabilization. This phase aims to:
Stimulate corneal re-epithelialization
Restore extracellular matrix
Prevent neovascularization and post-inflammatory irregular astigmatism
Both phases would utilize PROSE-type lenses (Boston Foundation) or custom hybrid lenses adapted for personalized printing.
Epidemiological and Economic Burden
Herpes zoster ophthalmicus (HZO): accounts for 10–25% of 500,000 annual shingles cases in the U.S.; 40–50% develop ocular complications (Wikipedia, HZO).
Herpes simplex keratitis: affects 1.5 million people annually; over 40,000 develop severe vision loss (Wikipedia, Herpes Simplex Keratitis).
CMV-associated keratitis (post-transplant): causes up to 70% graft failure (SpringerLink, 2024).
Direct economic burden (U.S., 2010): USD $175 million annually for keratitis care, including outpatient visits, ER visits, Medicare and Medicaid costs (CDC, MMWR).
Global impact of herpes zoster (2021): 4.5 million new cases in adults over 70 years; over 113,000 DALYs lost (PubMed, 2024).
These conditions often result in corneal scarring with irregular astigmatism, for which corneal transplantation remains the only effective solution—a high-cost, limited-access procedure in many regions.
The proposed immunoregenerative approach could significantly reduce this medical and economic burden by preventing irreversible damage and enhancing healthcare system efficiency.
Proposal Innovation
Non-invasive: avoids corneal transplantation and hospitalization
Autologous and personalized: reduces immunological risk
Sequential and modular: allows for iteration based on clinical response
Translational: leverages existing technologies (bioinks, SVF, therapeutic lenses)
Open Call for Co-Development
This idea is published explicitly to inspire collaborative research, preclinical proof-of-concept, or integration into existing platforms.
We invite stakeholders in ocular bioprinting, regenerative therapy, and clinical ophthalmology to consider this proposal as a launch point for partnerships, validation, and eventual clinical translation.
Open Access Declaration
This document does not seek to establish restrictive intellectual property, but to share a frontier vision to accelerate medical innovation.
Contact: yoonhwa.an@biopharmabusinessintelligenceunit.com
Author: Dr. YoonHwa An
Date: July 2025
Affiliation: Biopharma Business Intelligence Unit (BBIU)
