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Peer-reviewed articles

2025

Shokrollahi,P., Garg,P., Wulff,D., Hui,Al., Phan,C-M., Jones,L Vat Photopolymerization 3D Printing Optimization: Analysis of Print Conditions and Print Quality for Complex Geometries and Ocular Applications International Journal of Pharmaceutics 2025;668(January):124999 [ Show Abstract ]

Abstract: 3D printing, also known as additive manufacturing, continues to reshape manufacturing paradigms in healthcare by providing customized on-demand object fabrication. However, stereolithography-based 3D printers encounter a conflict between optimizing printing parameters, requiring more time, and print efficiency, requiring less time. Moreover, commonly used metrics to assess shape fidelity of 3D printed hydrogel materials like ‘circularity’ and ‘printability’ are limited by the soft nature of hydrogels, that can cause irregularities in their boundary. To unlock the full potential of 3D printing of biomaterials, it is also necessary to understand correlation between printing parameters and ink properties. In this work, a method based on curing depth, overcuring (cumulative cure), and print thickness was developed, which enables a time-efficient and reliable determination of printing conditions for complex geometries using gelatin methacrylate hydrogel biomaterial ink. We also examined the impact of printing direction on the print quality in terms of object/print thickness and aspect ratio. Moreover, the effects of dye concentration, exposure time, and layer thickness on print quality were evaluated, with discussions focused on the correlation between print dimension to layer thickness. Further evaluation was achieved by successfully printing bioinspired corneal stroma-like scaffold and delicate structures like a contact lens and a model eyeball, substantially expanding the scope of this method in producing high-quality prints with intricate details. We also demonstrate the effectiveness of ‘Feret ratio,’ another measure of object shape, in assessing the shape fidelity of different prints. Overall, the results highlight the practical potential of this method in enhancing the speed and reliability of the 3D printing processes involving complex geometries using a low-cost 3D printers.

2024

Mohseni,M., Shokrollahi,P., Barzin, J. Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release International Journal of Biological Macromolecules 2024;263, Part 1(April):Art No 130266 [ Show Abstract ]

Recently, a significantly greater clinical benefit has been reported with a combination of glucosamine sulfate and nonsteroidal anti-inflammatory drugs (NSAIDs) compared to either treatment alone for the growing osteoarthritis (OA) disease. So, this study introduces hydrogels using O-carboxymethyl chitosan (O-CMC, structurally akin glucosamine glycan), and Gelatin type A (GA) in a 1:2 ratio with β-glycerophosphate (βGPh) at varying percentages (5 %, 12.5 %, and 15 %). We show that hydrogel properties, adaptable for drug delivery or tissue engineering, can be fine-tuned based on OCMC:βGPh ratio. CMC/GA/βGPh-12.5 exhibited a swelling rate of 189 %, compressive stress of 164 kPa, and compressive modulus of 3.4 kPa. The self-healing hydrogel also exhibited excellent injectability through a 21-gauge needle, requiring only 5 N of force. Ibuprofen and Naproxen release from CMC/GA/βGPh-12.5 and CMC/GA/βGPh-15 of designed dimensions (bi-layer structures of different diameter and height) were measured, and drug release kinetics were estimated using mathematical equations (MATLAB and polyfit program). CMC/GA/βGPh-12.5 demonstrated significant antibacterial effects against E. coli and S. aureus, a high cell survival rate of 89 % against L929 fibroblasts, and strong cell adhesion, all indicating biocompatibility. These findings underscore potential of these hydrogels as promising candidates for treating inflammatory diseases such as osteoarthritis.

2023

Akbari,E., Imani,R., Shokrollahi,P., Keshel,S. H. Corneal sustained delivery of hyaluronic acid from nanofiber-containing ring-implanted contact lens Journal of Biomaterials Application 2023;37(6):992-1006 [ Show Abstract ]

Dry eye syndrome, as a persist corneal epithelial defect (PED), is an inconvenient ocular disorder that is generally treated by high-dosage, conventional eye drops. Addressing low efficacy and rather restricted bioavailability of the conventional eye drops, drug-eluting contact lenses (CLs) are widely used as alternatives in ophthalmic drug delivery applications. In the present study, a nanofiber-containing ring implant poly (vinyl alcohol) (PVA) hydrogel is designed as a carrier for hyaluronic acid (HA) delivery. hyaluronic acid is physically encapsulated in a nanofiber-containing ring-shaped hydrogel with a 2 mm width that is implanted in the final CLs hydrogel. The designed CL has 59% porosity, 275% swelling ratio and undergoes no weight loss at physiological conditions in14 days. In-vitro release studies were performed on the CLs with and without nanofibers. The results showed that nanofiber incorporation in the designed CL was highly influential in decreasing burst release and supported sustained release of HA over 14 days. In addition, nanofiber incorporation in the designed system strengthened the lens, and the young modulus of the PVA hydrogel increased from 6 to 10 kPa. Cell viability study also revealed no cell cytotoxicity and cell attachment. Overall, the study demonstrated the effective role of nanofibers in the physical strengthening of the CL. Also, the designed system holds promise as a potential candidate for HA delivery over an extended period for treating dry eye syndrome.

Scientific Presentations

2024

Garg P, Shokrollahi P, Phan CM, Jones L. 3D printing of PVA loaded ocular inserts for ocular drug delivery The Association for Research in Vision and Ophthalmology, Seattle, WA, May 9, 2024 [ Show Abstract ][ PDF ]

Purpose: To develop ocular inserts comprised of polyvinyl alcohol (PVA) and gelatin methacrylate (GelMA), using 3D printing technology.

Methods: Inserts were synthesized using a bioink formulation consisting of 10% (w/v) GelMA, 5% (w/v) and 7.5% (w/v) PVA, 0.6% (w/v) lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and 5% (v/v) yellow dye as a light absorbing agent to improve print resolution. They had a 4mm diameter, 1mm thickness and were fabricated using a commercial masked-stereolithography (mSLA) 3D printer at 95% humidity and 37°C temperature. Morphology of the inserts was investigated by freeze-drying samples and imaging them using a scanning electron microscope (SEM). Release of PVA over 5 hours was studied by incubating at 35°C in PBS in an incubator shaker at 50rpm. The hydrogel samples were freeze dried and their equilibrium swelling was studied in PBS using gravimetric method.

Results: The PVA-loaded ocular inserts were 3D printed within 30 minutes. SEM images showed that 7.5% PVA loaded inserts had more uniform pore size distribution compared to the gels with no PVA. Approximately 37% of PVA was released within the first 2 hrs from the inserts containing PVA, and the release continued up to approximately 4 hrs before reaching a plateau. The release kinetics can be attributed primarily due to passive diffusion. The swelling curves of these hydrogels suggest that they reach equilibrium swelling within 24hr. From the slope of the swelling curve in the first hour, it can be inferred that swelling happens at a slower rate for GelMA/PVA compared to GelMA alone. This slower swelling rate helps to control the release and supports a sustained release of PVA from the combination.

Conclusions: This study showed that a GelMA-PVA based bioink can be used to 3D print ocular inserts that can release PVA for up to 4 hours. Future work will focus on designing 3D scaffolds to increase the release duration of PVA from these gels.

Ho B, Phan CM, Garg P, Shokrollahi P, Jones L. A screening platform for simultaneous evaluation of biodegradation and therapeutic release from an ocular hydrogel and its effect on human corneal epithelial cells The Association for Research in Vision and Ophthalmology, Seattle, WA, May 7, 2024 [ Show Abstract ][ PDF ]

Purpose: To integrate human corneal epithelial cells (HCECs) into a millifluidic screening platform that quantifies biodegradation and release of an entrapped therapeutic from an ocular hydrogel.

Introduction: Biodegradable hydrogels are novel drug delivery methods designed to release entrapped drugs or therapeutics as the gel degrades in situ. The primary challenge in developing biodegradable hydrogels for drug delivery lies in accurately measuring their degradation over time, while simultaneously being able to evaluate the drug release kinetics, which is typically a cumbersome procedure. To properly evaluate the biodegradation of a hydrogel, it is also essential to simulate key factors of the target tissue environment. In the context of the eye, this includes ocular temperature, tear flow, and low tear volume. Recent advances in organ-on-a-chip technologies have made it possible to emulate the human corneal environment. This will allow more accurate measurements of hydrogel degradation rates, subsequent drug or therapeutic release, and ultimately the overall effect on human corneal epithelial cells.

Methods: Gelatin Methacrylate (GelMA) ocular inserts with polyvinyl alcohol (PVA) (10% GelMA 7.5% PVA) were placed inside a custom-designed millifluidic device. Ocular inserts were degraded with up to 200 μg/mL of matrix metallipeptidase 9 (MMP9) for 24 hours at 37oC in PBS. Biodegradation of the ocular insert was quantified using a computational image analysis pipeline. The eluates containing the degradation products were collected to measure PVA released using a spectrophotometric assay, and its toxicity on human corneal epithelial cells (HCECs) was determined by alamarBlueTM assays.

Results: There was significant biodegradation of the GelMA-PVA inserts with increasing concentration of MMP9 in the millifluidic device, which was accurately quantified using a custom computational analysis. Degradation products in the eluate were collected, and there was a ~2-fold increase of PVA released in samples treated with MMP9 compared to the control. The same eluates were non-toxic to HCECs, and interestingly protected HCECs from hyperosmotic conditions mimicking dry eye disease.

Professional Publications

2024

Shokrollahi P. Fast Forward to the Future: Material science innovation Contact Lens Spectrum 2024;39, June: 34