Two-photon polymerized poly(caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility

Thompson, Jessica R.; Worthington, Kristan S.; Green, Brian J.; Mullin, Nathaniel K.; Jiao, Chunhua; Kaalberg, Emily E.; Wiley, Luke A; Han, Ian C.; Russell, Stephen R.; Sohn, Elliott H.; Guymon, C. Allan; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

doi:10.1016/j.actbio.2019.04.057

Cited by 63 publications

(61 citation statements)

References 56 publications

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“…Their retention in the final structure is an improvement over our own previous design and results in 2-photon polymerized poly(caprolactone) scaffolds. 12 For both gelatin and gelatin/HA, scaffold width increased from bottom to top (Fig. 4).…”

Section: Discussionmentioning

confidence: 95%

“…Conversely, a faster-moving laser (at fast scanning speeds) provides a lower photon dose and theoretically, a lower crosslinking density than at slow scanning speeds. 12 The inverse relationship between crosslinking density and water uptake is well known; these structures are expected to expand as they absorb water during post-processing and thus also reach the fidelity point (and beyond) in this scanning speed range. On the other hand, we hypothesize that the scanning speed range in question (20,000-24,000 mm/s), where the fidelity point is not reached within the bounds of the experiment, represents a balanced region where neither overpolymerization nor swelling dominates the final structure characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…11 Recently, we also applied this fabrication technique to poly(caprolactone), a degradable polyester, and showed that the resulting scaffolds are well tolerated by retinal cells and in vivo retinal tissue. 12 However, high-fidelity disease models should mimic the in vivo environment of the diseased cell type as closely as possible, including both biochemical and biomechanical cues. If cells are not exposed to the same stiffness signals that they would experience in their innate environment, they could respond to disease treatment differently than they would in the body.…”

Section: Introductionmentioning

confidence: 99%

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Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells

Shrestha

Allen

Wiley

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Widely used approaches for retinal disease modeling and in vitro therapeutic testing can be augmented by using tissue-engineered scaffolds with a precise 3-dimensional structure. However, the materials currently used for these scaffolds are poorly matched to the biochemical and mechanical properties of the in vivo retina. Here, we create biopolymer-based scaffolds with a structure that is amenable to retinal tissue engineering and modeling. Methods: Optimal two-photon polymerization (TPP) settings, including laser power and scanning speed, are identified for 4 methacrylated biopolymer formulations: collagen, gelatin, hyaluronic acid (HA), and a 50/50 mixture of gelatin/HA, each with methylene blue as a photoinitiator. For select formulations, fabrication accuracy and swelling are determined and biocompatibility is evaluated by using human induced pluripotent stem cells and rat postnatal retinal cells. Results: TPP is feasible for each biopolymer formulation, but it is the most reliable for mixtures containing gelatin and the least reliable for HA alone. The mean size of microscaffold pores is within several microns of the intended value but the overall structure size is several times greater than the modeled volume. The addition of HA to gelatin scaffolds increases cell viability and promotes neuronal phenotype, including Tuj-1 expression and characteristic morphology. Conclusion: We successfully determined a useful range of TPP settings for 4 methacrylated biopolymer formulations. When crosslinked, these extracellular matrix-derived molecules support the growth and attachment of retinal cells. We anticipate that when combined with existing patient-specific approaches, this technique will enable more efficient and accurate retinal disease modeling and therapeutic testing in vitro than current techniques allow.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells

Shrestha

Allen

Wiley

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

Self Cite

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“…TPP was used to decrease the feature size even further, down to 1 µm for 3D structures [85]. By tuning the number of synthesized acrylate groups, decreasing the molecular weight of the oligomers, and varying the concentration of acrylated PCL, structures with~10 µm pore size, 3 µm feature size, and decreased polymerization threshold were produced via TPP [86]. Methacrylated copolymers of PCL and PLA were also used via TPP to produce scaffolds of~300 µm pore size [87].…”

Section: Polycaprolactone (Pcl)mentioning

confidence: 99%

“…The mechanical behavior of structures fabricated by photopolymerization can be adapted by changing the molecular weight and functionality of the prepolymers. For example, low molecular weight (300 g/mol) prepolymer of PCL triol leads to a higher tensile modulus of 6.9 MPa and a low strain of 13% at break [84,86] compared to the high molecular weight (1250 g/mol) PCL diol, which leads to a tensile modulus of 3.3 MPa and 39% strain at break. Also, the ratio of polymers can be reformed to control mechanical properties.…”

Section: Mechanical Propertiesmentioning

confidence: 99%

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

2019

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The realization of biomimetic microenvironments for cell biology applications such as organ-on-chip, in vitro drug screening, and tissue engineering is one of the most fascinating research areas in the field of bioengineering. The continuous evolution of additive manufacturing techniques provides the tools to engineer these architectures at different scales. Moreover, it is now possible to tailor their biomechanical and topological properties while taking inspiration from the characteristics of the extracellular matrix, the three-dimensional scaffold in which cells proliferate, migrate, and differentiate. In such context, there is therefore a continuous quest for synthetic and nature-derived composite materials that must hold biocompatible, biodegradable, bioactive features and also be compatible with the envisioned fabrication strategy. The structure of the current review is intended to provide to both micro-engineers and cell biologists a comparative overview of the characteristics, advantages, and drawbacks of the major 3D printing techniques, the most promising biomaterials candidates, and the trade-offs that must be considered in order to replicate the properties of natural microenvironments.

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Multiphoton Lithography as a Promising Tool for Biomedical Applications

Gréant

Durme

Hoorick

et al. 2023

Adv Funct Materials

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Multiphoton lithography (MPL) is a powerful and useful structuring tool capable of generating 2D and 3D arbitrary micro‐ and nanometer features of various materials with high spatial resolution down to nm‐scale. This technology has received tremendous interest in tissue engineering and medical device manufacturing, due to its ability to print sophisticated structures, which is difficult to achieve through traditional printing methods. Thorough consideration of two‐photon photoinitiators (PIs) and photoreactive biomaterials is key to the fabrication of such complex 3D micro‐ and nanostructures. In the current review, different types of two‐photon PIs are discussed for their use in biomedical applications. Next, an overview of biomaterials (both natural and synthetic polymers) along with their crosslinking mechanisms is provided. Finally, biomedical applications exploiting MPL are presented, including photocleaving and photopatterning strategies, biomedical devices, tissue engineering, organoids, organ‐on‐chip, and photodynamic therapy. This review offers a helicopter view on the use of MPL technology in the biomedical field and defines the necessary considerations toward selection or design of PIs and photoreactive biomaterials to serve a multitude of biomedical applications.

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Two-photon polymerized poly(caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility

Cited by 63 publications

References 56 publications

Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells

Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

Multiphoton Lithography as a Promising Tool for Biomedical Applications

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