Journal article
Two-photon polymerized poly(caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility
Acta biomaterialia, Vol.94, pp.204-218
08/2019
DOI: 10.1016/j.actbio.2019.04.057
PMID: 31055121
Abstract
[Display omitted]
Cell replacement therapies are often enhanced by utilizing polymer scaffolds to improve retention or direct cell orientation and migration. Obstacles to refinement of such polymer scaffolds often include challenges in controlling the microstructure of biocompatible molecules in three dimensions at cellular scales. Two-photon polymerization of acrylated poly(caprolactone) (PCL) could offer a means of achieving precise microstructural control of a material in a biocompatible platform. In this work, we studied the effect of various formulation and two-photon polymerization parameters on minimum laser power needed to achieve polymerization, resolution, and fidelity to a target 3D model designed to be used for retinal cell replacement. Overall, we found that increasing the concentration of crosslink-able groups decreased polymerization threshold and the size of resolvable features while increasing fidelity of the scaffold to the 3D model. In general, this improvement was achieved by increasing the number of acrylate groups per prepolymer molecule, increasing the acrylated PCL concentration, or decreasing its molecular weight. Resulting two-photon polymerized PCL scaffolds successfully supported human iPSC derived retinal progenitor cells in vitro. Sub-retinal implantation of cell free scaffolds in a porcine model of retinitis pigmentosa did not cause inflammation, infection or local or systemic toxicity after one month. In addition, comprehensive ISO 10993 testing of photopolymerized scaffolds revealed a favorable biocompatibility profile. These results represent an important step towards understanding how two-photon polymerization can be applied to a wide range of biologically compatible chemistries for various biomedical applications.
Inherited retinal degenerative blindness results from the death of light sensing photoreceptor cells. To restore high-acuity vision a photoreceptor cell replacement strategy will likely be necessary. Unfortunately, single cell injection typically results in poor cell survival and integration post-transplantation. Polymeric biomaterial cell delivery scaffolds can be used to promote donor cell viability, control cellular polarity and increase packing density. A challenge faced in this endeavor has been developing methods suitable for generating scaffolds that can be used to deliver stem cell derived photoreceptors in an ordered columnar orientation (i.e., similar to that of the native retina). In this study we combined the biomaterial poly(caprolactone) with two-photon lithography to generate a biocompatible, clinically relevant scaffold suitable for retina cell delivery.
Details
- Title: Subtitle
- Two-photon polymerized poly(caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility
- Creators
- Jessica R Thompson - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAKristan S Worthington - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USABrian J Green - Department of Chemical and Biochemical Engineering, The University of Iowa, 4133 Seamans Center, Iowa City, IA 52242, USANathaniel K Mullin - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAChunhua Jiao - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAEmily E Kaalberg - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USALuke A Wiley - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAIan C Han - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAStephen R Russell - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAElliott H Sohn - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAC. Allan Guymon - Department of Chemical and Biochemical Engineering, The University of Iowa, 4133 Seamans Center, Iowa City, IA 52242, USARobert F Mullins - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USAEdwin M Stone - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USABudd A Tucker - Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, The University of Iowa, 4111 Medical Education and Research Facility, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Acta biomaterialia, Vol.94, pp.204-218
- DOI
- 10.1016/j.actbio.2019.04.057
- PMID
- 31055121
- NLM abbreviation
- Acta Biomater
- ISSN
- 1742-7061
- eISSN
- 1878-7568
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100008982, name: National Science Foundation; DOI: 10.13039/100001818, name: Research to Prevent Blindness; DOI: 10.13039/100001694, name: International Retinal Research Foundation; DOI: 10.13039/100002089, name: Fight for Sight; DOI: 10.13039/100000002, name: National Institutes of Health
- Language
- English
- Date published
- 08/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Fraternal Order of Eagles Diabetes Research Center; Chemical and Biochemical Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070206202771
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