A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye.
Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 μm or <40 μm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi-PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells.
Department of Ophthalmology, Flinders University, Bedford Park, 5042 SA, Australia.
Yazad D
YD
Irani
Department of Chemistry, Texas Christian University, Fort Worth, TX 76129, USA.
Yuan
Y
Tian
Department of Chemistry, Texas Christian University, Fort Worth, TX 76129, USA.
Mengjia
M
Wang
Department of Anatomical Pathology, Flinders University, Bedford Park, 5042 SA, Australia.
Sonja
S
Klebe
Mawson Institute, University of South Australia, Mawson Lakes 5095, Australia.
Steven J
SJ
McInnes
Mawson Institute, University of South Australia, Mawson Lakes 5095, Australia.
Nicolas H
NH
Voelcker
Department of Chemistry, Texas Christian University, Fort Worth, TX 76129, USA.
Jeffery L
JL
Coffer
Department of Ophthalmology, Flinders University, Bedford Park, 5042 SA, Australia. Electronic address: keryn.williams@flinders.edu.au.
Keryn A
KA
Williams
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005128:Eye Diseases / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000494:pharmacology*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000494:pharmacology*; D013718:Tensile Strength
D001672:Biocompatible Materials; D004338:Drug Combinations; D011091:Polyesters; C016240:polycaprolactone; D012825:Silicon
Cell proliferation; Composite biomaterial; Drug release; Inflammation; Nanostructured porous silicon; Polycaprolactone