4.2 Fundamentals of Porous Silicon (pSi)
4.2.5 Advantages of pSi/Polymer Composites as Implants for Tissue Engineering
polymers (natural and synthetic) have been extensively employed in the field of tissue engineering due to the myriad of useful properties that are important for their use as scaffolds or drug delivery devices. among these properties are mechanical stiffness, flexibility, and degradability. in addition, polymers can be sculpted into different shapes/forms in order to be used in a wide range of applications. Some common biodegradable synthetic polymers extensively studied and used since the 1930s include poly(lactic acid), pla, poly(glycolic acid), pGa, poly(ε-caprolactone), pCl.42 however, there are a few disadvantages to their use. these include: a low drug loading capability, low melting tempera- tures, insufficient mechanical properties, and lack of optical properties that can be used for label-free sensing.43 therefore, there is an emerging interest in
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
Chapter 498 Figure 4.2 photographs of the cells’ gaps at 0 and 24 h after incubation with the samples at 37 °C in 5% Co2 and 95% relative humidity.
the cells were seeded into the two chambers of the inserts and left in the incubator overnight in order to attach to the µ-dish.
on the following day, the insert was removed, and the samples were seeded into the appropriate dish. the white lines mea- sure the width of the gaps in µm. Samples: dMeM without serum (M w/s); pl (1 : 40 dilution; pl 1/40); pl “as in particles”;
pl-modified thCpSi 1 and 1.5 mg ml−1; and thCpSi 1 and 1.5 mg ml−1. (reprinted (adapted) with permission from (fontana et al. ‘platelet lysate-Modified porous Silicon Microparticles for enhanced Cell proliferation in Wound healing applications, aCS appl. Mater. interfaces, 2016, 8, 988-996 41). Copyright (2016) american Chemical Society.)
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
the development of composite materials such as pSi/polymers with improved mechanical properties, optical properties for self-reporting, as well as a pre- cisely controlled degradation and drug delivery kinetics for adjuvant therapies.
Given the significance of eye-related diseases in quality-of-life issues, we choose to discuss here an example of the use of pSi/polymer implants for treat- ment of dysfunctional corneal surfaces that are responsible for painful and blinding diseases such as uveitis. in 2009, low et al used thermally oxidized, aminosilanised porous silicon membranes as a host scaffold for the attach- ment and growth of human ocular cells. after implantation of the pSi mem- brane into a rat eye, the seeded cells were viable and moved into ocular tissue causing very little host reaction. the duration of implantation was nine weeks, by the end of which most of the pSi was observed to have been degraded.44
these results were very encouraging and prompted further studies that were reported in 2010 by Kashanian et al., who proposed pSi encapsulation in microscale fibers of the biodegradable polymer polycaprolactone (pCl).45 the introduction of pCl fibers improved the system by providing mechanical flexibility to the construct, removed sharp edges present in pSi microparticles, inhibited a rapid hydrolysis of the pSi, and promoted better human lens epithe- lial (hle) cell line proliferation on the fiber template. as the dissolution rate of pSi particles is strongly dependent on pSi surface chemistry, two different types of pSi particle surfaces (hydrogen-terminated and surface-oxidized) were investigated. the rates of dissolution were governed by both the presence of the polymer and the surface chemistry of pSi particles, with the latter turning out to be more dominant. as expected, the hydride-terminated pSi samples had clearly dissolved to a greater extent by the end of a 30-day observation period.
also in these studies, in vivo experiments using a rat eye model showed no evidence of infection around the implant site.45 a foreign-body response was observed for all pSi/pCl composites, with some histiocyte infiltration at the sites of implantation that were completely resolved over time. Composite fibers containing the surface-oxidized pSi particles demonstrated a superior performance, showing no measurable fibrous capsule. overall, these results suggested further investigation including incorporation and release of useful therapeutics and transfer of cells.
in 2015, irani et al. extended this work by proposing a new method of fabricating pSi/pCl composites where pSi particles are only partially encap- sulated onto pCl fibers, which would allow for a higher drug loading and release.46 this new type of composite permits drug loading after prepara- tion of the composite, thereby posing a significant advantage over com- pletely encapsulated pSi, as exposure of many drugs to solvents present in pCl during composite fabrication would lead to drug denaturation. in this study, a model drug (fluorescein diacetate (fda)) and proteins such as insu- lin, transferrin, and epidermal growth factor (eGf) were successfully loaded into the composites. hle cell attachment assays were carried out, indicating very successful cell attachment and proliferation on the composites. lastly, these composites were also tested in vivo, with implantation under the rat conjunctiva resulting in no significant inflammation after eight weeks.
figure 4.3 demonstrates the progression of pSi and pSi/pCl implants in vivo.
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
Figure 4.3 (1) thermally-oxidized, amine-terminated porous silicon membranes implanted under rat conjunctiva, shown immediately after implanta- tion (a) and nine weeks (a-i), (reprinted from the biocompatibility of porous silicon in tissues of the eye, 30, S. p. low, N. h. Voelcker, l. t.
Canham and K. a. Williams, 2873–2880, Copyright (2009), with permis- sion from elsevier). (2) oxidized pSi in pCl at one week (B) and eight weeks (B-i) after implantation beneath the conjunctiva, (reprinted from evaluation of mesoporous silicon/polycaprolactone composites as oph- thalmic implants, 6, S. Kashanian, f. harding, y. irani, S. Klebe, K. Mar- shall, a. loni, l. Canham, d. M. fan, K. a. Williams, N. h. Voelcker, J.
l. Coffer, 3566–3572, Copyright (2010), with permission from elsevier).
(3) pressed pSi/pCl composite implanted under the rat conjunctiva, immediately after implantation (C) and eight weeks post implantation (C-i), (reprinted from a novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye, 139, y. d. irani, y. tian, M. J. Wang, S. Klebe, S. J. p. Mcinnes, N. h. Voelcker, J. l. Coffer, K. a. Williams, 123–131, Copyright (2015), with permission from elsevier). arrows mark the implants.
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
in figure 4.3(1), one can see that pSi membranes at the end of nine weeks showed definite migration from the starting implantation point, which can potentially end up in the vicinity of the visual axis and cause vision impair- ment. also, it is highly undesirable to have a rigid material with sharp edges such as pSi move within the tissue, possibly causing any additional inflamma- tory response. however, when pSi is combined with the polymer, there is no visible pSi particle migration from the site of the implantation as shown in figure 4.3(2) and (3). overall, pCl introduces flexibility and provides secure anchoring of pSi particles (or membranes). these pSi/pCl composites demon- strate great potential to be used for ocular surface disease treatment with the ability of high drug/protein load and release and biocompatibility in vivo.