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.
in 2005, Coffer et al. demonstrated studies on the in vitro calcification and proliferation of fibroblasts on the surfaces of pSi/pCl composites.76 these particular composites were prepared by mixing the mesoporous silicon (67%
porosity) in a 1% or 5% (w/w) polymer solution, thereby creating a well- dispersed suspension followed by salt leaching methods resulting in a highly porous composite as shown in figure 4.4.
figure 4.4(a) shows the porous morphology of the pSi/pCl material, with micron-sized holes. after two weeks of exposure to an acellular simulated body fluid (SBf) at 37 °C, there were small precipitates about 100 nm in size detected on the surface of the pSi/pCl composites with the confirmed com- position of calcium phosphate, figure 4.4(B). in addition to the performed calcification assays, in vitro cell proliferation data for human kidney fibro- blasts (heK293) were acquired, showing cell viability in the presence of the pSi/pCl composites.76
a significant advance was reported in 2006, when Batra et al. reported the controlled release of compounds from a semiconducting calcium phos- phate/pSi structure.75 this was demonstrated for the reversible adsorption and release of multiple compounds—an anionic salt of fluorescein, ethid- ium bromide, acridine orange—upon the switching of the direction of bias to the underlying porous Si/Si substrate. for all of these compounds, their delivery/uptake can be mediated in part by the use of a surface layer of the biodegradable polymer poly-(ε-caprolactone) (pCl).
in 2007, the Coffer group continued this work by adding polyaniline (paNi)—an electrically conductive polymer—to pSi/poly(ε-caprolactone) pCl composites.77 the goal was to fabricate a “smart” conductive scaffold in order to achieve an accelerated formation of calcium phosphate for an increased bone growth rate. typically, 10% paNi by weight was incorporated into pSi/pCl composites. figure 4.5 illustrates SeM images of a leached pCl sponge as well as leached pCl sponge with 10% paNi coating with ∼1% pSi incorporated into the scaffold.
the resultant pCl/paNi/pSi composite had a very smooth surface coat- ing of paNi and still retained its macroscopic porosity, which is eventually favored for tissue engineering.
Figure 4.4 (a) SeM image of a porous pSi/pCl composite scaffold (1% pSi). Scale bar
= 10 µm. (B) energy dispersive X-ray spectrum of a mesoporous Si (1%)/
pCl scaffold exposed to simulated body fluid (SBf) at 37 °C for 14 days.76
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
in order to assess whether it is possible for the application of electrical bias to influence calcification, a pCl/paNi/pSi composite (1% w/w) at a constant potential of 1.0 V under cathodic conditions was applied to the structure while immersed in SBf for seven hours at room temperature. Calcium phos- phate deposits were formed on a pSi-containing sample and were absent on a control sample. figure 4.6(a) shows SeM images of a pCl/paNi/1% pSi sample after the bias was applied.
the spectrum in figure 4.6(B) shows that the sponge is phosphate-rich with a p–Ca ratio of ∼4.4, but after an additional soaking time in SBf at 37 °C for one week, the calcium-to-phosphate ratio increased to a range of
∼1.1–1.7, which is consistent with dicalcium phosphate and hydroxyapatite, respectively. these results clearly demonstrate accelerated calcification of pCl/paNi/pSi composites in SBf when an electrical bias is applied. how- ever, in the absence of bias, calcification is not observed for periods up to a month. these “smart” composites were also tested for cytocompatibility using human kidney fibroblasts (heK 293) along with more orthopedically relevant mesenchymal stem cells from mouse stroma. in both cases, pCl/
paNi/pSi had no toxic effect on cell growth.
With further refinements, these composites can ideally prove to be very beneficial for responsive bone repair, as they are able to promote calcification on demand, and show non-toxic character in the growth and proliferation of cells. With proper tailoring of the polyaniline, it is possible to envision the full degradability of these composites after implantation.
4.5 Clinical Potential
as pointed out above, the fact that porous silicon induces calcification in vitro and in vivo suggests pragmatic investigation into difficult cases (e.g.
non-union bone growth) in orthopedics at the clinical level. in addition, the challenges of ocular tissue repair, with a concomitant need for adjuvant drug delivery, also make ophthalmological applications a clear area of promise Figure 4.5 (a) SeM images of a leached pCl sponge (90% porosity), (B) a leached pCl sponge with a 10% paNi surface coating and ∼1% porous silicon showing the smoother microstructure accompanying the addition of paNi.77
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
Chapter 4104 Figure 4.6 (a) SeM image of a leached pCl/paNi/1% pSi sponge after bias was applied showing the presence of Cap. Scale bar is 1 µm.
(B) Corresponding edX of (a). (C) a one-month soak of a similar sample in SBf at 37 °C with zero bias. Calcification occurred only after the sponge was soaked in SBf for one month.
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090
that warrants investment in the near term. in particular, given their favorable properties, pSi/biocompatible polymer composite scaffolds in conjunction with limbal stem cell seeding are appealing candidates for clinical investiga- tions for the possible treatment of chronic eye inflammatory diseases. these fields are ripe for additional discovery and, more importantly, will be of benefit to patients.
4.6 Summary and Future Opportunities
in this chapter we have summarized a number of the key useful properties of porous silicon and associated biocompatible polymer composites that make them relevant candidates for tissue engineering and related applica- tions. While the focus to date has been exclusively at the preclinical level, the demonstrated promise of those studies that center on the evaluation of the perceived “smart” functions of porous silicon—including electrical bias—
are just beginning to be realized. With dedicated effort, useful nanostruc- tures based on porous silicon and selected composites should one day be a part of the theranostic toolkit of the clinician.