Porous Silicon (pSi) Can Be Processed into a Variety of Shapes and Forms

4.2 Fundamentals of Porous Silicon (pSi)

4.2.1 Porous Silicon (pSi) Can Be Processed into a Variety of  Shapes and Forms

in the case of tissue engineering scaffold design, one has to consider the vari- ety of physical forms that a material needs to conform to in order to ensure optimum cellular attachment, differentiation, and proliferation. Multiple particle shapes have been investigated for the possible exploitation of pSi as a theranostic platform, including thin films, as-prepared coarse micro- particles, lithographically-designed hemispherical domes,⁵ square-shaped

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090

Chapter 492 Table 4.1    Key milestones for pSi as a “smart” material.

Milestone property evaluated reference

pH-Responsive thermally hydrocarbonized pSi nanoparticles functionalized with chitosan and coated with a ph- responsive polymer, hydroxyl-propylmethyl cellulose acetate succinate (hpMCaS-Mf) for a dual protein-drug (Glp-1 and dpp4) delivery system

49 (2015)

pSi loaded with sorafenib and functionalized with a ph-responsive polymer—polyethylene glycol- block-poly(l-histidine) and poly(ethylene glycol)-block-polylactide methyl ether—for a multi-stage drug delivery system (MddS)

50 (2015)

thermally hydrocarbonized pSi loaded with atorvastatin followed by encapsulation into the ph- responsive polymer (hypromellose acetate succinate) containing celecoxib to obtain a multi-drug loaded system for combination therapy

51 (2014)

the pSi external surface was functionalized with folic acid and fluorescein isothiocyanate for target- ing and imaging, respectively. the pore walls were functionalized with carboxyl groups to obtain a higher loading degree of doxorubicin and promote a ph-triggered drug release

52 (2014)

photonic pSi film coated with ph-responsive polymer 2-diethylaminoethyl acrylate (p-deaea), is used to detect ph changes during acidification of chronic wound fluid as a result of bacterial infection

53 (2014) pSi nanoparticles with a ph-responsive nano valve consisting of an aromatic amino group and a cyclo-

dextrin cap for drug release inside cells

54 (2011) the pore openings of the pSi nanoparticles were grafted with a ph-responsive nano valve of poly(β-amino

ester) and the external surface with pluronic f-127. the drug ptX was encapsulated into the external layer of pluronic f-127 and doX was loaded inside the pores thus enabling spatiotemporal drug release

55 (2015)

ph-triggered release of the antibiotic vancomycin from porous Si films containing a BSa protein- capping layer

56 (2008) pSi nanoparticles are functionalized with ph-responsive peGdB polymers. this nanocomposite exhibits

improved endosomal escape and thus improved pNa delivery to cytosol where target mirNa are located

57,58 (2016, 2014) Temperature-

responsive thermoresponsive amine-terminated poly(N-isopropylacrylamide) brushes are grafted to thin films of freshly-etched porous Si

59 (2009) pSi was loaded with camptothecin and coated with temperature-responsive poly(N-isopropylacrylamide-

co-diethylene glycol divinyl ether) to achieve a sustainable and temperature-dependent drug delivery

60 (2016) pSi films coated with thermoresponsive polymer, poly(N-isopropylacrylamide), for a feedback-

controlled drug release

61 (2011) pSi nanoparticles were loaded with doxorubicin hydrochloride and trigger the release either under

ir or rf irradiation

62 (2016)

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090

93Advances in Silicon Smart Materials for Tissue Engineering Self-reporting

(biosensor) psi-based system as a label-free, non-invasive method to continuously monitor cell morphology known as a “smart” petri dish

63 (2006) pSi-optical sensor interfaced with human epithelial cells on the peptide-functionalized regions for

detection of cellular responses

64 (2011) pSi-optical sensor coated with an enzymatic degradable polymer, poly(oligoethylene glycol-co-acrylic

acid)-N3 to monitor matrix metalloproteinases’ enzyme activity

65 (2014) pSi grafted with resazurin as a luminescence-enhancing optical biosensing platform for l-lactate

dehydrogenase detection

66 (2015) pSi rugate filter is biocompatible and optically functional in vitro, and importantly, in a subcutaneous

passive biosensing setting

67 (2016) pSi-optical sensor to monitor the release of bovine serum albumin (BSa), a model protein payload ⁶⁸ (2016) the incorporation of a chemically-sensitive hydrogel into a 1d photonic pSi transducer is evaluated

upon exposure to a target-reducing agent analyte, tris(2-carboxyethyl) phosphine. this sensing system is capable of direct visual color readout

69 (2010)

photonic pSi coated with a ph-responsive polymer can be used to detect ph changes in aqueous media in order to report on acidification of chronic wound fluid through a color change that is visible to the unaided eye

53 (2014)

pSi as a label-free sensor that is applicable for rapid detection of cell capture events and identification of microorganisms e.g., bacteria (E. coli)

70 (2014) intravitreal biocompatibility and dissolution of pSi microparticles with the feasibility of pSi as a plat-

form for an intraocular drug-delivery system with a non-invasive remote monitoring of drug release

71 (2008) Self-sealing pSi particles loaded with sirNa act as a self-sealing device through formation of an insoluble salt shell

(calcium silicate) inside the pores to protect high concentrations of sirNa

72,73 (2016, 2010) Self-assembling the suitably-modified pSi particles spontaneously align at an organic liquid–water interface, with the

hydrophobic side oriented toward the organic phase and the hydrophilic side toward the water.

Sensing is accomplished when liquid at the interface infuses into the porous mirrors, inducing predictable shifts in the optical spectra of both mirrors

2 (2003)

thermally hydrocarbonized pSi nanoparticles were modified with a self-assembled coating consisting of fungal hydrophobin (hfBii), which showed an increased accumulation in the liver and spleen compared to the uncoated nanoparticles

74 (2012)

Electronically-

responsive the controlled release of encapsulated charged species to and from a semi-conducting calcium phosphate/pSi structure was reported, utilizing the electrical conductivity of the material

75 (2006)

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090

nanoparticles created via perforated etching methods,⁶ silicon nanotubes,⁷ as well as porous machined cubes,⁸ and nanoneedles,⁹ some of which are illustrated in figure 4.1. the disc, cube, and related small nanoparticle morphologies of pSi are most commonly investigated with regard to circulatory system-based drug delivery, rather than selected areas of tissue regeneration.

Mesoporous silicon microparticles like those shown in figure 4.1(e) and (f) have been extensively studied as a drug delivery carrier due to multiple properties (in addition to shape) that are advantageous to drug delivery:

tunable pore size and volume; an ability to enhance drug solubility; as well as controlled degradation kinetics either via surface modification^11,12 or porosity⁴ (vide infra). this topic has been reviewed extensively in multiple recent reports.^13–16 relevant to tissue engineering, pSi can be loaded with various small molecule drugs as well as selected biologics (peptides, enzymes or genes) that can be released afterwards in a sustainable fashion inside a living body to promote tissue healing and regeneration.

one pointed example of this shape-influenced usefulness in therapeutics is the demonstration by Chiappini et al. of the successful injection of nucleic acids via vertical array of biodegradable porous nanoneedles,⁹ which are shown in figure 4.1(d). the intracellular delivery of nucleic acids enables gene expression regulation thus enabling in vivo cellular reprogramming.

Consequently, they were able to deliver an angiogenic gene, which triggered

Figure 4.1    representative shapes and pores of pSi: (a) macroporous Si film, scale bar = 2 µm¹⁰, (B) porous wall silicon nanotubes loaded with cisplatin, scale bar = 50 nm (photo credit: roberto Gonzalez-rodriguez, tCU), (C) nanosize pores of microparticles in (f), scale bar = 100 nm, (d) pSi nanoneedles with the tip diameter ranging from less than 100 nm to 400 nm, scale bar = 200 nm (adapted by permission from Macmillan publishers ltd: Nature Materials Chiappini et al.⁹ copyright (2015)), (e) perforated pSi nanostructures, scale bar = 1 µm⁶ (photo credit: Chia- Chen Wu, UCSd), (f) free-standing mesoporous Si microparticles, scale bar = 10 µm (photo credit: Nelli Bodiford, tCU).

Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00090

the patterned formation of new blood vessels within the tissue, thus estab- lishing local control of damaged tissue.