Abstract
Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are preloaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle-drug-polymer hybrids are prepared in the form of oriented poly(lactic-co-glycolic acid) nanofiber scaffolds. Three different therapeutic payloads are tested: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin-related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water-soluble payloads. The drug-loaded pSiNP-nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay.
| Original language | English |
|---|---|
| Article number | 2002560 |
| Journal | Advanced Functional Materials |
| Volume | 30 |
| Issue number | 25 |
| DOIs | |
| State | Published - Jun 1 2020 |
Bibliographical note
Publisher Copyright:© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Funding
J.M.Z. and C.M.D. contributed equally to this work. The authors thank Dr. Kendell Pawelec and Prof. Jeff Sakamoto for helpful discussions regarding this research. This study was supported by the National Science Foundation under Grant No. CBET‐1603177 (M.J.S.), and in vitro DRG studies were supported in part by the National Institutes of Health under Grant No. NIBIB‐RO1‐EB005678 (L.D.S.). Transmission electron micrographs were obtained in the Cellular and Molecular Medicine Electron microscopy core facility, which is supported in part by National Institutes of Health Award number S10OD023527. This work was performed in part at the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS‐1542148). This project received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement No 704120 (“MIRNANO”). A.B. is a Global Marie Sklodowska‐Curie Fellow. J.K. acknowledges financial support from the UCSD Frontiers of Innovation Scholars Program (FISP) fellowship. J.W. thanks the NIH for the predoctoral training grant 2T32CA1539106A1 (CRIN). J.M.Z. and C.M.D. contributed equally to this work. The authors thank Dr. Kendell Pawelec and Prof. Jeff Sakamoto for helpful discussions regarding this research. This study was supported by the National Science Foundation under Grant No. CBET-1603177 (M.J.S.), and in vitro DRG studies were supported in part by the National Institutes of Health under Grant No. NIBIB-RO1-EB005678 (L.D.S.). Transmission electron micrographs were obtained in the Cellular and Molecular Medicine Electron microscopy core facility, which is supported in part by National Institutes of Health Award number S10OD023527. This work was performed in part at the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS-1542148). This project received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sk?odowska-Curie grant agreement No 704120 (?MIRNANO?). A.B. is a Global Marie Sklodowska-Curie Fellow. J.K. acknowledges financial support from the UCSD Frontiers of Innovation Scholars Program (FISP) fellowship. J.W. thanks the NIH for the predoctoral training grant 2T32CA1539106A1 (CRIN).
| Funders | Funder number |
|---|---|
| European Union's Horizon 2020 research and innovation program | |
| National Science Foundation Arctic Social Science Program | CBET‐1603177 |
| National Institutes of Health (NIH) | ECCS‐1542148, NIBIB‐RO1‐EB005678, 2T32CA1539106A1, S10OD023527 |
| University of California San Diego Health | |
| Horizon 2020 | 704120 |
Keywords
- controlled release
- nerve growth factors
- neuron guidance
- PTEN inhibitor
- RNA aptamers
- tissue engineering
- TrkB
ASJC Scopus subject areas
- Electronic, Optical and Magnetic Materials
- General Chemistry
- Biomaterials
- General Materials Science
- Condensed Matter Physics
- Electrochemistry