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Int J Mol Sci. 2017 May 21;18(5). pii: E1104. doi: 10.3390/ijms18051104.

Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration.

Author information

1
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, 04317 Leipzig, Germany. caroline.kohn@uni-leipzig.de.
2
Collaborative Research Center (SFB-TR67), Matrixengineering Leipzig and Dresden, Germany. caroline.kohn@uni-leipzig.de.
3
New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8066, USA. bhatnagard@dls.rutgers.edu.
4
New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8066, USA. Woloszyn@bu.edu.
5
Boston University School of Medicine, Boston University, Boston, MA 02118, USA. Woloszyn@bu.edu.
6
New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8066, USA. mdr154@scarletmail.rutgers.edu.
7
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, 04317 Leipzig, Germany. annett.starke@uni-leipzig.de.
8
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, 04317 Leipzig, Germany. alexandra.springwald@uni-leipzig.de.
9
Collaborative Research Center (SFB-TR67), Matrixengineering Leipzig and Dresden, Germany. sandra.franz@medizin.uni-leipzig.de.
10
Department of Dermatology, Venereology and Allergology of Medical Faculty of Leipzig University, 04317 Leipzig, Germany. sandra.franz@medizin.uni-leipzig.de.
11
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, 04317 Leipzig, Germany. schulz@uni-leipzig.de.
12
Collaborative Research Center (SFB-TR67), Matrixengineering Leipzig and Dresden, Germany. schulz@uni-leipzig.de.
13
New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8066, USA. kaplanh@dls.rutgers.edu.
14
New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8066, USA. kohn@dls.rutgers.edu.
15
Institute of Pharmacy, Pharmaceutical Technology, Leipzig University, 04317 Leipzig, Germany. mhacker@uni-leipzig.de.
16
Collaborative Research Center (SFB-TR67), Matrixengineering Leipzig and Dresden, Germany. mhacker@uni-leipzig.de.

Abstract

Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.

KEYWORDS:

LM11A-31; bioconjugation; cross-linked gelatin; filler; human adipose-tissue derived stem cells; injectable hydrogel; maleic anhydride; nerve regeneration; oligomer; shear thinning

PMID:
28531139
PMCID:
PMC5455012
DOI:
10.3390/ijms18051104
[Indexed for MEDLINE]
Free PMC Article

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