Elsevier

Biomaterials

Volume 26, Issue 17, June 2005, Pages 3511-3519
Biomaterials

Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics

https://doi.org/10.1016/j.biomaterials.2004.09.037Get rights and content

Abstract

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

Introduction

As neurodegenerative diseases become a more pressing concern in society, the need for effective treatment methods increases. Therapeutic possibilities range from electrical interactions with the damaged neuronal circuits to the use of stem cells to replace injured tissue [1], [2], [3]. One challenge is finding materials that effectively interact with neural tissue for these applications. The stability and biocompatibility of different polymers have been studied by examining their effect on the surrounding tissue after implantation [4], [5], [6], [7], [8]. A unique subset of these materials, conducting polymers, has been investigated for use in biomedical applications [9], [10], [11]. Polypyrrole (PPy) has emerged as a promising candidate material that has been effective as a coating in both in vitro and in vivo neural studies [12], [13], [14]. PPy also has shown promise as a scaffold material for nerve regeneration [15].

PPy is an electrodeposited polymer that can be doped with various agents to alter its physical, chemical and electrical properties [16], [17], [18], [19]. The ability to control PPy's surface properties such as wettability and charge density creates the potential for modifying neural interactions with the polymer [20]. Two of the most common dopants that are co-deposited with PPy are polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). PSS/PPy and NaDBS/PPy polymers have been used in many applications ranging from actuators to neural electrode coatings to neural substrates [12], [18], [21]. Another strength of PPy is that erodible forms have been developed which increase the scope of biomedical applications including polymeric devices and neural scaffolds [10], [12]. The ease of deposition and the ability to control growth in both the horizontal and vertical dimensions [22] enables flexibility in the three-dimensional design of polymer implants.

The following in vitro and in vivo studies show the ability of PPy to interact with neural tissue from the mammalian cerebral cortex. The biocompatibility of the PPy implants is compared to stab wounds (where an implant-sized incision is made with no implant left behind) and Teflon implants with similar size and features, and these results demonstrate the positive surface interactions at the PPy implant-cortical interface.

Section snippets

Template design

Our research presents a novel method for fabricating stand-alone PPy neural implants. The implants were designed with several apertures to permit potential neural growth through the implant windows. AutoCad software was used to create the designs for the PPy templates used in electrodeposition. These files were converted to DXF format to fabricate chrome-on-glass masks (International Phototool Company). Two designs were produced, one for the dissociated primary cerebral cortical cell studies

Dissociated cortical neurons

To examine biocompatibility with standard PPy (doped with NaDBS or PSS), in vitro studies were performed with dissociated cortical neurons. Different plating conditions were used to produce differing surface characteristics of the PPy films. We attempted to modify the texture of the PPy surfaces by varying the electrodeposition temperature. The surface texture of PPy/NaDBS electrodeposited at 4 °C appears course and irregular, while at 25 °C, a smoother surface was obtained (Fig. 2a,b). There was

Conclusion

Here, we demonstrate the manufacture of three-dimensional, stand alone PPy substrates that can have a progressively positive biocompatibility profile with CNS parenchyma in vivo. These results support future investigations aimed at using PPy in the design and manufacture of neural prosthetics that are capable of integrating with CNS tissues based on specific chemical and physical properties of the PPy polymer. Such prosthetics should enable reliable transmission of external and internal

Acknowledgements

The authors gratefully acknowledge the contributions of Gwen Donahue. Funding was provided by the Whitaker Foundation, NIH and the Dupont—MIT Alliance. A portion of the work was carried out at the MTL and EMSEF facilities at MIT.

References (23)

  • h. Hsu S- et al.

    Biocompatibility and biostability of a series of poly(carbonate)urethanes

    Colloids and Surfaces BBiointerfaces

    (2004)
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