A hyaluronan-based nerve guide: in vitro cytotoxicity, subcutaneous tissue reactions, and degradation in the rat.

We investigated possible cytotoxic effects, biocompatibility, and degradation of a hyaluronan-based conduit for peripheral nerve repair. We subjected the conduits to an in vitro fibroblast cytotoxicity test and concluded that the conduits were not cytotoxic. Subsequently, we implanted the conduits subcutaneously in rats, in order to investigate tissue reactions and biodegradation. Initially, a fibrin matrix was formed around the material, while the surroundings were relatively quiet. Macrophages (MØ) migrated to the conduits and formed giant cells next to the material after 5 days. The maximum presence of MØ was found after 3-6 weeks. The appearance of MHC class II cells showed a similar pattern. Highest numbers of giants reached a maximum after 6-12 weeks. Angiogenesis was started in the surroundings of the hyaluronan-based conduit within a few days. Massive ingrowth of blood vessels into the biomaterial was found after 6 weeks as well as cellular ingrowth into the lumen of the tube. At that time the tubular structure of the conduit was lost and loose biomaterial fibers were observed. The results show that a hyaluronan-based conduit is not cytotoxic and shows good biocompatibility. Such a conduit may be suitable as a guide in peripheral nerve repair.

[1]  L Andreassi,et al.  Bioengineering in dermatology: general aspects and perspectives. , 1995, Clinics in dermatology.

[2]  M Moras,et al.  Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats. , 1993, Biomaterials.

[3]  J W Eaton,et al.  Inflammatory responses to biomaterials. , 1995, American journal of clinical pathology.

[4]  D. Williams,et al.  Quantitative assessment of the tissue response to films of hyaluronan derivatives. , 1996, Biomaterials.

[5]  S. Mackinnon,et al.  The Role of Conduits in Nerve Repair: A Review , 1996, Reviews in the neurosciences.

[6]  P. Warnke,et al.  Increased Axonal Regeneration Through a Biodegradable Amnionic Tube Nerve Conduit: Effect of Local Delivery and Incorporation of Nerve Growth Factor/Hyaluronic Acid Media , 2000, Annals of plastic surgery.

[7]  L. Andreassi,et al.  Practical applications of cutaneous colorimetry. , 1995, Clinics in dermatology.

[8]  L. Ambrosio,et al.  Biocompatibility and biodegradation of intravitreal hyaluronan implants in rabbits. , 2001, Biomaterials.

[9]  R. Cortivo,et al.  In vitro reconstructed dermis implanted in human wounds: degradation studies of the HA-based supporting scaffold. , 2000, Biomaterials.

[10]  J M Davidson,et al.  Hyaluronate derivatives and their application to wound healing: preliminary observations. , 1991, Clinical materials.

[11]  C. Cetrulo,et al.  Hyaluronic acid enhances peripheral nerve regeneration in vivo , 1998, Microsurgery.

[12]  P Nieuwenhuis,et al.  Cytotoxicity testing of wound dressings using methylcellulose cell culture. , 1992, Biomaterials.

[13]  J. Feijen,et al.  Calcification of subcutaneously implanted collagens in relation to cytotoxicity, cellular interactions and crosslinking , 1995 .

[14]  R. Giardino,et al.  Transplantation of chondrocytes seeded on a hyaluronan derivative (hyaff-11) into cartilage defects in rabbits. , 2001, Biomaterials.

[15]  V. Zacchi,et al.  In vitro engineering of human skin-like tissue. , 1998, Journal of biomedical materials research.

[16]  A. Urtti,et al.  Methylprednisolone esters of hyaluronic acid in ophthalmic drug delivery: in vitro and in vivo release studies , 1992 .

[17]  J. Feijen,et al.  Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen. , 1994, Journal of biomedical materials research.

[18]  E. Topp,et al.  Drug release from membranes of hyaluronic acid and its esters , 1992 .

[19]  J. Pachence,et al.  Collagen-based devices for soft tissue repair. , 1996, Journal of biomedical materials research.

[20]  B. Seckel,et al.  Hyaluronic acid through a new injectable nerve guide delivery system enhances peripheral nerve regeneration in the rat , 1995, Journal of neuroscience research.