Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration

Department of Endocrinology, Pathophysiology, and Applied Biology, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
Journal of Biomedical Materials Research Part A (Impact Factor: 3.37). 07/2011; 98(1):19-30. DOI: 10.1002/jbm.a.33091
Source: PubMed


Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine-deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post-surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration.

31 Reads
  • Source
    • "Different bioactive molecules can be incorporated into the PAA's backbone by covalent attachment during the synthetic process [11] [12] [13]. PAA-based hydrogels show good biocompatibility and are extremely versatile, being easily modifiable by introducing different co-monomers that carry additional chemical functions such as carboxylic acids, thiols and amino groups [14] [15] [16] [17] [18] [19] [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polyamidoamines (PAAs) hydrogels containing the 2,2-bisacrylamidoacetic acid - 4-amminobutyl guanidine monomeric unit have a known ability to enhance cellular adhesion by interacting with the RGD-binding αVβ3 integrin, expressed by a wide number of cell types. The scientific interest on this class of materials has been traditionally hampered by their poor mechanical properties and restricted range of degradation rate. Here we present the design of novel biocompatible, RGD-mimic PAA-based hydrogels with wide and tunable degradation rate as well as improved mechanical and biological properties for biomedical applications. This is achieved by radical polymerization of acrylamide-terminated PAA oligomers both in presence and absence of 2-hydroxyethylmethacrylate (HEMA). The degradation rate is found to be precisely tunable by adjusting the PAA oligomer molecular weight and acrylic comonomer concentration in the starting reaction mixture. Cell adhesion and proliferation tests on Madin-Darby Canine Kidney (MDCK) epithelial cells show that PAA-based hydrogels have the capacity to promote cell adhesion up to 200% compared to the control. Mechanical tests show higher compressive strength of acrylic chain containing hydrogels compared to traditional PAA hydrogels.
    Full-text · Article · Dec 2013 · Acta biomaterialia
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tacrolimus (FK506) is a widely used immunosuppressant in organ transplantation. However, it also has neurotrophic activity that occurs independently of its immunosuppressive effects. Other neurotrophic immunophilin ligands that do not exhibit immunosuppression have subsequently been developed and studied in various models of nerve injury. This article reviews the literature on the use of tacrolimus and other immunophilin ligands in peripheral nerve, cranial nerve and spinal cord injuries. The most convincing evidence of enhanced nerve regeneration is seen with systemic administration of tacrolimus in peripheral nerve injury, although clinical use is limited due to its immunosuppressive side effects. Local tacrolimus delivery to the site of nerve repair in peripheral and cranial nerve injury is less effective but requires further investigation. Tacrolimus can enhance outcomes in nerve allograft reconstruction and accelerates reinnervation of complex functional allograft transplants. Other non-immunosuppressive immunophilins ligands such as V-10367 and FK1706 demonstrate enhanced neuroregeneration in the peripheral nervous system and CNS. Mixed results are found in the application of immunophilin ligands to treat spinal cord injury. Immunophilin ligands have great potential in the treatment of nerve injury, but further preclinical studies are necessary to permit translation into clinical trials.
    No preview · Article · Sep 2011 · Regenerative Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Biodegradable and biocompatible poly(amidoamine)-(PAA-) based hydrogels have been considered for different tissue engineering applications. First-generation AGMA1 hydrogels, amphoteric but prevailing cationic hydrogels containing carboxylic and guanidine groups as side substituents, show satisfactory results in terms of adhesion and proliferation properties towards different cell lines. Unfortunately, these hydrogels are very swellable materials, breakable on handling, and have been found inadequate for other applications. To overcome this problem, second-generation AGMA1 hydrogels have been prepared adopting a new synthetic method. These new hydrogels exhibit good biological properties in vitro with satisfactory mechanical characteristics. They are obtained in different forms and shapes and successfully tested in vivo for the regeneration of peripheral nerves. This paper reports on our recent efforts in the use of first-and second-generation PAA hydrogels as substrates for cell culturing and tubular scaffold for peripheral nerve regeneration.
    Full-text · Article · Oct 2011 · International Journal of Polymer Science
Show more