title: Thermogelling bioadhesive scaffolds for intervertebral disk tissue engineering: preliminary in vitro comparison of aldehyde-based versus alginate microparticle-mediated adhesion.
abstract: Tissue engineering of certain load-bearing parts of the body can be dependent on scaffold adhesion or integration with the surrounding tissue to prevent dislocation. One such area is the regeneration of the intervertebral disc (IVD). In this work, poly(N-isopropylacrylamide) (PNIPAAm) was grafted with chondroitin sulfate (CS) (PNIPAAm-g-CS) and blended with aldehyde-modified CS to generate an injectable polymer that can form covalent bonds with tissue upon contact. However, the presence of the reactive aldehyde groups can compromise the viability of encapsulated cells. Thus, liposomes were encapsulated in the blend, designed to deliver the ECM derivative, gelatin, after the polymer has adhered to tissue and reached physiological temperature. This work is based on the hypothesis that the discharge of gelatin will enhance the biocompatibility of the material by covalently reacting with, or "end-capping", the aldehyde functionalities within the gel that did not participate in bonding with tissue upon contact. As a comparison, formulations were also created without CS aldehyde and with an alternative adhesion mediator, mucoadhesive calcium alginate particles. Gels formed from blends of PNIPAAm-g-CS and CS aldehyde exhibited increased adhesive strength compared to PNIPAAm-g-CS alone (p<0.05). However, the addition of gelatin-loaded liposomes to the blend significantly decreased the adhesive strength (p<0.05). The encapsulation of alginate microparticles within PNIPAAm-g-CS gels caused the tensile strength to increase twofold over that of PNIPAAm-g-CS blends with CS aldehyde (p<0.05). Cytocompatibility studies indicate that formulations containing alginate particles exhibit reduced cytotoxicity over those containing CS aldehyde. Overall, the results indicated that the adhesives composed of alginate microparticles encapsulated in PNIPAAm-g-CS have the potential to serve as a scaffold for IVD regeneration.
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: C
authors: C
authors: Wiltsey
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: T
authors: T
authors: Christiani
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: J
authors: J
authors: Williams
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: J
authors: J
authors: Scaramazza
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: C
authors: C
authors: Van Sciver
authors: Medical University of South Carolina, Department of Regenerative Medicine and Cell Biology, 171 Ashley Ave, Charleston, SC 29425, USA.
authors: K
authors: K
authors: Toomer
authors: Rowan University Graduate School of Biomedical Sciences, Department of Cell and Molecular Biology, 42 East Laurel Rd, Stratford, NJ 08084, USA.
authors: J
authors: J
authors: Sheehan
authors: Saint Joseph College School of Pharmacy, 229 Trumbull St., Hartford, CT 06103, USA.
authors: A
authors: A
authors: Branda
authors: Rowan University, Department of Biological Sciences, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: A
authors: A
authors: Nitzl
authors: Rowan University, Department of Biological Sciences, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: E
authors: E
authors: England
authors: Rowan University, Department of Mechanical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: J
authors: J
authors: Kadlowec
authors: Rowan University, Department of Biological Sciences, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors: C
authors: C
authors: Iftode
authors: Rowan University, Department of Chemical Engineering, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA. Electronic address: vernengo@rowan.edu.
authors: J
authors: J
authors: Vernengo
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology; D000268:Adhesiveness; D000447:Aldehydes / Q000494:pharmacology*; D000464:Alginates / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D020723:Glucuronic Acid / Q000494:pharmacology; D057809:HEK293 Cells; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000187:drug effects / Q000502:physiology*; D008081:Liposomes / Q000737:chemistry; D008863:Microspheres; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D000447:Aldehydes; D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020100:Hydrogels; D008081:Liposomes; C052970:poly-N-isopropylacrylamide; D020723:Glucuronic Acid
keywords: Bioadhesive; Copolymer; Hydrogel; Scaffold; Tissue engineering
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