The goal of this work is to develop an injectable nucleus pulposus (NP) tissue engineering scaffold with the ability to form an adhesive interface with surrounding disc tissue. A family of in situ forming hydrogels based on poly(N-isopropylacrylamide)-graft-chondroitin sulfate (PNIPAAm-g-CS) were evaluated for their mechanical properties, bioadhesive strength, and cytocompatibility. It was shown experimentally and computationally with the Neo-hookean hyperelastic model that increasing the crosslink density and decreasing the CS concentration increased mechanical properties at 37 °C, generating several hydrogel formulations with unconfined compressive modulus values similar to what has been reported for the native NP. The adhesive tensile strength of PNIPAAm increased significantly with CS incorporation (p < 0.05), ranging from 0.4 to 1 kPa. Live/Dead and XTT assay results indicate that the copolymer is not cytotoxic to human embryonic kidney (HEK) 293 cells. Taken together, these data indicate the potential of PNIPAAm-g-CS to function as a scaffold for NP regeneration.

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 two-fold 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.

Tissue engineering is a rapidly growing field of research that aims to repair damaged tissues within the body. Among tissue engineering approaches is the use of scaffolds to help regenerate lost tissues. Scaffolds provide structural support for specific areas within the body, namely load bearing regions, and allow for cells to be seeded within the scaffold for tissue regeneration. Scaffolds that specifically replicate the properties and/or composition of native tissues are referred to as biomimetic scaffolds.

Tissue engineering is a multidisciplinary field that aims to repair or regenerate lost or damaged tissues and organs in the body. One such area with significant medical applications is the degeneration of the intervertebral disc (IVD). The objective of this work is to generate a bioadhesive polymer that, in addition to bonding with tissue, can support and cell survival post•adhesion. A thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) and chondroitin sulfate (CS) scaffold with aldehydemodified CS adhesive and extracellular matrix (ECM) loaded lipid vesicles was examined as a potential minimally invasive method for repair and regeneration of degenerated IVD tissue. Samples containing varying percentages of aldehyde-modified CS and presence or absence of ECM loaded lipid vesicles were evaluated for physiological relevant performance with porcine skin. Maximum stress and work of adhesion were calculated for each polymer formulation based on force-distance data. Currently, work is being done to investigate the biocompatibility of various polymer compositions to optimize polymer blends for maximum work, stress and biocompatibility for use in vivo.