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 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.

Adhesive Materials for Biomedical Applications

“…Current strategies involve seeding biomaterials, called scaffolds, with cells and/or biologically active molecules that allow or induce tissue regrowth in a three-dimensional structure [139]. Tissue engineering of certain areas in the body, particularly cartilage [122] and the intervertebral disc [140,141], is not thought to be clinically feasible without a scaffold that can form an interface with surrounding tissue, eliminating the risk of dislocation and restoring mechanical functionality by adequately transmitting forces to and from the surrounding tissue [122,[140][141][142]. A scaffold could potentially be sutured in place, but ideally, it would integrate with surrounding tissues via a bioadhesive mechanism while supporting encapsulated cellular function.…”

“…More in-depth studies are warranted, as experimental outcomes are likely to be impacted by cell type and density, material reactivity, concentration of reactive groups, and the presence of biomolecular signals such as growth factors. Wiltsey et al [142] investigated the use of polysaccharides without reactive groups as bioadhesive tissue engineering scaffolds. Thermosensitive copolymers of poly(N-isopropylacrylamide) grafted with chondroitin sulfate (PNIPAAm-g-CS) containing mucoadhesive alginate microparticles as the adhesion mediators were developed.…”

3D Printed Composite Scaffolds Incorporating Ruthenium Complex–Loaded Liposomes as a Delivery System to Prevent the Proliferation of MG‐63 Cells

“…The good mechanical properties of the scaffold provide a suitable spatial environment for tissue regeneration and cell growth, thereby overcoming the drawbacks of poor absorption after systemic delivery of liposomes . Furthermore, liposomes reside on the scaffold primarily by physical adsorption or/and chemical bonding, which could allow for controlled delivery in a sustained and targeted manner, resulting in reduced adverse side effects . The combined liposome–scaffold approach, which provides complimentary synergy between the scaffolds and liposome delivery vectors, has been demonstrated to increased efficacy .…”

Review: unraveling the less explored flocking technology for tissue engineering scaffolds

“…Tissue engineering load-bearing parts of the body depends on either scaffold adhesion or integration with the surrounding tissue to avoid dislocation. 14 Thus, the tissue engineered scaffold is a cornerstone in regeneration of the intervertebral disc (IVD). Lower back pain (LBP)…”