Self-curing acrylic formulations with applications in intervertebral disk restoration: drug release and biological behaviour

Abstract

New injectable acrylic formulations have been prepared to be applied in restoration processes for intervertebral disks (IVDs). The solid phase of the formulations is composed of poly(methyl methacrylate) (PMMA), incorporating in some cases chondroitin sulphate (CS) as a regenerative bioactive molecule, whereas the liquid phase is constituted by an amphiphilic macromonomer (MT), 2-hydroxyethyl methacrylate (HEMA) and, in some formulations, acrylic acid (AA). The curing parameters and the mechanical properties of the IVD formulations make them excellent candidates for intervertebral application. In vitro and in vivo evaluation of the prepared IVD formulations is described in terms of CS release, surface analysis after immersion in SBF solutions, and biocompatibility studies based on MTT assay and Alamar blue test, as well as in vivo implantation in female Wistar rats, by injection of the IVD formulations followed by histological evaluations to assess tissue response.

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

“…''Frog-glue'' offers a stronger alternative to fibrin glue, has been used for the reattachment of bucket handle tears in knee joint menisci and offers potential in the non-surgical sealing of annular defects as an integral part of a repair strategy [35]. Injectable, selfcuring, acrylic formulations, also display potential in this regard and may be additionally supplemented with drugs and other biomimetics in microcarriers for their controlled release in a therapeutic setting to stimulate cellular responses and promote tissue repair [66]. Biphasic scaffolds have also been developed to mimic the known differences in the spatial organisation of the outer and inner AF and these should aid in the integration of constructs which recapitulate at least some aspects of the structure of the native AF.…”

Strategies towards injectable, load-bearing materials for the intervertebral disc: a review and outlook

“…High compressive strengths of 30MPa could be obtained with the use of less macromonomer and more HEMA (40 and 60% of the cement's liquid phase, respectively), together with a swelling rate of 10-100% (higher percentage with the addition of chondrotoin sulphate and acrylic acid). Cell viability tests on cured specimen extracts indicated an initial toxic effect, although in vivo tests in rats showed a normal tissue response [35]. However, no data was reported for the injectability and radiopacity of this material.…”

“…Here bone cement based on poly(methyl methacrylate) (PMMA) is injected into the vertebral body and hardens in situ through a radical polymerization reaction. Similar to this material, Larraz et al [35,36] used an amphiphilic macromonomer in combination with traditional (hydrophobic) PMMA and (hydrophilic) HEMA, and in some cases (hydrophilic) acrylic acid, in order to produce an injectable material for the intervertebral disc. The hydrophilic components were added in order to obtain a swelling behavior similar to the natural disc, which would confer viscoelastic properties to the material as well as the possibility to "transport nutrients and metabolism products" [36].…”

“…However, no complete investigation of their cell response has been performed. Larraz et al [35] investigated the effect on African green monkey fibroblastic cells of their cured material, and found no cell attachment and proliferation of the cells, and viability assays on extracts showed a decreased viability of cells when materials containing acrylic acid were used, which however returned to normal after seven days.…”

“…However, in vivo tests in rats showed what the authors concluded to be a normal tissue response [35]. In the case of the DASCOR device no peer-reviewed data appears to be readily available in terms of cell response, although early clinical results for the DASCOR device suggest it is biologically safe [44], Sterilization of the initial components has also been an issue for both acrylic and ceramic cements, where different types of sterilization procedures (e.g.…”