A biocompatibility study of injectable poly(caprolactone-trifumarate) for use as a bone substitute material

Abstract

The need for bone graft alternatives has led to the development of numerous bone graft substitutes. Here, the authors have synthesized a biodegradable poly(caprolactone-trifumarate) (PCLTF) polymer solution that could be injected into any bony defect. This polymer solution was synthesized using polycaprolactone-triol and fumaryl chloride (FCl). PCLTF is a multiple-branching, unsaturated and cross-linkable in situ material. The surface microstructure of PCLTF was investigated using a field emission scanning electron microscope. The incorporation of double bonds originating from FCl into the poly(caprolactone) backbone was confirmed in the Fourier transform infrared spectra. The in vitro cytotoxic effects of PCLTF, its leachable extracts and degradation products were evaluated in direct and indirect contact tests against human oral fibroblasts. Cell viability was evaluated using the microculture tetrazolium assay and cytotoxicity evaluations of PCLTF were tested in accordance with ISO 10993-5 standards. The results showed that there was evidence of reasonable cell growth, good cell viability and intact cell morphology after exposure to PCLTF, its extracts and degradation products. There was no evidence of critical cytotoxic effects.

Modified poly(caprolactone trifumarate) with embedded gelatin microparticles as a functional scaffold for bone tissue engineering

“…This proves that the C=C–H group had been successfully incorporated, and the PCLTF polymer solution has been successfully synthesized. This finding is similar to an earlier report that detailed the production of a dark PCLTF …”

“…In this study, the hardening process of PCLTF‐GMPs was relatively fast, and was able to achieve significant crosslinking in situ within an acceptable time frame ∼5–7 min at room temperature and with 26 °C heat emission that is lower than the body temperature. This is an improvement when compared to the 15 min recorded for the dark PCLTF …”

“…In clinical situation, once a scaffold is placed into an extraction socket, the biomaterial will first come into contact with the soft tissue (gingiva) before bone regeneration can take place within the scaffold. To ensure that the product is biocompatible with the soft tissue, it needs to be tested against human gingival fibroblasts similar to the process done in an earlier study …”

“…In addition, salt retention may also result in high osmolarity of the surrounding tissue, which leads to local tissue necrosis . Other shortcomings of the previously developed dark and white PCLTF were their availability as a highly viscous polymeric solution (therefore, less flowable) that resulted in decreased injectability, difficulty to produce (this includes handling and the reproducing procedures), as well as the presence of a non‐uniform distribution of porogen in the scaffold …”

“…To overcome these shortcomings, a modified form of those pre‐existing PCLTFs, now named as the poly(caprolactone trifumarate)‐gelatin microparticles (PCLTF‐GMPs) scaffold was developed. It was created by mixing 300 Mw PCL with gelatin microparticles (GMPs) which acted as porogen to create a new 3D porous scaffold, as an alternative to mixing the conventional 900 Mw PCL with sodium chloride salt (NaCl) porogen, as previously used in the creation of the white and dark PCLTFs . Gelatin (Gel) is a natural biopolymer, obtained by breaking up the triple‐helix structure of collagen into single‐strain molecules.…”