Calcium-Enriched Nanofibrillated Cellulose/Poloxamer in-situ Forming Hydrogel Scaffolds as a Controlled Delivery System of Raloxifene HCl for Bone Engineering

Int J Nanomedicine. 2021 Oct 5:16:6807-6824. doi: 10.2147/IJN.S323974. eCollection 2021.

Abstract

Purpose: TEMPO-oxidized nanofibrillated cellulose (TONFC) originating from an agricultural waste (sugar cane) was utilized to prepare injectable in-situ forming hydrogel scaffolds (IHS) for regenerative medicine.

Methods: TONFC was prepared and characterized for its morphology and chemical structure using TEM and FT-IR, respectively. The cold method was applied to prepare hydrogels. Various concentrations of poloxamer 407 were added to the prepared TONFC (0.5%w/w). Different sources of calcium, Fujicalin® (DCP) or hydroxyapatite (TCP), were used to formulate the aimed calcium-enriched raloxifene hydrochloride-loaded IHS. Gelation temperature, drug content, injectability and in-vitro drug release were evaluated along with the morphological characters. Cytocompatibility studies and tissue regeneration properties were assessed on Saos-2 cells.

Results: TEM photograph of TONFC showed fibrous nanostructure. The selected formulation "Ca-IHS4" composed of TONFC+15% P407+10% TCP showed the most prolonged release pattern for 12 days with the least burst effect (about 25% within 24 h). SEM micro-photographs of the in-situ formed scaffolds showed a highly porous 3D structure. Cytocompatibility studies of formulation "Ca-IHS4" revealed the biocompatibility as well as improved cell adhesion, alkaline phosphatase enzyme activity and calcium ion deposition.

Conclusion: The outcomes suggest that Ca-IHS4 presents a simple, safe-line and non-invasive strategy for bone regeneration.

Keywords: bone regeneration; calcium phosphate; in-situ forming hydrogel scaffolds; nanofibrillated cellulose; raloxifene hydrochloride.

Publication types

  • Retracted Publication

MeSH terms

  • Calcium
  • Cellulose
  • Hydrogels*
  • Poloxamer
  • Raloxifene Hydrochloride*
  • Spectroscopy, Fourier Transform Infrared
  • Tissue Engineering
  • Tissue Scaffolds

Substances

  • Hydrogels
  • Poloxamer
  • Raloxifene Hydrochloride
  • Cellulose
  • Calcium

Grants and funding

This work was supported by the National Research Centre, Cairo, Egypt (grant agreement no. 12010109).