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

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.