Lactoferrin-Hydroxyapatite Containing Spongy-Like Hydrogels for Bone Tissue Engineering

Abstract

The development of bioactive and cell-responsive materials has fastened the field of bone tissue engineering. Gellan gum (GG) spongy-like hydrogels present high attractive properties for the tissue engineering field, especially due to their wide microarchitecture and tunable mechanical properties, as well as their ability to entrap the responsive cells. Lactoferrin (Lf) and Hydroxyapatite (HAp) are bioactive factors that are known to potentiate faster bone regeneration. Thus, we developed an advanced three-dimensional (3D) biomaterial by integrating these bioactive factors within GG spongy-like hydrogels. Lf-HAp spongy-like hydrogels were characterized in terms of microstructure, water uptake, degradation, and concomitant release of Lf along the time. Human adipose-derived stem cells (hASCs) were seeded and the capacity of these materials to support hASCs in culture for 21 days was assessed. Lf addition within GG spongy-like hydrogels did not change the main features of GG spongy-like hydrogels in terms of porosity, pore size, degradation, and water uptake commitment. Nevertheless, HAp addition promoted an increase of the pore wall thickness (from ~13 to 28 µm) and a decrease on porosity (from ~87% to 64%) and mean pore size (from ~12 to 20 µm), as well as on the degradability and water retention capabilities. A sustained release of Lf was observed for all the formulations up to 30 days. Cell viability assays showed that hASCs were viable during the culture period regarding cell-laden spongy-like hydrogels. Altogether, we demonstrate that GG spongy-like hydrogels containing HAp and Lf in high concentrations gathered favorable 3D bone-like microenvironment with an increased hASCs viability with the presented results.

Simultaneous incorporation of PTH(1–34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration

“…In addition, hydroxyapatite (HAP), a calcium phosphate bioceramic, is an essential component for bone regeneration [ [31] , [32] , [33] , [34] ]. Combining HAP with hydrogels enables emulation of the natural structures of bone and promotes bone regeneration [ [35] , [36] , [37] ]. The intrinsic mechanical properties of HAP and its interaction with bone tissues are intimately dependent on the size of HAP.…”

Human Mesenchymal Stem Cell Response to Lactoferrin-based Composite Coatings

“…In addition, lactoferrin has a protective role against oxidative stress, senescence, and apoptosis of hMSCs, increasing the efficiency of some therapies involving the use of Lf-based biomaterials [53]. Different concentrations of Lf-functionalised biomimetic HA nanocrystals maintained the viability and proliferation of rabbit MSC cells [18] and murine pre-osteoblasts [19] for up to 14 days and Lf and HA in spongy-like hydrogels increased metabolic activity of human adipose-derived stem cells (hASCs) for up to 21 days [54].…”

Effect of Gellan Gum/Tuna Skin Film in Guided Bone Regeneration in Artificial Bone Defect in Rabbit Calvaria

“…Lactoferrin was also used for bone tissue engineering. Bastos et al integrated bioactive factors of lactoferrin and hydroxyapatite to GEL sponge-like hydrogels and observed sustained release of lactoferrin and increased human adipose stem cell viability [34].…”