Alginate/Hydroxyapatite-Based Nanocomposite Scaffolds for Bone Tissue Engineering Improve Dental Pulp Biomineralization and Differentiation

Abstract

Tissue engineering is widely recognized as a promising approach for bone repair and reconstruction. Several attempts have been made to achieve materials that must be compatible, osteoconductive, and osteointegrative and have mechanical strength to provide a structural support. Composite scaffolds consisting in biodegradable natural polymers are very promising constructs. Hydroxyapatite (HAp) can support alginate as inorganic reinforcement and osteoconductive component of alginate/HAp composite scaffolds. Therefore, HAp-strengthened polymer biocomposites offer a solid system to engineer synthetic bone substitutes. In the present work, HAp was incorporated into an alginate solution and internal gelling was induced by addition of slowly acid-hydrolyzing D-gluconic acid delta-lactone for the direct release of calcium ions from HAp. It has been previously demonstrated that alginate-based composites efficiently support adhesion of cancer bone cell lines. Human dental pulp stem cells (DPSCs) identified in human dental pulp are clonogenic cells capable of differentiating in multiple lineage. Thus, this study is aimed at verifying the mineralization and differentiation potential of human DPSCs seeded onto scaffolds based on alginate and nano-hydroxyapatite. For this purpose, gene expression profile of early and late mineralization-related markers, extracellular matrix components, viability parameters, and oxidative stress occurrence were evaluated and analyzed. In summary, our data show that DPSCs express osteogenic differentiation-related markers and promote calcium deposition and biomineralization when growing onto Alg/HAp scaffolds. These findings confirm the use of Alg/HAp scaffolds as feasible composite materials in tissue engineering, being capable of promoting a specific and successful tissue regeneration as well as mineralized matrix deposition and sustaining natural bone regeneration.

Dual-Drug-Loaded Silk Fibroin/PLGA Scaffolds for Potential Bone Regeneration Applications

“…The results showed that nanofiber scaffolds containing both DXM and rhBMP2 drugs could synergistically induce the upregulation of ALP activity in rBMSCs and had better bone induction ability. Alizarin red reacts with calcium to produce a dark red compound, which stains the calcium nodules deposited [28]. Therefore, ARS was further used to characterized the degree of differentiation.…”

Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration

“…However, alginate exhibits some limitations in the regard of prospective bone tissue applications, such as the absence of sites for cell attachment or specific receptor interactions, which limits its long-term functionality, further impaired by the swelling-disintegration-erosion of these hydrogels' upon implantation, week biomechanical properties, poor bioresorbability and bioactivity [10][11][12][13]. Therefore, the use of nanohydroxyapatite (nanoHA) as a reinforcing component with osteocondutive capabilities can contribute to overcome some of these potential limitations [4,14]. NanoHA is commonly used in bone tissue regeneration due to its chemical similarity to the inorganic component of the bone matrix and its inherent characteristics such as biocompatibility, osteoinduction, osteocondutive and osteointegration [4,15,16].…”

“…NanoHA is commonly used in bone tissue regeneration due to its chemical similarity to the inorganic component of the bone matrix and its inherent characteristics such as biocompatibility, osteoinduction, osteocondutive and osteointegration [4,15,16]. Although in some studies nanoHA was already used to reinforce Alg matrixes [14,[17][18][19][20], no studies have yet addressed the systematic influence of nanoHA on alginate-based hydrogel systems, neither the effect of distinct nanoHA amounts on its physic-chemical properties and biological response. This is of the utmost relevance, since the amount of nanoHA within the composition of polymer-based hydrogels is crucial to design an efficient composite for bone tissue regeneration.…”

The Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Dental Pulp in Modular Alginate-Gelatin/Nano-Hydroxyapatite Microcapsules

“…The aim of BTE is not only to provide 3D structutres and cell proliferation without cell cytotoxicity or foreign body reaction but also the regeneration of new bone by provoking osteogenic differentiation of stem cells (4,61).…”