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

Abstract

Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related diseases. Here, we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone (PTH) peptide PTH(1–34) and nano-hydroxyapatite (nHAP). A combination of the positively charged natural polymer chitosan (CS) and negatively charged sodium alginate led to the formation of hydrogels with porous structures, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1–34). In vitro experiments showed that the hydrogel containing nHAP and PTH(1–34) exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) via the Notch signaling pathway, as shown by the upregulated expression of osteogenic-related proteins. We found that increasing the content of PTH(1–34) in the hydrogels resulted in enhanced osteogenic differentiation of BMSCs. Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP, indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process. Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.

Hydroxyapatite Based Materials for Bone Tissue Engineering: A Brief and Comprehensive Introduction

“…Chitosan (CS) is a copolymer of D-glucosamine and N-acetyl-D-glucosamine [116]. Due to its biodegradable, non-toxic, antibacterial and biocompatible properties, CS can be used as a scaffold material or growth factor carrier in bone tissue engineering, and has attracted much attention [117,118]. Unfortunately, pure chitosan scaffolds have poor mechanical properties, and lack osteoconductivity.…”

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…In fact, the 1–34 amino acid fragment of PTH (PTH(1–34), also known as teriparatide), is the active sequence responsible for the bone remodeling function of PTH [ 88 ] and it has been approved for its use as an osteoanabolic drug in the clinical treatment of bone defects, such as osteoporosis [ 89 ]. PTH(1–34) along with nano-HA (nHA) and hydrogel combinations (to emulate the natural structures of bone) have been integrated to facilitate osteogenic differentiation of BM-MSCs [ 90 ]. The nanofibers and porous structure of the Gel-nHA-PTH scaffolds enhanced cell adhesion and showed good binding with bone tissue.…”

Hierarchical Nanostructured Electrospun Membrane with Periosteum‐Mimic Microenvironment for Enhanced Bone Regeneration

“…Moreover, the mature collagen component can be stained red by Masson's to assess the maturity of the new bone tissue. [ 36 ] From Figure 9b, it is intuitively observed that the regenerated new bone treated with PTBSK presented a layer‐by‐layer structure with the largest red area, indicating the formation of mature bone tissue in the bone defect. The quantitative results are shown in Figure 9d, after 8 weeks, the mature bone area of PTBSK was 26.33 ± 1.32%, which was significantly higher than 22.11 ± 1.61% of PTB and 17.32 ± 0.99% of PB ( p < 0.01), indicated that the synergistic effect of the calcium‐binding peptide and the shish‐kebab structure could greatly promote the regeneration of mature bone.…”