Recombinant PTH modification: A new strategy for a multifunctional CaP material to enhance bone regeneration

Bone regeneration requires the interaction of osteogenesis, osteolysis, and angiogenesis as well as an appropriate immune microenvironment. Recombinant human parathyroid hormone (PTH1-34) is approved for clinical anti-osteoporosis treatment because of its good osteogenic activity, osteoclastosis, and angiogenesis. However, the phenomenon of net bone resorption limits its use in local bone repair. Our group provides an effective strategy for multifunctional calcium phosphate (CaP) ceramics with modulating M1 macrophage pro-inflammatory effects, and bone regeneration. CaP ceramic scaffold is functionalized with parathyroid hormone related peptide-1 (PTHrP-1) for bone defect repair. First, peptide-functionalized true bone ceramic (TBC) scaffold exhibit limited M1 macrophage pro-inflammatory effects to improve the osteogenic microenvironment. Second, PTHrP-1 retains the osteogenic activity and angiogenic properties of PTH1-34 while downregulating osteoclast activity to induce favorable bone formation. Third, the peptide modified by tri-continuous aspartic acids (D3) and serine phosphorylation (PSer) has high affinity to the natural CaP matrix, achieving a slow release of PTHrP-1 in the TBC scaffold. Fourth, the carboxyl group of aspartate combined with calcium effectively promotes hydroxyapatite (HAP) nucleation and completes self-assembled mineralization. which is beneficial for bone regeneration. The results show that PTHrP-1-TBC is more suitable for bone regeneration than TBC scaffold and unmodified peptide alone.