A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Supramolecular peptide nanofiber hydrogels are promising for tissue engineering.
• Fabricating multi-functional hydrogels with combined peptides is challenging due to hindered nanofiber formation.
• Coupling bioactive factors to peptide backbones is an ideal strategy for multi-functional biomaterials.

Purpose of the Study:

• To develop a multi-functional supramolecular peptide by conjugating parathyroid hormone related peptide 1 (PTHrP-1) to a self-assembling peptide backbone.
• To investigate the self-assembly and co-assembly behavior of the modified peptide.
• To evaluate the in vitro and in vivo efficacy of the resulting nanofiber hydrogels for bone regeneration.

Main Methods:

• Solid-phase synthesis was used to create the multi-functional peptide P1R16 by coupling PTHrP-1 to RADA16-Ⅰ.
• P1R16 was assessed for self-assembly into nanofibers and co-assembly with RADA16-Ⅰ to form hydrogels.
• In vitro studies evaluated osteoinductivity, osteogenesis, angiogenesis, and osteoclastogenesis.
• In vivo studies loaded P1R16/RADA16-Ⅰ hydrogels onto collagen scaffolds to assess osteoregeneration in bone defects.

Main Results:

• P1R16 self-assembled into long nanofibers and co-assembled with RADA16-Ⅰ to form hydrogel matrix.
• P1R16 nanofibers exhibited dose-dependent osteoinductive activity.
• P1R16/RADA16-Ⅰ hydrogels promoted osteogenesis, angiogenesis, and osteoclastogenesis in vitro.
• In vivo, P1R16/collagen scaffolds induced multi-functional osteoregeneration, showing abundant red blood marrow formation, ideal osteointegration, and adapted degradation.

Conclusions:

• A novel multi-functional supramolecular peptide (P1R16) was successfully developed by conjugating PTHrP-1.
• The P1R16/RADA16-Ⅰ nanofiber hydrogels effectively promote bone regeneration through enhanced osteogenesis, angiogenesis, and bone remodeling.
• This approach offers a promising strategy for developing advanced biomaterials and a new method for administering PTHrP for treating non-healing bone defects.