Local injection of abaloparatide promotes mandibular condyle lengthening in adolescent rats via enhancing chondrogenesis and ossification.

BACKGROUND: Mandibular condylar hypoplasia negatively affects patient's facial appearance and dentofacial function. OBJECTIVE: To investigate the effect of local injection of the drug abaloparatide (ABL), an analogue of parathyroid hormone related protein (PTHrP), on promoting lengthening of the mandibular condyle. METHODS: Thirty adolescent male Sprague-Dawley rats were randomly divided into two groups, which received the injection of ABL or normal saline (the control) every 3 days in the temporomandibular joint (TMJ) cavity. Cone-beam computed tomography and immunohistochemistry assays were performed at 2, 4 and 6 weeks since the injection. Mandibular condylar chondrocytes (MCC) and pre-osteoblasts were treated with ABL or PBS, followed by the CCK-8 detection, IC50, real-time PCR assay, Western Blot and immunofluorescence staining. RESULTS: In vivo, compared with the control, the ABL group significantly increased the mandibular condylar process length (by 1.34 ± 0.59 mm at 6 weeks), the thickness of the cartilage layer, and enhanced the matrix synthesis. The ABL group had significant up-regulation of SOX 9, COL II, PTHrP and PTH1R, down-regulation of COL X in the cartilage, up-regulation of RUNX 2, and unchanged osteoclastogenesis in the subchondral bone. In vitro, the intra-TMJ injection of ABL promoted the MCC proliferation, with up-regulated expression of chondrogenic genes, and enhanced osteogenic differentiation of the pre-osteoblasts. CONCLUSIONS: Intra-TMJ injection of abaloparatide promotes mandibular condyle lengthening in the adolescent rats via enhancing chondrogenesis in the mandibular condylar cartilage and ossification in the subchondral bone.

Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion.

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5-3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.