Incorporation of Bone Morphogenetic Protein-2 and Osteoprotegerin in 3D-Printed Ti6Al4V Scaffolds Enhances Osseointegration Under Osteoporotic Conditions

Abstract

Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis

“…Drugs can be loaded into hydrogels through a manifold of mechanisms and strategies. Here, we speculate that icariin is retained in the hydrogel through the formation of hydrogen bonds and being physically entrapped in hydrogel ( Vermonden et al, 2012 ; Li et al, 2021b ; Wang et al, 2021 ). The release curves of icariin in PHa@I-L, PHa@I-M, and PHa@I-H groups were similar, as illustrated in Figure 1G .…”

A Review of Conventional and Novel Treatments for Osteoporotic Hip Replacements

“…Several scholars have studied the feasibility of using hydrogels as drug delivery vehicles for osteoporotic bones owing to their desirable biocompatibility in addition to their ability to provide a medium where impregnated cells can survive during the desired course of release Table 6 [37][38][39][40]. Hydrogels have been studied within metallic scaffolds as a treatment approach in fracture site for enhancement of bone remodelling and osteointegration processes.…”

Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects

“…Since a high concentration of BMP-2 promotes osseointegration, it is one of the most common drugs loaded in hydrogel scaffolds (Lee et al, 2015;Segredo-Morales et al, 2018;García-García et al, 2019;Bai et al, 2020;García-García et al, 2020;Wang et al, 2021b;van Houdt et al, 2021). BMP-7 or BMP-6 loaded hydrogels have been used in local treatment, are potent stimulators of osteogenesis, and can reduce the risk of further osteoporosis-associated secondary fractures (Pelled et al, 2016;Neuerburg et al, 2019).…”