Nanocatalytic Biofunctional MOF Coating on Titanium Implants Promotes Osteoporotic Bone Regeneration through Cooperative Pro-osteoblastogenesis MSC Reprogramming

Abstract

An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction of bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report the in situ construction of bone microenvironment-responsive biofunctional metal–organic framework (bio-MOF) coating on the titanium surface through the coordination between p-xylylenebisphosphonate (PXBP) and Ce/Sr ions by a hydrothermal method. Taking advantage of the anchored Ce and Sr ions, the AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase and catalase-like catalytic activities to decompose ROS in MSCs and restore their mitochondrial functions. In vitro analysis showed that the AHT-Ce/SrMOF implants substantially activated the AMP-activated protein kinase (AMPK) signaling pathway in MSCs and reduced the ROS levels. Meanwhile, MSCs grown on AHT-Ce/SrMOF implants displayed significantly higher expressions of the mitochondrial fission marker (DRP1), mitochondrial fusion marker (MFN2 and OPA1), and mitophagy marker (PINK1 and LC3) than those of the AHT-CeMOF and AHT-SrMOF groups, which indicated that the bio-MOF could amend mitochondrial function in MSCs to reverse senescence. In vivo evaluations showed that the bio-MOF-coated Ti implants could restore MSC function in the implant site and promote new bone formation, leading to improved osteointegration in osteoporotic rat. This study may improve implant-mediated fracture healing in the clinics.

A Mitochondrial Perspective on Noncommunicable Diseases

“…Ling et al designed MoO3-xNUs to target the tumor environment to induce CAT-like reactions and generate cytotoxic superoxide radicals to induce apoptosis in tumor cells [ 89 ]. Coated organic backbone AHT-Ce/SrMOF containing Ce and Sr metal ions implanted in rats exhibited superoxide dismutase and catalytic peroxidase-like activity, activated AMPK signaling pathway, catabolized ROS in bone-related mesenchymal stem cells (BMSCs) and restored their mitochondrial function, and reversing the cellular senescence process [ 90 ]. At the same time, CaF2, a metal compound with peroxidase-like activity, can also be used as a nanoenzyme for tumor therapy.…”

Bone regeneration strategies based on organelle homeostasis of mesenchymal stem cells

“…For the treatment of osteoporosis, Chen et al constructed microenvironmentally responsive biofunctional metal-organic framework (bioMOF) coatings in situ by hydrothermal method on titanium surface through the coordination of phydroxydiphosphonate (PXBP) and cerium (Ce)/strontium (Sr) ions. Specifically, Ce ions can exhibit catalytic properties similar to CAT and SOD to break down ROS in MSCs and restore their mitochondrial function (100). In addition, several studies have demonstrated that Sr can promote CAT/SOD activity and regulate mitochondrial dynamics, thereby enhancing diabetic osseointegration (101).…”

Surface Modification of Titanium Implants by Metal Ions and Nanoparticles for Biomedical Application

“…Some researchers constructed a biofunctional metal–organic framework coating on the surface of Ti implants using hydrothermal binding Ce/Sr ions with xylene bisphosphonate. This modification effectively enhanced in situ functional recovery and the osteogenesis of mesenchymal stem cells …”

“…This modification effectively enhanced in situ functional recovery and the osteogenesis of mesenchymal stem cells. 20 The metal ion surface modification of implants using metal NP coatings or their compounds has also been applied 21 for enhanced surface morphology and biological properties. NP surface modification can improve the osseointegration activity.…”