Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment

Chen, Maohua; Sun, Yuting; Hou, Yanhua; Luo, Zhong; Li, Menghuan; Wei, Yujia; Chen, Maowen; Tan, Lu; Cai, Kaiyong; Hu, Yan

doi:10.1016/j.bioactmat.2022.02.006

Cited by 36 publications

(29 citation statements)

References 71 publications

(72 reference statements)

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“…However, the classic markers of late osteogenesis, OPN and OCN showed significant difference between H 2 O 2 +PBS group and H 2 O 2 +Hydrogel group until the 14th day ( Figures 5G, H ). To sum up, the presence of H 2 O 2 will inhibit the osteogenic differentiation ability of rBMSCs, which is specifically manifested by the reduction of calcium nodule deposition and the downregulation of osteogenic markers, consistent with previous studies ( Chen M. et al, 2022 ; Shen et al, 2022 ). However, the introduction of EGCG-based hydrogel with ROS-scavenging capacity can reshape the oxidative stress microenvironment in order to facilitate the osteogenic differentiation of rBMSCs.…”

Section: Resultssupporting

confidence: 90%

“…In addition, BMSCs also have a hand in the healing stages of inflammation, repair, and remodeling together with stromal cells, progenitor cells, pro-inflammatory (M1 phenotype) macrophages, and anti-inflammatory (M2 phenotype) macrophages ( Zou et al, 2021 ; Arostegui et al, 2022 ). After directional differentiation into osteoblasts, BMSCs secrete a series of components of extracellular bone matrix to enhance the deposition of calcium ions in situ , thus inducing the formation of mature bone tissues ( Grayson et al, 2015 ; Chen M. et al, 2022 ). Therefore, the quantity of BMSCs and their capacity to differentiate into osteoblasts in the injury microenvironment play a critical role in the early bone repair process.…”

Section: Introductionmentioning

confidence: 99%

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ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

Ding

Zhou

et al. 2023

Front. Bioeng. Biotechnol.

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Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

Ding

Zhou

et al. 2023

Front. Bioeng. Biotechnol.

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“…Despite the fact that BMSCs have excellent regenerative capabilities in various tissues, the characteristics of BMSCs under pathological conditions differ significantly [32]. Previous in vitro studies of regenerative medicine mainly used normalstate BMSCs or MC3T3-E1 preosteoblast cell lines, ignoring the importance of directly studying BMSCs with impaired functions under pathological conditions [33,34]. Therefore, we first confirmed the successful establishment of aged osteoporosis (18-month-old male rats) by 3D reconstruction of micro-CT (Figures S2(a)).…”

Section: Isolation Identification and Characterization Of Bmscsmentioning

confidence: 99%

Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration

Bai

Wang

et al. 2022

Research

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For patients with osteoporosis, the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation, migration, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). To improve bone-implant integration in osteoporotic condition, here we reported a one-step biomimetic surface strategy to introduce BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. In our design, the bioadhesive molecular peptide mimic inspired by mussel foot proteins (Mfps) was used as molecular bridging for surface functionalization. Specifically, a BMSC-targeting peptide sequence (E7) and an osteogenic growth peptide (Y5) were grafted onto the titanium implant surfaces through a mussel adhesion mechanism. We found that a rational E7/Y5 feeding ratio could lead to an optimal dual functionalization capable of not only significantly improving the biocompatibility of the implant but also enabling it to recruit endogenous BMSCs for colonization, proliferation, and osteogenic differentiation. Mechanistically, the E7-assisted in situ recruitment of endogenous BMSCs as well as the enhanced interfacial osteogenesis and osteointegration was associated with activation of the C-X-C chemokine receptor type 4 (CXCR4) receptor on the cell surface and promotion of stromal cell-derived factor (SDF-1α) autocrine secretion. We anticipated that rational dual-functional surfaces through bioadhesive molecular mimics will provide a simple, effective, nonimmunogenic, and safe means to improve the clinical outcomes of intraosseous implants, especially under osteoporotic conditions.

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“…The released calcium and phosphate ions were assembled into amorphous calcium phosphate (ACP) in the endoplasmic reticulum and might be involved in the formation of new bone apatite. The binding of ACP and collagen promoted the formation of mineralized extracellular matrix, providing a favorable environment for further bone regeneration and osseointegration in vivo …”

Section: Resultsmentioning

confidence: 99%

“…It was found that PPENK3-PDA/P-HA and PPENK-PDA/P-HA reached higher expression of the ALP and Col-1 genes at day 7 and the Runx2 gene was able to show a significant increase at 14 days. The phosphonate-induced apatite coating was able to promote the upregulation of ALP and Col-1 in the early stage, which increased the expression of 55 Among the differentiation characteristics of the MC3T3-E1 preosteoblasts, we found significant differences between PPENK-PDA/P-HA and PPENK3-PDA/P-HA in terms of osteogenic differentiation. The samples were cocultured with cells for a longer period of time and were susceptible to loss of coating due to external forces on experimental manipulation.…”

Section: Osteogenic Differentiationmentioning

confidence: 96%

Stabilization of Apatite Coatings on PPENK Surfaces by Mechanical Interlocking to Promote Bioactivity and Osseointegration In Vivo

Cheng

Yang

Liu

et al. 2022

ACS Appl. Mater. Interfaces

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Apatite coatings with high stability can effectively improve the surface bioactivity and osteogenic activity of implant materials. In clinical practice, the ability of apatite coatings to bond with the substrate is critical to the effect of implants. Here, we propose a strategy to construct a three-dimensional (3D) nanoporous structure on the surface of a poly(phthalazinone ether nitrile ketone) (PPENK) substrate and introduce a polydopamine (PDA) coating with grafted phosphonate groups to enhance the overall deposition of a bone-like apatite coating in the 3D nanoporous structure during mineralization. This method leads to a mechanical interlocking between the apatite coating and the substrate, which increases the stability of the apatite coating. The apatite coating confers a better bioactive surface to PPENK and also promotes osteogenic differentiation and adhesion of MC3T3-E1 osteoblasts in vitro. The samples are then implanted into rat femurs to characterize in vivo osseointegration. Micro-CT data and histological staining of tissue sections reveal that PPENK with a stable apatite coating induces less fibrous capsule formation and no inflammatory response and promotes osteogenic differentiation and bone-bonding strength. This enhances the long-term use of PPENK implant materials and shows great potential for clinical application as orthopedic implants.

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Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment

Cited by 36 publications

References 71 publications

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration

Stabilization of Apatite Coatings on PPENK Surfaces by Mechanical Interlocking to Promote Bioactivity and Osseointegration In Vivo

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