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Advanced Healthcare Materials · 2023 · IF 10

Ultraviolet Light-Based Micropattern Printing on Titanium Surfaces to Promote Early Osseointegration

Yiting Lou,Mouyuan Sun,Jingyu Zhang,Yu Wang,Haiying Ma,Zheyuan Sun,Shengjie Li,Xiaoyan Weng,Binbin Ying,Chao Liu,Mengfei Yu,Huiming Wang

Patterned interfaces are widely used for surface modification of biomaterials because of a morphological unit similar to that of native tissue. However, engineering fast and cost-effective high-resolution micropatterns directly onto titanium surfaces remains a grand challenge. Herein, a simply designed ultraviolet (UV) light-based micropattern printing to obtain geometrical patterns on implant interfaces is fabricated by utilizing customized photomasks and titanium dioxide (TiO 2 ) nanorods as a photo-responsive platform. The technique manipulates the cytoskeleton of micropatterning cells on the surface of TiO 2 nanorods. The linear pattern surface shows the elongated morphology and parallel linear arrangements of human mesenchymal stem cells (hMSCs), significantly enhancing their osteogenic differentiation. In addition to the upregulated expression of key osteo-specific function genes in vitro, the accelerated osseointegration between the implant and the host bone is obtained in vivo. Further investigation indicates that the developed linear pattern surface has an outstanding effect on the cytoskeletal system, and finally activates Yes-Associated Protein (YAP)-mediated mechanotransduction pathways, initiating hMSCs osteogenic differentiation. This study not only offers a microfabrication method that can be extended to fabricate various shape- and size-controlled micropatterns on titanium surfaces, but also provides insight into the surface structure design for enhanced bone regeneration.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 细胞生物学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 38 ·7732-7743 · IF 7.571

The role of nanopores constructed on the micropitted titanium surface in the immune responses of macrophages and the potential mechanisms

Ruiyue Hang,Yuyu Zhao,Yi Zhang,Runhua Yao,Xiaohong Yao,Yonghua Sun,Di Huang,Ruiqiang Hang

The delayed transition of macrophages (MΦs) from pro-inflammatory M1 to the pro-healing M2 state on implant surfaces is one of the most important reasons for poor osseointegration. This work reports the construction of closely packed nanopores with a small diameter on the micropitted titanium (Ti) surface by two-step acid etching to promote the M1-to-M2 transition of MΦs and pays special attention to the potential mechanisms by which the nanopores decorating the micropits exert immunomodulatory effects. The results show that the structure composed of hybrid nanopores (10–25 nm) and micropits (5–15 μm) can be produced on the Ti surface by a two-step acid etching process. Compared with the unitary micropits, the micropit/nanopore surface could facilitate the switch of MΦs from the pro-inflammatory M1 to the pro-healing M2 phenotype. RNA sequencing reveals that the MAPK, PI3K-AKT and C-type lectin signaling pathways play key roles in the micro/nano-structure-mediated transition. In addition, the micro/nano-structured surface down-regulated CYP1A2 expression, reducing the generation of mitochondrial ROS, in turn restraining the oxidative stress and further attenuating inflammation. This work provides novel insights into the underlying mechanisms of immunomodulation by the nano-structure-decorated micro-structures on the Ti surface, which is significant for designing the surface of orthopedic implants from the perspective of immunomodulation.

CAS / MDL: 3810-74-0
研究领域: 生物材料 · 免疫学 · 组织工程 · 骨科
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BIOMATERIALS · 2021 · IF 12.479

A multifunctional hydrogel coating to direct fibroblast activation and infected wound healing via simultaneously controllable photobiomodulation and photodynamic therapies

Ye He,Jin Leng,Ke Li,Kun Xu,Chuanchuan Lin,Zhang Yuan,Rui Zhang,Danyang Wang,Bailong Tao,Tony Jun Huang,Kaiyong Cai

Bacterial infection treatment and subsequent tissue rebuilding are the main tasks of biomaterial research . To endow implants with antibacterial activity and biological functions, the material systems are usually very complicated and ineffective. Recently, the concept of photobiomodulation (PBM), or low-level laser therapy (LLLT), has attracted increasing attention in tissue repair applications but still has not obtained wide acceptance. Because of the same laser resource, PBM could simultaneously work with 660 nm laser triggered photodynamic therapy (PDT), which will significantly simplify the material system and achieve the multiple functions of antibacterial activity and biological modulation effects. Herein, we attempt to validate the effectiveness of PBM and combine PBM with a PDT-based material system. A catechol motif-modified methacrylated gelatin containing photosensitizer Chlorin e6-loaded mesoporous polydopamine nanoparticles was fabricated (GelMAc/ [email protected] ). This hydrogel could be tightly adhered to titanium surfaces to serve as surface coating materials or directly used as dressings. Because of the 660 nm laser-triggered ROS generation property of Ce6, GelMAc/ [email protected] exhibited a remarkable and rapid antibacterial activity when the laser power was 1 W cm −2 . After bacterial elimination , when the power was adjusted to 100 mW cm −2 , daily irradiation brought an excellent PBM effect: the fibroblast activation was realized to accelerate wound repair. According to our in vitro and in vivo results, the fabricated hydrogel coating possessed both antibacterial activity and fibroblast activation ability only by adjusting the power of laser irradiation, which will greatly strengthen the confidence of using PBM in broader fields and give a good example to combine PBM with traditional biomaterial design .

CAS / MDL: 62-31-7 108-67-8 77-86-1
研究领域: 生物材料 · 组织工程 · 伤口愈合 · 光疗 · 感染治疗
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Multifunctional photothermal PB@EGCG-Sr nanocoating design on titanium surface: To achieve short-term rapid osseointegration and on-demand photothermal long-term osteogenesis

Pengfei Gao,Yangpeng Zuo,Yulu Yang,Jinxiu Yu,Wuzhe Fan,Ruqing Bai,Weihu Yang,Kaiyong Cai

To resolve the short-term inflammatory storm after the operation and the long-term osteointegration deficiency of titanium (Ti) implant as an artificial hip joint, in this work, a novel functionalized Ti implant with an “on-demand” treatment strategy was explored. The metallopolyphenol network (Epigallocatechin gallate (EGCG) and Strontium) wrapped Prussian blue nanoparticles were prepared and anchored on the Ti surface. During the acute inflammatory phase, the inflammatory acidic microenvironment will result in the degradation of the metallopolyphenol network and the responsive release of EGCG and strontium (Sr) ions. The released EGCG could reduce oxidative stress damage and promote the transition of macrophages from M1 to M2. In comparison, Sr ions could stimulate osteoblast differentiation and achieve the rapid osteogenesis and fixation of implants. To achieve long-term osteointegration efficacy, “on-demand” near-infrared light irradiation for the remained PB particles could be adopted if necessary. The mild photothermal conversion temperature could upregulate the expressions of heat shock proteins around the implant and promote the biosynthesis of type I collagen, as well as the formation of bone matrix. In vitro and in vivo results proved the feasibility of our strategy. It is a prospective method for the modification of Ti implants.

研究领域: 材料科学 · 生物医学工程 · 生物材料 · 组织工程 · 骨科
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Acta Biomaterialia · 2022 · IF 10.633

Antifouling poly(PEGMA) grafting modified titanium surface reduces osseointegration through resisting adhesion of bone marrow mesenchymal stem cells

Tingben Huang,Chenxi Tu,Tong Zhou,Zhou Yu,Yuchen Wang,Qiong Yu,Ke Yu,Zhiwei Jiang,Changyou Gao,Guoli Yang

As an alternative strategy to achieve the desired bone augmentation, tenting screw technology (TST) has considerably broadened the indications for implant treatment. Titanium tenting screws are typically used in TST to maintain the space for bone regeneration . However, a high degree of osteogenic integration complicate titanium tenting screw removal and impact the bone healing micro-environment. Previous efforts have been focused on modifying titanium surfaces to enhance osseointegration while ignoring the opposite process. Due to the vital role of bone marrow mesenchymal stem cells (BMSCs) in bone regeneration, it might be feasible to reduce osseointegration around titanium tenting screws by resisting the adhesion of BMSCs. Herein, poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was incorporated with a Ti surface in terms of surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The cell apoptosis analysis showed that the new surface would not induce the apoptosis of BMSCs. Then, the adhesive and proliferative behaviors of BMSCs on the surface were analyzed which indicated that the poly(PEGMA) surface could inhibit the proliferation of BMSCs through resisting the adhesion process. Furthermore, in vivo experiments revealed the presence of the poly(PEGMA) on the surface resulted in a lower bone formation and osseointegration compared with the Ti group. Collectively, this dense poly(PEGMA) surface of Ti may serve as a promising material for clinical applications in the future. Statement of significance The poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was grafted onto a Ti surface by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The PEGMA surface could reduce the osteogenic integration by preventing the adhesion of cells, resulting in a lower pullout force of the modified implant and thereby desirable and feasible applications in dental surgery.

CAS / MDL: 75-50-3 33527-91-2
研究领域: 生物材料 · 生物医学工程 · 骨科 · 牙科手术 · 组织工程
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Materials Science & Engineering C-Materials for Biological Applications · 2021 · IF 7.328

Dopamine-assisted co-deposition of hydroxyapatite-functionalised nanoparticles of polydopamine on implant surfaces to promote osteogenesis in environments with high ROS levels

Yilin Yu,Xiaolei Li,Jiarun Li,Dongying Li,Qinmei Wang,Wei Teng

Environments with high reactive oxygen species (ROS) levels, which are common in patients with diseases such as diabetes, periodontitis, and osteoporosis, impair the osseointegration of implants. To address this issue, by using a one-pot dopamine-assisted co-deposition method, we constructed a three-dimensional coating of hydroxyapatite-functionalised nanoparticles of polydopamine (HA/nPDAs) on implant surfaces, where polydopamine is designed to protect cells via scavenging excessive ROS and HA facilitates osteogenesis. First, nanoparticles of polydopamine (nPDAs) were prepared by self-polymerization and assembly of dopamine under alkaline conditions, and HA/nPDAs were obtained by incubating nPDAs in simulated body fluid (SBF) due to metal chelation and ionic interactions triggered by the catechol moieties of PDA. Thereafter, HA/nPDAs with thickness of ~4 μm were constructed on titanium surfaces by immersing titanium discs in a weak alkaline solution of HA/nPDAs and dopamine through interface interactions driven by catechol chemistry. The properties of coatings (e.g., thickness, composition, hydrophilia and morphology) can be controlled by preparation conditions such as mineralization time and reactant concentration. The coatings display efficient ROS-scavenging ability, promote cell proliferation, and upregulate the activity of alkaline phosphatase and the expression of osteogenesis-related genes in environments with high or normal ROS levels, demonstrating the great promise of such coatings for osseointegration promotion, especially in the state of high ROS in diseases. This study provides a facile, efficient, mild, and universal strategy in engineering functional surfaces on any substrates for diversified applications by simple variation of co-deposited components, through taking advantages of versatile catechol chemistry and nanoparticles with stereo structure and great specific surface area.

研究领域: 生物材料 · 组织工程 · 骨科 · 材料科学 · 生物医学工程
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