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ACS Nano · 2022 · IF 18.027

Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration

Kun Liu,Lin Li,Jingsheng Chen,Yizhi Li,Wei Wen,Lu Lu,Lihua Li,Hong Li,Mingxian Liu,Changren Zhou,Binghong Luo

Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.

CAS / MDL: 9012-76-4
研究领域: 生物医学工程 · 组织工程 · 材料科学
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MATERIALS & DESIGN · 2025 · IF 7.9

3D-printed titanium dioxide-reinforced calcium silicate composite scaffold promotes efficient bone defect repair through activation of osteogenic and angiogenic differentiation

Zhiqiang Huang,Xinyi Wang,Zhaowenbin Zhang,Bin Yu,Suqi Wang,Xiaoting Chen,Yi Zhang,Jin Yang,Zhen Zeng,Zhihong Dong

Addressing the challenges of insufficient mechanical strength, high fragility, and rapid degradation in calcium silicate (CS) 3D-printed bone regeneration scaffolds and acknowledging the necessity to enhance performance of CS in bone and vascular regeneration, this study innovatively presents a titanium dioxide (TiO 2 ) reinforcement strategy. This strategy has led to the successful creation of a novel TiO 2 -reinforced CS composite 3D-printed bone regeneration scaffold (CST). By forming a solid solution during the sintering process between TiO 2 and CS, a marked improvement in the overall material strength is attained. Additionally, by leveraging the synergistic pro-regenerative effects of bioactive Si ions Ti ions, the capacity of CST for bone and vascular regeneration is significantly enhanced. In comparison to the pure CS scaffold, the CST scaffold, when reinforced with TiO 2 , not only maintains a similar porosity but also exhibits enhanced compressive strength, a slower degradation rate, and notably increased osteogenic induction and angiogenic activity. In vivo studies employing a cranial bone defect model have confirmed that the CST scaffold can substantially promote vascular neogenesis and bone regeneration, fully demonstrating its wide-ranging application potential in the field of bone defect treatment.

研究领域: 生物医学工程 · 骨组织工程 · 材料科学
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Advanced Science · 2025 · IF 14.1

3D-Printed Biomimetic Vascular Scaffold Crosslinked with Heparan Sulfate for Sustained Release of PDGFB-LG4 Fusion Protein Promotes Bone Regeneration

Jiahua Duan,Gaofei Qian,Huikang Zhang,Feifan Wang,Qiang Tian,Dong Lei,Jianning Zhao

A central focus of bone tissue engineering is the construction of vascular systems, which provide nutrients for cell survival, remove metabolic waste, and accelerate tissue regeneration. Platelet-derived growth factor-BB (PDGFB) has the ability to stimulate both vascularization and bone regeneration; however, its clinical application has been hindered by side effects and low efficacy due to suboptimal delivery systems. In this study, a biomimetic vascular scaffold crosslinked with heparan sulfate (HS) is developed to enable sustained delivery of the PDGFB-LG4 fusion protein, targeting the regeneration of critically sized bone defects. The scaffold is designed with a vascular-like hierarchical structure, incorporating a customized 3D framework, multibranched microchannels, and permeable porous walls, which facilitates mass exchange and cell infiltration. PDGFB-LG4 exhibits superior osteoinductive and angiogenic activity compared to PDGFB. In a calvarial defect model, the composite scaffold (PCLHS-PDGFB-LG4) significantly enhances both vascularization and bone regeneration, demonstrating improved efficacy at lower doses compared to PDGFB. This approach may be applicable to other growth factors and gelatin-based materials, offering the potential for a wide range of applications in regenerative medicine.

CAS / MDL: 9050-30-0 57459-72-0
研究领域: 组织工程学 · 再生医学 · 生物材料科学
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Research · 2022 · IF 11.036

Photopolymerized 3D Printing Scaffolds with Pt(IV) Prodrug Initiator for Postsurgical Tumor Treatment

Qingfei Zhang,Xiaocheng Wang,Gaizhen Kuang,Yunru Yu,Yuanjin Zhao

Biomedical scaffolds have shown great success in postsurgical tumor treatment; their current efforts are focusing on eradicating residual tumor cells and circulating tumor cells and simultaneously repairing postoperative tissue defects. Herein, we report a novel photopolymerized 3D scaffold with Pt(IV) prodrug initiator to achieve the desired features for tumor comprehensive therapy. The Pt-GelMA scaffold was fabricated from the microfluidic 3D printing of methacrylate gelatin (GelMA) bioinks through a Pt(IV)-induced photocrosslinked process without any other additional photoinitiator and chemotherapeutic drug. Thus, the resultant scaffold displayed efficient cell killing ability against breast cancer cells in vitro and significantly inhibited the local tumor growth and distant metastases on an orthotopic postoperative breast cancer model in vivo. Besides, benefiting from their ordered porous structures and favorable biocompatibility, the scaffolds supported the cell attachment, spreading, and proliferation of normal cells in vitro; could facilitate the nutrient transportation; and induced new tissue ingrowth for repairing tissue defects caused by surgery. These properties indicate that such 3D printing scaffold is a promising candidate for efficient postoperative tumor treatment in the practical application.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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Materials Today Bio · 2024 · IF 8.7

Optimizing silicon doping levels for enhanced osteogenic and angiogenic properties of 3D-printed biphasic calcium phosphate scaffolds: An in vitro screening and in vivo validation study

Teliang Lu,Guohao Li,Luhui Zhang,Xinyuan Yuan,Tingting Wu,Jiandong Ye

Biphasic calcium phosphate (BCP) ceramics are valued for their osteoconductive properties but have limited osteogenic and angiogenic activities, which restricts their clinical utility in bone defect repair. Silicon doping has emerged as an effective strategy to enhance these biological functions of BCP. However, the biological impact of BCP is influenced by the level of silicon doping, necessitating determination of the optimal concentration to maximize efficacy in bone repair. This study investigated the effects of silicon doping on both the physicochemical and biological properties of BCP, with a specific focus on osteogenic and angiogenic potentials. Results indicated that silicon doping exceeding 4 mol.% led to the formation of α-TCP, accelerating BCP degradation, enhancing silicon ion release, and promoting mineralization product formation. Simultaneously, silicon doping increased the porosity of BCP scaffolds, which typically reduces their compressive strength. Nevertheless, scaffolds doped with ≤4 mol.% silicon maintained compressive strengths exceeding 2 MPa. In vitro biological experiments indicated that higher levels of silicon doping (≥6 mol.%) partially inhibited the successful differentiation of stem cells and the vascularization of endothelial cells. Optimal conditions for promoting osteogenic differentiation and angiogenesis were identified between 2 and 4 mol.% silicon doping, with an optimal level of approximately 4 mol.%. Subsequent in vivo experiments confirmed that BCP scaffolds doped with 4 mol.% silicon effectively promoted vascularization and new bone formation, highlighting their potential for clinical bone defect repair.

CAS / MDL: 78-10-4
研究领域: 材料科学 · 生物医学工程 · 组织工程
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ACS Applied Bio Materials · 2025 · IF 4.7

3D-Printed Scaffold Achieves Synergistic Chemo-Sonodynamic Therapy for Tumorous Bone Defect

Cijun Shuai,Zihao Zhang,Min Chen,Bingxin Sun,Xingming Long,Guoyong Wang,Shuping Peng

Various smart scaffolds have recently been developed to address the regeneration of tumor bone defect. However, the recurrence of residual tumor cells poses a serious challenge to postoperative management, highlighting the need for effective therapeutic interventions. In this study, a multifunctional antitumor nanoplatform (Ti3C2/CuO2) for synergistic chemo-sonodynamic tumor therapy was developed and then rationally integrated into a poly(l-lactic acid) (PLLA) scaffold via selective laser sintering. CuO2 not only releases Cu2+ ions to facilitate chemodynamic antitumor therapy through the Fenton reaction but also generates H2O2, which further oxidizes Ti3C2 to produce TiO2 sonosensitizers. More importantly, the carbon-based substrates after oxidation of Ti3C2 have created favorable conditions for carrier transmission in the sonodynamic process, thereby amplifying the sonodynamic therapy. Additionally, moderate local hyperthermia form periodic sonodynamic therapy produces moderate localized heat therapy to further stimulate bone tissue regeneration. Meanwhile, the sustained release of bioactive ions (such as Cu and Ti ions) from the scaffold also fosters vascularization, further accelerating bone regeneration. This work presents a viable approach to developing multifunctional scaffolds for repairing tumorous bone defects.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Bifunctional Hydrogel-Integrated 3D Printed Scaffold for Repairing Infected Bone Defects

Qianqian Zhang,Xiaojun Zhou,Haibo Du,Yujie Ha,Yao Xu,Rongguang Ao,Chuanglong He

The clinical treatment of infectious bone defects is difficult and time-consuming due to the coexistence of infection and bone defects, and the simultaneous control of infection and repair of bone defects is considered a promising therapy. In this study, a dual-drug delivery scaffold system was fabricated by the combination of a three-dimensional (3D) printed scaffold with hydrogel for infected bone defects repair. The 3D printed polycaprolactone scaffold was incorporated with biodegradable mesoporous silica nanoparticles containing the small molecular drug fingolimod (FTY720) to provide structural support and promote angiogenesis and osteogenesis. The vancomycin (Van)-loaded hydrogel was prepared from aldehyde hyaluronic acid (AHA) and carboxymethyl chitosan (NOCC) by the Schiff base reaction, which can fill the pores of the 3D-printed scaffold to produce a bifunctional composite scaffold. The in vitro results demonstrated that the composite scaffold had Van concentration-dependent antimicrobial properties. Furthermore, the FTY720-loaded composite scaffold demonstrated excellent biocompatibility, vascularization, and osteogenic ability in vitro. In the rat femoral defect model with bacterial infection, the dual-drug composite scaffold showed a better outcome in both infection control and bone regeneration compared to other groups. Therefore, the prepared bifunctional composite scaffold has potential application in the treatment of infected bone defects.

CAS / MDL: 7790-28-5
研究领域: 生物材料学 · 组织工程学 · 药物递送系统
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Materials Today Bio · 2023 · IF 8.2

3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization

Qiuju Miao,Xiaopeng Yang,Jingjing Diao,Huanwen Ding,Yan Wu,Xiangyang Ren,Jianbo Gao,Mengze Ma,Shenyu Yang

The vascularization of bone repair materials is one of the key issues that urgently need to be addressed in the process of bone repair. The changes in macrophage phenotype and function play an important role in the process of vascularization, and endowing bone repair materials with immune regulatory characteristics to enhance angiogenesis is undoubtedly a new strategy to improve the effectiveness of bone repair. In order to improve the effect of tricalcium phosphate (TCP) on vascularization and bone repair, we doped strontium ions (Sr) into TCP (SrTCP) and prepared porous 3D printed SrTCP scaffolds using 3D printing technology, and studied the scaffold mediated macrophage polarization and subsequent vascularization and bone regeneration. The results of the interaction between the scaffold and macrophages showed that the SrTCP scaffold can promote the polarization of macrophages from M1 to M2 and secrete high concentrations of VEGF and PDGF-bb cytokines, which shows excellent angiogenic potential. When human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium of SrTCP scaffold, HUVECs exhibited excellent early angiogenesis-promoting effects in terms of scratch healing, angiogenic gene expression, and in vitro tube formation performance. The results of in vivo bone repair experiments showed that the SrTCP scaffold formed a vascular network with high density and quantity in the bone defect area, which could increase the rate of new bone formation and advance the period of bone formation, and finally achieved a better bone repair effect. We observed a cascade effect in which Sr-doped SrTCP scaffold regulate macrophage polarization to enhance angiogenesis and promote bone repair, which may provide a new strategy for the repair of clinical bone defects.

研究领域: 生物材料学 · 组织工程学 · 免疫学
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MATERIALS CHEMISTRY AND PHYSICS · 2025 · IF 4.7

Fiber-reinforced hydrogel combined with 3D printed scaffolds for regeneration of osteochondral defects

Huan Liu,Yichen Dou,Jiawei Wei,Shiqi Xiao,Shue Jin,Li Yuan,Jing Wen,Jiangshan Liu,Yubao Li,Jidong Li

Osteochondral defects present a formidable challenge within the realm of orthopedic medicine. The burgeoning field of tissue engineering holds potential for the amelioration of these injuries. In this vein, we meticulously engineered an integrated osteochondral repair scaffold by combining a short-cut fiber-reinforced hydrogel as a cartilaginous layer with 3D printed scaffold as bone layer. The cartilaginous layer hydrogel is composed of sodium alginate (Alg) and hyaluronic acid (HA), which are similar to the extracellular matrix of chondrocytes. The incorporation of 25 wt% short-cut fibers into the hydrogel substantially enhanced its mechanical integrity and fostered in vitro proliferation and adhesion of bone marrow stromal cells (BMSCs). The bone layer of polylactic glycolic acid copolymer (PLGA)/nano-hydroxyapatite (n-HA)/gelatin (Gel) gradient scaffold (PHG) was successfully prepared by constructing Gel network in 3D printed PLGA/n-HA framework. A PHG scaffold semi-immersed in hydrogel forms a comb-toothed interlocking structure with the hydrogel to simulate the bone-cartilage interface at the natural knee joint of the human body. In vivo examinations of osteochondral defect repair corroborate that the integrated scaffold, enriched with 25 % short-cut fibers, efficaciously promotes simultaneous regeneration of cartilage and subchondral bone. Collectively, our findings advocate that the combination of 3D-printed scaffolds and hydrogels could be a promising candidate for functional osteochondral regeneration.

研究领域: 生物医学工程 · 再生医学 · 骨科医学
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Materials Today Bio · 2025 · IF 10.2

Study of bioactive 3D-printed scaffolds incorporating zinc-based MOF for bone defect repair and anti-inflammatory applications

Yu Han,Xiufeng Jia,Yinwei Yang,Pei Guo,Chao Li,Yunze Zhang,Li Yin,Bo Jia,Haitao Wang

The development of bioactive scaffolds capable of orchestrating osteogenesis while modulating inflammatory responses remains a critical challenge in bone tissue engineering. To address this unmet need, we engineered a multifunctional composite scaffold through precise integration of poly(lactic-co-glycolic acid) (PLGA), type I collagen, zinc-imbued metal-organic frameworks (Zn-MOFs), and macrophage chemotactic factor (MCF) via extrusion-based 3D printing. Systematic biological assessments in vitro revealed the scaffold's remarkable osteoinductive capacity, evidenced by significant upregulation of alkaline phosphatase (ALP) activity (2.78±0.10 fold increase vs control, p<0.05) and enhanced collagen type I deposition (10.79±1.12 fold increase vs control, p<0.05) within 14 days of culture. In vivo implantation in rat femoral defect models demonstrated superior bone regeneration outcomes, with micro-CT analysis showing bone volume/ total volume (BV/TV) 31.39±3.04% compared to 16.44±3.26% in control (P<0.05). The Zn-MOF component mediated sustained release of Zn 2+ ions (cumulative release: 89.6±9.08% over 18 days). This dual-functional system synergistically combines MCF-driven cellular recruitment with Zn 2+ -mediated immunomodulation, creating a pro-regenerative microenvironment. Our findings not only demonstrate the feasibility of 3D-printed multi-material constructs for complex tissue engineering applications but also establish a new paradigm for developing smart biomaterials that concurrently address biological regeneration and inflammatory control.

CAS / MDL: 26780-50-7 9007-34-5
研究领域: 生物医学工程 · 组织工程 · 材料科学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Oxygen self-supplied BTOv-Ru heterojunction boosts the sonodynamic antibacterial efficiency of scaffold

Wenjie Ma,Ru Jia,Huixing Li,Lanlan Dong,Wurikaixi Aiyiti,Cijun Shuai,Chongxian He

Transplantation-related bacterial infections often slow new tissue regeneration and even cause transplant failure. Sonodynamic therapy is a promising antibacterial method, which kills bacteria by triggering sonosensitizers to generate reactive oxygen species (ROS). Nevertheless, the generation efficiency of ROS is hindered by the fast electron-hole pair recombination in sonosensitizers and the hypoxic of bacteria microenvironment. Herein, ruthenium nanoparticles (Ru NPs) are grown in-situ on the oxygen vacancies-rich barium titanate nanoparticles (BTOv NPs) to form a Schottky heterojunction. The resulting BTOv-Ru NPs as sonosensitizers is uniformly distributed with poly-L-lactic acid (PLLA) powders to fabricate ultrasound-responsive scaffolds via selective laser sintering. On the one hand, the Schottky heterojunction facilitates electron injection from BTOv to Ru, while the resultant charge separation significantly suppresses electron-hole recombination. On the other hand, the catalase-like activity of Ru catalyzes the overexpressed hydrogen peroxide to generate O 2 to achieve O 2 self-supply. This not only alleviates hypoxia but also facilitates the oxygen vacancies of BTOv adsorb more O 2 to generate ROS. The results confirmed PLLA/BTOv-Ru scaffold generated numerous ROS and exhibited excellent antibacterial effects under ultrasonic irradiation, with inhibiting E. coli (89.3 %) and S. aureus (88.1 %). This O 2 self-supplying sonodynamic therapy shows great promise in antibacterial treatment.

研究领域: 生物医学工程 · 纳米医学 · 感染控制 · 组织工程 · 声动力治疗 · 抗菌材料
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Advanced Healthcare Materials · 2015 ·Vol. 4 ·期 11 ·1701-1708 · IF 5.797

3D-Printed Atsttrin-Incorporated Alginate/Hydroxyapatite Scaffold Promotes Bone Defect Regeneration with TNF/TNFR Signaling Involvement

Quan Wang,Qingqing Xia,Yan Wu,Xiaolei Zhang,Feiqiu Wen,Xiaowen Chen,Shufang Zhang,Boon Chin Heng,Yong He,Hong-Wei Ouyang

High expression levels of pro-inflammatory tumor necrosis factor (TNF)-α within bone defects can decelerate and impair bone regeneration. However, there are few available bone scaffolds with anti-inflammatory function. The progranulin (PGRN)-derived engineered protein, Atsttrin, is known to exert antagonistic effects on the TNF-α function. Hence, this study investigates whether 3D-printed Atsttrin-incorporated alginate(Alg)/hydroxyapatite(nHAp) scaffolds can facilitate bone healing through affecting the TNF/TNFR signaling. A 3D bioprinting system is used to fabricate Atsttrin-Alg/nHAp composite scaffolds, and the Atsttrin release from this scaffold is characterized, followed by evaluation of its efficacy on bone regeneration both in vitro and in vivo. The 3D-printed Atsttrin-Alg/nHAp scaffold exhibits a precisely defined structure, can sustain Atsttrin release for at least 5 days, has negligible cytotoxicity, and supports cell adhesion. Atsttrin can also attenuate the suppressive effects of TNF-α on BMP-2-induced osteoblastic differentiation in vitro. The 3D-printed Atsttrin-Alg/nHAp scaffold significantly reduces the number of TNF-α positive cells within wound sites, 7 days after post-calvarial defect surgery. Additionally, histological staining and X-ray scanning results also show that the 3D-printed Atsttrin-Alg/nHAp scaffold enhances the regeneration of mice calvarial bone defects. These findings thus demonstrate that the precise structure and anti-inflammatory properties of 3D-printed Atsttrin-Alg/nHAp scaffolds may promote bone defect repair.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 生物材料
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