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MATERIALS & DESIGN · 2019 · IF 5.77

3D printing of biomimetic multi-layered GelMA/nHA scaffold for osteochondral defect repair

Jingyi Liu,Liang Li,Hairui Suo,Mengling Yan,Jun Yin,Jianzhong Fu

Currently, osteochondral defects frequently cause limited motion and impaired function of the joint, leading to serious healthcare problems, and it is still very challenging to realize the simultaneous regeneration of subchondral bone with cartilage. In the current study, we designed a tri-layered scaffold and fabricated it using the extrusion-based multi-nozzle 3D printing technology. The bioinks used for 3D printing included a 15% methacrylated gelatin (GelMA) hydrogel for cartilage on top layer, a combination of 20% GelMA and 3% nanohydroxyapatite (nHA) (20/3% GelMA/nHA) hydrogel for interfacial layer, and a 30/3% GelMA/nHA hydrogel for subchondral bone at bottom layer. The water absorption capacity, biodegradation, and mechanical properties of hydrogels and scaffolds were characterized, and in vitro assay with bone marrow mesenchymal stem cells (BMSCs) was performed to indicate the biocompatibility of scaffolds. Based on the results of in vivo repair of rabbit osteochondral defect, the neo-tissues in defects integrated better with the surrounding tissues, the joint surface of the defects was smoother, and more cartilage-specific extracellular matrix and collagen type II were observed using the tri-layered scaffolds. This study not only provides a potential manufacturing method for multi-layered scaffolds, but also is helpful for understanding the regeneration mechanism of cartilage-subchondral bone.

研究领域: 组织工程 · 再生医学 · 生物医用材料 · 骨科手术
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BIOMATERIALS · 2022 · IF 15.304

Biomimetic glycopeptide hydrogel coated PCL/nHA scaffold for enhanced cranial bone regeneration via macrophage M2 polarization-induced osteo-immunomodulation

Yaping Wang,Jingrong Wang,Rui Gao,Xiang Liu,Zujian Feng,Chuangnian Zhang,Pingsheng Huang,Anjie Dong,Deling Kong,Weiwei Wang

The reconstruction of large cranial bone defects by bioactive materials without exogenous cells or growth factors remains a substantial clinical challenge. Here, synthetic fibrous glycopeptide hydrogel (GR gel ) self-assembled by β-sheet RADA16-grafted glucomannan was designed to mimic the glycoprotein composition and the fibrillar architecture of natural extracellular matrix (ECM), which was non-covalently composited with 3D-printed polycaprolactone/nano hydroxyapatite (PCL/nHA) scaffold for cranial bone regeneration . The glycopeptide hydrogel significantly promoted the proliferation, osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by GR gel -induced macrophage M2-phonotype polarization and the effective M2 macrophage-BMSC crosstalk . The repair of critical-size skull bone defect in rat indicated a superior efficacy of PCL/ [email protected] gel implant on bone regeneration and osseointegration , with an average bone area of 83.3% throughout the defect location at 12 weeks post treatment. Furthermore, the osteo-immunomodulatory GR gel induced a reparative microenvironment similar with that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and osteoblasts, and high-level vascularization . Collectively, the composite scaffold developed here with macrophage polarization-mediated osteo-immunomodulation may represent a promising implant for expediting in situ bone regeneration by providing biochemical and osteoinductive cues at the injured tissue.

研究领域: 生物材料学 · 组织工程学 · 再生医学
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RSC Advances · 2024 ·Vol. 14 ·期 14 ·9848-9859 · IF 3.9

Preparation and properties of a 3D printed nHA/PLA bone tissue engineering scaffold loaded with a β-CD–CHX combined dECM hydrogel

Shangbo Li,Zijian Liu,Xiaohan Gao,Lidi Cheng,Zexian Xu,Li Li,Yaru Diao,Liqiang Chen,Yanshan Liu,Jian Sun

Jaw defects, which can result from a multitude of causes, significantly affect the physical well-being and psychological health of patients. The repair of these infected defects presents a formidable challenge in the clinical and research fields, owing to their intricate and diverse nature. This study aims to develop a personalized bone tissue engineering scaffold that synergistically offers antibacterial and osteogenic properties for treating infected maxillary defects. This study engineered a novel temperature-sensitive, sustained-release hydrogel by amalgamating β-cyclodextrin (β-CD) with chlorhexidine (CHX) and a decellularized extracellular matrix (dECM). This hydrogel was further integrated with a polylactic acid (PLA)–nano hydroxyapatite (nHA) scaffold, fabricated through 3D printing, to form a multifaceted composite scaffold (nHA/PLA/dECM/β-CD–CHX). Drug release assays revealed that this composite scaffold ensures prolonged and sustained release. Bacteriological studies confirmed that the β-CD–CHX loaded scaffold exhibits persistent antibacterial efficacy, thus effectively inhibiting bacterial growth. Moreover, the scaffold demonstrated robust mechanical strength. Cellular assays validated its superior biocompatibility, attributed to dECM and nHA components, significantly enhancing the proliferation, adhesion, and osteogenic differentiation of osteogenic precursor cells (MC3T3-E1). Consequently, the nHA/PLA/dECM/β-CD–CHX composite scaffold, synthesized via 3D printing technology, shows promise in inducing bone regeneration, preventing infection, and facilitating the repair of jaw defects, positioning itself as a potential breakthrough in bone tissue engineering.

CAS / MDL: 9002-93-1
研究领域: 生物材料学 · 组织工程学 · 口腔医学
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ACS Applied Polymer Materials · 2025 · IF 4.7

Preparation and Evaluation of Digital 3D-Printed PLA/nHA/CNTs-CG Composite Bone Tissue-Engineering Scaffold for Enhanced Osteogenic and Antibacterial Properties

Yaru Diao,Li Li,Yaoxiang Xu,Yanshan Liu,Ruxi Sun,Liqiang Chen,Yupeng Wu,Xiaohan Gao,Wenhao Cheng,Chen Chen,Zexian Xu,Jian Sun

In bone tissue reconstruction, infection is a critical limiting factor affecting treatment efficacy. So it is necessary to introduce antibacterial agents onto scaffold surfaces for functional modification while balancing osteoblast activity. Carbon nanotubes (CNTs), with their exceptional osteogenic properties and drug-loading capacity, emerge as ideal materials. Digital 3D printing technology was employed to composite CNTs loaded with the antibacterial agent chlorhexidine gluconate (CG) with polylactic acid-nano hydroxyapatite (PLA/nHA), and a novel composite scaffold with a controllable porous structure (PLA/nHA/CNTs-CG) was successfully constructed. TEM observations revealed the hollow structure of CNTs, while XPS, XRD, N2 adsorption–desorption tests, and TGA confirmed successful CG loading. SEM analysis demonstrated the porous network-like structure of PLA/nHA/CNTs-CG scaffolds, exhibiting compressive strength of (8.44 ± 0.24) MPa. Initial biosafety validation through CCK-8 assay, live/dead cell staining, and hemocompatibility tests confirmed good biocompatibility. Cell adhesion experiments demonstrated enhanced cellular attachment on PLA/nHA/CNTs-CG scaffolds. Osteogenic performance tests revealed that CNTs incorporation improved MC3T3-E1 cell osteogenic differentiation, with CG presence not compromising scaffold osteogenic activity. Antibacterial experiments demonstrated potent antibacterial effects against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The PLA/nHA/CNTs-CG composite scaffold demonstrates dual functionality in infectious bone defect repair by simultaneously promoting bone regeneration and exerting antibacterial effects, providing novel insights for designing bone repair materials for infected defects.

研究领域: 生物材料学 · 再生医学 · 骨科
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Materials Science & Engineering C-Materials for Biological Applications · 2013 · IF 2.404

Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering

Junmin Qian,Weijun Xu,Xueqing Yong,Xinxia Jin,Wei Zhang

In this study, biomorphic poly( dl -lactic- co -glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164   ±   52   μm and 13   ±   8   μm, respectively, with a porosity of 89.3   ±   1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400   μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering.

CAS / MDL: 1306-06-5 12167-74-7
研究领域: 生物材料 · 组织工程 · 生物医学工程
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

nHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair

Xiaohu Zhou,Jiwei Sun,Keqi Wo,Haojie Wei,Haoqi Lei,Junyuan Zhang,Xiaofeng Lu,Feng Mei,Qingming Tang,Yifan Wang,Zhiqiang Luo,Lihong Fan,Yingying Chu,Lili Chen

Critical-sized maxillofacial bone defects have been a tough clinical challenge considering their requirements for functional and structural repair. In this study, an injectable in-situ forming double cross-linked hydrogel was prepared from gelatin (Gel), 20 mg/mL alginate dialdehyde (ADA), 4.5 mg/mL Ca 2+ and borax . Improved properties of composite hydrogel might well fit and cover irregular geometric shape of facial bone defects, support facial structures and conduct masticatory force . We innovatively constructed a bioactive poly-porous structure by decoration with nano-sized hydroxyapatite (nHA). The highly ordered, homogeneous and size-confined porous surface served as an interactive osteogenic platform for communication and interplay between macrophages and bone marrow derived stem cells (BMSCs). Effective macrophage-BMSC crosstalk well explained the remarkable efficiency of nHA-loaded gelatin/alginate hydrogel ( [email protected] /ADA) in the repair of critical-size skull bone defect. Collectively, the composite hydrogel constructed here might serve as a promising alternative in repair process of complex maxillofacial bone defects.

CAS / MDL: 9000-70-8 9005-38-3
研究领域: 生物材料 · 组织工程 · 骨科 · 牙科科学 · 生物医学工程
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AMERICAN JOURNAL OF SPORTS MEDICINE · 2025 · IF 4.5

An Aligned-to-Random PLGA/Col1-PLGA/nHA Bilayer Electrospun Nanofiber Membrane Enhances Tendon-to-Bone Healing in a Murine Model

Baoyun Xu,Yunjiao Wang,Gang He,Xu Tao,Shang Gao,Mei Zhou,Yuzhen Tang,Kang-lai Tang,Lin Guo,Wan Chen

Background:The challenge of achieving effective tendon-to-bone healing remains a significant concern in sports medicine, necessitating further exploration. Biomimetic electrospun nanomaterials present promising avenues for improving this critical healing process.Purpose:To investigate the biological efficacy of a novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer electrospun nanofiber membrane in facilitating tendon-to-bone healing.Study Design:Controlled laboratory study.Methods:The bilayer membrane’s composition, combining PLGA/Col1 for tendon attachment and PLGA/nHA for bone integration, was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing. Positioned between the Achilles tendon and bone, its design aimed for harmonious integration with both types of tissue. In vitro, biocompatibility, cell adhesion, and proliferation of the biomaterial were evaluated using live/dead staining and the CCK-8 assay. Collagen secretion and mineralization were measured for 2 cell types. In vivo, tendon-to-bone insertion samples harvested from mice were analyzed: micro–computed tomography assessed bone formation; histological staining evaluated chondrogenesis, tendinogenesis, and the 4-layer structure of the insertion; and biomechanical testing measured insertion strength. Real-time polymerase chain reaction identified genes involved in tendon-to-bone healing, and transcriptome analysis elucidated the underlying cellular and molecular mechanisms.Results:The optimal composition was determined as 10% 3:1 for aligned PLGA/Col1 and 9% 5:1 for PLGA/nHA. Coculture showed minimal cell death, firm cell adherence, and steady proliferation, with PLGA/Col1 enhancing collagen secretion. In vivo, the material promoted bone and cartilage formation and improved tendon-to-bone interface strength. Transcriptome analysis indicated links to TNF and NF-κB pathways and to genes IL-1β, ADAM8, and EGR2.Conclusion:The novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer nanofiber membrane outperformed other materials in both in vitro and in vivo evaluations, significantly enhancing tendon-to-bone healing. It notably improved cartilage and bone formation, tendon maturation, and biomechanical strength at the surgical interface. These effects may be associated with the TNF and NF-κB pathways and with the genes IL-1β, ADAM8, and EGR2.Clinical Relevance:This study introduces a biomimetic nanofiber membrane enhancing tendon-to-bone healing, which is crucial for sports medicine. Its efficacy in improving healing outcomes, including bone and cartilage formation and biomechanical strength, could significantly lower failure rates in surgical procedures such as rotator cuff repair and anterior cruciate ligament reconstruction. This advancement offers promising implications for patient recovery and the effectiveness of surgical interventions in tendon-to-bone injuries.

研究领域: 运动医学 · 组织工程 · 生物材料科学 · 骨科 · 生物医学工程
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Biomaterials Science · 2023 · IF 6.6

Supercritical CO2-assisted fabrication of CM-PDA/SF/nHA nanofibrous scaffolds for bone regeneration and chemo-photothermal therapy against osteosarcoma

Ruijia Han,Yajun Min,Guanlin Li,Shilu Chen,Maobin Xie,Zheng Zhao

Concurrent treatment of tumor recurrence and bone defects after surgical resection of osteosarcoma remains a clinical challenge. Combination therapy based on local drug delivery systems shows great promise in the treatment of osteosarcoma. In this study, curcumin modified polydopamine nanoparticle loaded silk fibroin doped with nano-hydroxyapatite (CM-PDA/SF/nHA) nanofibrous scaffolds were developed to induce bone defect regeneration and chemo-photothermal synergistic effects against osteosarcoma. These scaffolds exhibited good photothermal conversion efficiency and photostability. Moreover, the results of ALP staining and alizarin red S (ARS) staining indicated that the CM-PDA/SF/1%nHA scaffolds had the most obvious promotion effect on early osteogenic differentiation. The results of in vitro and in vivo anti-osteosarcoma activity showed that the CM-PDA/SF/1%nHA scaffolds exhibited higher anti-osteosarcoma activity compared to the control and SF scaffolds. In addition, the CM-PDA/SF/1%nHA scaffolds could promote the proliferation and differentiation of bone marrow mesenchymal stem cells in vitro and new bone production in vivo. Thus, these results suggested that the CM-PDA/SF/1%nHA scaffolds could improve bone defect regeneration and achieve chemo-photothermal synergistic effects against osteosarcoma.

研究领域: 生物医学工程 · 组织工程 · 癌症治疗 · 材料科学 · 纳米技术
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Materials · 2020 ·Vol. 13 ·期 17 ·3735 · IF 3.057

A GelMA-PEGDA-nHA Composite Hydrogel for Bone Tissue Engineering

Yihu Wang,Xiaofeng Cao,Ming Ma,Weipeng Lu,Bing Zhang,Yanchuan Guo

A new gelatin methacrylamine (GelMA)-poly (ethylene glycol) diacrylate (PEGDA)-nano hydroxyapatite (nHA) composite hydrogel scaffold was developed using UV photo-crosslinking technology. The Ca2+from nHA can form a [HO]Ca2+[OH] bridging structure with the hydroxyl group in GelMA, thereby enhancing the stability. Compared with GelMA-PEGDA hydrogel, the addition of nHA can control the mechanical properties of the composite hydrogel and reduce the degradation rate. In vitro cell culture showed that osteoblast can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-PEGDA-nHA hydrogel had good cell viability and biocompatibility. Furthermore, GelMA-PEGDA-nHA has excellent injectability and rapid prototyping properties and is a promising 3D printed bone repair scaffold material.Keywords:hydrogel;GelMA;nHA;photo-crosslinking

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MATERIALS LETTERS · 2012 · IF 2.307

Preparation and characterization of PLLA/nHA nonwoven mats via laser melt electrospinning

Xiuyan Li,Huichao Liu,Jiaona Wang,Congju Li

Laser melt electrospinning is a novel technology to fabricate tissue engineering (TE) scaffolds, and this solvent-free process is far safer than common solution electrospinning. In this paper, the electrospun poly(L-lactide)/nano-hydroxyapatite (PLLA/nHA) composite fiber scaffolds were prepared by this method. The scanning electron microscopy (SEM) indicated that the fibers with diameters ranging from 4 to 7   μm were obtained, and the nHA particles were well-dispersed in the PLLA fibers matrix. The energy dispersion spectroscopy (EDS) and X-ray diffraction (XRD) analysis results demonstrated the existence of nHA in the PLLA fibers. With the modification of incorporating HA nanocrystalline particles, the hydrophilicity of the electrospun PLLA/nHA mats surface can be improved.

CAS / MDL: 1306-06-5 12167-74-7
研究领域: 生物材料学 · 医学工程
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International Journal of Polymeric Materials and Polymeric Biomaterials · 2022 · IF 3.221

Preparation of SF/SF-nHA double-layer scaffolds for periodental tissue regeneration

Ying Guo,Xuefeng Jiang,Peng Pan,Xueping Liu,Linling Huang,Mingzhong Li,Yu Liu

Silk fibroin (SF) film/porous SF-nanohydroxyapatite (nHA) double-layer composite scaffolds were fabricated by a combination of electrospinning, casting and freeze-drying. The results showed that the tensile strength and elongation of the SF film layer were significantly improved through the bridging effect of SF/(ε-caprolactone) fibers in the SF matrix. The pore size in SF-nHA porous scaffold layer was approximately 213 μm, and nHA enhanced the compressive strength of the scaffold. CCK-8 assay showed that the SF/SF-nHA scaffold not only had no obvious cytotoxicity but also significantly promoted cell proliferation. The scaffold has the potential to be used for periodontal tissue regeneration.

CAS / MDL: 1306-06-5 12167-74-7
研究领域: 生物材料 · 组织工程 · 牙科材料 · 生物医学工程
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MATERIALS LETTERS · 2016 · IF 2.437

Microscale electrohydrodynamic printing of biomimetic PCL/nHA composite scaffolds for bone tissue engineering

Xiaoli Qu,Peng Xia,Jiankang He,Dichen Li

Electrohydrodynamic printing provides an innovative strategy to fabricate high-resolution tissue-engineering scaffolds with fiber orientation and scale similar to native extracellular matrix. However, few studies have been conducted to incorporate functional nanobiomaterials into microscale fibrous structures. In this study, we presented to fabricate microscale poly (ε-caprolactone) (PCL) and hydroxyapatite nanoparticles (nHA) composite scaffolds with the average fiber diameter of 8.85±1.12   µm based on electrohydrodynamic 3D printing to better mimic collagen fibers and HA nanocrystals in natural bones. The composite scaffolds exhibited good biocompatibility and facilitated cell alignment and proliferation in vitro . This strategy might be useful to regulate cellular microenvironment in multiscale and multimaterial levels for improved tissue regeneration.

CAS / MDL: 1306-06-5 12167-74-7
研究领域: 生物材料学 · 组织工程学
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