3D-bioprinted functional and biomimetic hydrogel scaffolds incorporated with nanosilicates to promote bone healing in rat calvarial defect model

Liu, Bin; Li, Junqin; Lei, Xing; Cheng, Pengzhen; Song, Yong; Gao, Yi; Hu, Jingzhi; Wang, Chunmei; Zhang, Shuaishuai; Li, Donglin; Wu, Hao; Sang, Hongxun; Bi, Long; Pei, Guoxian

doi:10.1016/j.msec.2020.110905

Cited by 63 publications

(50 citation statements)

References 58 publications

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“…Furthermore, the ALP activity values for the cells seeded on the PCL@CMC/LAP3.5% scaffold were significantly higher than those for the cells on the PCL@CMC scaffold ( P ≤ .001). These results agree with previous reports about enhancing the osteodifferentiation of stem cells on polymeric scaffolds containing LAP nanoplatelets 1,25,35 …”

Section: Resultssupporting

confidence: 93%

Immobilization of carboxymethyl chitosan/laponite on polycaprolactone nanofibers as osteoinductive bone scaffolds

Arab‐Ahmadi

Irani

Bakhshi

et al. 2020

Polymers for Advanced Techs

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The side effects and high cost of growth factors and drugs in bone tissue engineering have led to outstanding investigations of alternative osteoinductive supplements. Herein, the electrospun polycaprolactone (PCL) nanofibers were immobilized with carboxymethyl chitosan (CMC) and laponite nanoplatelets (LAP, 0.5‐3.5 wt%) to fabricate osteoinductive scaffolds for bone tissue engineering. The Fourier‐transform infrared)FTIR(and energy dispersive X‐ray (EDX) spectroscopy confirmed the chemical immobilization of CMC and LAP on the surface of PCL nanofibers. Water contact angle measurements exhibited significant improvement of surface hydrophilicity for immobilized scaffolds (<10°) comparing to the virgin PCL nanofibers (125°). The immobilization of CMC and LAP enhanced the attachment, proliferation, and osteodifferentiation of the seeded human bone marrow mesenchymal stem cells (hBM‐MSCs), as evidenced by increased calcium deposition, alkaline phosphatase (ALP) activity, and Osteonectin gene expression. Therefore, the fabricated scaffolds can serve as an appropriate substrate to support the proliferation and differentiation of stem cells to osteoplasts without any external osteoinductive stimulation.

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Section: Resultssupporting

confidence: 93%

Immobilization of carboxymethyl chitosan/laponite on polycaprolactone nanofibers as osteoinductive bone scaffolds

Arab‐Ahmadi

Irani

Bakhshi

et al. 2020

Polymers for Advanced Techs

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“…The use of this biodegradable polymer along with the GET peptide controlled release delivery system would allow new in-vivo applications, especially in bone regeneration. The ability to paste the scaffold at a defect site can offer improved clinical translation when compared to metallic implants [ 1 ]. Moreover, this material can be formulated with simple addition of PF127 and Tri-acetin to be 3D printable as demonstrated here; which gives the ability to fill complex and difficult to reach geometric defects or as a pre-fabricated implant [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additive manufacturing of custom, defect-matched implants for regenerative medicine has significantly developed over the last decade [ 1 ]. For bone tissue engineering these approaches employ ceramic and polymeric materials to enable bone-like mechanically strong scaffolds to be generated, however the manufacturing process may not be bio-compatible (using high-temperatures, UV-light or organic solvents) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…As such only acellular implants are created and the incorporation of stem cells or therapeutic molecules can only occur post-fabrication. This prevents uniform seeding, patterning of cells or molecules to produce functionally complex tissues and long-term delivery is inhibited; thus bio-inductive strategies are often not effective or have less controlled activity [ 1 ]. Development of production processes which can be used intraoperatively; with cells and biomolecules directly included in the process is therefore vital for their clinical use.…”

Section: Introductionmentioning

confidence: 99%

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Genetically-programmed, mesenchymal stromal cell-laden & mechanically strong 3D bioprinted scaffolds for bone repair

Awwad

Thiagarajan

Kanczler

et al. 2020

Journal of Controlled Release

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Additive manufacturing processes used to create regenerative bone tissue engineered implants are not biocompatible, thereby restricting direct use with stem cells and usually require cell seeding post-fabrication. Combined delivery of stem cells with the controlled release of osteogenic factors, within a mechanically-strong biomaterial combined during manufacturing would replace injectable defect fillers (cements) and allow personalized implants to be rapidly prototyped by 3D bioprinting. Through the use of direct genetic programming via the sustained release of an exogenously delivered transcription factor RUNX2 (delivered as recombinant GET-RUNX2 protein) encapsulated in PLGA microparticles (MPs) , we demonstrate that human mesenchymal stromal (stem) cells (hMSCs) can be directly fabricated into a thermo-sintered 3D bioprintable material and achieve effective osteogenic differentiation. Importantly we observed osteogenic programming of gene expression by released GET-RUNX2 (8.2-, 3.3- and 3.9-fold increases in OSX, RUNX2 and OPN expression, respectively) and calcification (von Kossa staining) in our scaffolds. The developed biodegradable PLGA/PEG paste formulation augments high-density bone development in a defect model (~2.4-fold increase in high density bone volume) and can be used to rapidly prototype clinically-sized hMSC-laden implants within minutes using mild, cytocompatible extrusion bioprinting. The ability to create mechanically strong 'cancellous bone-like’ printable implants for tissue repair that contain stem cells and controlled-release of programming factors is innovative, and will facilitate the development of novel localized delivery approaches to direct cellular behaviour for many regenerative medicine applications including those for personalized bone repair.

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“…Third, these multifunctional Nb 2 C@SiR NSs were integrated onto the 3D-printing biodegradable bioglass (BG) scaffolds (denoted as BG@NbSiR scaffolds). In particular, mesoporous Nb 2 C@Si NSs not only endowed the as-fabricated scaffolds with excellent photonic hyperthermia property under near-infrared light (NIR) irradiation, [15] but also enhanced the bone-regeneration process due to their degradation products of Nb- [16] and Si-based [17] species. R837 offered immune-activating function, [18] and 3D-printing BG scaffolds supplied the personalized substrate for bone healing.…”

Section: Introductionmentioning

confidence: 99%

Combinatorial Photothermal 3D‐Printing Scaffold and Checkpoint Blockade Inhibits Growth/Metastasis of Breast Cancer to Bone and Accelerates Osteogenesis

Yao

et al. 2020

Adv Funct Materials

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Cancer metastases are the main causes for the high mortality of cancer. The current treatment modality for bone metastasis of breast cancer is dominantly destructive, which urges the engineering of multifunctional biomaterials, not only for eliminating primary/metastases tumors effectively but also for enhancing bone–tissue regeneration. Herein, an immune adjuvant (R837)‐loaded and niobium carbide (Nb2C) MXene‐modified 3D‐printing biodegradable scaffold (BG@NbSiR) is designed and constructed to effectively treat bone metastasis of breast cancer. The engineered BG@NbSiR scaffold can eradicate primary tumors, activate the immune response, suppress metastases, prevent tumor relapses (long‐term immunological memory) by synergizing with checkpoint blockade immunotherapy, and accelerate osteogenesis as evidenced by multiple in vivo murine models. In particular, single‐cell sequencing (scRNA‐seq) is employed to further determine the critical factors responding to BG@NbSiR scaffold‐based photothermia plus checkpoint blockade‐combined immunotherapy. Several gene functional terms are identified in both tumor biology (including copy number variation) and immune response, which further reveal the underlying therapeutic mechanisms from the perspective of single‐cell transcriptome. This work not only demonstrates the promising clinical application potentials of BG@NbSiR scaffold‐based therapy against bone metastasis of breast cancer, but also provides distinctive avenues to optimize the design and construction of multifunctional tissue‐engineering biomaterials based on single‐cell genomes.

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3D-bioprinted functional and biomimetic hydrogel scaffolds incorporated with nanosilicates to promote bone healing in rat calvarial defect model

Cited by 63 publications

References 58 publications

Immobilization of carboxymethyl chitosan/laponite on polycaprolactone nanofibers as osteoinductive bone scaffolds

Immobilization of carboxymethyl chitosan/laponite on polycaprolactone nanofibers as osteoinductive bone scaffolds

Genetically-programmed, mesenchymal stromal cell-laden & mechanically strong 3D bioprinted scaffolds for bone repair

Combinatorial Photothermal 3D‐Printing Scaffold and Checkpoint Blockade Inhibits Growth/Metastasis of Breast Cancer to Bone and Accelerates Osteogenesis

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