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1.
Nat Commun ; 15(1): 3565, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38670999

ABSTRACT

Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.


Subject(s)
Bioprinting , Bone Regeneration , Hydrogels , Tissue Engineering , Tissue Scaffolds , Animals , Tissue Scaffolds/chemistry , Hydrogels/chemistry , Bioprinting/methods , Tissue Engineering/methods , Humans , Bone and Bones , Mice , Mesenchymal Stem Cells/cytology , Biocompatible Materials/chemistry , Osteoporosis/therapy
2.
RSC Adv ; 14(3): 2016-2026, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38196914

ABSTRACT

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

3.
Regen Ther ; 24: 617-629, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38034857

ABSTRACT

Introduction: Bones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. Methods: PLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions. Results: The prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation. Conclusion: Low-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.

4.
Adv Clin Exp Med ; 32(5): 551-561, 2023 May.
Article in English | MEDLINE | ID: mdl-36881365

ABSTRACT

BACKGROUND: Bone mesenchymal stem cell (BMSC)-derived exosomes (B-exos) are attractive for applications in enabling alloantigen tolerance. An in-depth mechanistic understanding of the interaction between B-exos and dendritic cells (DCs) could lead to novel cell-based therapies for allogeneic transplantation. OBJECTIVES: To examine whether B-exos exert immunomodulatory effects on DC function and maturation. MATERIAL AND METHODS: After mixed culture of BMSCs and DCs for 48 h, DCs from the upper layer were collected to analyze the expression levels of surface markers and mRNAs of inflammation-related cytokines. Then, before being collected to detect the mRNA and protein expression levels of indoleamine 2,3-dioxygenase (IDO), the DCs were co-cultured with B-exos. Then, the treated DCs from different groups were co-cultured with naïve CD4+ T cells from the mouse spleen. The proliferation of CD4+ T cells and the proportion of CD4+CD25+Foxp3+ T cells were analyzed. Finally, the skins of BALB/c mice were transplanted to the back of C57 mice in order to establish a mouse allogeneic skin transplantation model. RESULTS: The co-culture of DCs with BMSCs downregulated the expression of the major histocompatibility complex class II (MHC-II) and CD80/86 costimulatory molecules on DCs. Moreover, B-exos increased the expression of IDO in DCs treated with lipopolysaccharide (LPS). The proliferation of CD4+CD25+Foxp3+ T cells increased when cultured with B-exos-exposed DCs. Finally, mice recipients injected with B-exos-treated DCs had significantly prolonged survival after receiving the skin allograft. CONCLUSIONS: Taken together, these data suggest that the B-exos suppress the maturation of DCs and increase the expression of IDO, which might shed light on the role of B-exos in inducing alloantigen tolerance.


Subject(s)
Exosomes , Mesenchymal Stem Cells , Mice , Animals , Exosomes/metabolism , Transplantation, Homologous , Dendritic Cells , Forkhead Transcription Factors/metabolism , Bone Marrow Cells
5.
PeerJ ; 10: e13744, 2022.
Article in English | MEDLINE | ID: mdl-36168439

ABSTRACT

Background: In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. Methods: BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) between OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses. Results: Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified between OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic differentiation markers in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic markers in osteoclast. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways. Conclusion: BMSC-derived exosomal miR-27a-3p and miR-196b-5p may play a positive regulatory role in bone remodeling.


Subject(s)
Bone Remodeling , Mesenchymal Stem Cells , MicroRNAs , Animals , Rats , Bone Resorption/metabolism , Cell Differentiation/genetics , Mesenchymal Stem Cells/physiology , MicroRNAs/genetics , Osteogenesis/genetics , Female , Bone Remodeling/genetics , Exosomes/genetics
6.
Biomater Adv ; 136: 212792, 2022 May.
Article in English | MEDLINE | ID: mdl-35929323

ABSTRACT

Zinc is becoming one of the leading candidate materials for biodegradable orthopedic implants owing to its attractive properties in terms of degradation behavior and mechanical properties. However, the insufficient surface bio-activities postpone its clinical application. In this study, an organic-inorganic collagen entrapped calcium/zinc phosphates coating was constructed on Zn surface to lessen Zn2+ releasing rate and to leverage the surface osteogenic and angiogenic properties. Collagen molecules were immobilized onto Zn substrate and subsequently coordinated with calcium and zinc ions to promote the CaZnP inorganic phase growth, ensuing an intertwined collagen-CaZnP hybrid system. Consequently, the hybrid coating was highly coalesced and compact. Such high quality warranted the contained Zn2+ releasing in a tolerable rate favorable for cells viability. The collagen-CaZnP coated Zn showed remarkedly stronger osteogenicity as compared to the untreated Zn, ascertained by the MC3T3-E1 osteoblast cell proliferation and differentiation assays, such as alkaline phosphatase expression and calcium nodule formation results. In addition, this hybrid coating supported human umbilical vein endothelial cells (HUVECs) migration and tube formation. The enhanced osteogenic and angiogenic properties could be ascribed to the nature of collagen and calcium/zinc phosphate components, the hybrid micro/nano-structure as well as the ability of controlling the Zn2+ release of Zn substrate into a suitable concentration range. Our strategy provides a new avenue to surface modification of biodegradable metals for bone regenerative perspective.


Subject(s)
Osteogenesis , Zinc , Absorbable Implants , Calcium , Collagen/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Phosphates/pharmacology , Zinc/pharmacology
7.
Macromol Rapid Commun ; 43(17): e2200255, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35587472

ABSTRACT

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.


Subject(s)
Bone Neoplasms , Nanocomposites , Nanoparticles , Osteosarcoma , Humans , Nanocomposites/therapeutic use , Polymerization
8.
World Neurosurg ; 160: e372-e380, 2022 04.
Article in English | MEDLINE | ID: mdl-35026455

ABSTRACT

BACKGROUND: The most common complication of oblique lumbar interbody fusion (OLIF) is endplate fracture/subsidence. The aim of this study was to evaluate biomechanical stability in patients undergoing OLIF surgery with anterolateral screw fixation (ASF). METHODS: Based on a previously validated model technique, L4-L5 functional surgical models corresponding to the ASF and bilateral pedicle screw fixation (BPSF) methods were created. Finite element models were developed to compare the biomechanics of the ASF and BPSF groups. We retrospectively analyzed 18 patients with lumbar degenerative diseases who underwent OLIF with ASF in Shenzhen Hospital of Southern Medical University from April 2020 to April 2021. Intraoperative and postoperative complications were observed. RESULTS: Compared with the BPSF model, the maximum stresses of the L4 inferior endplate and L5 superior endplate were greatly increased in the ASF model. The contact surface between the vertebrae and screw (CSVS) in the ASF model produced nearly 100% more stress than the BPSF model at all moments. In clinical practice, after a 12-month follow-up, 7 adverse events were observed, including 3 cases of left thigh pain/numbness, 3 cases of cage subsidence, and 1 case of screw loosening. CONCLUSIONS: OLIF surgery with ASF could not reduce the maximum stresses on the endplate and CSVS, which may be a potential risk factor for cage subsidence and screw loosening.


Subject(s)
Pedicle Screws , Spinal Fusion , Biomechanical Phenomena , Humans , Lumbar Vertebrae/surgery , Lumbosacral Region/surgery , Retrospective Studies , Spinal Fusion/methods
9.
Biomater Adv ; 133: 112619, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35034816

ABSTRACT

Integration of biological factors and hierarchical rigid scaffolds is of great interest in bone tissue engineering for fabrication of biomimetic constructs with high physical and biological performance for enhanced bone repair. Core/shell microspheres (CSMs) delivering bone morphogenetic protein-2 (BMP-2) and a strategy to integrate CSMs with 3D-printed scaffolds were developed herein to form a hybrid 3D system for bone repair. The scaffold was printed with polycaprolactone (PCL) and then coated with polydopamine. Shells of CSMs were electrosprayed with alginate. Cores were heparin-coated polylactic acid (PLA) microparticles fabricated via simple emulsion and heparin coating strategy. Assembly of microspheres and scaffolds was realized via a self-locking method with the assistance of controlled expansion of CSMs. The hybrid system was evaluated in the rat critical-sized bone defect model. CSMs released BMP-2 in a tunable manner and boosted osteogenic performance in vitro. CSMs were then successfully integrated inside the scaffolds. The assembled system effectively promoted osteogenesis in vitro and in vivo. These observations show the importance of how BMP-2 is delivered, and the core/shell microspheres represent effective BMP-2 carriers that could be integrated into scaffolds, together forming a hybrid system as a promising candidate for enhanced bone regeneration.


Subject(s)
Printing, Three-Dimensional , Tissue Scaffolds , Animals , Heparin , Microspheres , Polyesters , Rats
10.
Front Cell Dev Biol ; 9: 763347, 2021.
Article in English | MEDLINE | ID: mdl-34957096

ABSTRACT

Background: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents, with rapid growth, frequent metastasis, and a poor prognosis, but its pathogenesis has not been fully elucidated. Exploring the pathogenesis of OS is of great significance for improving diagnoses and finding new therapeutic targets. Methods: Differentially expressed circRNAs (DECs), miRNAs (DEMs), methylated DNA sites (DMSs), and mRNAs (DEGs) were identified between OS and control cell lines. GSEA of DEGs and functional enrichment analysis of methylated DEGs were carried out to further identify potential biological processes. Online tools were used to predict the miRNA binding sites of DECs and the mRNA binding sites of DEMs, and then construct a circRNA-miRNA-mRNA network. Next, an analysis of the interaction between methylated DEGs was performed with a protein-protein interaction (PPI) network, and hub gene identification and survival analysis were carried out. The expression pattern of circRNA-miRNA-mRNA was validated by real-time PCR. Results: GSEA and functional enrichment analysis indicated that DEGs and methylated DEGs are involved in important biological processes in cancer. Hsa_circ_0001753/has_miR_760/CD74 network was constructed and validated in cell lines. Low expression levels of CD74 are associated with poor overall survival times and show good diagnostic ability. Conclusion: Methylated DEGs may be involved in the development of OS, and the hsa_circ_0001753/has_miR_760/CD74 network may serve as a target for the early diagnosis of and targeted therapy for OS.

11.
Front Cell Dev Biol ; 9: 706395, 2021.
Article in English | MEDLINE | ID: mdl-34513836

ABSTRACT

The ubiquitin-proteasome system (UPS) is an essential pathway that regulates the homeostasis and function of intracellular proteins and is a crucial protein-degradation system in osteoblast differentiation and bone formation. Abnormal regulation of ubiquitination leads to osteoblast differentiation disorders, interfering with bone formation and ultimately leading to osteoporosis. E3 ubiquitin ligases (E3) promote addition of a ubiquitin moiety to substrate proteins, specifically recognizing the substrate and modulating tyrosine kinase receptors, signaling proteins, and transcription factors involved in the regulation of osteoblast proliferation, differentiation, survival, and bone formation. In this review, we summarize current progress in the understanding of the function and regulatory effects of E3 ligases on the transcription factors and signaling pathways that regulate osteoblast differentiation and bone formation. A deep understanding of E3 ligase-mediated regulation of osteoblast differentiation provides a scientific rationale for the discovery and development of novel E3-targeting therapeutic strategies for osteoporosis.

12.
Int J Oncol ; 59(3)2021 Sep.
Article in English | MEDLINE | ID: mdl-34296296

ABSTRACT

Osteosarcoma (OS) is the most common primary bone tumor worldwide. OS exhibits a range of aggressive behaviors, including early metastasis potential, rapid progression, poor clinical prognosis and insensitivity to chemoradiotherapy. Non­coding RNAs are transcripts that do not encode proteins. A significant number of studies published on OS have been focused on the aberrant expression of non­coding RNAs and their involvement in tumor initiation and progression. It has been confirmed that non­coding RNAs exert their regulatory functions at both the transcriptional and post­transcriptional level, which leads to tumor initiation or progression in OS. According to present knowledge, this review provides a state­of­the­art overview of the functions and mechanisms of microRNAs, long non­coding RNAs and circular RNAs in terms of their involvement with OS. The review also covers their potential clinical application in the diagnosis, prognosis and treatment of OS. It is hoped that the information presented in this review on the involvement of non­coding RNAs in OS will lead to a more comprehensive understanding of OS and provide a useful perspective on the potential diagnostic and therapeutic applications of non­coding RNAs for patients with OS.


Subject(s)
Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Osteosarcoma/genetics , RNA, Untranslated/genetics , Bone Neoplasms/diagnosis , Bone Neoplasms/drug therapy , Early Detection of Cancer , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Osteosarcoma/diagnosis , Osteosarcoma/drug therapy , Prognosis , RNA, Circular/genetics , RNA, Long Noncoding/genetics
14.
Mol Med Rep ; 23(2)2021 02.
Article in English | MEDLINE | ID: mdl-33313954

ABSTRACT

Dendritic cells release bioactive exosomes involved in immune regulation. Long non­coding RNAs (lncRNAs) are implicated in a number of immunoregulatory mechanisms. However, the roles of lncRNAs in dendritic cell­derived exosomes remain to be elucidated. The present study aimed to investigate the roles of lncRNAs in exosomes derived from mature and immature dendritic cells and to find specific lncRNAs with immunoregulatory function. The expression profiles of lncRNAs in exosomes derived from bone marrow dendritic cells of C57 mice were illustrated. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene Set Enrichment Analysis were performed to identify potential targets correlated with immune regulation. In addition, lncRNA­miRNA­mRNA networks were predicted using bioinformatics methods. Representative lncRNAs were further validated via reverse transcription­quantitative PCR. A total of 437 lncRNAs were analyzed using RNA­seq. Among these, the expression of ~87 lncRNAs was upregulated and 21 lncRNAs was downregulated in mature dendritic cell­derived exosomes (Dex) compared with immature Dex. GO analyses indicated the involvement of upregulated lncRNAs in multiple biological functions, such as the immune system process, while downregulated lncRNAs were involved in poly(A) RNA binding. Analysis of the KEGG pathway identified the relationship of TNF signaling and ribosome pathway with upregulated lncRNAs and downregulated lncRNAs, respectively. The results of gene set enrichment analysis identified that three lncRNA­associated transcripts (Procr­203, Clec4e­202 and Traf1­203) were highly associated with immunoregulatory functions including T helper cell differentiation and Janus kinase­STAT signaling pathway. The results indicated the involvement of candidate lncRNAs in immunoregulation and suggested a new perspective on the modulation of lncRNAs in Dex.


Subject(s)
Dendritic Cells/metabolism , Exosomes/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Animals , Bone Marrow Cells/metabolism , Cell Differentiation , Cells, Cultured , Computational Biology , Dendritic Cells/cytology , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Male , Mice, Inbred C57BL , MicroRNAs/metabolism , RNA, Long Noncoding/immunology , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction
15.
World Neurosurg ; 141: e204-e212, 2020 09.
Article in English | MEDLINE | ID: mdl-32502627

ABSTRACT

BACKGROUND: The most common complication of oblique lumbar interbody fusion (OLIF) is endplate fracture/subsidence. The mechanics of endplate fracture in OLIF surgery are still unclear. The aim of the present study was to evaluate the biomechanical stability in patients undergoing OLIF surgery with stand-alone (SA) and bilateral pedicle screw fixation (BPSF) methods. METHODS: A finite element model of the L1-L5 spinal unit was established and validated. Using the validated model technique, L4-L5 functional surgical models corresponding to the SA and BPSF methods were created. Simulations using the models were performed to investigate OLIF surgery. A 500-N compression force was applied to the superior surface of the model to represent the upper body weight, and a 7.5-Nm moment was applied to simulate the 6 movement directions of the lumbar spinal model: flexion and extension, right and left lateral bending, and right and left axial rotation. Finite element models were developed to compare the biomechanics of the SA and BPSF groups. RESULTS: Compared with the range of motion of the intact lumbar model, that of the SA model was decreased by 79.6% in flexion, 54.5% in extension, 57.2% in lateral bending, and 50.0% in axial rotation. The BPSF model was decreased by 86.7% in flexion, 77.3% in extension, 76.2% in lateral bending, and 75.0% in axial rotation. Compared with the BPSF model, the maximum stresses of the L4 inferior endplate and L5 superior endplate were greatly increased in the SA model. The L4 inferior endplate stress was increased to 49.7 MPa in extension, and the L5 superior endplate stress was increased to 47.7 MPa in flexion, close to the yield stress of the lamellar bone (60 MPa). CONCLUSIONS: OLIF surgery with BPSF could reduce the maximum stresses on the endplate, which might reduce the incidence of cage subsidence. OLIF surgery with the SA method produced more stress compared with BPSF, especially in extension and flexion, which might be a potential risk factor for cage subsidence.


Subject(s)
Finite Element Analysis , Lumbar Vertebrae/surgery , Lumbosacral Region/surgery , Pedicle Screws , Biomechanical Phenomena/physiology , Humans , Lumbar Vertebrae/pathology , Lumbosacral Region/pathology , Models, Anatomic , Range of Motion, Articular/physiology , Spinal Fusion/methods
16.
Mater Sci Eng C Mater Biol Appl ; 112: 110905, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32409059

ABSTRACT

Three-dimensional (3D) bioprinting is an extremely convenient biofabrication technique for creating biomimetic tissue-engineered bone constructs and has promising applications in regenerative medicine. However, existing bioinks have shown low mechanical strength, poor osteoinductive ability, and lacking a suitable microenvironment for laden cells. Nanosilicate (nSi) has shown to be a promising biomaterial, due to its unique properties such as excellent biocompatibility, degrade into nontoxic products, and with osteoinductive properties, which has been used in bone bioprinting. However, the long term bone healing effects and associating risks, if any, of using nSi in tissue engineering bone scaffolds in vivo are unclear and require a more thorough assessment prior to practical use. Hence, a functional and biomimetic nanocomposite bioink composed of rat bone marrow mesenchymal stem cells (rBMSCs), nSi, gelatin and alginate for the 3D bioprinting of tissue-engineered bone constructs is firstly demonstrated, mimicking the structure of extracellular matrix, to create a conducive microenvironment for encapsulated cells. It is shown that the addition of nSi significantly increases the printability and mechanical strength of fabricated human-scale tissue or organ structures (up to 15 mm height) and induces osteogenic differentiation of the encapsulated rBMSCs in the absence of in vitro osteoinductive factors. A systematic in vivo research of the biomimetic nanocomposite bioink scaffolds is further demonstrated in a rat critical-size (8 mm) bone defect-repair model. The in vivo results demonstrate that the 3D bioprinted nanocomposite scaffolds can significantly promote the bone healing of the rat calvarial defects compared to other scaffolds without nSi or cells, and show rarely side effects on the recipients. Given the above advantageous properties, the 3D bioprinted nanocomposite scaffolds can greatly accelerate the bone healing in critical bone defects, thus providing a clinical potential candidate for orthopedic applications.


Subject(s)
Biocompatible Materials/chemistry , Bioprinting/methods , Hydrogels/chemistry , Nanocomposites/chemistry , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/pharmacology , Biocompatible Materials/therapeutic use , Bone Diseases/pathology , Bone Diseases/therapy , Cell Differentiation/drug effects , Disease Models, Animal , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Printing, Three-Dimensional , Rats , Rats, Sprague-Dawley , Regenerative Medicine , Rheology , Silicates/chemistry , Tissue Engineering
17.
Biomed Mater ; 15(5): 055013, 2020 07 27.
Article in English | MEDLINE | ID: mdl-32252046

ABSTRACT

Osteoporotic bone defects are a major challenge in clinics for bone regeneration. With the condition of osteoporosis, excessive bone absorption and impaired osteogenesis result in unexpectedly long healing procedures for defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffold was designed, to be integrated with anti-catabolic drug zoledronic acid nanoparticles (ZOL loaded gelatin NPs), which was able to achieve a local sustained release of ZOL as expected. The in vitro study demonstrated that extracts of the composite scaffolds would stimulate osteoblast differentiation; they also inhibited osteoclastogenesis at a ZOL loading concentration of 50 µmol l-1. In the subsequent in vivo study, the composite scaffolds were implanted into ovariectomy-induced osteoporotic rabbits suffering from femoral condyles defects. The results indicated that the composite scaffolds without ZOL loaded gelatin NPs only induced callus formation, mainly at the interface margin between the implant and bone, whereas the composite scaffolds with ZOL loaded gelatin NPs were capable of further enhancing osteogenesis and bone growth into the scaffolds. Moreover, the research proved that the promoting effect was optimal at a ZOL loading concentration of 50 µmol l-1. In summary, the present research indicated that a new type of porous titanium scaffold integrated with ZOL loaded gelatin NPs inherited a superior biocompatibility and bone regeneration capability. It would be an optimal alternative for the reconstruction of osteoporosis-related defects compared to a traditional porous titanium implant; in other words, the new type of scaffold offers a new effective and practical procedure option for patients suffering from osteoporotic bone defects.


Subject(s)
Gelatin/chemistry , Nanoparticles/chemistry , Titanium/chemistry , Zoledronic Acid/chemistry , Animals , Biocompatible Materials/chemistry , Bone Regeneration , Bone Resorption , Bone and Bones , Cell Adhesion , Cell Differentiation , Cell Proliferation , Female , In Vitro Techniques , Osteoclasts/cytology , Osteogenesis , Osteoporosis/pathology , Porosity , Rabbits , Static Electricity , Tissue Scaffolds
18.
Med Sci Monit ; 25: 7370-7375, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31571675

ABSTRACT

BACKGROUND Many clinical studies have assessed the association of laminoplasty opening size (LOS) with sagittal canal diameter (SCD) based on single-door cervical laminoplasty (SDCL). Nevertheless, the "worn-off" lamina extracted in SDCL was neglected in these reports. We aimed to develop a simple mathematical model to analyze the relationship between the effective LOS and SCD, taking into consideration the worn-off lamina. MATERIAL AND METHODS A total of 106 patients treated by SDCL at our hospital were included in this study. Pre-operative and post-operative SCDs were assessed using a picture archiving and communication system (PACS) based on computed tomography scans. Mini-plate sizes as well as drill bit diameters were recorded in detail in order to determine the effective LOS for each vertebral lamina involved. RESULTS SCD in all patients was increased significantly after SDCL (P<0.01). A linear correlation was found between effective LOS and the post-operative SCD increment from C3 to C7 (R²>0.933, P<0.001). The 12 mm mini-plate was most often used in SDCL, accounting for 64.45% of all cases, whereas 10 mm and 16 mm mini-plates were the least used, accounting for 3.85% and 3.00%, respectively. CONCLUSIONS There is a strong linear correlation between effective LOS and the post-operative SCD increment. The SCD was increased by about 0.5 mm per mm increase in effective LOS. Thus, post-operative SCD could be precisely calculated and predicted, enabling the selection of optimal mini-plate prior to SDCL.


Subject(s)
Cervical Vertebrae/surgery , Laminectomy/methods , Laminoplasty/methods , Bone Plates , China , Humans , Models, Theoretical , Spinal Canal/surgery , Spinal Stenosis/surgery
19.
Eur Spine J ; 28(10): 2302-2310, 2019 10.
Article in English | MEDLINE | ID: mdl-31053937

ABSTRACT

PURPOSE: To build a mathematical model which could calculate the desired laminoplasty opening size (LOS) based on the target sagittal canal diameter (SCD) before single-door cervical laminoplasty (SDCL) when taking the effects of surgery drill into consideration. METHODS: The model was based on geometric analysis on deformation of spinal canal; the formula was derived and characterized as: y (mm) = 2 [Formula: see text] × sin(ß/2) = c - d (y is the size of LOS, [Formula: see text] the size of transverse canal diameter, ß the size of laminoplasty opening size, c the size of mini-plate and d the diameter of the drill bit used during the surgery operation). The parameters of pre- and postoperative computed tomography scans of 20 patients who had undergone SDCL were measured by the picture archiving and communication system (PACS) software and a new instrument named as Lei's ruler, respectively. RESULTS: The effects of surgery SDCL were very significant; for each patient, the SCD was enlarged dramatically after the surgery (P < 0.01). The differences between the data obtained by PACS and Lei's ruler were no statistically significant (P > 0.05). According to the derived formula, the 95% confidence intervals of SCD after the surgery were within the range of 14 mm and 14.5 mm. CONCLUSION: Applying the mathematical model and derived formula, the desired LOS could be calculated according to the target SCD which could help the surgeon select an optimum mini-plate before SDCL. At the same time, a new measuring device named Lei's ruler is designed for the convenience of the derived formula. These slides can be retrieved under Electronic Supplementary Material.


Subject(s)
Cervical Vertebrae/surgery , Laminoplasty/methods , Models, Theoretical , Adult , Aged , Female , Humans , Male , Middle Aged
20.
Med Sci Monit ; 24: 7438-7443, 2018 Oct 18.
Article in English | MEDLINE | ID: mdl-30334549

ABSTRACT

BACKGROUND The incidence of hip fracture is steadily increasing. We aimed to establish a creative approach to precisely estimate the risk of hip fracture by exploring the relationship between hip fracture and bone mineral density (BMD)/femur geometry. MATERIAL AND METHODS Sixteen samples of cadaveric female proximal femora were randomly selected. Experiments were performed experimental measurement of the femoral neck BMD and geometric parameters (including neck length, neck diameter, head diameter, and neck-shaft angle). In addition, the experimental measurements contain the failure load, which represents the mechanical strength of the femoral neck, and we calculated the correlation coefficient among BMD, geometric parameters, and failure load. RESULTS Significant correlations were discovered between femoral mechanical properties and femoral neck BMD (r=0.792, r²=0.628, P<0.001), trochanteric BMD (r=0.749, r²=0.560, P=0.001), and head diameter (r=0.706, r²=0.499, P=0.002). Multiple linear regression analyses indicated that the best predictor of hip fracture was the combination of femoral neck BMD, head diameter, and neck diameter (r²=0.844, P<0.001). CONCLUSIONS The results confirmed that, compared with BMD alone, the combination of BMD and geometric parameters of proximal femur is a better estimation of hip fracture. The geometry of the proximal femur played an important role in assessing the biomechanical strength of femur. This method greatly assists in predicting the risk of hip fracture in clinical trials and will assist studies on why the incidence of hip fracture varies among races.


Subject(s)
Femur/anatomy & histology , Hip Fractures/etiology , Hip Fractures/prevention & control , Aged , Aged, 80 and over , Asian People , Bone Density/physiology , Cadaver , China , Female , Femur/physiology , Femur Neck/anatomy & histology , Femur Neck/physiology , Humans , Male , Osteoporosis, Postmenopausal , Pelvic Bones , Risk Factors
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