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Liu Y, Yuan K, Lin Y, Yang Y, Kong W, Shan J, Niu H, Kong W, Li F, Yue X, Du Y, Liang Y, Chang H, Yu Z, Wang J, Yang G, Cao L, Huang K, Yang S, Tang T. Directional Freeze-Casting Cryogel Loaded with Quaternized Chitosan Modified Gallium Metal-Organic Frameworks to Capture and Eradicate the Resistant Bacteria for Guided Regeneration in Infected Bone Defects. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2414437. [PMID: 39846310 DOI: 10.1002/adma.202414437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/16/2024] [Indexed: 01/24/2025]
Abstract
Antimicrobial resistance and impaired bone regeneration are the great challenges in treating infected bone defects. Its recurrent and resistant nature, high incidence rate, long-term hospitalization, and high medical costs have driven the efforts of the scientific community to develop new therapies to improve the situation. Considering the complex microenvironment and persistent mechanisms mediated by resistant bacteria, it is crucial to develop an implant with enhanced osseointegration and sustained and effective infection clearance effects. Here, a positively charged quaternized chitosan (QCS) coated gallium-based metal-organic framework (GaMOF) is designed, to capture the antibiotic-resistant bacteria (Methicillin-resistant Staphylococcus aureus, MRSA) as a "captor", and rejuvenate Methicillin (Me) via disturbing the tricarboxylic acid (TCA) cycle. Then, a radially oriented porous cryogel loaded with the Me and QCSGaMOF is fabricated by the directional freeze-casting method. The oriented porous structure has an enhanced osseointegration effect by guiding the ingrowth of osteogenic cells. In vitro and in vivo experiments prove the advantages of as-prepared Me/QCSGa-MOF@Cryogel in combating resistant bacteria and guiding bone regeneration in infected bone defects.
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Affiliation(s)
- Yihao Liu
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Kai Yuan
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P. R. China
| | - Yixuan Lin
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Yiqi Yang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, P. R. China
| | - Weiqing Kong
- Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 199Jiefang South Road, Xuzhou, 221009, P. R. China
| | - Jing Shan
- School of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia
| | - Haoyi Niu
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Weize Kong
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Fupeng Li
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Xiaokun Yue
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Yun Du
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Yakun Liang
- Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, P. R. China
| | - Haishuang Chang
- Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, P. R. China
| | - Zhifeng Yu
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Jinwu Wang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Guangzheng Yang
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Lingyan Cao
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Kai Huang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Shengbing Yang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
| | - Tingting Tang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China
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Chen J, Qian Y, Li H, Zuo W, Sun W, Xing D, Zhou X. Lysophosphatidic Acid/Polydopamine-Modified nHA Composite Scaffolds for Enhanced Osteogenesis via Upregulating the Wnt/Beta-Catenin Pathway. ACS APPLIED MATERIALS & INTERFACES 2024; 16:13466-13480. [PMID: 38445450 DOI: 10.1021/acsami.3c16545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of β-catenin and further activating the Wnt/β-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.
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Affiliation(s)
- Jiahong Chen
- Department of Stomatology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou 215123, People's Republic of China
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China
| | - Yunzhu Qian
- Department of Stomatology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou 215123, People's Republic of China
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China
| | - Heng Li
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, People's Republic of China
| | - Wei Zuo
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China
| | - Wentao Sun
- Nano Science and Technology Institute, University of Science and Technology of China, Suzhou 215123, People's Republic of China
| | - Danlei Xing
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China
| | - Xuefeng Zhou
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, People's Republic of China
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Sui P, Yu T, Sun S, Chao B, Qin C, Wang J, Wang E, Zheng C. Advances in materials used for minimally invasive treatment of vertebral compression fractures. Front Bioeng Biotechnol 2023; 11:1303678. [PMID: 37954022 PMCID: PMC10634476 DOI: 10.3389/fbioe.2023.1303678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 10/16/2023] [Indexed: 11/14/2023] Open
Abstract
Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures.
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Affiliation(s)
| | | | | | | | | | | | | | - Changjun Zheng
- Orthopaedic Medical Center, Second Hospital of Jilin University, Changchun, China
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Dorozhkin SV. There Are over 60 Ways to Produce Biocompatible Calcium Orthophosphate (CaPO4) Deposits on Various Substrates. JOURNAL OF COMPOSITES SCIENCE 2023; 7:273. [DOI: 10.3390/jcs7070273] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
A The present overview describes various production techniques for biocompatible calcium orthophosphate (abbreviated as CaPO4) deposits (coatings, films and layers) on the surfaces of various types of substrates to impart the biocompatible properties for artificial bone grafts. Since, after being implanted, the grafts always interact with the surrounding biological tissues at the interfaces, their surface properties are considered critical to clinical success. Due to the limited number of materials that can be tolerated in vivo, a new specialty of surface engineering has been developed to desirably modify any unacceptable material surface characteristics while maintaining the useful bulk performance. In 1975, the development of this approach led to the emergence of a special class of artificial bone grafts, in which various mechanically stable (and thus suitable for load-bearing applications) implantable biomaterials and artificial devices were coated with CaPO4. Since then, more than 7500 papers have been published on this subject and more than 500 new publications are added annually. In this review, a comprehensive analysis of the available literature has been performed with the main goal of finding as many deposition techniques as possible and more than 60 methods (double that if all known modifications are counted) for producing CaPO4 deposits on various substrates have been systematically described. Thus, besides the introduction, general knowledge and terminology, this review consists of two unequal parts. The first (bigger) part is a comprehensive summary of the known CaPO4 deposition techniques both currently used and discontinued/underdeveloped ones with brief descriptions of their major physical and chemical principles coupled with the key process parameters (when possible) to inform readers of their existence and remind them of the unused ones. The second (smaller) part includes fleeting essays on the most important properties and current biomedical applications of the CaPO4 deposits with an indication of possible future developments.
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Affiliation(s)
- Sergey V. Dorozhkin
- Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory 1-2, Moscow 119991, Russia
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Yoo KH, Kim Y, Kim YI, Bae MK, Yoon SY. Lithium doped biphasic calcium phosphate: Structural analysis and osteo/odontogenic potential in vitro. Front Bioeng Biotechnol 2022; 10:993126. [PMID: 36425651 PMCID: PMC9679216 DOI: 10.3389/fbioe.2022.993126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 10/28/2022] [Indexed: 10/13/2023] Open
Abstract
Biphasic calcium phosphate (BCP) is generally considered a good synthetic bone graft material with osteoinductive potential. Lithium ions are trace elements that play a role in the bone-remodeling process. This study aimed to investigate the effects of lithium ions on the phase, crystal structure, and biological responses of lithium doped BCPs and to identify improvements in their osteogenic properties. Lithium-doped BCP powders with different doping levels (0, 5, 10, and 20 at%) were synthesized via the co-precipitation method. We found that the four types of lithium-doped BCP powders showed different phase compositions of hydroxyapatite and β-tricalcium phosphate. In addition, lithium ions favored entering the β-tricalcium phosphate structure at the Ca (4) sites and calcium vacancy sites [VCa(4)] up to 10 at%. This substitution improves the crystal stabilization by filling the vacancies with Ca2+ and Li+ in all Ca sites. However, when the concentration of Li ions was higher than 10 at%, lithium-induced crystal instability resulted in the burst release of lithium ions, and the osteogenic behavior of human dental pulp stem cells did not improve further. Although lithium ions regulate osteogenic properties, it is important to determine the optimal amount of lithium in BCPs. In this study, the most effective lithium doping level in BCP was approximately 10 at% to improve its biological properties and facilitate medical applications.
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Affiliation(s)
- Kyung-Hyeon Yoo
- School of Materials Science and Engineering, Pusan National University, Busan, South Korea
| | - Yeon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Yong-Il Kim
- Department of Orthodontics, Dental Research Institute, Pusan National University, Yangsan, South Korea
| | - Moon-Kyoung Bae
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Seog-Young Yoon
- School of Materials Science and Engineering, Pusan National University, Busan, South Korea
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Liu Y, He L, Li J, Luo J, Liang K, Yin D, Tao S, Yang J, Li J. Mussel-Inspired Organic–Inorganic Implant Coating Based on a Layer-by-Layer Method for Anti-infection and Osteogenesis. Ind Eng Chem Res 2022. [DOI: 10.1021/acs.iecr.2c01646] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Yifang Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- School of Stomatology, Shandong First Medical University, Jinan 250021, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Libang He
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jianshu Li
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, P. R. China
- Med-X Center for Materials, Sichuan University, Chengdu 610065, P. R. China
| | - Jun Luo
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Kunneng Liang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Derong Yin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Siying Tao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jiaojiao Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jiyao Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Miller A, Jeyapalina S, Agarwal J, Mansel M, Beck JP. A preliminary, observational study using whole-blood RNA sequencing reveals differential expression of inflammatory and bone markers post-implantation of percutaneous osseointegrated prostheses. PLoS One 2022; 17:e0268977. [PMID: 35617338 PMCID: PMC9135298 DOI: 10.1371/journal.pone.0268977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 05/11/2022] [Indexed: 11/20/2022] Open
Abstract
AIMS While the benefits of direct skeletal attachment of artificial limbs are well recognized, device failure due to infection and insufficient osseointegration remain obstacles to obtaining consistently successful outcomes. Currently, the potential for device failure is assessed by subjective pain, clinical function scores, radiographic evidence of bone atrophy, and the presence of radiolucent lines at the bone-implant interface, and subjective pain and function scores. Our hypothesis is that measurable biological indices might add another objective means to assess trends toward bone and stomal healing. This longitudinal cohort study was undertaken to identify potential serological biomarkers suggestive of bone remodeling and the presence of stomal tissue inflammation. METHODS Ten unilateral transfemoral amputee veterans, who were implanted with a percutaneous osseointegrated (OI) skeletal limb docking system, were recruited to participate in this IRB-approved study. Venous blood samples were obtained from before the Stage 1 Surgery up to 1 year following the Stage 2 Surgery. Whole-blood RNA was extracted, sequenced, mapped, and analyzed. Of the significant differentially expressed (DEGs) genes (p<0.05) identified, four genes of interest (IL12B, IL33, COL2A1, and SOST) were validated using qPCR. Enrichment analysis was performed to identify significant (p<0.01) Gene Ontology (GO) terms. RESULTS Most differentially expressed genes were only detected at PoS1 immediately after the first surgery. Of the significant genes identified, IL12B and IL33 were related to inflammation, and COL2A1 and SOST were associated with bone remodeling. These four genes were identified with greater than 20 log fold-change. CONCLUSION Whole-blood RNA-seq data from 10 patients who previously underwent percutaneous osseointegrated lower limb implantation revealed four genes of interest that are known to be involved in inflammation or bone remodeling. If verified in future studies, these genes may serve as markers for predicting optimal bone remodeling and stomal tissue healing following OI device implantation.
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Affiliation(s)
- Andrew Miller
- Research, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Department of Biomedical Engineering, University of Utah School of Engineering, Salt Lake City, Utah, United States of America
| | - Sujee Jeyapalina
- Research, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Jay Agarwal
- Research, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Mitchell Mansel
- Undergraduate Research Opportunities Program, University of Utah, Salt Lake City, Utah, United States of America
| | - James Peter Beck
- Research, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America
- Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
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Aglan HA, Fouad-Elhady EA, Hassan RE, Sabry GM, Ahmed HH. Nanoplatforms for Promoting Osteogenesis in Ovariectomy-Induced
Osteoporosis in the Experimental Model. CURRENT NANOMEDICINE 2022; 12:44-62. [DOI: 10.2174/2468187312666220217104650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 12/19/2021] [Accepted: 01/12/2022] [Indexed: 01/05/2025]
Abstract
Background:
Osteoporosis is a debilitating bone ailment characterized by the obvious loss of bone mass and bone microarchitecture impairment.
Objective:
This study aimed to illuminate the in vivo usefulness of nanotechnology as a treatment for osteoporosis via analyzing the effectiveness of nano-hydroxyapatite (nHa), nano-hydroxy- apatite/chitosan (nHa/C), and nano-hydroxyapatite/silver (nHa/S) in mitigation of osteoporosis in ovariectomized rats.
Method:
The characterization of the nHa, nHa/C, and nHa/S was carried out using TEM, SEM, FTIR, and Zeta potential measurements. This in vivo study included 48 adult female rats that were randomized into six groups (8 rats/group): (1) Sham-operated control, (2) osteoporotic, (3) nHa, (4) nHa/C, (5) nHa/S, and (6) Fosamax®. Serum osterix level was quantified using ELISA. Femur bone morphogenetic protein 2 and SMAD1 mRNA levels were evaluated by qPCR. The femur bones were scanned by DEXA for measurement of bone mineral density and bone mineral content. In ad-dition, a histopathological examination of femur bones was performed.
Results:
The present approach denoted that the treatment with nHa, nHa/C, or nHa/S yields a signif-icant rise in serum level of osterix and mRNA levels of bone morphogenetic protein 2 and SMAD1 as well as significant enhancements of bone tissue minerals.
Conclusion:
The findings affirmed the potency of nHa, nHa/C, and nHa/S as auspicious nanoplat-forms for repairing bone defects in the osteoporotic rat model. The positive effect of the inspected nanoformulations arose from bone formation indicators in serum and tissue, and additionally, the reinforcement of bone density and content, which were verified by the histopathological description of bone tissue sections.
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Affiliation(s)
- Hadeer A. Aglan
- Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Giza, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | | | - Rasha E. Hassan
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Gilane M. Sabry
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hanaa H. Ahmed
- Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Giza, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
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Widholz B, Westhauser F. Biomaterials for angiogenesis applications in an orthopedic context. BIOMATERIALS FOR VASCULOGENESIS AND ANGIOGENESIS 2022:415-438. [DOI: 10.1016/b978-0-12-821867-9.00016-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Li B, Lei Y, Hu Q, Li D, Zhao H, Kang P. Porous copper- and lithium-doped nano-hydroxyapatite composite scaffold promotes angiogenesis and bone regeneration in the repair of glucocorticoids-induced osteonecrosis of the femoral head. Biomed Mater 2021; 16. [PMID: 34492640 DOI: 10.1088/1748-605x/ac246e] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 09/07/2021] [Indexed: 02/08/2023]
Abstract
Glucocorticoids-induced osteonecrosis of the femoral head (GIONFH) is a common refractory disease. In the present study, we aimed to synthesize the nano-hydroxyapatite-copper-lithium (Cu-Li-nHA) composite porous scaffold to promote osteogenesis and angiogenesis functions to repair GIONFH by regulating the Wnt/β-catenin and HIF-1α/VEGF pathways. The physicochemical property of the scaffold was characterized and their osteogenic and angiogenic effects were tested through a serial of experimentsin vitroandin vivo. Results showed that 0.25% Cu-Li-nHA scaffolds possessed the highest mechanical and biocompatibilityin vitro. Then the 0.25% Cu-Li-nHA scaffolds significantly enhanced the new bone formation on defects in GIONFH rabbitsin vivo. Moreover, the scaffold could increase the expression of osteogenic and angiogenic factors along with the activation of factors in Wnt/β-catenin and HIF-1α/VEGF pathwaysin vitroandin vivo. In conclusion, the 0.25% Cu-Li-nHA scaffold could improve the osteogenesis and angiogenesis by upregulating the Wnt/β-catenin and HIF-1α/VEGF pathways which benefited to repair the GIONFH in rabbit models.
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Affiliation(s)
- Bohua Li
- Department of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, People's Republic of China
| | - Yan Lei
- Arts College of Sichuan University, Chengdu 610041, People's Republic of China
| | - Qinsheng Hu
- Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China
| | - Donghai Li
- Department of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, People's Republic of China
| | - Haiyan Zhao
- Department of Orthopedics, The First Hospital of Lanzhou University, 1# West Donggang Road, Lanzhou 730000, People's Republic of China
| | - Pengde Kang
- Department of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, People's Republic of China
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Zhao QM, Li B, Yu FX, Li YK, Wu JS, Peng Z, He J, Han QS, Zhang LB, Yi L, Xu RS, Jiao Y. Cu-Co Co-Doped Microporous Coating on Titanium with Osteogenic and Antibacterial Properties. J Biomed Nanotechnol 2021; 17:1435-1447. [PMID: 34446146 DOI: 10.1166/jbn.2021.3120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Titanium (Ti) and its alloys are widely used in bone surgery by virtue of their excellent mechanical properties and good biocompatibility; however, complications such as loosening and sinking have been reported post-implantation. Herein we deposited a copper-cobalt (Cu-Co) co-doped titanium dioxide (TUO) coating on the surface of Ti implants by microarc oxidation. The osteogenic and antimicrobial properties of the coating were evaluated by in vitro experiments, and we also assessed β-catenin expression levels on different sample surfaces. Our results revealed that the coating promoted the adhesion, proliferation, and differentiation of MG63 osteoblasts, and TUO coating promoted β-catenin expression; moreover, the proliferation of Staphylococcus aureus was inhibited. To summarize, we report that Cu-Co co-doping can enhance the osteogenic and antibacterial activities of orthopedic Ti implants, leading to potentially improved clinical performance.
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Affiliation(s)
- Quan-Ming Zhao
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Bo Li
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Fu-Xun Yu
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Yan-Kun Li
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Jie-Shi Wu
- Department of Orthopaedics, Affiliated Hospital of Jiangnan University (Wuxi Translational Medicine Center), Wuxi 214000, Jangsu, China
| | - Zhi Peng
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Jie He
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Quan-Sheng Han
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Lei-Bing Zhang
- Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China
| | - Lei Yi
- Department of Burn, Ruijin Hospital Affliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Rui-Sheng Xu
- Department of Orthopaedics, Affiliated Hospital of Jiangnan University (Wuxi Translational Medicine Center), Wuxi 214000, Jangsu, China
| | - Yang Jiao
- Department of Stomatology, The 7th Medical Center, Chinese PLA General Hospital, Beijing 100700, China
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12
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Jiang P, Zhang Y, Hu R, Wang X, Lai Y, Rui G, Lin C. Hydroxyapatite-modified micro/nanostructured titania surfaces with different crystalline phases for osteoblast regulation. Bioact Mater 2021; 6:1118-1129. [PMID: 33134605 PMCID: PMC7577196 DOI: 10.1016/j.bioactmat.2020.10.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/21/2020] [Accepted: 10/08/2020] [Indexed: 12/19/2022] Open
Abstract
Surface structures and physicochemical properties critically influence osseointegration of titanium (Ti) implants. Previous studies have shown that the surface with both micro- and nanoscale roughness may provide multiple features comparable to cell dimensions and thus efficiently regulate cell-material interaction. However, less attention has been made to further optimize the physicochemical properties (e.g., crystalline phase) and to further improve the bioactivity of micro/nanostructured surfaces. Herein, micro/nanostructured titania surfaces with different crystalline phases (amorphous, anatase and anatase/rutile) were prepared and hydroxyapatite (HA) nanorods were deposited onto the as-prepared surfaces by a spin-assisted layer-by-layer assembly method without greatly altering the initial multi-scale morphology and wettability. The effects of crystalline phase, chemical composition and wettability on osteoblast response were investigated. It is noted that all the micro/nanostructured surfaces with/without HA modification presented superamphiphilic. The activities of MC3T3-E1 cells suggested that the proliferation trend on the micro/nanostructured surfaces was greatly influenced by different crystalline phases, and the highest proliferation rate was obtained on the anatase/rutile surface, followed by the anatase; but the cell differentiation and extracellular matrix mineralization were almost the same among them. After ultrathin HA modification on the micro/nanostructured surfaces with different crystalline phases, it exhibited similar proliferation trend as the original surfaces; however, the cell differentiation and extracellular matrix mineralization were significantly improved. The results indicate that the introduction of ultrathin HA to the micro/nanostructured surfaces with optimized crystalline phase benefits cell proliferation, differentiation and maturation, which suggests a favorable biomimetic microenvironment and provides the potential for enhanced implant osseointegration in vivo.
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Affiliation(s)
- Pinliang Jiang
- College of Materials, Xiamen University, Xiamen, 361005, China
- State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Yanmei Zhang
- State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Ren Hu
- State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Xiankuan Wang
- State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Yuekun Lai
- National Engineering Research Center of Chemical Fertilizer Catalyst (NERC-CFC), College of Chemical Engineering, Fuzhou University, Fuzhou, 350116, China
| | - Gang Rui
- Department of Orthopedics Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Changjian Lin
- College of Materials, Xiamen University, Xiamen, 361005, China
- State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
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Ou M, Huang X. Influence of bone formation by composite scaffolds with different proportions of hydroxyapatite and collagen. Dent Mater 2021; 37:e231-e244. [PMID: 33509634 DOI: 10.1016/j.dental.2020.12.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 11/14/2020] [Accepted: 12/30/2020] [Indexed: 10/22/2022]
Abstract
Composite scaffolds with different proportions of hydroxyapatite (HA) and collagen (COL) produced different bone induction results. OBJECTIVE To examine the composite scaffolds with optimal proportion of HA and COL to achieve earlier bone induction and maximum bone formation. METHODS Composite scaffolds with the HA/COL weight ratio of 7:3, 3:7, 5:5 and 9:1 were prepared, as HA powder was added to collagen solution at 130℃ for 48 h. Then, the composites with different proportions of HA/COL were implanted into the extraction socket of right upper central incisor of C57BL/6 J mice. The bone formation of the extraction socket was observed by Hematoxylin-eosin (HE) and Masson-trichrome (Masson) staining at 1 and 2 weeks after operation. Five weeks later, the bone formation of extraction socket was observed by micro computed tomography (micro-CT). After MC3T3-E1 cells were co-cultured with materials of different proportions for 3 days, the number of cells attached on the surface of the materials and entering the materials were counted, and the expression of osteogenic related genes (Runx2, Ocn. Osx and Alp) was detected by reverse transcription polymerase chain reaction (RT-PCR). The composite scaffolds with different proportion of HA/COL with and without mouse bone marrow mesenchymal stem cells (BMMSCs) were implanted into the back of adult mice and cultured subcutaneously for 30 days, and observed histologically by HE and Masson staining. RESULTS After one week implantation with the composite HA/COL scaffolds with the weight ratio of 7:3, 3:7, 5:5 and 9:1, there was no new bone formation in the extraction socket in mouse. However, two weeks later, new bone was firstly observed in the tooth socket with the composite HA/COL scaffolds of 7:3. 5 weeks later, micro-CT scanning showed that the total amount of newly formed bone, trabecular width and bone mineral density of the HA/COL scaffolds of 7:3 were higher than the other HA/COL scaffolds (P < 0.05). After MC3T3-E1 cells were co-cultured with different composite HA/COL scaffolds for 3 days. The number of cells on the surface and inside of the HA/COL scaffolds of 7:3 was more than the other materials, and the difference was statistically significant (P < 0.05). The expression levels of Ocn and Osx of MC3T3-E1 cells were also the highest in the HA/COL scaffolds of 7:3 (P < 0.01). Bone formation was observed in the composite HA/COL scaffold of 7:3 with BMMSCs subcutaneously in mouse for 30 days, while only osteoid formation was observed in the same scaffold without BMMSCs. but bone formation was not detected in the other proportions of the HA/COL scaffolds. SIGNIFICANCE Compared with other proportions of HA/COL, the composite HA/COL scaffolds of 7:3 has stronger ability to promote bone formation, recruit osteoblasts to attach and enter into the scaffolds, and promote the osteogenesis of BMMSCs.
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Affiliation(s)
- Mingming Ou
- Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaofeng Huang
- Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration-A Review. Molecules 2020; 25:molecules25245879. [PMID: 33322654 PMCID: PMC7763898 DOI: 10.3390/molecules25245879] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/03/2020] [Accepted: 12/09/2020] [Indexed: 02/07/2023] Open
Abstract
The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better tissue regeneration? Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.
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15
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Osteogenic effects of the bioactive small molecules and minerals in the scaffold-based bone tissue engineering. Colloids Surf B Biointerfaces 2020; 198:111462. [PMID: 33239252 DOI: 10.1016/j.colsurfb.2020.111462] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 10/30/2020] [Accepted: 11/08/2020] [Indexed: 12/26/2022]
Abstract
Reconstruction of the damaged bone is a striking challenge in the medical field. The bone grafts as a current treatment is associated with inherent limitations; hence, the bone tissue engineering as an alternative therapeutic approach has been considered in the recent decades. Bone tissue engineering aims at replacing the lost tissue and restoring its function by recapitulating the natural regeneration process. Concerted participation and combination of the biocompatible materials, osteoprogenitor/ stem cells and bioactive factors closely mimic the bone microenvironment. The bioactive factors regulate the cell behavior and they induce the stem cells to osteogenic differentiation by activating specific signaling cascades. Growth factors (GFs) are the most important bioactive molecules and mediators of the natural bone repair process. Although these soluble factors have approved applications in the bone regeneration, however, there are several limitations such as the instability, high dose requirements, and serious side effects which could restrict their clinical usage. Alternatively, a new generation of bioactive molecules with the osteogenic properties are used. The non-peptide organic or inorganic molecules are physiologically stable and non-immunogenic due to their small size. Many of them are obtained from the natural resources and some are synthesized through the chemical methods. As a result, these molecules have been introduced as the cost-effective osteogenic agents in the bone tissue regeneration. In this paper, three groups of these bioactive agents including the organic small molecules, minerals and metallic nanoparticles have been investigated, considering their function in accelerating the bone regeneration. We review the recent in vitro and in vivo studies that utilized the osteogenic molecules to promote the bone formation in the scaffold-based bone tissue engineering systems.
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16
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Xu L, Li J, Xu X, Lei X, Zhang K, Wu C, Zhang Z, Shi X, Wang X, Ding J. A Novel Cytocompatibility Strengthening Strategy of Ultrafine-Grained Pure Titanium. ACS APPLIED MATERIALS & INTERFACES 2019; 11:47680-47694. [PMID: 31789503 DOI: 10.1021/acsami.9b13554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Ultrafine-grained pure (UFG) titanium processed by equal channel angular pressing possesses mechanical properties comparable to those of Ti-6Al-4V and features more favorable friction resistance, biocompatibility, and corrosion resistance than does commercially pure (CP) titanium. Nevertheless, UFG titanium is still a bio-inert material with a lack of bone-inducing ability. Here, TiO2-hydroxyapatite (TiO2-HA) coatings were fabricated on CP titanium and UFG titanium through combining micro-arc oxidation and hydrothermal treatment together to improve their cytocompatibility. The results indicate that, compared with conventional coatings that use CP titanium as the substrate, such coatings formed on the UFG titanium possess additional hydrophilicity and in vitro cytocompatibility. The fantastic hierarchical structure of the UFG TiO2-HA coating (UG-MH coating), including microscale and nanoscale pores and short column-shaped and sheet-shaped HA grains with varying geometric shapes, excellent hydrophilicity, and high polar force, enhances the mutual effects between the osteoblasts and titanium implant since it provides an adequate microenvironment for the ingrowth of osteoblasts, inducing osteoblast adhesion, proliferation, and differentiation. The UG-MH coating has a synergistic effect due to its fantastic hydrophilic hierarchical structure and high polar force on the up-regulated expression of cytoskeletal actin proteins as well as osteocalcin, protein kinase C (PKC), nuclear factor of activated T-cells (NFAT), and Wnt5, enabling osteoblasts to differentiate via the Wnt calcium-dependent signaling pathway. This study highlights the idea that the modified UFG titanium will be more suitable than CP titanium in dental and orthopedic applications.
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Affiliation(s)
| | | | | | | | | | | | | | - Xingling Shi
- School of Materials Science and Engineering , Jiangsu University of Science and Technology , Zhenjiang 212003 , China
| | | | - Jianning Ding
- Jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering , Changzhou University , Changzhou 213164 , China
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17
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Lu RJ, Wang X, He HX, E LL, Li Y, Zhang GL, Li CJ, Ning CY, Liu HC. Tantalum-incorporated hydroxyapatite coating on titanium implants: its mechanical and in vitro osteogenic properties. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2019; 30:111. [PMID: 31583537 DOI: 10.1007/s10856-019-6308-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 08/30/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVE The fabrication of bioactive coatings on metallic implants to enhance osseointegration has become a topic of general interest in orthopedics and dentistry. Hydroxyapatite (HA) coating has been shown to induce bone formation and promote bone-implant integration. Unfortunately, poor mechanical performance has hindered this from becoming a favorable coating material. The majority of present studies have focused in incorporating different elements into HA coatings to improve mechanical properties. In recent years, tantalum (Ta) has received increasing attention due to its excellent biocompatibility and corrosion resistance. The aim of on the present study was to investigate the fabrication and biological performance of Ta-incorporated HA coatings. METHODS Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate, and the surface characteristics and mechanical properties were examined. In addition, the effects of Ta-incorporated HA coatings on the biological behavior of mesenchymal stem cells (BMSCs) were investigated. RESULTS Ta-incorporated HA coatings with microporous structure had higher roughness and wettability. In addition, the bonding strength of Ta/HA coatings with the substrate was substantially superior to HA coatings. Furthermore, Ta-incorporated HA coatings not only facilitated initial cell adhesion and faster proliferation, but also promoted the osteogenic differentiation of BMSCs. CONCLUSION These results indicate that the incorporation of Ta could improve mechanical performance and increase the osteogenic activity of HA coatings. The Ta-incorporated HA coating fabricated by plasma spraying is expected to be a promising bio-coating material for metallic implants.
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Affiliation(s)
- Rong-Jian Lu
- Department of Stomatology, the Fifth Medical Center, Chinese PLA General Hospital, 100071, Beijing, China
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China
| | - Xing Wang
- Shanxi Medical University School and Hospital of Stomatology, 030001, Taiyuan, China
| | - Hui-Xia He
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China
| | - Ling-Ling E
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China
| | - Ying Li
- School of Materials Science and Technology, South China University of Technology, 510641, Guangzhou, China
| | - Gui-Lan Zhang
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China
| | - Chuan-Jie Li
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China
| | - Cheng-Yun Ning
- School of Materials Science and Technology, South China University of Technology, 510641, Guangzhou, China
| | - Hong-Chen Liu
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.
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18
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Goonoo N, Bhaw-Luximon A. Mimicking growth factors: role of small molecule scaffold additives in promoting tissue regeneration and repair. RSC Adv 2019; 9:18124-18146. [PMID: 35702423 PMCID: PMC9115879 DOI: 10.1039/c9ra02765c] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 06/02/2019] [Indexed: 12/31/2022] Open
Abstract
The primary aim of tissue engineering scaffolds is to mimic the in vivo environment and promote tissue growth. In this quest, a number of strategies have been developed such as enhancing cell-material interactions through modulation of scaffold physico-chemical parameters. However, more is required for scaffolds to relate to the cell natural environment. Growth factors (GFs) secreted by cells and extracellular matrix (ECM) are involved in both normal repair and abnormal remodeling. The direct use of GFs on their own or when incorporated within scaffolds represent a number of challenges such as release rate, stability and shelf-life. Small molecules have been proposed as promising alternatives to GFs as they are able to minimize or overcome many shortcomings of GFs, in particular immune response and instability. Despite the promise of small molecules in various TE applications, their direct use is limited by nonspecific adverse effects on non-target tissues and organs. Hence, they have been incorporated within scaffolds to localize their actions and control their release to target sites. However, scanty rationale is available which links the chemical structure of these molecules with their mode of action. We herewith review various small molecules either when used on their own or when incorporated within polymeric carriers/scaffolds for bone, cartilage, neural, adipose and skin tissue regeneration.
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Affiliation(s)
- Nowsheen Goonoo
- Biomaterials, Drug Delivery and Nanotechnology (BDDN) Unit, Centre for Biomedical and Biomaterials Research, University of Mauritius Réduit Mauritius
| | - Archana Bhaw-Luximon
- Biomaterials, Drug Delivery and Nanotechnology (BDDN) Unit, Centre for Biomedical and Biomaterials Research, University of Mauritius Réduit Mauritius
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Sun X, Wu Z, He D, Shen K, Liu X, Li H, Jin W. Bioactive injectable polymethylmethacrylate/silicate bioceramic hybrid cements for percutaneous vertebroplasty and kyphoplasty. J Mech Behav Biomed Mater 2019; 96:125-135. [PMID: 31035063 DOI: 10.1016/j.jmbbm.2019.04.044] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 04/21/2019] [Accepted: 04/23/2019] [Indexed: 12/30/2022]
Abstract
Polymethylmethacrylate (PMMA) cement has been widely used to fill and stabilize hard tissue defects in clinical surgery, especially in percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP). However, the dense body of pure PMMA in defects has no ability to promote bone regeneration. We herein aim to fabricate novel PMMA/silicate bioceramic hybrid cements by adding bioactive calcium silicate (CS) particles into PMMA to endow PMMA/CS hybrid cements with bioactivity and biodegradability without losing the excellent mechanical strength and injectability. Following comprehensive characterization of the physicochemical properties and in vitro bioactivity study, our results showed compared with PMMA cement, the constructed PMMA/CS hybrid cements possessed significantly lower curing temperatures and simultaneously retained the acceptable mechanical strength and injectability. Moreover, obvious bioactive ion release and hydroxyapatite formation could be detected and observed after the PMMA/CS hybrid cements were soaked in simulated body fluid, indicating their pronounced bioactivity. A further in vivo study of the PMMA/CS hybrid cements on goat vertebral body defect models reflected that the PMMA/CS hybrid cements could be biodegraded well and could significantly promote new bone formation in defects 6 months of post-injection. Our results suggest that PMMA/CS hybrid cements may be promising candidates for PVP and PKP in clinic.
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Affiliation(s)
- Xin Sun
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 280 Mohe Road, Shanghai, 201999, China
| | - Zhi Wu
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China
| | - Dan He
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China
| | - Kangping Shen
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 280 Mohe Road, Shanghai, 201999, China
| | - Xingzhen Liu
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 280 Mohe Road, Shanghai, 201999, China
| | - Haiyan Li
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.
| | - Wenjie Jin
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 280 Mohe Road, Shanghai, 201999, China.
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20
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Wang T, Qian S, Zha GC, Zhao XJ, Ding L, Sun JY, Li B, Liu XY. Synergistic effects of titania nanotubes and silicon to enhance the osteogenic activity. Colloids Surf B Biointerfaces 2018; 171:419-426. [PMID: 30075417 DOI: 10.1016/j.colsurfb.2018.07.052] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 07/10/2018] [Accepted: 07/23/2018] [Indexed: 11/29/2022]
Abstract
In this study, titania nanotubes (TNTs) incorporating silicon (Si) were formed on Ti disks using anodization and electron beam evaporation (EBE) technology to improve the osteogenic activity. The amount of Si was exquisitely adjusted by controlling the duration of EBE to optimize the biofunctionality. As the Si was incorporated, the samples exhibited hydrophilic surfaces. Long lasting and controllable Si release was observed from the EBE-modified samples without cytotoxicity. Moreover, initial cell adhesion, spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells were evaluated. The results showed a notable enhancement of spreading, osteogenesis and differentiation of cells on silicon-coated TNTs (Si-TNTs). In particular, samples with highest amount of silicon (∼5.93% Si) displayed greatest augmentation of ALP activity, osteogenic-related gene expression and mineralization compared to the others in the present study. It was indicated that the modification with TNTs and appropriated Si content resulted in enhanced osteoblastic spreading, proliferation and differentiation, and therefore has the potential for future applications in the field of orthopedics.
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Affiliation(s)
- Tao Wang
- Department of Orthopedics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China; School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Shi Qian
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
| | - Guo-Chun Zha
- Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
| | - Xi-Jiang Zhao
- Department of Orthopedics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China
| | - Lei Ding
- School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jun-Ying Sun
- Department of Orthopedics, the First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, China.
| | - Bin Li
- Department of Orthopedics, the First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, China.
| | - Xuan-Yong Liu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
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Silk fibroin/hydroxyapatite composites for bone tissue engineering. Biotechnol Adv 2018; 36:68-91. [DOI: 10.1016/j.biotechadv.2017.10.001] [Citation(s) in RCA: 239] [Impact Index Per Article: 34.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 09/12/2017] [Accepted: 10/04/2017] [Indexed: 12/22/2022]
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Ding L, Zhang P, Wang X, Hao J, Aoki K, Kuroda S, Kasugai S. Effect of doxycycline-treated hydroxyapatite surface on bone apposition: A histomophometric study in murine maxillae. Dent Mater J 2017; 37:130-138. [PMID: 29176300 DOI: 10.4012/dmj.2017-007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Improved osseointegration of dental implants is imperative in clinic. Effect of doxycycline on promoting bone formation after implant placement was expected due to its inhibitory properties on inflammation and osteoclastogenesis. To evaluate new bone formation on the hydroxyapatite (HA)-coated implant surface, which was treated with doxycycline, in comparison with the untreated HA surface, half of the HA-coated implants were soaked in doxycycline solution (DOX group) whereas the other HA-coated implants were untreated (HA group). Eight weeks after extracting the maxillary first molars of 4-week-old male mice, the implants of both groups were placed at the extracted site. 4 and 8 weeks after surgery, the samples were evaluated radiologically and histomorphometrically. Bone-implant contact of DOX group was statistically higher than the one of HA group at 4 and 8 weeks. New bone area between the threads of the implants also statistically increased at 8 weeks in DOX group compared to HA group.
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Affiliation(s)
- Lin Ding
- Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Peng Zhang
- Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Xin Wang
- VIP Clinic, Beijing Stomatological Hospital, Capital Medical University
| | - Jia Hao
- Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Kazuhiro Aoki
- Department of Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Shinji Kuroda
- Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Shohei Kasugai
- Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
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Duan W, Haque M, Kearney MT, Lopez MJ. Collagen and Hydroxyapatite Scaffolds Activate Distinct Osteogenesis Signaling Pathways in Adult Adipose-Derived Multipotent Stromal Cells. Tissue Eng Part C Methods 2017; 23:592-603. [PMID: 28877641 PMCID: PMC5653142 DOI: 10.1089/ten.tec.2017.0078] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 07/19/2017] [Indexed: 12/13/2022] Open
Abstract
Osteogenic cell signaling pathway disruption varies among bone diseases. This investigation was designed to identify adipose-derived multipotent stromal cell (ASC) and bone graft scaffold combinations for local, targeted restoration of gene expression and extracellular matrix (ECM) deposition. Human ASC osteogenesis on bone graft materials was quantified following culture in stromal (S), osteogenic (O), or osteogenic for 48 h followed by stromal medium (OS) to test the two-part hypothesis: (1) identical ASC isolates on distinct bone graft scaffolds demonstrate unique viability, differentiation, ECM production, and gene expression in the same culture conditions; (2) identical ASC-bone graft scaffold combinations have different cell viability, differentiation, ECM production, and gene expression when cultured in S, O, or OS medium. Three commercially available bone graft scaffold materials, type I bovine collagen (C), hydroxyapatite + β-tricalcium phosphate + type I bovine collagen (HT), and β-tricalcium phosphate + type I bovine collagen (CT) were evaluated. Passage 3 ASCs were loaded onto scaffold blocks with a spinner flask bioreactor, and constructs were cultured up to 28 days. Cell viability, gene expression (alkaline phosphatase [ALPL], osteoprotegerin [TNFRSF11B], osteocalcin [BGLAP], cannabinoid receptors type I [CNR1] and II [CNR2], receptor activator of nuclear factor kappa β ligand [TNFSF11]), as well as ECM DNA, collagen, sulfated glycosaminoglycan, and protein content were quantified. Matrix organization was evaluated with scanning electron microscopy. Effects of scaffold, medium, or culture duration on cell viability were minimal. Significantly higher initial ALPL expression decreased with time, while BGLAP expression increased in HT constructs in O medium, and the constructs had the most abundant ECM components and ultrastructural organization. There was a similar, although delayed, pattern of gene expression and greater ECM collagen with less organization in C constructs in O medium. Higher CNR1 expression in C versus higher TNFRSF11B/TNFSF11 expression in HT constructs throughout the study support stimulation of unique osteogenic signaling pathways by identical cell isolates. These results suggest that bone scaffold composition may be used to selectively target specific osteogenic cell signaling pathways in ASC constructs to stimulate ECM deposition based on therapeutic needs.
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Affiliation(s)
- Wei Duan
- 1 Laboratory for Equine and Comparative Orthopedic Research, School of Veterinary Medicine, Louisiana State University , Baton Rouge, Louisiana
| | - Masudul Haque
- 1 Laboratory for Equine and Comparative Orthopedic Research, School of Veterinary Medicine, Louisiana State University , Baton Rouge, Louisiana
| | - Michael T Kearney
- 2 Department of Pathobiological Sciences, Louisiana State University , Baton Rouge, Louisiana
| | - Mandi J Lopez
- 1 Laboratory for Equine and Comparative Orthopedic Research, School of Veterinary Medicine, Louisiana State University , Baton Rouge, Louisiana
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Haro Durand LA, Vargas GE, Vera-Mesones R, Baldi A, Zago MP, Fanovich MA, Boccaccini AR, Gorustovich A. In Vitro Human Umbilical Vein Endothelial Cells Response to Ionic Dissolution Products from Lithium-Containing 45S5 Bioactive Glass. MATERIALS (BASEL, SWITZERLAND) 2017; 10:E740. [PMID: 28773103 PMCID: PMC5551783 DOI: 10.3390/ma10070740] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 06/24/2017] [Accepted: 06/29/2017] [Indexed: 12/27/2022]
Abstract
Since lithium (Li⁺) plays roles in angiogenesis, the localized and controlled release of Li⁺ ions from bioactive glasses (BGs) represents a promising alternative therapy for the regeneration and repair of tissues with a high degree of vascularization. Here, microparticles from a base 45S5 BG composition containing (wt %) 45% SiO₂, 24.5% Na₂O, 24.5% CaO, and 6% P₂O₅, in which Na₂O was partially substituted by 5% Li₂O (45S5.5Li), were obtained. The results demonstrate that human umbilical vein endothelial cells (HUVECs) have greater migratory and proliferative response and ability to form tubules in vitro after stimulation with the ionic dissolution products (IDPs) of the 45S5.5Li BG. The results also show the activation of the canonical Wnt/β-catenin pathway and the increase in expression of proangiogenic cytokines insulin like growth factor 1 (IGF1) and transforming growth factor beta (TGFβ). We conclude that the IDPs of 45S5.5Li BG would act as useful inorganic agents to improve tissue repair and regeneration, ultimately stimulating HUVECs behavior in the absence of exogenous growth factors.
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Affiliation(s)
- Luis A Haro Durand
- Department of Pathology and Molecular Pharmacology, IByME-CONICET, C1428ADN Buenos Aires, Argentina.
| | - Gabriela E Vargas
- Department of Developmental Biology, National University of Salta, A4408FVY Salta, Argentina.
| | - Rosa Vera-Mesones
- Department of Developmental Biology, National University of Salta, A4408FVY Salta, Argentina.
| | - Alberto Baldi
- Department of Pathology and Molecular Pharmacology, IByME-CONICET, C1428ADN Buenos Aires, Argentina.
| | - María P Zago
- Institute of Experimental Pathology, IPE-CONICET, A4408FVY Salta, Argentina.
| | - María A Fanovich
- Research Institute for Materials Science and Technology, INTEMA-CONICET, B7608FDQ Mar del Plata, Argentina.
| | - Aldo R Boccaccini
- Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
| | - Alejandro Gorustovich
- Interdisciplinary Materials Group-IESIING-UCASAL, INTECIN UBA-CONICET, A4400EDD Salta, Argentina.
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25
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Zhou D, Qi C, Chen YX, Zhu YJ, Sun TW, Chen F, Zhang CQ. Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects. Int J Nanomedicine 2017; 12:2673-2687. [PMID: 28435251 PMCID: PMC5388207 DOI: 10.2147/ijn.s131251] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Hydroxyapatite (HAP; Ca10(PO4)6(OH)2) and whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12) are widely utilized in bone repair because they are the main components of hard tissues such as bones and teeth. In this paper, we synthesized HAP and WH hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through microwave-assisted hydrothermal method. Then, we prepared HAP/chitosan and WH/chitosan composite membranes to evaluate their biocompatibility in vitro and prepared porous HAP/chitosan and WH/chitosan scaffolds by freeze drying to compare their effects on bone regeneration in calvarial defects in a rat model. The experimental results indicated that the WH/chitosan composite membrane had a better biocompatibility, enhancing proliferation and osteogenic differentiation ability of human mesenchymal stem cells than HAP/chitosan. Moreover, the porous WH/chitosan scaffold can significantly promote bone regeneration in calvarial defects, and thus it is more promising for applications in tissue engineering such as calvarial repair compared to porous HAP/chitosan scaffold.
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Affiliation(s)
- Ding Zhou
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiaotong University
| | - Chao Qi
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Yi-Xuan Chen
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiaotong University
| | - Ying-Jie Zhu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Tuan-Wei Sun
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Feng Chen
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Chang-Qing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiaotong University
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26
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Jiang D, Zhao H, Yang Y, Zhu Y, Chen X, Sun J, Yu K, Fan H, Zhang X. Investigation of luminescent mechanism: N-rich carbon dots as luminescence centers in fluorescent hydroxyapatite prepared using a typical hydrothermal process. J Mater Chem B 2017; 5:3749-3757. [DOI: 10.1039/c6tb03184f] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
N-Rich carbon dots (CDs) generated in the hydrothermal synthesis of HAp were trapped by growing HAp crystals to form fluorescent HAp materials.
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Affiliation(s)
- Dongli Jiang
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
- Pharmacy College
| | - Huan Zhao
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - You Yang
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Yuda Zhu
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xiaoqin Chen
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Jing Sun
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Kui Yu
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Hongsong Fan
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials
- Sichuan University
- Chengdu
- China
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27
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Williams DF. Biocompatibility Pathways: Biomaterials-Induced Sterile Inflammation, Mechanotransduction, and Principles of Biocompatibility Control. ACS Biomater Sci Eng 2016; 3:2-35. [DOI: 10.1021/acsbiomaterials.6b00607] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- David F. Williams
- Wake Forest Institute of Regenerative Medicine, Richard H. Dean Biomedical Building, 391 Technology Way, Winston-Salem, North Carolina 27101, United States
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28
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Comparison of the Influence of Phospholipid-Coated Porous Ti-6Al-4V Material on the Osteosarcoma Cell Line Saos-2 and Primary Human Bone Derived Cells. METALS 2016. [DOI: 10.3390/met6030066] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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29
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Hirota M, Shima T, Sato I, Ozawa T, Iwai T, Ametani A, Sato M, Noishiki Y, Ogawa T, Hayakawa T, Tohnai I. Development of a biointegrated mandibular reconstruction device consisting of bone compatible titanium fiber mesh scaffold. Biomaterials 2016; 75:223-236. [DOI: 10.1016/j.biomaterials.2015.09.034] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 09/21/2015] [Accepted: 09/23/2015] [Indexed: 11/30/2022]
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Cernea M, Tang W, Guan H, Yang K. Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation. J Mol Endocrinol 2016; 56:39-46. [PMID: 26489765 DOI: 10.1530/jme-15-0217] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/21/2015] [Indexed: 12/25/2022]
Abstract
Adipose tissue expansion, resulting from adipocyte hyperplasia and/or hypertrophy, is a hallmark of obesity. Adipocytes are derived from mesenchymal stem cells (MSCs) through adipogenesis, a process involving three key steps: proliferation, commitment and differentiation. Although studies have elaborated on the mechanisms regulating adipocyte commitment and differentiation, the factors that control MSC proliferation remain largely unknown. Previously, we demonstrated that bone morphogenetic protein 3 (Bmp3), the expression of which was upregulated in our rat model of hyperplasic visceral adiposity, potently stimulated MSC proliferation. In the present study, we investigate the molecular target of Bmp3. We conducted DNA microarray analysis on MSCs treated with and without Bmp3 and identified WNT1-inducible signaling pathway protein 1 (Wisp1) as a differentially expressed gene, whose expression was upregulated 3.7-fold by Bmp3. Wisp1 is a proliferative agent in various non-adipose cell types and is implicated in adipogenesis. Therefore, we tested the hypothesis that Wisp1 mediates Bmp3 stimulation of MSC proliferation. We showed that Bmp3 increased the expression of Wisp1 as early as 3 h following Bmp3 treatment in MSCs. Importantly, the upregulated Wisp1 expression preceded Bmp3-induced MSC proliferation, as determined by [(3)H]-thymidine incorporation. Furthermore, treatment of MSCs with recombinant Wisp1 led to a concentration-dependent increase in [(3)H]-thymidine incorporation with a maximal increase of 300%. In addition, siRNA-mediated knockdown of Wisp1 expression attenuated Bmp3-induced MSC proliferation. Taken together, our present findings reveal Wisp1 as a novel target of Bmp3 and suggest that the Bmp3/Wisp1 signaling pathway play a key role in MSC proliferation, and consequently adipogenesis.
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Affiliation(s)
- Maria Cernea
- Departments of Obstetrics and Gynaecologyand Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, Room A5-132, 800 Commissioners Road East, London, Ontario, Canada, N6C 2V5
| | - Wei Tang
- Departments of Obstetrics and Gynaecologyand Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, Room A5-132, 800 Commissioners Road East, London, Ontario, Canada, N6C 2V5
| | - Haiyan Guan
- Departments of Obstetrics and Gynaecologyand Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, Room A5-132, 800 Commissioners Road East, London, Ontario, Canada, N6C 2V5
| | - Kaiping Yang
- Departments of Obstetrics and Gynaecologyand Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, Western University, Room A5-132, 800 Commissioners Road East, London, Ontario, Canada, N6C 2V5
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31
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Alm JJ, Moritz N, Aro HT. In vitro osteogenic capacity of bone marrow MSCs from postmenopausal women reflect the osseointegration of their cementless hip stems. Bone Rep 2016; 5:124-135. [PMID: 28326353 PMCID: PMC4926811 DOI: 10.1016/j.bonr.2016.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 04/25/2016] [Accepted: 05/20/2016] [Indexed: 11/06/2022] Open
Abstract
Age-related dysfunction of mesenchymal stromal cells (MSCs) is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA) aging, low bone mineral density (BMD) and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity. A total of 19 postmenopausal women with primary hip osteoarthritis (mean age 65 years, range 50–78) and well-defined bone quality underwent successful preoperative in vitro analysis of osteogenic capacity of iliac crest bone marrow MSCs as well as two-year radiostereometric (RSA) follow-up of femoral stem migration after cementless THA. In patients with MSCs of low osteogenic capacity, the magnitude of cumulative stem subsidence after the settling period of three months was greater (p = 0.028) and the time point for translational osseointegration was significantly delayed (p = 0.030) compared to patients with MSCs of high osteogenic capacity. This study suggests that patients with MSCs of low in vitro osteogenic capacity may display increased stem subsidence after the settling period of 3 months and thereby delayed osseointegration. Our study presents a novel approach for studying the biological progress of hip implant osseointegration and to verify the impact of decreased MSCs function, especially in patients with age-related dysfunction of MSCs and bone healing capacity.
Age-related dysfunction of MSCs is a main cause of altered bone repair with aging. MSCs play a critical role in osseointegration of cementless hip replacement. We explored if hip implant osseointegration in postmenopausal women is mirrored by in vitro osteogenic ability of their MSCs. Low osteogenic differentiation of MSCs correlated with increased implant migration.
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Affiliation(s)
- Jessica J Alm
- Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku/Turku University Hospital, Turku, Finland
| | - Niko Moritz
- Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku/Turku University Hospital, Turku, Finland
| | - Hannu T Aro
- Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku/Turku University Hospital, Turku, Finland
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Mao L, Liu J, Zhao J, Chang J, Xia L, Jiang L, Wang X, Lin K, Fang B. Effect of micro-nano-hybrid structured hydroxyapatite bioceramics on osteogenic and cementogenic differentiation of human periodontal ligament stem cell via Wnt signaling pathway. Int J Nanomedicine 2015; 10:7031-44. [PMID: 26648716 PMCID: PMC4648603 DOI: 10.2147/ijn.s90343] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The surface structure of bioceramic scaffolds is crucial for its bioactivity and osteoinductive ability, and in recent years, human periodontal ligament stem cells have been certified to possess high osteogenic and cementogenic differential ability. In the present study, hydroxyapatite (HA) bioceramics with micro-nano-hybrid surface (mnHA [the hybrid of nanorods and microrods]) were fabricated via hydrothermal reaction of the α-tricalcium phosphate granules as precursors in aqueous solution, and the effects of mnHA on the attachment, proliferation, osteogenic and cementogenic differentiations of human periodontal ligament stem cells as well as the related mechanisms were systematically investigated. The results showed that mnHA bioceramics could promote cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and expression of osteogenic/cementogenic-related markers including runt-related transcription factor 2 (Runx2), ALP, osteocalcin (OCN), cementum attachment protein (CAP), and cementum protein (CEMP) as compared to the HA bioceramics with flat and dense surface. Moreover, mnHA bioceramics stimulated gene expression of low-density lipoprotein receptor-related protein 5 (LRP5) and β-catenin, which are the key genes of canonical Wnt signaling. Moreover, the stimulatory effect on ALP activity and osteogenic and cementogenic gene expression, including that of ALP, OCN, CAP, CEMP, and Runx2 of mnHA bioceramics could be repressed by canonical Wnt signaling inhibitor dickkopf1 (Dkk1). The results suggested that the HA bioceramics with mnHA could act as promising grafts for periodontal tissue regeneration.
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Affiliation(s)
- Lixia Mao
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Jiaqiang Liu
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Jinglei Zhao
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Jiang Chang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Tongji University, Shanghai, People’s Republic of China
| | - Lunguo Xia
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Lingyong Jiang
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Xiuhui Wang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Tongji University, Shanghai, People’s Republic of China
| | - Kaili Lin
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Tongji University, Shanghai, People’s Republic of China
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration, School of Stomatology, Tongji University, Shanghai, People’s Republic of China
| | - Bing Fang
- Center of Craniofacial Orthodontics, Department of Oral and Craniomaxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
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Vahabzadeh S, Hack VK, Bose S. Lithium-doped β-tricalcium phosphate: Effects on physical, mechanical and in vitro osteoblast cell-material interactions. J Biomed Mater Res B Appl Biomater 2015; 105:391-399. [PMID: 26525914 DOI: 10.1002/jbm.b.33485] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 05/02/2015] [Accepted: 07/05/2015] [Indexed: 01/24/2023]
Abstract
In this work, we have investigated the effects of lithium (Li) dopant at different concentrations and sintering temperatures on the physical and mechanical properties of β-tricalcium phosphate (β-TCP). Our results showed that Li addition at concentrations of 0.65 and 1.0 wt % inhibits the β-TCP to α-TCP phase transformation. 0.15 wt % Li addition resulted in grain growth and extensive liquid phase was formed at higher concentrations. At 1150°C, compressive strength of β-TCP increased from 138.7 ± 19.9 MPa to 170.9 ± 29.8 MPa with the addition of 0.15 wt % Li. Addition of higher amounts of Li decreased the compressive strength and the lowest compressive strength of 99.8 ± 13.7 MPa was found in samples containing 1.0 wt % Li. After 3 days of culture, osteoblast cells grew to confluence on samples containing 0.65 and 1.0 wt % Li. Cells grew to confluence on all doped samples after 11 days of culture and optical cell density was 4-5 folds higher on 0.15 and 1.0 wt % Li-doped TCP samples. Our results show that both Li content and sintering temperature have significant influence toward physicochemical and mechanical properties of β-TCP which affects the osteoblast cell-materials interaction in Li-doped TCP scaffolds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 391-399, 2017.
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Affiliation(s)
- Sahar Vahabzadeh
- W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington, 99164-2920
| | - Vaughn Kohsei Hack
- W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington, 99164-2920
| | - Susmita Bose
- W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington, 99164-2920
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Mahmood S, Bhatti A, Syed NA, John P. The microRNA regulatory network: a far-reaching approach to the regulate the Wnt signaling pathway in number of diseases. J Recept Signal Transduct Res 2015; 36:310-8. [PMID: 26523375 DOI: 10.3109/10799893.2015.1080273] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Wnt signaling pathway plays an important role in cell renewal, tumorigenesis, organogenesis, bone formation and bone resorption. Wnt signaling pathway is divided into two outlets: Wnt-β-catenin pathway (canonical pathway) and Wnt-calcium pathway (non-canonical pathway). miRNAs play a key role in the regulation of Wnt signaling pathway. In this review, we highlight the basic indulgent of miRNAs-mediated regulation of Wnt signaling pathway. We focus on the role of miRNAs at different levels of Wnt signaling: signaling molecules, their associated signaling proteins, regulatory proteins, transcription factors and related cytokines. Finally, we concluded that these multiple levels of targeting may have diagnostic potential as well as therapeutic prospective in future treatment.
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Affiliation(s)
- Shahid Mahmood
- a Immunogenetic Lab, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST) , Islamabad , Pakistan
| | - Attya Bhatti
- a Immunogenetic Lab, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST) , Islamabad , Pakistan
| | - Nida Ali Syed
- a Immunogenetic Lab, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST) , Islamabad , Pakistan
| | - Peter John
- a Immunogenetic Lab, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST) , Islamabad , Pakistan
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35
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Dorozhkin SV. Calcium orthophosphate deposits: Preparation, properties and biomedical applications. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2015; 55:272-326. [PMID: 26117762 DOI: 10.1016/j.msec.2015.05.033] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 03/21/2015] [Accepted: 05/08/2015] [Indexed: 01/12/2023]
Abstract
Since various interactions among cells, surrounding tissues and implanted biomaterials always occur at their interfaces, the surface properties of potential implants appear to be of paramount importance for the clinical success. In view of the fact that a limited amount of materials appear to be tolerated by living organisms, a special discipline called surface engineering was developed to initiate the desirable changes to the exterior properties of various materials but still maintaining their useful bulk performances. In 1975, this approach resulted in the introduction of a special class of artificial bone grafts, composed of various mechanically stable (consequently, suitable for load bearing applications) implantable biomaterials and/or bio-devices covered by calcium orthophosphates (CaPO4) to both improve biocompatibility and provide an adequate bonding to the adjacent bones. Over 5000 publications on this topic were published since then. Therefore, a thorough analysis of the available literature has been performed and about 50 (this number is doubled, if all possible modifications are counted) deposition techniques of CaPO4 have been revealed, systematized and described. These CaPO4 deposits (coatings, films and layers) used to improve the surface properties of various types of artificial implants are the topic of this review.
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36
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Maiese K. Stem cell guidance through the mechanistic target of rapamycin. World J Stem Cells 2015; 7:999-1009. [PMID: 26328016 PMCID: PMC4550632 DOI: 10.4252/wjsc.v7.i7.999] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Revised: 06/29/2015] [Accepted: 07/17/2015] [Indexed: 02/06/2023] Open
Abstract
Stem cells offer great promise for the treatment of multiple disorders throughout the body. Critical to this premise is the ability to govern stem cell pluripotency, proliferation, and differentiation. The mechanistic target of rapamycin (mTOR), 289-kDa serine/threonine protein kinase, that is a vital component of mTOR Complex 1 and mTOR Complex 2 represents a critical pathway for the oversight of stem cell maintenance. mTOR can control the programmed cell death pathways of autophagy and apoptosis that can yield variable outcomes in stem cell survival and be reliant upon proliferative pathways that include Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and trophic factors. mTOR also is a necessary component for the early development and establishment of stem cells as well as having a significant impact in the regulation of the maturation of specific cell phenotypes. Yet, as a proliferative agent, mTOR can not only foster cancer stem cell development and tumorigenesis, but also mediate cell senescence under certain conditions to limit invasive cancer growth. mTOR offers an exciting target for the oversight of stem cell therapies but requires careful consideration of the diverse clinical outcomes that can be fueled by mTOR signaling pathways.
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New Insights for Oxidative Stress and Diabetes Mellitus. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:875961. [PMID: 26064426 PMCID: PMC4443788 DOI: 10.1155/2015/875961] [Citation(s) in RCA: 149] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 04/15/2015] [Indexed: 12/12/2022]
Abstract
The release of reactive oxygen species (ROS) and the generation of oxidative stress are considered critical factors for the pathogenesis of diabetes mellitus (DM), a disorder that is growing in prevalence and results in significant economic loss. New therapeutic directions that address the detrimental effects of oxidative stress may be especially warranted to develop effective care for the millions of individuals that currently suffer from DM. The mechanistic target of rapamycin (mTOR), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), and Wnt1 inducible signaling pathway protein 1 (WISP1) are especially justified to be considered treatment targets for DM since these pathways can address the complex relationship between stem cells, trophic factors, impaired glucose tolerance, programmed cell death pathways of apoptosis and autophagy, tissue remodeling, cellular energy homeostasis, and vascular biology that greatly impact the biology and disease progression of DM. The translation and development of these pathways into viable therapies will require detailed understanding of their proliferative nature to maximize clinical efficacy and limit adverse effects that have the potential to lead to unintended consequences.
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Composite scaffolds of nano-hydroxyapatite and silk fibroin enhance mesenchymal stem cell-based bone regeneration via the interleukin 1 alpha autocrine/paracrine signaling loop. Biomaterials 2015; 49:103-12. [DOI: 10.1016/j.biomaterials.2015.01.017] [Citation(s) in RCA: 113] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 01/19/2015] [Accepted: 01/20/2015] [Indexed: 12/31/2022]
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Maiese K. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease. Neural Regen Res 2015; 10:518-28. [PMID: 26170801 PMCID: PMC4424733 DOI: 10.4103/1673-5374.155427] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2015] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4) to foster control over stem cell proliferation, wound repair, cognitive decline, β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.
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Affiliation(s)
- Kenneth Maiese
- Cellular and Molecular Signaling, Newark, New Jersey 07101, USA
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Li Y, Yang W, Li X, Zhang X, Wang C, Meng X, Pei Y, Fan X, Lan P, Wang C, Li X, Guo Z. Improving osteointegration and osteogenesis of three-dimensional porous Ti6Al4V scaffolds by polydopamine-assisted biomimetic hydroxyapatite coating. ACS APPLIED MATERIALS & INTERFACES 2015; 7:5715-24. [PMID: 25711714 DOI: 10.1021/acsami.5b00331] [Citation(s) in RCA: 124] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Titanium alloys with various porous structures can be fabricated by advanced additive manufacturing techniques, which are attractive for use as scaffolds for bone defect repair. However, modification of the scaffold surfaces, particularly inner surfaces, is critical to improve the osteointegration of these scaffolds. In this study, a biomimetic approach was employed to construct polydopamine-assisted hydroxyapatite coating (HA/pDA) onto porous Ti6Al4V scaffolds fabricated by the electron beam melting method. The surface modification was characterized with the field emission scanning electron microscopy, energy dispersive spectroscopy, water contact angle measurement, and confocal laser scanning microscopy. Attachment and proliferation of MC3T3-E1 cells on the scaffold surface were significantly enhanced by the HA/pDA coating compared to the unmodified surfaces. Additionally, MC3T3-E1 cells grown on the HA/pDA-coated Ti6Al4V scaffolds displayed significantly higher expression of runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 compared with bare Ti6Al4V scaffolds after culture for 14 days. Moreover, microcomputed tomography analysis and Van-Gieson staining of histological sections showed that HA/pDA coating on surfaces of porous Ti6Al4V scaffolds enhanced osteointegration and significantly promoted bone regeneration after implantation in rabbit femoral condylar defects for 4 and 12 weeks. Therefore, this study provides an alternative to biofunctionalized porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions for orthopedic applications.
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Affiliation(s)
- Yong Li
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Wei Yang
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Xiaokang Li
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Xing Zhang
- ‡Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, People's Republic of China
| | - Cairu Wang
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Xiangfei Meng
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Yifeng Pei
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Xiangli Fan
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Pingheng Lan
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Chunhui Wang
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Xiaojie Li
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
| | - Zheng Guo
- †Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China
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Maiese K. Programming apoptosis and autophagy with novel approaches for diabetes mellitus. Curr Neurovasc Res 2015; 12:173-88. [PMID: 25742566 PMCID: PMC4380829 DOI: 10.2174/1567202612666150305110929] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Revised: 02/16/2015] [Accepted: 02/19/2015] [Indexed: 12/13/2022]
Abstract
According to the World Health Organization, diabetes mellitus (DM) in the year 2030 will be ranked the seventh leading cause of death in the world. DM impacts all systems of the body with oxidant stress controlling cell fate through endoplasmic reticulum stress, mitochondrial dysfunction, alterations in uncoupling proteins, and the induction of apoptosis and autophagy. Multiple treatment approaches are being entertained for DM with Wnt1 inducible signaling pathway protein 1 (WISP1), mechanistic target of rapamycin (mTOR), and silent mating type information regulation 2 homolog) 1 (S. cerevisiae) (SIRT1) generating significant interest as target pathways that can address maintenance of glucose homeostasis as well as prevention of cellular pathology by controlling insulin resistance, stem cell proliferation, and the programmed cell death pathways of apoptosis and autophagy. WISP1, mTOR, and SIRT1 can rely upon similar pathways such as AMP activated protein kinase as well as govern cellular metabolism through cytokines such as EPO and oral hypoglycemics such as metformin. Yet, these pathways require precise biological control to exclude potentially detrimental clinical outcomes. Further elucidation of the ability to translate the roles of WISP1, mTOR, and SIRT1 into effective clinical avenues offers compelling prospects for new therapies against DM that can benefit hundreds of millions of individuals throughout the globe.
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Affiliation(s)
- Kenneth Maiese
- MD, Cellular and Molecular Signaling, Newark, New Jersey 07101, USA.
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Synergistic effect of nanomaterials and BMP-2 signalling in inducing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:219-28. [DOI: 10.1016/j.nano.2014.09.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 09/03/2014] [Accepted: 09/15/2014] [Indexed: 12/22/2022]
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Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy. Sci Rep 2014; 4:6044. [PMID: 25116435 PMCID: PMC4131220 DOI: 10.1038/srep06044] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 07/18/2014] [Indexed: 02/07/2023] Open
Abstract
Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy.
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