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Yang Q, Xu F, Zhu J, Sun L, Qu Q, Liu S, Wang S. Clinical investigation of extracorporeal shock wave therapy combined with kinesitherapy on the treatment of delayed union of tibia and fibula fractures. Am J Transl Res 2025; 17:1860-1871. [PMID: 40225982 PMCID: PMC11982830 DOI: 10.62347/wwfd7121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/11/2025] [Indexed: 04/15/2025]
Abstract
OBJECTIVE To investigate the therapeutic efficacy of extracorporeal shock wave therapy (ESWT) combined with kinesitherapy (KT) for the treatment of delayed union of tibia and fibula fractures. METHODS A total of 68 patients with delayed healing of tibiofibular fractures were enrolled. These patients were divided into three groups: control, ESWT, and ESWT+KT. All patients underwent standard surgical treatment following the fracture. Patients in the ESWT group received shockwave therapy twice a week for 4 months, while those in the ESWT+KT group received additional exercise therapy twice a week over the same duration. The control group did not receive any specific intervention during this period. The pain levels of patients in all three groups were assessed using the Numerical Rating Scale (NRS) before and after treatment. Bone repair and callus formation were evaluated using the Lane-Sandhu and Fernandez-Esteve X-ray grading scales before and after treatment. Additionally, walking ability was assessed using the Functional Ambulation Classification (FAC), Hoffer walking ability grade, and Holden walking ability grade before and after treatment. RESULTS No significant differences were observed in patient baseline characteristics across the three groups (P > 0.05), indicating comparability among groups. Post-treatment, improvements were noted in the NRS, Lane-Sandhu X-ray scale, Fernandez-Esteve X-ray scale, FAC level, Hoffer grade, and Holden grade in all three groups compared to their respective pre-treatment values (P < 0.05). Notably, the Lane-Sandhu X-ray scale, FAC level, Hoffer grade, and Holden grade showed significant improvements in the ESWT+KT group after treatment compared to the control group (P < 0.05). Additionally, the ESWT group demonstrated significant improvements in FAC level and Holden grade compared to the control group after treatment (P < 0.05). CONCLUSION ESWT can enhance the walking function in patients with delayed union of tibia and fibula fractures. ESWT combined with KT demonstrates superior efficacy compared to monotherapy, as it not only improves walking function but also promotes bone healing.
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Affiliation(s)
- Qing Yang
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
- Graduate School of Dalian Medical UniversityDalian 116000, Liaoning, China
| | - Feng Xu
- Department of Nephrology, The Second People’s Hospital of NantongNantong 226001, Jiangsu, China
| | - Jing Zhu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
| | - Li Sun
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
| | - Qingming Qu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
| | - Su Liu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
| | - Siye Wang
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong UniversityNantong 226001, Jiangsu, China
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Hu F, Liang H, Xie J, Yuan M, Huang W, Lei Y, Li H, Lv L, Liu Q, Zhang J, Su W, Chen R, Wang Z, Chang YN, Li J, Wei C, Xing G, Xing G, Chen K. A novel shockwave-driven nanomotor composite microneedle transdermal delivery system for the localized treatment of osteoporosis: a basic science study. Int J Surg 2024; 110:6243-6256. [PMID: 39259829 PMCID: PMC11486941 DOI: 10.1097/js9.0000000000001280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 02/22/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUND Clinical protocols in osteoporosis treatment could not meet the requirement of increasing local bone mineral density. A local delivery system was brought in to fix this dilemma. The high-energy extracorporeal shock wave (ESW) can travel into the deep tissues with little heat loss. Hence, ESW-driven nanoparticles could be used for local treatment of osteoporosis. MATERIALS AND METHODS An ESW-actuated nanomotor (NM) sealed into microneedles (MNs) (ESW-NM-MN) was constructed for localized osteoporosis protection. The NM was made of calcium phosphate nanoparticles with a high Young's modulus, which allows it to absorb ESW energy efficiently and convert it into kinetic energy for solid tissue penetration. Zoledronic (ZOL), as an alternative phosphorus source, forms the backbone of the NM (ZOL-NM), leading to bone targeting and ESW-mediated drug release. RESULTS After the ZOL-NM is sealed into hyaluronic acid (HA)-made microneedles, the soluble MN tips could break through the stratum corneum, injecting the ZOL-NM into the skin. As soon as the ESW was applied, the ZOL-NM would absorb the ESW energy to move from the outer layer of skin into the deep tissue and be fragmented to release ZOL and Ca 2+ for anti-osteoclastogenesis and pro-osteogenesis. In vivo , the ZOL-NM increases localized bone parameters and reduces fracture risk, indicating its potential value in osteoporotic healing and other biomedical fields. CONCLUSION The ESW-mediated transdermal delivery platform (ESW-NM-MN) could be used as a new strategy to improve local bone mineral density and protect local prone-fracture areas.
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Affiliation(s)
- Fan Hu
- The Third Medical Center of Chinese People’s Liberation Army General Hospital
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
- The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Haojun Liang
- The Third Medical Center of Chinese People’s Liberation Army General Hospital
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Jing Xie
- State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing
| | - Meng Yuan
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Wanxia Huang
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Yinze Lei
- State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing
| | - Hao Li
- The Third Medical Center of Chinese People’s Liberation Army General Hospital
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
- The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Linwen Lv
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Qiuyang Liu
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Junhui Zhang
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Wenxi Su
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Ranran Chen
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Zhe Wang
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Ya-nan Chang
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Juan Li
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Cunfeng Wei
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Gengyan Xing
- The Third Medical Center of Chinese People’s Liberation Army General Hospital
- The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Gengmei Xing
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
| | - Kui Chen
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanosciences and Technology, Chinese Academy of Sciences
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Kou D, Chen Q, Wang Y, Xu G, Lei M, Tang X, Ni H, Zhang F. The application of extracorporeal shock wave therapy on stem cells therapy to treat various diseases. Stem Cell Res Ther 2024; 15:271. [PMID: 39183302 PMCID: PMC11346138 DOI: 10.1186/s13287-024-03888-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/16/2024] [Indexed: 08/27/2024] Open
Abstract
In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.
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Affiliation(s)
- Dongyan Kou
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Qingyu Chen
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Yujing Wang
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Guangyu Xu
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China
| | - Mingcheng Lei
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China
| | - Xiaobin Tang
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Hongbin Ni
- Department of Neurosurgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
| | - Feng Zhang
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China.
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Xiang JY, Kang L, Li ZM, Tseng SL, Wang LQ, Li TH, Li ZJ, Huang JZ, Yu NZ, Long X. Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing. World J Stem Cells 2024; 16:334-352. [PMID: 38690516 PMCID: PMC11056631 DOI: 10.4252/wjsc.v16.i4.334] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/20/2024] [Accepted: 03/12/2024] [Indexed: 04/25/2024] Open
Abstract
Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.
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Affiliation(s)
- Jie-Yu Xiang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lin Kang
- Biomedical Engineering Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
| | - Zi-Ming Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Song-Lu Tseng
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Li-Quan Wang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Tian-Hao Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zhu-Jun Li
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jiu-Zuo Huang
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Nan-Ze Yu
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao Long
- Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
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He Y, Zhang L, Huang S, Tang Y, Li Y, Li H, Chen G, Chen X, Zhang X, Zhao W, Deng F, Yu D. Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis. Int J Nanomedicine 2024; 19:3143-3166. [PMID: 38585472 PMCID: PMC10999216 DOI: 10.2147/ijn.s454718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/20/2024] [Indexed: 04/09/2024] Open
Abstract
Background The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.
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Affiliation(s)
- Yi He
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Lejia Zhang
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Siyuan Huang
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Yuquan Tang
- Zhujiang Hospital, Southern Medical University, Guangzhou, 510080, People’s Republic of China
| | - Yiming Li
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Hongyu Li
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Guanhui Chen
- Department of Stomatology, the Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, 518107, People’s Republic of China
| | - Xun Chen
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Xiliu Zhang
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Wei Zhao
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Feilong Deng
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
| | - Dongsheng Yu
- Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China
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Katebifar S, Arul M, Abdulmalik S, Yu X, Alderete JF, Kumbar SG. NOVEL HIGH-STRENGTH POLYESTER COMPOSITE SCAFFOLDS FOR BONE REGENERATION. POLYM ADVAN TECHNOL 2023; 34:3770-3791. [PMID: 38312483 PMCID: PMC10836609 DOI: 10.1002/pat.6178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 08/14/2023] [Indexed: 02/06/2024]
Abstract
Repair of critical sized bone defects, particularly in load-bearing areas, is a major clinical problem that requires surgical intervention and implantation of biological or engineered grafts. For load-bearing sites, it is essential to use engineered grafts that have both sufficient mechanical strength and appropriate pore properties to support bone repair and tissue regeneration. Unfortunately, the mechanical properties of such grafts are often compromised due to the creation of pores required to facilitate tissue ingrowth following implantation. To overcome the limitations associated with porous scaffolds and their reduced mechanical strength, we have developed a methodology for creating a solid structure that retains its bulk mechanical properties while also evolving into a porous structure in a biological environment through degradation and erosion. In this study, we utilized polyesters that have been approved by the FDA, including poly (lactic acid) (PLA), poly(glycolic acid) (PGA), their copolymer PLGA (PLGA, with a ratio of 85:15 and 50:50 of PLA:PGA), and poly(caprolactone) (PCL). These polymers and their ceramic composites with tricalcium phosphate (TCP) were compression molded into solid forms, which exhibited mechanical properties with compressive modulus as high as 2745 ± 364 MPa within the range of human trabecular bone and in the lower range of human cortical bone. The use of fast-degrading PLGA (50:50) and PGA as porogens allowed the formation of pores within the solid structures due to their degradation, and the TCP acts as a buffering agent to neutralize their acidic degradation byproducts. These scaffolds facilitated the growth of new blood vessels and tissue ingrowth in a subcutaneous implantation model. In addition, in a rat critical-sized mandibular bone defects these scaffolds supported bone growth with 70% of new bone volume fraction. Furthermore, the extent of bone regeneration was found to be higher for the scaffolds with bone morphogenic proteins (BMP2), indicating their suitability for bone repair and regeneration.
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Affiliation(s)
- Sara Katebifar
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, 06030, USA
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
| | - Michael Arul
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, 06030, USA
| | - Sama Abdulmalik
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, 06030, USA
| | - Xiaojun Yu
- Department of Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA
| | - Joseph F. Alderete
- Departments of Orthopedic Surgery, Brooke Army Medical Center, Joint Base San Antonio, Texas
| | - Sangamesh G. Kumbar
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, 06030, USA
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, 06269, USA
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Mai TP, Park JB, Nguyen HD, Min KA, Moon C. Current application of dexamethasone-incorporated drug delivery systems for enhancing bone formation. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2023; 53:643-665. [DOI: 10.1007/s40005-023-00629-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/31/2023] [Indexed: 03/10/2025]
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Wang H, Shi Y. Extracorporeal shock wave treatment for post‑surgical fracture nonunion: Insight into its mechanism, efficacy, safety and prognostic factors (Review). Exp Ther Med 2023; 26:332. [PMID: 37346403 PMCID: PMC10280326 DOI: 10.3892/etm.2023.12031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 04/21/2023] [Indexed: 06/23/2023] Open
Abstract
Post-surgical fracture nonunion (PSFN) represents the failure to achieve cortical continuity at radiological examination after an orthopedic operation, which causes a considerable disease burden in patients with fractures. As one of the traditional treatment modalities, surgical therapy is associated with a high fracture union rate; however, post-surgical complications are not negligible. Therefore, less invasive therapies are needed to improve the prognosis of patients with PSFN. Extracorporeal shock wave treatment (ESWT) is a noninvasive method that presents a similar efficacy profile and favorable safety profile compared with surgical treatment. However, the application and detailed mechanism of ESWT in patients with PSFN remain unclear. The present review focuses on the mechanism, efficacy, safety and prognostic factors of ESWT in patients with PSFN, aiming to provide a theoretical basis for its application and improve the prognosis of these patients.
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Affiliation(s)
- Haoyu Wang
- Department of Orthopaedics, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Yaxuan Shi
- Department of Internal Medicine (Bone Oncology), Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
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Khoramgah MS, Ghanbarian H, Ranjbari J, Ebrahimi N, Tabatabaei Mirakabad FS, Ahmady Roozbahany N, Abbaszadeh HA, Hosseinzadeh S. Repairing rat calvarial defects by adipose mesenchymal stem cells and novel freeze-dried three-dimensional nanofibrous scaffolds. BIOIMPACTS : BI 2023; 13:31-42. [PMID: 36817003 PMCID: PMC9923815 DOI: 10.34172/bi.2021.23711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 07/14/2021] [Accepted: 07/24/2021] [Indexed: 11/09/2022]
Abstract
Introduction: Treatment of critical-sized bone defects is challenging. Tissue engineering as a state-of-the-art method has been concerned with treating these non-self-healing bone defects. Here, we studied the potentials of new three-dimensional nanofibrous scaffolds (3DNS) with and without human adipose mesenchymal stem cells (ADSCs) for reconstructing rat critical-sized calvarial defects (CSCD). Methods: Scaffolds were made from 1- polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA) (PTFE/ PVA group), and 2- PTFE, PVA, and graphene oxide (GO) nanoparticle (PTFE/ PVA/GO group) and seeded by ADSCs and incubated in osteogenic media (OM). The expression of key osteogenic proteins including Runt-related transcription factor 2 (Runx2), collagen type Iα (COL Iα), osteocalcin (OCN), and osteonectin (ON) at days 14 and 21 of culture were evaluated by western blot and immunocytochemistry methods. Next, 40 selected rats were assigned to five groups (n=8) to create CSCD which will be filled by scaffolds or cell-containing scaffolds. The groups were denominated as the following order: Control (empty defects), PTFE/PVA (PTFE/PVA scaffolds implant), PTFE/PVA/GO (PTFE/PVA/GO scaffolds implant), PTFE/PVA/Cell group (PTFE/PVA scaffolds containing ADSCs implant), and PTFE/PVA/GO/Cell group (PTFE/PVA/GO scaffolds containing ADSCs implant). Six and 12 weeks after implantation, the animals were sacrificed and bone regeneration was evaluated using computerized tomography (CT), and hematoxylin-eosin (H&E) staining. Results: Based on the in-vitro study, expression of bone-related proteins in ADSCs seeded on PTFE/PVA/GO scaffolds were significantly higher than PTFE/PVA scaffolds and TCPS (P<0.05). Based on the in-vivo study, bone regeneration in CSCD were filled with PTFE/PVA/GO scaffolds containing ADSCs were significantly higher than PTFE/PVA scaffolds containing ADSCs (P<0.05). CSCD filled with cell-seeded scaffolds showed higher bone regeneration in comparison with CSCD filled with scaffolds only (P<0.05). Conclusion: The data provided evidence showing new freeze-dried nanofibrous scaffolds formed from hydrophobic (PTFE) and hydrophilic (PVA) polymers with and without GO provide a suitable environment for ADSCs due to the expression of bone-related proteins. ADSCs and GO in the implanted scaffolds had a distinct effect on the bone regeneration process in this in-vivo study.
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Affiliation(s)
- Maryam Sadat Khoramgah
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Ghanbarian
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Ranjbari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nilufar Ebrahimi
- Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Department of Biomedical Engineering, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Sadat Tabatabaei Mirakabad
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Navid Ahmady Roozbahany
- Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Private Practice, Bradford ON, Canada
| | - Hojjat Allah Abbaszadeh
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Corresponding authors: Hojjat-Allah Abbaszadeh, ; Simzar Hosseinzadeh,
| | - Simzar Hosseinzadeh
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Corresponding authors: Hojjat-Allah Abbaszadeh, ; Simzar Hosseinzadeh,
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10
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The Use of Newly Synthesized Composite Scaffolds for Bone Regeneration - A Review of Literature. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2022. [DOI: 10.2478/sjecr-2021-0071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Abstract
Bone tissue engineering is a multidisciplinary concept that combines biological and engineering principles to repair bone defects. Three elements that have a fundamental role in bone tissue engineering are scaffolds, stem cells, and bioactive components. Scaffolds mimic extracellular matrix functions and provide mechanical support for the new tissue formation. They are made of different natural and synthetic materials that can be categorized into three main groups: ceramics, metals, and polymers. Among them, synthetic polyesters and their combination with bioceramics, have been the most frequently used for scaffold fabrication. They could be potentially applied in clinical practice in the future as an alternative to the standard use of bone grafts but more studies are needed to assess their performance in the challenging conditions of human bone defects.
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11
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Shariati S, Seyedjafari E, Mahdavi FS, Maali A, Ferdosi-Shahandashti E. NiFe2O4/ZnO-coated Poly(L-Lactide) nanofibrous scaffold enhances osteogenic differentiation of human mesenchymal stem cells. Front Bioeng Biotechnol 2022; 10:1005028. [PMID: 36324893 PMCID: PMC9618592 DOI: 10.3389/fbioe.2022.1005028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 09/26/2022] [Indexed: 11/29/2022] Open
Abstract
Background: A combination of bioceramics and polymeric materials has attracted the research community’s interest in bone tissue engineering. These composites are essential to support cell attachment, proliferation, and osteogenesis differentiation, which are vital as a classic strategy in bone tissue engineering. In this study, NiFe2O4/ZnO-coated poly L-Lactide (PLLA) was employed as a scaffold to evaluate the osteogenic differentiation capability of human adipose tissue derived mesenchymal stem cells (hAMSCs). Material and methods: The electrospun PLLA nanofibers were fabricated, coated with nanocomposite (NiFe2O4/ZnO), and evaluated by the water contact angle (WCA), tensile test, attenuated total reflectance fourier-transform infrared (ATR-FTIR) and scanning electron microscopy (SEM). Then, the osteogenic differentiation potential of hAMSCs was assessed using NiFe2O4/ZnO-coated PLLA compared to tissue culture plastic (TCP) and a simple scaffold (PLLA) in vitro conditions. Results: The adhesion, proliferation, and differentiation of hAMSCs were supported by the mechanical and biological properties of the NiFe2O4/ZnO-coated PLLA scaffold, according to SEM and 4′,6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining patterns. During bone differentiation, Alkaline phosphatase (ALP) enzyme activity, biomineralization, calcium content, and osteogenic gene expression (ALP, Osteonectin, Osteocalcin, Collagen type I, and Runx2) were higher on NiFe2O4/ZnO-coated PLLA scaffold than on PLLA scaffold and TCP. Conclusion: Based on our results, the osteogenic differentiation of hAMSCs on the improved biological scaffold (PLLA coated with NiFe2O4/ZnO) could accelerate due to the stimulating effect of this nanocomposite.
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Affiliation(s)
- Shiva Shariati
- Department of Medical Biotechnology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
- Department of Medical Biotechnology, School of Advanced Medical Sciences, Golestan University of Medical Sciences, Golestan, Iran
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Ehsan Seyedjafari
- Department of Biotechnology, College of Sciences, University of Tehran, Tehran, Iran
- *Correspondence: Elaheh Ferdosi-Shahandashti, , ; Ehsan Seyedjafari,
| | - Fatemeh Sadat Mahdavi
- Department of Biotechnology, College of Sciences, University of Tehran, Tehran, Iran
| | - Amirhosein Maali
- Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
- Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Elaheh Ferdosi-Shahandashti
- Department of Medical Biotechnology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- *Correspondence: Elaheh Ferdosi-Shahandashti, , ; Ehsan Seyedjafari,
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12
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Zhou YH, Guo Y, Zhu JY, Tang CY, Zhao YQ, Zhou HD. Spheroid co-culture of BMSCs with osteocytes yields ring-shaped bone-like tissue that enhances alveolar bone regeneration. Sci Rep 2022; 12:14636. [PMID: 36030312 PMCID: PMC9420131 DOI: 10.1038/s41598-022-18675-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/17/2022] [Indexed: 11/09/2022] Open
Abstract
Oral and maxillofacial bone defects severely impair appearance and function, and bioactive materials are urgently needed for bone regeneration. Here, we spheroid co-cultured green fluorescent protein (GFP)-labeled bone marrow stromal cells (BMSCs) and osteocyte-like MLO-Y4 cells in different ratios (3:1, 2:1, 1:1, 1:2, 1:3) or as monoculture. Bone-like tissue was formed in the 3:1, 2:1, and 1:1 co-cultures and MLO-Y4 monoculture. We found a continuous dense calcium phosphate structure and spherical calcium phosphate similar to mouse femur with the 3:1, 2:1, and 1:1 co-cultures, along with GFP-positive osteocyte-like cells encircled by an osteoid-like matrix similar to cortical bone. Flake-like calcium phosphate, which is more mature than spherical calcium phosphate, was found with the 3:1 and 2:1 co-cultures. Phosphorus and calcium signals were highest with 3:1 co-culture, and this bone-like tissue was ring-shaped. In a murine tooth extraction model, implantation of the ring-shaped bone-like tissue yielded more bone mass, osteoid and mineralized bone, and collagen versus no implantation. This tissue fabricated by spheroid co-culturing BMSCs with osteocytes yields an internal structure and mineral composition similar to mouse femur and could promote bone formation and maturation, accelerating regeneration. These findings open the way to new strategies in bone tissue engineering.
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Affiliation(s)
- Ying-Hui Zhou
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.,Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Yue Guo
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.,Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Jia-Yu Zhu
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Chen-Yi Tang
- Department of Nutrition, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China
| | - Ya-Qiong Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Hou-De Zhou
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
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13
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Guo J, Hai H, Ma Y. Application of extracorporeal shock wave therapy in nervous system diseases: A review. Front Neurol 2022; 13:963849. [PMID: 36062022 PMCID: PMC9428455 DOI: 10.3389/fneur.2022.963849] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/21/2022] [Indexed: 11/29/2022] Open
Abstract
Neurological disorders are one of the leading causes of morbidity and mortality worldwide, and their therapeutic options remain limited. Recent animal and clinical studies have shown the potential of extracorporeal shock wave therapy (ESWT) as an innovative, safe, and cost-effective option to treat neurological disorders. Moreover, the cellular and molecular mechanism of ESWT has been proposed to better understand the regeneration and repairment of neurological disorders by ESWT. In this review, we discuss the principles of ESWT, the animal and clinical studies involving the use of ESWT to treat central and peripheral nervous system diseases, and the proposed cellular and molecular mechanism of ESWT. We also discuss the challenges encountered when applying ESWT to the human brain and spinal cord and the new potential applications of ESWT in treating neurological disorders.
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14
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Wuerfel T, Schmitz C, Jokinen LLJ. The Effects of the Exposure of Musculoskeletal Tissue to Extracorporeal Shock Waves. Biomedicines 2022; 10:biomedicines10051084. [PMID: 35625821 PMCID: PMC9138291 DOI: 10.3390/biomedicines10051084] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/01/2022] [Accepted: 05/04/2022] [Indexed: 12/14/2022] Open
Abstract
Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies address the molecular and cellular mechanisms of action of ESWT. However, to date, no uniform concept could be established on this matter. In the present study, we perform a systematic review of the effects of exposure of musculoskeletal tissue to extracorporeal shock waves (ESWs) reported in the literature. The key results are as follows: (i) compared to the effects of many other forms of therapy, the clinical benefit of ESWT does not appear to be based on a single mechanism; (ii) different tissues respond to the same mechanical stimulus in different ways; (iii) just because a mechanism of action of ESWT is described in a study does not automatically mean that this mechanism is relevant to the observed clinical effect; (iv) focused ESWs and radial ESWs seem to act in a similar way; and (v) even the most sophisticated research into the effects of exposure of musculoskeletal tissue to ESWs cannot substitute clinical research in order to determine the optimum intensity, treatment frequency and localization of ESWT.
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15
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Alvarez Echazú MI, Perna O, Olivetti CE, Antezana PE, Municoy S, Tuttolomondo MV, Galdopórpora JM, Alvarez GS, Olmedo DG, Desimone MF. Recent Advances in Synthetic and Natural Biomaterials-Based Therapy for Bone Defects. Macromol Biosci 2022; 22:e2100383. [PMID: 34984818 DOI: 10.1002/mabi.202100383] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/04/2021] [Indexed: 12/31/2022]
Abstract
Synthetic and natural biomaterials are a promising alternative for the treatment of critical-sized bone defects. Several parameters such as their porosity, surface, and mechanical properties are extensively pointed out as key points to recapitulate the bone microenvironment. Many biomaterials with this pursuit are employed to provide a matrix, which can supply the specific environment and architecture for an adequate bone growth. Nevertheless, some queries remain unanswered. This review discusses the recent advances achieved by some synthetic and natural biomaterials to mimic the native structure of bone and the manufacturing technology applied to obtain biomaterial candidates. The focus of this review is placed in the recent advances in the development of biomaterial-based therapy for bone defects in different types of bone. In this context, this review gives an overview of the potentialities of synthetic and natural biomaterials: polyurethanes, polyesters, hyaluronic acid, collagen, titanium, and silica as successful candidates for the treatment of bone defects.
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Affiliation(s)
- María I Alvarez Echazú
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina.,Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Anatomía Patológica, Marcelo T. de Alvear 2142 (1122), CABA, Argentina
| | - Oriana Perna
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Christian E Olivetti
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Pablo E Antezana
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Sofia Municoy
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - María V Tuttolomondo
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Juan M Galdopórpora
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Gisela S Alvarez
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
| | - Daniel G Olmedo
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Anatomía Patológica, Marcelo T. de Alvear 2142 (1122), CABA, Argentina.,CONICET, Consejo Nacional de Investigaciones Científicas y Técnicas, Godoy Cruz 2290, Buenos Aires, 1425, Argentina
| | - Martín F Desimone
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Junín 956, Piso 3°, (1113) Buenos Aires, Argentina., Universidad de Buenos Aires, Junín 956, Piso 3°, Buenos Aires, 1113, Argentina
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16
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Chen Q, Xia C, Shi B, Chen C, Yang C, Mao G, Shi F. Extracorporeal Shock Wave Combined with Teriparatide-Loaded Hydrogel Injection Promotes Segmental Bone Defects Healing in Osteoporosis. Tissue Eng Regen Med 2021; 18:1021-1033. [PMID: 34427911 DOI: 10.1007/s13770-021-00381-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/09/2021] [Accepted: 07/25/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Osteoporosis is a systemic bone disease characterized by decreased bone density and deterioration of bone microstructure, leading to an increased probability of fragility fractures. Once segmental bone defect occurs, it is easy to cause delayed union and nonunion. METHODS The aim of this study is to investigate the efficacy of extracorporeal shock wave (ESW) and teriparatide-loaded hydrogel (T-Gel) combined strategy on the cell activity and differentiation of osteoporosis derived bone marrow mesenchymal stem cells (OP-BMSCs) in vitro and bone regeneration in osteoporotic segmental bone defects in vivo. RESULTS In vitro, the strategy of combining ESW and T-Gel significantly enhanced OP-BMSCs proliferation, survival, migration, and osteogenic differentiation by up-regulating the alkaline phosphatase activity, mineralization, and expression of runt-related transcription factor-2, type I collagen, osteocalcin, and osteopontin. In the segmental bone defect models of osteoporotic rabbits, Micro-CT evaluation and histological observation demonstrated this ESW-combined with T-Gel injection significantly induced bone healing by enhancing the osteogenic activity of the local microenvironment in osteoporotic defects. CONCLUSION In conclusion, ESW-combined with T-Gel injection could regulate the poor osteogenic microenvironment in osteoporotic defects and show potential for enhancing fragility fractures healing.
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Affiliation(s)
- Qi Chen
- Department of Orthopedic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, People's Republic of China
| | - Chen Xia
- Department of Orthopedic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, People's Republic of China
| | - Binbin Shi
- Department of Orthopedic Surgery, Tongxiang First People's Hospital, Tongxiang, 314500, People's Republic of China
| | - Chuyong Chen
- Department of Orthopedic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, People's Republic of China
| | - Chen Yang
- Department of Orthopedic Surgery, No 1 People's Hospital of AkeSu, AkeSu, 843000, Xinjiang, People's Republic of China
| | - Guangfeng Mao
- Department of Orthopedic Surgery, The Third People Hospital of Zhuji, Shaoxing, 310014, People's Republic of China
| | - Fangfang Shi
- Department of Hematology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, People's Republic of China.
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Mesenchymal Stem Cells, Bioactive Factors, and Scaffolds in Bone Repair: From Research Perspectives to Clinical Practice. Cells 2021; 10:cells10081925. [PMID: 34440694 PMCID: PMC8392210 DOI: 10.3390/cells10081925] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/24/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cell-based therapies are promising tools for bone tissue regeneration. However, tracking cells and maintaining them in the site of injury is difficult. A potential solution is to seed the cells onto a biocompatible scaffold. Construct development in bone tissue engineering is a complex step-by-step process with many variables to be optimized, such as stem cell source, osteogenic molecular factors, scaffold design, and an appropriate in vivo animal model. In this review, an MSC-based tissue engineering approach for bone repair is reported. Firstly, MSC role in bone formation and regeneration is detailed. Secondly, MSC-based bone tissue biomaterial design is analyzed from a research perspective. Finally, examples of animal preclinical and human clinical trials involving MSCs and scaffolds in bone repair are presented.
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Jin S, Xia X, Huang J, Yuan C, Zuo Y, Li Y, Li J. Recent advances in PLGA-based biomaterials for bone tissue regeneration. Acta Biomater 2021; 127:56-79. [PMID: 33831569 DOI: 10.1016/j.actbio.2021.03.067] [Citation(s) in RCA: 141] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/29/2021] [Accepted: 03/31/2021] [Indexed: 12/14/2022]
Abstract
Bone regeneration is an interdisciplinary complex lesson, including but not limited to materials science, biomechanics, immunology, and biology. Having witnessed impressive progress in the past decades in the development of bone substitutes; however, it must be said that the most suitable biomaterial for bone regeneration remains an area of intense debate. Since its discovery, poly (lactic-co-glycolic acid) (PLGA) has been widely used in bone tissue engineering due to its good biocompatibility and adjustable biodegradability. This review systematically covers the past and the most recent advances in developing PLGA-based bone regeneration materials. Taking the different application forms of PLGA-based materials as the starting point, we describe each form's specific application and its corresponding advantages and disadvantages with many examples. We focus on the progress of electrospun nanofibrous scaffolds, three-dimensional (3D) printed scaffolds, microspheres/nanoparticles, hydrogels, multiphasic scaffolds, and stents prepared by other traditional and emerging methods. Finally, we briefly discuss the current limitations and future directions of PLGA-based bone repair materials. STATEMENT OF SIGNIFICANCE: As a key synthetic biopolymer in bone tissue engineering application, the progress of PLGA-based bone substitute is impressive. In this review, we summarized the past and the most recent advances in the development of PLGA-based bone regeneration materials. According to the typical application forms and corresponding crafts of PLGA-based substitutes, we described the development of electrospinning nanofibrous scaffolds, 3D printed scaffolds, microspheres/nanoparticles, hydrogels, multiphasic scaffolds and scaffolds fabricated by other manufacturing process. Finally, we briefly discussed the current limitations and proposed the newly strategy for the design and fabrication of PLGA-based bone materials or devices.
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Global Research Trends in Shock Wave for Therapy from 1990 to 2019: A Bibliometric and Visualized Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:3802319. [PMID: 33506013 PMCID: PMC7810560 DOI: 10.1155/2021/3802319] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 12/18/2020] [Accepted: 12/24/2020] [Indexed: 12/03/2022]
Abstract
Objective The publications of application and development of shock wave therapy showed consistent growth. The aim of this study was to investigate the global status and trends in the shock wave therapy field. Methods Publications about shock wave therapy from 1990 to 2019 were collected from the Web of Science database. The data were studied and indexed by using bibliometric methodology. For a visualized study, VOSviewer software was used to conduct bibliographic coupling analysis, coauthorship analysis, cocitation analysis, and co-occurrence analysis and to analyze the publication trends in shock wave therapy. Results A total of 3,274 articles were included. The number of publications was increasing per year globally. The USA made the largest contributions to the global research with the most citations (the highest h-index). The Journal of Urology had the highest publication number. The University of California System was the most contributive institution. Studies could be divided into seven clusters: urology, hepatology, cardiology, orthopedics, mechanism research of shock wave therapy, andrology, and principle of shock wave therapy. Orthopedics, andrology, and mechanism research of shock wave therapy could be the next hot topics in this field. Conclusions Base on the trends, shock wave therapy is the theme of a globally active research field which keeps developing and extends from bench to bedside.
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Lu CC, Chou SH, Shen PC, Chou PH, Ho ML, Tien YC. Extracorporeal shock wave promotes activation of anterior cruciate ligament remnant cells and their paracrine regulation of bone marrow stromal cells' proliferation, migration, collagen synthesis, and differentiation. Bone Joint Res 2020; 9:458-468. [PMID: 32832074 PMCID: PMC7418778 DOI: 10.1302/2046-3758.98.bjr-2019-0365.r1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Aims Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells' activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)' viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells' capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis.Cite this article: Bone Joint Res 2020;9(8):458-468.
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Affiliation(s)
- Cheng-Chang Lu
- Department of Orthopedics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Hsiang Chou
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Chih Shen
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Hsi Chou
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mei-Ling Ho
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yin-Chun Tien
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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21
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Golafshan N, Vorndran E, Zaharievski S, Brommer H, Kadumudi FB, Dolatshahi-Pirouz A, Gbureck U, van Weeren R, Castilho M, Malda J. Tough magnesium phosphate-based 3D-printed implants induce bone regeneration in an equine defect model. Biomaterials 2020; 261:120302. [PMID: 32932172 PMCID: PMC7116184 DOI: 10.1016/j.biomaterials.2020.120302] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 07/16/2020] [Accepted: 08/04/2020] [Indexed: 12/25/2022]
Abstract
One of the important challenges in bone tissue engineering is the development of biodegradable bone substitutes with appropriate mechanical and biological properties for the treatment of larger defects and those with complex shapes. Recently, magnesium phosphate (MgP) doped with biologically active ions like strontium (Sr2+) have shown to significantly enhance bone formation when compared with the standard calcium phosphate-based ceramics. However, such materials can hardly be shaped into large and complex geometries and more importantly lack the adequate mechanical properties for the treatment of load-bearing bone defects. In this study, we have fabricated bone implants through extrusion assisted three-dimensional (3D) printing of MgP ceramics modified with Sr2+ ions (MgPSr) and a medical-grade polycaprolactone (PCL) polymer phase. MgPSr with 30 wt% PCL (MgPSr-PCL30) allowed the printability of relevant size structures (>780 mm3) at room temperature with an interconnected macroporosity of approximately 40%. The printing resulted in implants with a compressive strength of 4.3 MPa, which were able to support up to 50 cycles of loading without plastic deformation. Notably, MgPSr-PCL30 scaffolds were able to promote in vitro bone formation in medium without the supplementation with osteo-inducing components. In addition, long-term in vivo performance of the 3D printed scaffolds was investigated in an equine tuber coxae model over 6 months. The micro-CT and histological analysis showed that implantation of MgPSr-PCL30 induced bone regeneration, while no bone formation was observed in the empty defects. Overall, the novel polymer-modified MgP ceramic material and extrusion-based 3D printing process presented here greatly improved the shape ability and load-bearing properties of MgP-based ceramics with simultaneous induction of new bone formation.
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Affiliation(s)
- Nasim Golafshan
- Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands
| | - Elke Vorndran
- Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Germany
| | - Stefan Zaharievski
- Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands
| | - Harold Brommer
- Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands
| | - Firoz Babu Kadumudi
- Technical University of Denmark, Department of Health Technology, 2800 Kgs, Lyngby, Denmark
| | - Alireza Dolatshahi-Pirouz
- Technical University of Denmark, Department of Health Technology, Center for Intestinal Absorption and Transport of Biopharmaceuticals, 2800 Kgs, Lyngby, Denmark; Department of Regenerative Biomaterials, Radboud University Medical Center, Philips van Leydenlaan 25, Nijmegen, 6525 EX, the Netherlands
| | - Uwe Gbureck
- Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Germany
| | - René van Weeren
- Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands
| | - Miguel Castilho
- Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands; Orthopedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
| | - Jos Malda
- Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands; Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands
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Liu DD, Ullah M, Concepcion W, Dahl JJ, Thakor AS. The role of ultrasound in enhancing mesenchymal stromal cell-based therapies. Stem Cells Transl Med 2020; 9:850-866. [PMID: 32157802 PMCID: PMC7381806 DOI: 10.1002/sctm.19-0391] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 02/17/2020] [Indexed: 12/18/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) have been a popular platform for cell-based therapy in regenerative medicine due to their propensity to home to damaged tissue and act as a repository of regenerative molecules that can promote tissue repair and exert immunomodulatory effects. Accordingly, a great deal of research has gone into optimizing MSC homing and increasing their secretion of therapeutic molecules. A variety of methods have been used to these ends, but one emerging technique gaining significant interest is the use of ultrasound. Sound waves exert mechanical pressure on cells, activating mechano-transduction pathways and altering gene expression. Ultrasound has been applied both to cultured MSCs to modulate self-renewal and differentiation, and to tissues-of-interest to make them a more attractive target for MSC homing. Here, we review the various applications of ultrasound to MSC-based therapies, including low-intensity pulsed ultrasound, pulsed focused ultrasound, and extracorporeal shockwave therapy, as well as the use of adjunctive therapies such as microbubbles. At a molecular level, it seems that ultrasound transiently generates a local gradient of cytokines, growth factors, and adhesion molecules that facilitate MSC homing. However, the molecular mechanisms underlying these methods are far from fully elucidated and may differ depending on the ultrasound parameters. We thus put forth minimal criteria for ultrasound parameter reporting, in order to ensure reproducibility of studies in the field. A deeper understanding of these mechanisms will enhance our ability to optimize this promising therapy to assist MSC-based approaches in regenerative medicine.
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Affiliation(s)
- Daniel D. Liu
- Interventional Regenerative Medicine and Imaging Laboratory, Department of RadiologyStanford UniversityPalo AltoCalifornia
| | - Mujib Ullah
- Interventional Regenerative Medicine and Imaging Laboratory, Department of RadiologyStanford UniversityPalo AltoCalifornia
| | | | - Jeremy J. Dahl
- Interventional Regenerative Medicine and Imaging Laboratory, Department of RadiologyStanford UniversityPalo AltoCalifornia
| | - Avnesh S. Thakor
- Interventional Regenerative Medicine and Imaging Laboratory, Department of RadiologyStanford UniversityPalo AltoCalifornia
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Dubey N, Ferreira JA, Malda J, Bhaduri SB, Bottino MC. Extracellular Matrix/Amorphous Magnesium Phosphate Bioink for 3D Bioprinting of Craniomaxillofacial Bone Tissue. ACS APPLIED MATERIALS & INTERFACES 2020; 12:23752-23763. [PMID: 32352748 PMCID: PMC7364626 DOI: 10.1021/acsami.0c05311] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Bioprinting, a promising field in regenerative medicine, holds great potential to create three-dimensional, defect-specific vascularized bones with tremendous opportunities to address unmet craniomaxillofacial reconstructive challenges. A cytocompatible bioink is a critical prerequisite to successfully regenerate functional bone tissue. Synthetic self-assembling peptides have a nanofibrous structure resembling the native extracellular matrix (ECM), making them an excellent bioink component. Amorphous magnesium phosphates (AMPs) have shown greater levels of resorption while maintaining high biocompatibility, osteoinductivity, and low inflammatory response, as compared to their calcium phosphate counterparts. Here, we have established a novel bioink formulation (ECM/AMP) that combines an ECM-based hydrogel containing 2% octapeptide FEFEFKFK and 98% water with AMP particles to realize high cell function with desirable bioprintability. We analyzed the osteogenic differentiation of dental pulp stem cells (DPSCs) encapsulated in the bioink, as well as in vivo bone regeneration, to define the potential of the formulated bioink as a growth factor-free bone-forming strategy. Cell-laden AMP-modified bioprinted constructs showed an improved cell morphology but similar cell viability (∼90%) compared to their AMP-free counterpart. In functional assays, the cell-laden bioprinted constructs modified with AMP exhibited a high level of mineralization and osteogenic gene expression without the use of growth factors, thus suggesting that the presence of AMP-triggered DPSCs' osteogenic differentiation. Cell-free ECM-based bioprinted constructs were implanted in vivo. In comparison with the ECM group, bone volume per total volume for ECM/1.0AMP was approximately 1.7- and 1.4-fold higher at 4 and 8 weeks, respectively. Further, a significant increase in the bone density was observed in ECM/1.0AMP from 4 to 8 weeks. These results demonstrate that the presence of AMP in the bioink significantly increased bone formation, thus showing promise for in situ bioprinting strategies. We foresee significant potential in translating this innovative bioink toward the regeneration of patient-specific bone tissue for regenerative dentistry.
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Affiliation(s)
- Nileshkumar Dubey
- Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, United States
| | - Jessica A Ferreira
- Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, United States
| | - Jos Malda
- Regenerative Medicine Center, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
- Department of Orthopedics, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, The Netherlands
| | - Sarit B Bhaduri
- Department of Mechanical, Industrial and Manufacturing Engineering and Surgery (Dentistry), University of Toledo, Toledo, Ohio 43606, United States
- EEC Division, Directorate of Engineering, The National Science Foundation, Alexandria, Virginia 22314, United States
| | - Marco C Bottino
- Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, United States
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Grumezescu V, Gherasim O, Negut I, Banita S, Holban AM, Florian P, Icriverzi M, Socol G. Nanomagnetite-embedded PLGA Spheres for Multipurpose Medical Applications. MATERIALS 2019; 12:ma12162521. [PMID: 31398805 PMCID: PMC6719237 DOI: 10.3390/ma12162521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/03/2019] [Accepted: 08/05/2019] [Indexed: 12/25/2022]
Abstract
We report on the synthesis and evaluation of biopolymeric spheres of poly(lactide-co-glycolide) containing different amounts of magnetite nanoparticles and Ibuprofen (PLGA-Fe3O4-IBUP), but also chitosan (PLGA-CS-Fe3O4-IBUP), to be considered as drug delivery systems. Besides morphological, structural, and compositional characterizations, the PLGA-Fe3O4-IBUP composite microspheres were subjected to drug release studies, performed both under biomimetically-simulated dynamic conditions and under external radiofrequency magnetic fields. The experimental data resulted by performing the drug release studies evidenced that PLGA-Fe3O4-IBUP microspheres with the lowest contents of Fe3O4 nanoparticles are optimal candidates for triggered drug release under external stimulation related to hyperthermia effect. The as-selected microspheres and their chitosan-containing counterparts were biologically assessed on macrophage cultures, being evaluated as biocompatible and bioactive materials that are able to promote cellular adhesion and proliferation. The composite biopolymeric spheres resulted in inhibited microbial growth and biofilm formation, as assessed against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans microbial strains. Significantly improved antimicrobial effects were reported in the case of chitosan-containing biomaterials, regardless of the microorganisms' type. The nanostructured composite biopolymeric spheres evidenced proper characteristics as prolonged and controlled drug release platforms for multipurpose biomedical applications.
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Affiliation(s)
- Valentina Grumezescu
- Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, 077125 Magurele, Romania.
| | - Oana Gherasim
- Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, 077125 Magurele, Romania
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, 011061 Bucharest, Romania
| | - Irina Negut
- Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, 077125 Magurele, Romania
| | - Stefan Banita
- Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, 077125 Magurele, Romania
| | - Alina Maria Holban
- Microbiology & Immunology Department, Faculty of Biology, University of Bucharest, 77206 Bucharest, Romania
| | - Paula Florian
- Ligand-Receptor Interactions Department, Institute of Biochemistry, Romanian Academy, 060031 Bucharest, Romania
| | - Madalina Icriverzi
- Ligand-Receptor Interactions Department, Institute of Biochemistry, Romanian Academy, 060031 Bucharest, Romania
| | - Gabriel Socol
- Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, 077125 Magurele, Romania.
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Stamatopoulos A, Stamatopoulos T, Gamie Z, Kenanidis E, Ribeiro RDC, Rankin KS, Gerrand C, Dalgarno K, Tsiridis E. Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice. J Bone Oncol 2019; 16:100231. [PMID: 30956944 PMCID: PMC6434099 DOI: 10.1016/j.jbo.2019.100231] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 03/14/2019] [Accepted: 03/18/2019] [Indexed: 12/12/2022] Open
Abstract
Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cells selectively. Recently, Mesenchymal Stromal Cells (MSCs) have been the subject of significant research in orthopaedic clinical practice through their use in regenerative medicine. Further research has been directed at the use of MSCs for more personalized bone sarcoma treatments, taking advantage of their wide range of potential biological functions, which can be augmented by using tissue engineering approaches to promote healing of large defects. In this review, we explore the use of MSCs in bone sarcoma treatment, by analyzing MSCs and tumour cell interactions, transduction of MSCs to target sarcoma, and their clinical applications on humans concerning bone regeneration after bone sarcoma extraction.
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Key Words
- 5-FC, 5-fluorocytosine
- AAT, a1-antitrypsin
- APCs, antigen presenting cells
- ASC, adipose-derived stromal/stem cells
- Abs, antibodies
- Ang1, angiopoietin-1
- BD, bone defect
- BMMSCs, bone marrow-derived mesenchymal stromal cells
- Biology
- Bone
- CAM, cell adhesion molecules
- CCL5, chemokine ligand 5
- CCR2, chemokine receptor 2
- CD, classification determinants
- CD, cytosine deaminase
- CLUAP1, clusterin associated protein 1
- CSPG4, Chondroitin sulfate proteoglycan 4
- CX3CL1, chemokine (C-X3-C motif) ligand 1
- CXCL12/CXCR4, C-X-C chemokine ligand 12/ C-X-C chemokine receptor 4
- CXCL12/CXCR7, C-X-C chemokine ligand 12/ C-X-C chemokine receptor 7
- CXCR4, chemokine receptor type 4
- Cell
- DBM, Demineralized Bone Marrow
- DKK1, dickkopf-related protein 1
- ECM, extracellular matrix
- EMT, epithelial-mesenchymal transition
- FGF-2, fibroblast growth factors-2
- FGF-7, fibroblast growth factors-7
- GD2, disialoganglioside 2
- HER2, human epidermal growth factor receptor 2
- HGF, hepatocyte growth factor
- HMGB1/RACE, high mobility group box-1 protein/ receptor for advanced glycation end-products
- IDO, indoleamine 2,3-dioxygenase
- IFN-α, interferon alpha
- IFN-β, interferon beta
- IFN-γ, interferon gamma
- IGF-1R, insulin-like growth factor 1 receptor
- IL-10, interleukin-10
- IL-12, interleukin-12
- IL-18, interleukin-18
- IL-1b, interleukin-1b
- IL-21, interleukin-21
- IL-2a, interleukin-2a
- IL-6, interleukin-6
- IL-8, interleukin-8
- IL11RA, Interleukin 11 Receptor Subunit Alpha
- MAGE, melanoma antigen gene
- MCP-1, monocyte chemoattractant protein-1
- MMP-2, matrix metalloproteinase-2
- MMP2/9, matrix metalloproteinase-2/9
- MRP, multidrug resistance protein
- MSCs, mesenchymal stem/stromal cells
- Mesenchymal
- NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
- OPG, osteoprotegerin
- Orthopaedic
- PBS, phosphate-buffered saline
- PDGF, platelet-derived growth factor
- PDX, patient derived xenograft
- PEDF, pigment epithelium-derived factor
- PGE2, prostaglandin E2
- PI3K/Akt, phosphoinositide 3-kinase/protein kinase B
- PTX, paclitaxel
- RANK, receptor activator of nuclear factor kappa-B
- RANKL, receptor activator of nuclear factor kappa-B ligand
- RBCs, red blood cells
- RES, reticuloendothelial system
- RNA, ribonucleic acid
- Regeneration
- SC, stem cells
- SCF, stem cells factor
- SDF-1, stromal cell-derived factor 1
- STAT-3, signal transducer and activator of transcription 3
- Sarcoma
- Stromal
- TAAs, tumour-associated antigens
- TCR, T cell receptor
- TGF-b, transforming growth factor beta
- TGF-b1, transforming growth factor beta 1
- TNF, tumour necrosis factor
- TNF-a, tumour necrosis factor alpha
- TRAIL, tumour necrosis factor related apoptosis-inducing ligand
- Tissue
- VEGF, vascular endothelial growth factor
- VEGFR, vascular endothelial growth factor receptor
- WBCs, white blood cell
- hMSCs, human mesenchymal stromal cells
- rh-TRAIL, recombinant human tumour necrosis factor related apoptosis-inducing ligand
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Affiliation(s)
- Alexandros Stamatopoulos
- Academic Orthopaedic Unit, Papageorgiou General Hospital, Aristotle University Medical School, West Ring Road of Thessaloniki, Pavlos Melas Area, N. Efkarpia, 56403 Thessaloniki, Greece
- Center of Orthopaedics and Regenerative Medicine (C.O.RE.), Center for Interdisciplinary Research and Innovation (C.I.R.I.), Aristotle University Thessaloniki, Greece
| | - Theodosios Stamatopoulos
- Academic Orthopaedic Unit, Papageorgiou General Hospital, Aristotle University Medical School, West Ring Road of Thessaloniki, Pavlos Melas Area, N. Efkarpia, 56403 Thessaloniki, Greece
- Center of Orthopaedics and Regenerative Medicine (C.O.RE.), Center for Interdisciplinary Research and Innovation (C.I.R.I.), Aristotle University Thessaloniki, Greece
| | - Zakareya Gamie
- Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
| | - Eustathios Kenanidis
- Academic Orthopaedic Unit, Papageorgiou General Hospital, Aristotle University Medical School, West Ring Road of Thessaloniki, Pavlos Melas Area, N. Efkarpia, 56403 Thessaloniki, Greece
- Center of Orthopaedics and Regenerative Medicine (C.O.RE.), Center for Interdisciplinary Research and Innovation (C.I.R.I.), Aristotle University Thessaloniki, Greece
| | - Ricardo Da Conceicao Ribeiro
- School of Mechanical and Systems Engineering, Stephenson Building, Claremont Road, Newcastle upon Tyne NE1 7RU, UK
| | - Kenneth Samora Rankin
- Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
| | - Craig Gerrand
- Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, HA7 4LP, UK
| | - Kenneth Dalgarno
- School of Mechanical and Systems Engineering, Stephenson Building, Claremont Road, Newcastle upon Tyne NE1 7RU, UK
| | - Eleftherios Tsiridis
- Academic Orthopaedic Unit, Papageorgiou General Hospital, Aristotle University Medical School, West Ring Road of Thessaloniki, Pavlos Melas Area, N. Efkarpia, 56403 Thessaloniki, Greece
- Center of Orthopaedics and Regenerative Medicine (C.O.RE.), Center for Interdisciplinary Research and Innovation (C.I.R.I.), Aristotle University Thessaloniki, Greece
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Takahashi T, Nakagawa K, Tada S, Tsukamoto A. Low-energy shock waves evoke intracellular Ca 2+ increases independently of sonoporation. Sci Rep 2019; 9:3218. [PMID: 30824781 PMCID: PMC6397190 DOI: 10.1038/s41598-019-39806-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 11/14/2018] [Indexed: 12/12/2022] Open
Abstract
Low-energy shock waves (LESWs) accelerate the healing of a broad range of tissue injuries, including angiogenesis and bone fractures. In cells, LESW irradiations enhance gene expression and protein synthesis. One probable mechanism underlying the enhancements is mechanosensing. Shock waves also can induce sonoporation. Thus, sonoporation is another probable mechanism underlying the enhancements. It remains elusive whether LESWs require sonoporation to evoke cellular responses. An intracellular Ca2+ increase was evoked with LESW irradiations in endothelial cells. The minimum acoustic energy required for sufficient evocation was 1.7 μJ/mm2. With the same acoustic energy, sonoporation, by which calcein and propidium iodide would become permeated, was not observed. It was found that intracellular Ca2+ increases evoked by LESW irradiations do not require sonoporation. In the intracellular Ca2+ increase, actin cytoskeletons and stretch-activated Ca2+ channels were involved; however, microtubules were not. In addition, with Ca2+ influx through the Ca2+ channels, the Ca2+ release through the PLC-IP3-IP3R cascade contributed to the intracellular Ca2+ increase. These results demonstrate that LESW irradiations can evoke cellular responses independently of sonoporation. Rather, LESW irradiations evoke cellular responses through mechanosensing.
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Affiliation(s)
- Toru Takahashi
- Department of Applied Physics, Graduate School of Science and Engineering, National Defense Academy, Hashirimizu 1-10-20, Yokosuka, Kanagawa, 239-8686, Japan
| | - Keiichi Nakagawa
- Department of Precise Engineering, Graduate School of Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8656, Japan
| | - Shigeru Tada
- Department of Applied Physics, Graduate School of Science and Engineering, National Defense Academy, Hashirimizu 1-10-20, Yokosuka, Kanagawa, 239-8686, Japan
| | - Akira Tsukamoto
- Department of Applied Physics, Graduate School of Science and Engineering, National Defense Academy, Hashirimizu 1-10-20, Yokosuka, Kanagawa, 239-8686, Japan.
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Trombetta RP, Ninomiya MJ, El-Atawneh IM, Knapp EK, de Mesy Bentley KL, Dunman PM, Schwarz EM, Kates SL, Awad HA. Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis. Pharmaceutics 2019; 11:E94. [PMID: 30813284 PMCID: PMC6410209 DOI: 10.3390/pharmaceutics11020094] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/12/2019] [Accepted: 02/17/2019] [Indexed: 12/15/2022] Open
Abstract
Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision.
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Affiliation(s)
- Ryan P Trombetta
- Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
| | - Mark J Ninomiya
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
- Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
| | - Ihab M El-Atawneh
- Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
| | - Emma K Knapp
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
- Department of Orthopedics, University of Rochester Medical Center, Rochester, NY 14642, USA.
| | - Karen L de Mesy Bentley
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
- Department of Pathology & Laboratory Medicine, University of Rochester, Rochester, NY 14642, USA.
- Department of Orthopedics, University of Rochester Medical Center, Rochester, NY 14642, USA.
| | - Paul M Dunman
- Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
| | - Edward M Schwarz
- Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
- Department of Pathology & Laboratory Medicine, University of Rochester, Rochester, NY 14642, USA.
- Department of Orthopedics, University of Rochester Medical Center, Rochester, NY 14642, USA.
| | - Stephen L Kates
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
- Department of Orthopaedic Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA 0153, USA.
| | - Hani A Awad
- Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA.
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28
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Allen MJ. What's New in Musculoskeletal Basic Science. J Bone Joint Surg Am 2018; 100:2082-2086. [PMID: 30516632 DOI: 10.2106/jbjs.18.01055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Matthew J Allen
- Department of Veterinary Medicine, Surgical Discovery Centre, University of Cambridge, Cambridge, United Kingdom
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29
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Wang Q, Zhao G, Xing Z, Zhan J, Ma J. Comparative evaluation of the osteogenic capacity of human mesenchymal stem cells from bone marrow and umbilical cord tissue. Exp Ther Med 2018; 17:764-772. [PMID: 30651861 DOI: 10.3892/etm.2018.6975] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 09/27/2018] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been extensively investigated in the field of regenerative medicine. Human bone MSCs (BMSCs) have become a common type of seed cell for bone tissue engineering. However, the viability and cell number of BMSCs are negatively correlated with donor age, and as the extraction process is painful, this method has not been widely used. As human umbilical cord MSCs (UCMSCs) may be harvested inexpensively and inexhaustibly, the present study evaluated and compared the regenerative potential of UCMSCs and BMSCs to determine whether UCMSCs may be used as a novel cell type for bone regeneration. In the present study, the proliferation and osteogenic capacity of BMSCs and UCMSCs was compared in vitro. BMSCs and UCMSCs were respectively combined with biofunctionalized macroporous calcium phosphate cement, and their bone regenerative potentials were determined by investigating their capacity for ectopic bone formation in a nude mouse model as well as their efficacy in a rat model of tibia bone defect. The extent of bone regeneration was examined by X-ray, histological and immunohistochemical analyses. The results revealed that UCMSCs exhibited a good osteogenic differentiation potential, similarly to that of BMSCs, and that UCMSCs were able to contribute to the regeneration of bone and blood vessels. Furthermore, no significant differences were identified between BMSCs and UCMSCs in terms of their bone regenerative effect.
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Affiliation(s)
- Qian Wang
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Gang Zhao
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Zijun Xing
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Juming Zhan
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
| | - Jie Ma
- Institute of Biomedical Science, Tianjin Kang Ting Biological Engineering Co., Ltd., Tianjin 300385, P.R. China
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30
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Garcia Garcia A, Hébraud A, Duval JL, Wittmer CR, Gaut L, Duprez D, Egles C, Bedoui F, Schlatter G, Legallais C. Poly(ε-caprolactone)/Hydroxyapatite 3D Honeycomb Scaffolds for a Cellular Microenvironment Adapted to Maxillofacial Bone Reconstruction. ACS Biomater Sci Eng 2018; 4:3317-3326. [PMID: 33435068 DOI: 10.1021/acsbiomaterials.8b00521] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The elaboration of biomimetic materials inspired from the specific structure of native bone is one the main goal of tissue engineering approaches. To offer the most appropriate environment for bone reconstruction, we combined electrospinning and electrospraying to elaborate an innovative scaffold composed of alternating layers of polycaprolactone (PCL) and hydroxyapatite (HA). In our approach, the electrospun PCL was shaped into a honeycomb-like structure with an inner diameter of 160 μm, capable of providing bone cells with a 3D environment while ensuring the material biomechanical strength. After 5 days of culture without any differentiation factor, the murine embryonic cell line demonstrated excellent cell viability on contact with the PCL-HA structures as well as active colonization of the scaffold. The cell differentiation, as tested by RT-qPCR, revealed a 6-fold increase in the expression of the RNA of the Bglap involved in bone mineralization as compared to a classical 2D culture. This differentiation of the cells into osteoblasts was confirmed by alkaline phosphatase staining of the scaffold cultivated with the cell lineage. Later on, organotypic cultures of embryonic bone tissues showed the high capacity of the PCL-HA honeycomb structure to guide the migration of differentiated bone cells throughout the cavities and the ridge of the biomaterial, with a colonization surface twice as big as that of the control. Taken together, our results indicate that PCL-HA honeycomb structures are biomimetic supports that promotes in vitro osteocompatibility, osteoconduction, and osteoinduction and could be suitable for being used for bone reconstruction in complex situations such as the repair of maxillofacial defects.
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Affiliation(s)
- Alejandro Garcia Garcia
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Rue du Dr. Schweitzer, 60200 Compiegne, France
| | - Anne Hébraud
- ICPEES UMR 7515, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé, CNRS, Université de Strasbourg, 25 Rue Becquerel, 67087 Strasbourg, France
| | - Jean-Luc Duval
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Rue du Dr. Schweitzer, 60200 Compiegne, France
| | - Corinne R Wittmer
- ICPEES UMR 7515, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé, CNRS, Université de Strasbourg, 25 Rue Becquerel, 67087 Strasbourg, France
| | - Ludovic Gaut
- CNRS, UMR 7622, IBPS-Developmental Biology Laboratory, Sorbonne Université, 7-9 Quai Saint Bernard, 75005 Paris, France.,Inserm U1156, 7-9 Quai Saint Bernard, 75005 Paris, France
| | - Delphine Duprez
- CNRS, UMR 7622, IBPS-Developmental Biology Laboratory, Sorbonne Université, 7-9 Quai Saint Bernard, 75005 Paris, France.,Inserm U1156, 7-9 Quai Saint Bernard, 75005 Paris, France
| | - Christophe Egles
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Rue du Dr. Schweitzer, 60200 Compiegne, France
| | - Fahmi Bedoui
- Roberval Laboratory for Mechanics, Sorbonne Universités, Université de Technologie de Compiègne, Rue du Dr. Schweitzer, 60200 Compiègne, France
| | - Guy Schlatter
- ICPEES UMR 7515, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé, CNRS, Université de Strasbourg, 25 Rue Becquerel, 67087 Strasbourg, France
| | - Cecile Legallais
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Rue du Dr. Schweitzer, 60200 Compiegne, France
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31
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Moradi SL, Golchin A, Hajishafieeha Z, Khani M, Ardeshirylajimi A. Bone tissue engineering: Adult stem cells in combination with electrospun nanofibrous scaffolds. J Cell Physiol 2018; 233:6509-6522. [DOI: 10.1002/jcp.26606] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 03/16/2018] [Indexed: 01/09/2023]
Affiliation(s)
- Sadegh L. Moradi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Ali Golchin
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Zahra Hajishafieeha
- Department of Microbiology Qazvin University of Medical Sciences Qazvin Iran
| | - Mohammad‐Mehdi Khani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Abdolreza Ardeshirylajimi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
- Edward A. Doisy Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine Saint Louis MO
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32
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Vanderburgh JP, Guelcher SA, Sterling JA. 3D bone models to study the complex physical and cellular interactions between tumor and the bone microenvironment. J Cell Biochem 2018; 119:5053-5059. [PMID: 29600556 DOI: 10.1002/jcb.26774] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 02/02/2018] [Indexed: 12/13/2022]
Abstract
As the complexity of interactions between tumor and its microenvironment has become more evident, a critical need to engineer in vitro models that veritably recapitulate the 3D microenvironment and relevant cell populations has arisen. This need has caused many groups to move away from the traditional 2D, tissue culture plastic paradigms in favor of 3D models with materials that more closely replicate the in vivo milieu. Creating these 3D models remains a difficult endeavor for hard and soft tissues alike as the selection of materials, fabrication processes, and optimal conditions for supporting multiple cell populations makes model development a nontrivial task. Bone tissue in particular is uniquely difficult to model in part because of the limited availability of materials that can accurately capture bone rigidity and architecture, and also due to the dependence of both bone and tumor cell behavior on mechanical signaling. Additionally, the bone is a complex cellular microenvironment with multiple cell types present, including relatively immature, pluripotent cells in the bone marrow. This prospect will focus on the current 3D models in development to more accurately replicate the bone microenvironment, which will help facilitate improved understanding of bone turnover, tumor-bone interactions, and drug response. These studies have demonstrated the importance of accurately modelling the bone microenvironment in order to fully understand signaling and drug response, and the significant effects that model properties such as architecture, rigidity, and dynamic mechanical factors have on tumor and bone cell response.
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Affiliation(s)
- Joseph P Vanderburgh
- Vanderbilt Center for Bone Biology, Nashville, Tennessee.,Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee
| | - Scott A Guelcher
- Vanderbilt Center for Bone Biology, Nashville, Tennessee.,Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee.,Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.,Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee
| | - Julie A Sterling
- Vanderbilt Center for Bone Biology, Nashville, Tennessee.,Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.,Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.,Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee
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33
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Liu Y, Chen X, Guo A, Liu S, Hu G. Quantitative Assessments of Mechanical Responses upon Radial Extracorporeal Shock Wave Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2018; 5:1700797. [PMID: 29593978 PMCID: PMC5867036 DOI: 10.1002/advs.201700797] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Indexed: 05/03/2023]
Abstract
Although radial extracorporeal shock wave therapy (rESWT) has been widely used to treat orthopedic disorders with promising clinical results, rESWT largely relies on clinicians' personal experiences and arbitrary judgments, without knowing relationships between administration doses and effective doses at target sites. In fact, practitioners lack a general and reliable way to assess propagation and distribution of pressure waves inside biological tissues quantitatively. This study develops a methodology to combine experimental measurements and computational simulations to obtain pressure fields from rESWT through calibrating and validating computational models with experimental measurements. Wave pressures at the bottom of a petri dish and inside biological tissues are measured, respectively, by attaching and implanting flexible membrane sensors. Detailed wave dynamics are simulated through explicit finite element analyses. The data decipher that waves from rESWT radiate directionally and can be modeled as acoustic waves generated from a vibrating circular piston. Models are thus established to correlate pressure amplitudes at the bottom of petri dishes and in the axial direction of biological tissues. Additionally, a pilot simulation upon rESWT for human lumbar reveals a detailed and realistic pressure field mapping. This study will open a new avenue of personalized treatment planning and mechanism research for rESWT.
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Affiliation(s)
- Yajun Liu
- Orthopedic Shock Wave Treatment CenterSpine Surgery DepartmentBeijing Jishuitan HospitalBeijing100035China
| | - Xiaodong Chen
- The State Key Laboratory of Nonlinear MechanicsBeijing Key Laboratory of Engineered Construction and MechanobiologyInstitute of MechanicsChinese Academy of SciencesBeijing100190China
- School of Engineering ScienceUniversity of Chinese Academy of SciencesBeijing100049China
| | - Anyi Guo
- Orthopedic Shock Wave Treatment CenterSpine Surgery DepartmentBeijing Jishuitan HospitalBeijing100035China
| | - Sijin Liu
- The State Key Laboratory of Environmental Chemistry and EcotoxicologyResearch Center for Eco‐Environmental SciencesChinese Academy of SciencesBeijing100085China
| | - Guoqing Hu
- The State Key Laboratory of Nonlinear MechanicsBeijing Key Laboratory of Engineered Construction and MechanobiologyInstitute of MechanicsChinese Academy of SciencesBeijing100190China
- School of Engineering ScienceUniversity of Chinese Academy of SciencesBeijing100049China
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34
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Huang Z, Xu J, Chen J, Chen H, Wang H, Huang Z, Chen Y, Lu X, Lu F, Hu J. Photoacoustic stimulation promotes the osteogenic differentiation of bone mesenchymal stem cells to enhance the repair of bone defect. Sci Rep 2017; 7:15842. [PMID: 29158525 PMCID: PMC5696557 DOI: 10.1038/s41598-017-15879-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 10/30/2017] [Indexed: 02/05/2023] Open
Abstract
The aim of this study was to evaluate the direct photoacoustic (PA) effect on bone marrow mesenchymal stem cells (BMSCs) which is a key cell source for osteogenesis. As scaffold is also an indispensable element for tissue regeneration, here we firstly fabricated a composited sheet using polylactic-co-glycolic acid (PLGA) mixing with graphene oxide (GO). BMSCs were seeded on the PLGA-GO sheets and received PA treatment in vitro for 3, 9 and 15 days, respectively. Then the BMSCs were harvested and subjected to assess alkaline phosphatase (ALP) activity, calcium content and osteopontin (OPN) on 3, 9 and 15 days. For in vivo study, PLGA-GO sheet seeded with BMSCs after in vitro PA stimulation for 9 days were implanted to repair the bone defect established in the femoral mid-shaft of Sprague-Dawley rat. PLGA-GO group with PA pretreatment showed promising outcomes in terms of the expression of ALP, OPN, and calcium content, thus enhanced the repair of bone defect. In conclusion, we have developed an alternative approach to enhance the repair of bone defect by making good use of the beneficial effect of PA.
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Affiliation(s)
- Zebin Huang
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Jiankun Xu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
- Department of Orthopaedics and Traumatology, Prince of Wales Hospital, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jiebin Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Hongjiang Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Hailong Wang
- Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Guangdong Province, China
| | - Zhonglian Huang
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Youbin Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Xiaolin Lu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Fushen Lu
- Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Guangdong Province, China.
| | - Jun Hu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China.
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35
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Hernandez I, Kumar A, Joddar B. A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering. Gels 2017; 3. [PMID: 29354645 PMCID: PMC5770986 DOI: 10.3390/gels3030026] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL) filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC) to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF) showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.
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Affiliation(s)
- Ivan Hernandez
- Inspired Materials & Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, El Paso, TX 79968, USA;
| | - Alok Kumar
- Inspired Materials & Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, El Paso, TX 79968, USA;
- Correspondence:
| | - Binata Joddar
- Inspired Materials & Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, El Paso, TX 79968, USA;
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA;
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