|
1
|
Cai Y, Chen Y, Li H, Wang Y, Zhang G, Liang J, Lv L, Huang Y, Zhang W, Dang X, Fang X, Wang Y. Fabrication of GDNF-Gel/HA-Mg nerve conduit and its role in repairing peripheral nerve defects. Mater Today Bio 2025; 32:101764. [PMID: 40290886 PMCID: PMC12022700 DOI: 10.1016/j.mtbio.2025.101764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/05/2025] [Accepted: 04/11/2025] [Indexed: 04/30/2025] Open
Abstract
Background Magnesium (Mg) and its alloys are receiving increasing attention in peripheral nerve regeneration, but they were limited due to the low corrosion resistance and rapid degradation. In this study, GDNF-Gel/HA-Mg was prepared and its value in peripheral nerve defects repairment was explored both in vitro and in vivo. Methods A hydroxyapatite (HA) coating was first applied to the pure Mg surface, followed by the formation of gelatin methacrylate (GelMA) loaded with glial cell-derived neurotrophic factor (GDNF) on the HA-coated Mg surface. GDNF-Gel/HA-Mg corrosion resistance was explored. The effect of GDNF-Gel/HA-Mg conduit on Schwann cell proliferation and migration abilities were investigated. And sciatic nerve defects models were established to explored the role of GDNF-Gel/HA-Mg conduit in peripheral nerve defects repairment. Findings The electrochemical, immersion, and hydrogen evolution experiments indicated that the corrosion resistance in phosphate buffer saline (PBS) of pure Mg was significantly improved by the GDNF-Gel/HA coating. Cell cycle, Cell Count Kit-8 (CCK-8), and clone formation assays indicated that GDNF-Gel/HA-Mg promoted the proliferation of Schwann cells. Scratch and Transwell assay results demonstrated that GDNF-Gel/HA-Mg promoted Schwann cell migration ability dose-dependently. GDNF-Gel/HA-Mg was found to enhance the secretion of nerve growth factor (NGF) and the expression of p75NTR. Flow cytometry results showed that GDNF-Gel/HA-Mg could reduce H2O2-induced oxidative stress and Schwann cell apoptosis. GDNF-Gel/HA-Mg inhibited M1 macrophage polarization while facilitated M2 macrophage polarization in a concentration-dependent manner. The in vivo studies demonstrated that GDNF-Gel/HA-Mg conduit could significantly promote the regeneration and myelination of sciatic nerve, as well as the recovery of denervated gastrocnemius atrophy. Interpretation The GDNF-Gel/HA-Mg conduit prepared in this study exhibited good hydrophilicity and corrosion resistance and greatly enhanced the proliferation, migration, and invasion abilities of Schwann cells, as well as peripheral nerve regeneration.
Collapse
Affiliation(s)
- Yuanqing Cai
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Yi Chen
- College of Materials Science & Engineering, National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing, 400045, China
| | - Hongyan Li
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Yanyu Wang
- Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, China
| | - Guangyang Zhang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710006, China
| | - Jialin Liang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710006, China
| | - Leifeng Lv
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710006, China
| | - Ying Huang
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Wenming Zhang
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Xiaoqian Dang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710006, China
| | - Xinyu Fang
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Yong Wang
- College of Materials Science & Engineering, National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing, 400045, China
| |
Collapse
|
|
2
|
Kim H, Kwon J, Kim H, Lee S, Kim S, Lee JY, Rahaman KA, Kim T, Lee H, Ok MR, Chung S, Han HS, Kim YC. Controlled Magnesium Ion Delivery via Mg-Sputtered Nerve Conduit for Enhancing Peripheral Nerve Regeneration. Adv Healthc Mater 2025:e2500063. [PMID: 40289425 DOI: 10.1002/adhm.202500063] [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: 01/05/2025] [Revised: 04/07/2025] [Indexed: 04/30/2025]
Abstract
Autologous nerve grafting remains the gold standard for treating peripheral nerve injuries; however, it is constrained by limited donor nerve availability, the need for secondary surgeries, and sensory loss at the donor site. Biodegradable material-based nerve conduits have emerged as a promising alternative to address these limitations and enhance nerve regeneration. Among these materials, magnesium stands out due to its exceptional biocompatibility, biofunctionality, and neuroprotective properties. Despite its potential, magnesium's rapid corrosion rate and the need for controlled ion release necessitate advanced modifications, such as the development of Mg alloys. However, these approaches often face challenges, including viability concerns and material hardness, which can hinder nerve repair and damage surrounding tissues. In this study, a novel solution is introduced by sputtering magnesium onto a soft collagen sheet, achieving controlled magnesium ion release while preserving the material's nerve-like softness. This Mg-sputtered collagen sheet demonstrates excellent biocompatibility and significantly improves axon regeneration, muscle reinnervation, and functional recovery in a sciatic nerve defect model. These findings highlight the potential of an innovative Mg-based biodegradable nerve conduit, offering transformative applications across various medical fields.
Collapse
Affiliation(s)
- Hyewon Kim
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Department of Biomicro System Technology, Korea University, Seoul, 02841, Republic of Korea
| | - Jieun Kwon
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Hyeok Kim
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Sunhee Lee
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Seongchan Kim
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, 52828, Republic of Korea
| | - Ji-Young Lee
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, Republic of Korea
| | - Khandoker Asiqur Rahaman
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Taeyeon Kim
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Hyojin Lee
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- SKKU-KIST, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Gyeonggi, Suwon, 16419, South Korea
| | - Myoung-Ryul Ok
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, Republic of Korea
| | - Seok Chung
- Department of Biomicro System Technology, Korea University, Seoul, 02841, Republic of Korea
| | - Hyung-Seop Han
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, Republic of Korea
| | - Yu-Chan Kim
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, Republic of Korea
| |
Collapse
|
|
3
|
Yao Z, Chen Z, He X, Wei Y, Qian J, Zong Q, He S, Song L, Ma L, Lin S, Li L, Xue L, Fu SN, Zhang J, Li Y, Wang D. Bioactive MgO/MgCO3/Polycaprolactone Multi-gradient Fibers Facilitate Peripheral Nerve Regeneration by Regulating Schwann Cell Function and Activating Wingless/Integrase-1 Signaling. ADVANCED FIBER MATERIALS 2025; 7:315-337. [DOI: 10.1007/s42765-024-00489-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 09/29/2024] [Indexed: 01/12/2025]
Abstract
Abstract
Peripheral nerve defects present complex orthopedic challenges with limited efficacy of clinical interventions. The inadequate proliferation and dysfunction of Schwann cells within the nerve scaffold impede the effectiveness of nerve repair. Our previous studies suggested the effectiveness of a magnesium-encapsulated bioactive hydrogel in repairing nerve defects. However, its rapid release of magnesium ions limited its efficacy to long-term nerve regeneration, and its molecular mechanism remains unclear. This study utilized electrospinning technology to fabricate a MgO/MgCO3/polycaprolactone (PCL) multi-gradient nanofiber membrane for peripheral nerve regeneration. Our findings indicated that by carefully adjusting the concentration or proportion of rapidly degradable MgO and slowly degradable MgCO3, as well as the number of electrospun layers, the multi-gradient scaffold effectively sustained the release of Mg2+ over a period of 6 weeks. Additionally, this study provided insight into the mechanism of Mg2+-induced nerve regeneration and confirmed that Mg2+ effectively promoted Schwann cell proliferation, migration, and transition to a repair phenotype. By employing transcriptome sequencing technology, the study identified the Wingless/integrase-1 (Wnt) signaling pathway as a crucial mechanism influencing Schwann cell function during nerve regeneration. After implantation in 10 mm critically sized nerve defects in rats, the MgO/MgCO3/PCL multi-gradient nanofiber combined with a 3D-engineered PCL nerve conduit showed enhanced axonal regeneration, remyelination, and reinnervation of muscle tissue 12 weeks post-surgery. In conclusion, this study successfully developed an innovative multi-gradient long-acting MgO/MgCO3/PCL nanofiber with a tunable Mg2+ release property, which underscored the molecular mechanism of magnesium-encapsulated biomaterials in treating nervous system diseases and established a robust theoretical foundation for future clinical translation.
Graphical abstract
Collapse
|
|
4
|
Lyu W, Zhang Y, Ding S, Li X, Sun T, Luo J, Wang J, Li J, Li L. A bilayer hydrogel mimicking the periosteum-bone structure for innervated bone regeneration. J Mater Chem B 2024; 12:11187-11201. [PMID: 39356311 DOI: 10.1039/d4tb01923g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2024]
Abstract
In bone tissue, nerves are primarily located in the periosteum and play an indispensable role in bone defect repair. However, most bone tissue engineering approaches ignored the reconstruction of the nerve network. Herein, we aimed to develop a bilayer hydrogel simulating periosteum-bone structure to induce innervated bone regeneration. The bottom "bone" layer consisted of gelatin methacryloyl (GelMA), poly(ethylene glycol) diacrylate (PEGDA), and nano-hydroxyapatite (nHA), whereas the upper "periosteum" layer consisted of GelMA, sodium alginate (SA) and MgCl2. The mechanical properties of the upper and bottom hydrogels were designed to be suitable for neurogenesis and osteogenesis, respectively. Besides, Mg2+ from the "periosteum" layer released at the early stage (within 7 d), which aligned with the optimal time window for nerve regeneration and osteogenic related neuropeptide release. Simultaneously, the prevention of long-term Mg2+ release (after 7 d) could avoid osteogenic inhibition caused by prolonged Mg2+ exposure. Additionally, the incorporation of nHA in the bottom "bone" layer supported the long-term osteogenesis due to its osteoconductivity and slow degradation. In vitro biological experiments revealed that the bilayer hydrogel (GS@Mg/GP@nHA) promoted neurite growth and calcitonin gene-related peptide (CGRP) expression in rat dorsal root ganglion (DRG) neurons, as well as the osteogenesis of rat bone-derived mesenchymal stem cells (BMSCs). Moreover, the in vivo experiments demonstrated that the GS@Mg/GP@nHA hydrogel efficiently promoted nerve network reconstruction and bone regeneration of rat calvarial bone defects. Altogether, the bilayer hydrogel GS@Mg/GP@nHA could promote innervated bone regeneration, providing new insights for biomaterial design for bone tissue engineering.
Collapse
Affiliation(s)
- Wenhui Lyu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Yuyue Zhang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Shaopei Ding
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Xiang Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Tong Sun
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Jun Luo
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Jian Wang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Jianshu Li
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
- Med-X Center for Materials, Sichuan University, Chengdu 610041, China
| | - Lei Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| |
Collapse
|
|
5
|
Alateeq K, Walsh EI, Cherbuin N. High Blood Pressure and Impaired Brain Health: Investigating the Neuroprotective Potential of Magnesium. Int J Mol Sci 2024; 25:11859. [PMID: 39595928 PMCID: PMC11594239 DOI: 10.3390/ijms252211859] [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: 09/07/2024] [Revised: 10/27/2024] [Accepted: 10/30/2024] [Indexed: 11/28/2024] Open
Abstract
High blood pressure (BP) is a significant contributor to the disease burden globally and is emerging as an important cause of morbidity and mortality in the young as well as the old. The well-established impact of high BP on neurodegeneration, cognitive impairment, and dementia is widely acknowledged. However, the influence of BP across its full range remains unclear. This review aims to explore in more detail the effects of BP levels on neurodegeneration, cognitive function, and dementia. Moreover, given the pressing need to identify strategies to reduce BP levels, particular attention is placed on reviewing the role of magnesium (Mg) in ageing and its capacity to lower BP levels, and therefore potentially promote brain health. Overall, the review aims to provide a comprehensive synthesis of the evidence linking BP, Mg and brain health. It is hoped that these insights will inform the development of cost-effective and scalable interventions to protect brain health in the ageing population.
Collapse
Affiliation(s)
- Khawlah Alateeq
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
- Radiological Science, College of Applied Medical Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Erin I. Walsh
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
| | - Nicolas Cherbuin
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
| |
Collapse
|
|
6
|
Demir CY, Bozan N. Serum Magnesium Concentration in Patients With Bell's Palsy: A Case-Control Study. EAR, NOSE & THROAT JOURNAL 2024:1455613241266694. [PMID: 39056518 DOI: 10.1177/01455613241266694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024] Open
Abstract
Introduction: Some conditions such as hyperglycemia, preeclampsia, migraine, inflammation, oxidative stress, and peripheral neuropathy are associated with magnesium deficiency and Bell's palsy. To date, however, studies have not addressed serum magnesium concentration in patients with Bell's palsy. In this article, we hypothesized that these patients may have a decreased serum magnesium concentration compared to healthy controls. Materials and Methods: In the study, a total of 24 patients with Bell's palsy and 24 healthy individuals matched were investigated. Atomic absorption spectrometry was used to determine serum magnesium concentration. The groups were then statistically compared for demographics and serum magnesium concentration. Results: No significant differences were found between Bell's palsy patients and healthy controls in age (P = .846), sex (P = 1.0), and body mass index (P = .410). However, patients with Bell's palsy had significantly lower serum magnesium levels (µg/dL) compared to healthy controls [11.44 ± 1.54 (8.9-15.8)] versus [27.35 ± 2.82 (24.3-36.2); (P < .001)]. Conclusions: Our results suggest an association between decreased serum magnesium concentration and Bell's palsy. However, this is the first study on the topic and its limitations should be considered.
Collapse
Affiliation(s)
- Canser Yilmaz Demir
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkiye
| | - Nazim Bozan
- Department of Otorhinolaryngology, Faculty of Medicine, Van Yüzüncü Yil University, Van, Turkiye
| |
Collapse
|
|
7
|
Yang M, Cai X, Wang C, Li P, Chen S, Liu C, Wang Y, Qian K, Dong Q, Xue F, Chu C, Bai J, Liu Q, Ni X. Humidity-Responsive Amorphous Calcium-Magnesium Pyrophosphate/Cassava Starch Scaffold for Enhanced Neurovascular Bone Regeneration. ACS APPLIED MATERIALS & INTERFACES 2024; 16:35964-35984. [PMID: 38968558 DOI: 10.1021/acsami.4c03204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/07/2024]
Abstract
Developing a neurovascular bone repair scaffold with an appropriate mechanical strength remains a challenge. Calcium phosphate (CaP) is similar to human bone, but its scaffolds are inherently brittle and inactive, which require recombination with active ions and polymers for bioactivity and suitable strength. This work discussed the synthesis of amorphous magnesium-calcium pyrophosphate (AMCP) and the subsequent development of a humidity-responsive AMCP/cassava starch (CS) scaffold. The scaffold demonstrated enhanced mechanical properties by strengthening the intermolecular hydrogen bonds and ionic bonds between AMCP and CS during the gelatinization and freeze-thawing processes. The release of active ions was rapid initially and stabilized into a long-term stable release after 3 days, which is well-matched with new bone growth. The release of pyrophosphate ions endowed the scaffold with antibacterial properties. At the cellular level, the released active ions simultaneously promoted the proliferation and mineralization of osteoblasts, the proliferation and migration of endothelial cells, and the proliferation of Schwann cells. At the animal level, the scaffold was demonstrated to promote vascular growth and peripheral nerve regeneration in a rat skull defect experiment, ultimately resulting in the significant and rapid repair of bone defects. The construction of the AMCP/CS scaffold offers practical suggestions and references for neurovascular bone repair.
Collapse
Affiliation(s)
- Mengmeng Yang
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Jiangsu Key Laboratory for Advanced Metallic Materials, Nanjing 211189, Jiangsu, China
- Institute of Biomedical Devices (Suzhou), Southeast University, Suzhou 215163, China
| | - Xiang Cai
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Jiangsu Key Laboratory for Advanced Metallic Materials, Nanjing 211189, Jiangsu, China
| | - Cheng Wang
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
| | - Pengyin Li
- Center of Medical Physics, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China
| | - Shaoqing Chen
- Center of Medical Physics, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China
| | - Chun Liu
- Center of Medical Physics, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China
| | - Yao Wang
- Department of Emergency, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Kun Qian
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
| | - Qiangsheng Dong
- School of Materials Science and Engineering, Nanjing Institute of Technology, Nanjing 211167, China
| | - Feng Xue
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Jiangsu Key Laboratory for Advanced Metallic Materials, Nanjing 211189, Jiangsu, China
- Institute of Biomedical Devices (Suzhou), Southeast University, Suzhou 215163, China
| | - Chenglin Chu
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Jiangsu Key Laboratory for Advanced Metallic Materials, Nanjing 211189, Jiangsu, China
| | - Jing Bai
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Jiangsu Key Laboratory for Advanced Metallic Materials, Nanjing 211189, Jiangsu, China
- Institute of Biomedical Devices (Suzhou), Southeast University, Suzhou 215163, China
- Jiangsu Key Laboratory for Light Metal Alloys, Nanjing 211212, China
| | - Qizhan Liu
- School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu, China
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China
| | - Xinye Ni
- Center of Medical Physics, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China
| |
Collapse
|
|
8
|
Ratan Y, Rajput A, Pareek A, Pareek A, Kaur R, Sonia S, Kumar R, Singh G. Recent Advances in Biomolecular Patho-Mechanistic Pathways behind the Development and Progression of Diabetic Neuropathy. Biomedicines 2024; 12:1390. [PMID: 39061964 PMCID: PMC11273858 DOI: 10.3390/biomedicines12071390] [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: 05/07/2024] [Revised: 06/12/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
Diabetic neuropathy (DN) is a neurodegenerative disorder that is primarily characterized by distal sensory loss, reduced mobility, and foot ulcers that may potentially lead to amputation. The multifaceted etiology of DN is linked to a range of inflammatory, vascular, metabolic, and other neurodegenerative factors. Chronic inflammation, endothelial dysfunction, and oxidative stress are the three basic biological changes that contribute to the development of DN. Although our understanding of the intricacies of DN has advanced significantly over the past decade, the distinctive mechanisms underlying the condition are still poorly understood, which may be the reason behind the lack of an effective treatment and cure for DN. The present study delivers a comprehensive understanding and highlights the potential role of the several pathways and molecular mechanisms underlying the etiopathogenesis of DN. Moreover, Schwann cells and satellite glial cells, as integral factors in the pathogenesis of DN, have been enlightened. This work will motivate allied research disciplines to gain a better understanding and analysis of the current state of the biomolecular mechanisms behind the pathogenesis of DN, which will be essential to effectively address every facet of DN, from prevention to treatment.
Collapse
Affiliation(s)
- Yashumati Ratan
- Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; (A.R.); (A.P.); (A.P.)
| | - Aishwarya Rajput
- Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; (A.R.); (A.P.); (A.P.)
| | - Ashutosh Pareek
- Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; (A.R.); (A.P.); (A.P.)
| | - Aaushi Pareek
- Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India; (A.R.); (A.P.); (A.P.)
| | - Ranjeet Kaur
- Adesh Institute of Dental Sciences and Research, Bathinda 151101, Punjab, India;
| | - Sonia Sonia
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India;
| | - Rahul Kumar
- Baba Ragav Das Government Medical College, Gorakhpur 273013, Uttar Pradesh, India;
| | - Gurjit Singh
- Department of Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60607, USA
| |
Collapse
|
|
9
|
Sun Y, Xiao Z, Chen B, Zhao Y, Dai J. Advances in Material-Assisted Electromagnetic Neural Stimulation. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2400346. [PMID: 38594598 DOI: 10.1002/adma.202400346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 03/26/2024] [Indexed: 04/11/2024]
Abstract
Bioelectricity plays a crucial role in organisms, being closely connected to neural activity and physiological processes. Disruptions in the nervous system can lead to chaotic ionic currents at the injured site, causing disturbances in the local cellular microenvironment, impairing biological pathways, and resulting in a loss of neural functions. Electromagnetic stimulation has the ability to generate internal currents, which can be utilized to counter tissue damage and aid in the restoration of movement in paralyzed limbs. By incorporating implanted materials, electromagnetic stimulation can be targeted more accurately, thereby significantly improving the effectiveness and safety of such interventions. Currently, there have been significant advancements in the development of numerous promising electromagnetic stimulation strategies with diverse materials. This review provides a comprehensive summary of the fundamental theories, neural stimulation modulating materials, material application strategies, and pre-clinical therapeutic effects associated with electromagnetic stimulation for neural repair. It offers a thorough analysis of current techniques that employ materials to enhance electromagnetic stimulation, as well as potential therapeutic strategies for future applications.
Collapse
Affiliation(s)
- Yuting Sun
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhifeng Xiao
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Bing Chen
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Yannan Zhao
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Jianwu Dai
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China
| |
Collapse
|
|
10
|
Raducanu D, Cojocaru VD, Nocivin A, Drob SI, Hendea RE, Stanciu D, Ivanescu S, Raducanu VA, Serban N, Cojocaru EM, Campian RS. The Characterization of a Biodegradable Mg Alloy after Powder Bed Fusion with Laser Beam/Metal Processing for Custom Shaped Implants. MATERIALS (BASEL, SWITZERLAND) 2024; 17:1682. [PMID: 38612195 PMCID: PMC11012606 DOI: 10.3390/ma17071682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/01/2024] [Accepted: 04/03/2024] [Indexed: 04/14/2024]
Abstract
A new Mg-Zn-Zr-Ca alloy in a powder state, intended to be used for custom shaped implants, was obtained via a mechanical alloying method from pure elemental powder. Further, the obtained powder alloy was processed by a PBF-LB/M (powder bed fusion with laser beam/of metal) procedure to obtain additive manufactured samples for small biodegradable implants. A series of microstructural, mechanical and corrosion analyses were performed. The SEM (scanning electron microscopy) analysis of the powder alloy revealed a good dimensional homogeneity, with a uniform colour, no agglutination and almost rounded particles, suitable for the powder bed fusion procedure. Further, the PBF-LB/M samples revealed a robust and unbreakable morphology, with a suitable porosity (that can reproduce that of cortical bone) and without an undesirable balling effect. The tested Young's modulus of the PBF-LB/M samples, which was 42 GPa, is close to that of cortical bone, 30 GPa. The corrosion tests that were performed in PBS (Phosphate-buffered saline) solution, with three different pH values, show that the corrosion parameters have a satisfactory evolution comparative to the commercial ZK 60 alloy.
Collapse
Affiliation(s)
- Doina Raducanu
- Department of Metallic Materials Processing and Ecometallurgy, University POLITEHNICA of Bucharest, 060042 Bucharest, Romania; (D.R.); (V.D.C.); (N.S.); (E.M.C.)
| | - Vasile Danut Cojocaru
- Department of Metallic Materials Processing and Ecometallurgy, University POLITEHNICA of Bucharest, 060042 Bucharest, Romania; (D.R.); (V.D.C.); (N.S.); (E.M.C.)
| | - Anna Nocivin
- Faculty of Mechanical, Industrial and Maritime Engineering, OVIDIUS University of Constanta, 900527 Constanța, Romania
| | - Silviu Iulian Drob
- Institute of Physical Chemistry “Ilie Murgulescu”, Romanian Academy, Spl. Independentei 202, 060021 Bucharest, Romania;
| | - Radu Emil Hendea
- Department of Oral Rehabilitation, Faculty of Dental Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (R.E.H.); (R.S.C.)
| | - Doina Stanciu
- ZIRCON DENT SRL, 400690 Cluj-Napoca, Romania; (D.S.); (S.I.)
| | | | - Vlad Andrei Raducanu
- Faculty of Decorative Arts and Design, National University of Arts, 010702 Bucharest, Romania;
| | - Nicolae Serban
- Department of Metallic Materials Processing and Ecometallurgy, University POLITEHNICA of Bucharest, 060042 Bucharest, Romania; (D.R.); (V.D.C.); (N.S.); (E.M.C.)
| | - Elisabeta Mirela Cojocaru
- Department of Metallic Materials Processing and Ecometallurgy, University POLITEHNICA of Bucharest, 060042 Bucharest, Romania; (D.R.); (V.D.C.); (N.S.); (E.M.C.)
| | - Radu Septimiu Campian
- Department of Oral Rehabilitation, Faculty of Dental Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (R.E.H.); (R.S.C.)
| |
Collapse
|
|
11
|
Bhat K, Hanke L, Helmholz H, Quandt E, Pixley S, Willumeit-Römer R. Influence of Magnesium Degradation on Schwannoma Cell Responses to Nerve Injury Using an In Vitro Injury Model. J Funct Biomater 2024; 15:88. [PMID: 38667545 PMCID: PMC11050989 DOI: 10.3390/jfb15040088] [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: 02/14/2024] [Revised: 03/29/2024] [Accepted: 03/29/2024] [Indexed: 04/28/2024] Open
Abstract
Nerve guidance conduits for peripheral nerve injuries can be improved using bioactive materials such as magnesium (Mg) and its alloys, which could provide both structural and trophic support. Therefore, we investigated whether exposure to Mg and Mg-1.6wt%Li thin films (Mg/Mg-1.6Li) would alter acute Schwann cell responses to injury. Using the RT4-D6P2T Schwannoma cell line (SCs), we tested extracts from freeze-killed cells (FKC) and nerves (FKN) as in vitro injury stimulants. Both FKC and FKN induced SC release of the macrophage chemoattractant protein 1 (MCP-1), a marker of the repair SC phenotype after injury. Next, FKC-stimulated cells exposed to Mg/Mg-1.6Li reduced MCP-1 release by 30%, suggesting that these materials could have anti-inflammatory effects. Exposing FKC-treated cells to Mg/Mg-1.6Li reduced the gene expression of the nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and myelin protein zero (MPZ), but not the p75 neurotrophin receptor. In the absence of FKC, Mg/Mg-1.6Li treatment increased the expression of NGF, p75, and MPZ, which can be beneficial to nerve regeneration. Thus, the presence of Mg can differentially alter SCs, depending on the microenvironment. These results demonstrate the applicability of this in vitro nerve injury model, and that Mg has wide-ranging effects on the repair SC phenotype.
Collapse
Affiliation(s)
- Krathika Bhat
- Institute of Metallic Biomaterials, Helmholtz Zentrum Hereon, 21502 Geesthacht, Germany
| | - Lisa Hanke
- Institute of Materials Science, University of Kiel, 24143 Kiel, Germany
| | - Heike Helmholz
- Institute of Metallic Biomaterials, Helmholtz Zentrum Hereon, 21502 Geesthacht, Germany
| | - Eckhard Quandt
- Institute of Materials Science, University of Kiel, 24143 Kiel, Germany
| | - Sarah Pixley
- College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0576, USA
| | | |
Collapse
|
|
12
|
Cai Y, Chen Y, Zhang G, Lin Y, Zhang J, Liang J, Lv L, Wang Y, Fang X, Dang X. The GDNF-gel/HA-Mg conduit promotes the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. iScience 2024; 27:108969. [PMID: 38322994 PMCID: PMC10844047 DOI: 10.1016/j.isci.2024.108969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 11/16/2023] [Accepted: 01/16/2024] [Indexed: 02/08/2024] Open
Abstract
Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience.
Collapse
Affiliation(s)
- Yuanqing Cai
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China
| | - Yi Chen
- College of Materials Science & Engineering, National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400045, China
| | - Guangyang Zhang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China
| | - Yi Lin
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
| | - Jianan Zhang
- Zonglian College, Xi’an Jiaotong University, Xi’an 710054, China
| | - Jialin Liang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China
| | - Leifeng Lv
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China
| | - Yong Wang
- College of Materials Science & Engineering, National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400045, China
| | - Xinyu Fang
- Department of Orthopaedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China
| | - Xiaoqian Dang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China
| |
Collapse
|
|
13
|
Ron T, Leon A, Kafri A, Ashraf A, Na J, Babu A, Banerjee R, Brookbank H, Muddaluri SR, Little KJ, Aghion E, Pixley S. Nerve Regeneration with a Scaffold Incorporating an Absorbable Zinc-2% Iron Alloy Filament to Improve Axonal Guidance. Pharmaceutics 2023; 15:2595. [PMID: 38004574 PMCID: PMC10674795 DOI: 10.3390/pharmaceutics15112595] [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: 10/09/2023] [Revised: 10/30/2023] [Accepted: 11/02/2023] [Indexed: 11/26/2023] Open
Abstract
Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair.
Collapse
Affiliation(s)
- Tomer Ron
- Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Avi Leon
- Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Alon Kafri
- Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
- Nuclear Research Centre-Negev, Beer-Sheva 84190, Israel
| | - Ahmed Ashraf
- College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
| | - John Na
- College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
| | - Ashvin Babu
- School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Runima Banerjee
- College of Engineering & Applied Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Hunter Brookbank
- College of Arts & Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | | | - Kevin J. Little
- Department of Orthopedic Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
- Pediatric Hand & Upper Extremity Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Eli Aghion
- Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Sarah Pixley
- Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
| |
Collapse
|
|
14
|
Sun Y, Zhang H, Zhang Y, Liu Z, He D, Xu W, Li S, Zhang C, Zhang Z. Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration. Bioact Mater 2023; 28:227-242. [PMID: 37292230 PMCID: PMC10245070 DOI: 10.1016/j.bioactmat.2023.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/18/2023] [Accepted: 05/20/2023] [Indexed: 06/10/2023] Open
Abstract
Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a β-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.
Collapse
Affiliation(s)
- Yiting Sun
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Hongjian Zhang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yu Zhang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Zheqi Liu
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Dongming He
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Wanlin Xu
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Siyi Li
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Chenping Zhang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| | - Zhen Zhang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China
| |
Collapse
|
|
15
|
Wu Z, Yang X, Ruan Z, Li L, Wu J, Wang B. Nonlinear relationship between dietary calcium and magnesium intake and peripheral neuropathy in the general population of the United States. Front Nutr 2023; 10:1217465. [PMID: 37789899 PMCID: PMC10544963 DOI: 10.3389/fnut.2023.1217465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 09/07/2023] [Indexed: 10/05/2023] Open
Abstract
Background Calcium and magnesium are essential minerals that have significant roles in nerve function and regulation. There may be a correlation between dietary calcium and magnesium intake and peripheral neuropathy. However, this relationship remains unclear and requires further study. Methods Data from 7,726 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 were analyzed in this study. The relationship between total dietary calcium and magnesium intake, as well as each quantile, and peripheral neuropathy was analyzed using a multifactor logistic regression model. To illustrate the dose-response relationship between calcium and magnesium intake and peripheral neuropathy, we utilized a restricted cubic spline (RCS) plot. Results Our analysis found a positive correlation between dietary intake of calcium and magnesium and peripheral neuropathy (calcium: OR 1.000, 95% CI 1.000-1.000; magnesium: OR 1.001, 95% CI 1.00-1.002). Participants in the first and third quantiles of dietary calcium intake had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.333, 95% CI 1.034-1.719, OR 1.497, 95% CI 1.155-1.941). Those in the first and third quantiles of dietary magnesium intake also had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.275, 95% CI 1.064-1.528, OR 1.525, 95% CI 1.231-1.890). The restricted cubic spline analysis revealed a U-shaped nonlinear relationship between dietary intake of calcium and magnesium and peripheral neuropathy. Conclusion The study found a U-shaped non-linear relationship between dietary calcium and magnesium intake levels and peripheral neuropathy, indicating that both excessive and insufficient intake of calcium and magnesium can increase the incidence of peripheral neuropathy.
Collapse
Affiliation(s)
- Zhe Wu
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuesong Yang
- Department of Vascular Surgery, The First Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhishen Ruan
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lianlian Li
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jianlin Wu
- The Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Bin Wang
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Department of Vascular Surgery, The First Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
16
|
Li D, Dai D, Xiong G, Lan S, Zhang C. Composite Nanocoatings of Biomedical Magnesium Alloy Implants: Advantages, Mechanisms, and Design Strategies. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2300658. [PMID: 37097626 PMCID: PMC10288271 DOI: 10.1002/advs.202300658] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/25/2023] [Indexed: 06/19/2023]
Abstract
The rapid degradation of magnesium (Mg) alloy implants erodes mechanical performance and interfacial bioactivity, thereby limiting their clinical utility. Surface modification is among the solutions to improve corrosion resistance and bioefficacy of Mg alloys. Novel composite coatings that incorporate nanostructures create new opportunities for their expanded use. Particle size dominance and impermeability may increase corrosion resistance and thereby prolong implant service time. Nanoparticles with specific biological effects may be released into the peri-implant microenvironment during the degradation of coatings to promote healing. Composite nanocoatings provide nanoscale surfaces to promote cell adhesion and proliferation. Nanoparticles may activate cellular signaling pathways, while those with porous or core-shell structures may carry antibacterial or immunomodulatory drugs. Composite nanocoatings may promote vascular reendothelialization and osteogenesis, attenuate inflammation, and inhibit bacterial growth, thus increasing their applicability in complex clinical microenvironments such as those of atherosclerosis and open fractures. This review combines the physicochemical properties and biological efficiency of Mg-based alloy biomedical implants to summarize the advantages of composite nanocoatings, analyzes their mechanisms of action, and proposes design and construction strategies, with the purpose of providing a reference for promoting the clinical application of Mg alloy implants and to further the design of nanocoatings.
Collapse
Affiliation(s)
- Dan Li
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| | - Danni Dai
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| | - Gege Xiong
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| | - Shuquan Lan
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| | - Chao Zhang
- Stomatological HospitalSchool of StomatologySouthern Medical UniversityGuangzhou510280China
| |
Collapse
|
|
17
|
Kurian SJ, Baral T, Unnikrishnan MK, Benson R, Munisamy M, Saravu K, Rodrigues GS, Rao M, Kumar A, Miraj SS. The association between micronutrient levels and diabetic foot ulcer: A systematic review with meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1152854. [PMID: 37065742 PMCID: PMC10090454 DOI: 10.3389/fendo.2023.1152854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 03/14/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU. METHODS A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed. RESULTS Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)]. CONCLUSION This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.
Collapse
Affiliation(s)
- Shilia Jacob Kurian
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of High Education, Manipal, Karnataka, India
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Tejaswini Baral
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of High Education, Manipal, Karnataka, India
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Ruby Benson
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of High Education, Manipal, Karnataka, India
| | - Murali Munisamy
- Department of Translational Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Kavitha Saravu
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
- Department of Infectious Diseases, Kasturba Medical College and Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of High Education, Manipal, Karnataka, India
| | - Amit Kumar
- Department of Laboratory Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
| | - Sonal Sekhar Miraj
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of High Education, Manipal, Karnataka, India
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
- *Correspondence: Sonal Sekhar Miraj,
| |
Collapse
|
|
18
|
Abstract
PURPOSE OF REVIEW To review advances in the diagnostic evaluation and management of traumatic peripheral nerve injuries. RECENT FINDINGS Serial multimodal assessment of peripheral nerve injuries facilitates assessment of spontaneous axonal regeneration and selection of appropriate patients for early surgical intervention. Novel surgical and rehabilitative approaches have been developed to complement established strategies, particularly in the area of nerve grafting, targeted rehabilitation strategies and interventions to promote nerve regeneration. However, several management challenges remain, including incomplete reinnervation, traumatic neuroma development, maladaptive central remodeling and management of fatigue, which compromise functional recovery. SUMMARY Innovative approaches to the assessment and treatment of peripheral nerve injuries hold promise in improving the degree of functional recovery; however, this remains a complex and evolving area.
Collapse
|
|
19
|
Ghahramanzadeh Asl H, Celik-Uzuner S, Uzuner U, Sert Y, Küçükömeroğlu T. The effect of friction stir process on the mechanical, tribological, and biocompatibility properties of AZ31B magnesium alloy as a biomaterial: A pilot study. Proc Inst Mech Eng H 2022; 236:1720-1731. [DOI: 10.1177/09544119221135687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Recently, AZ31B magnesium alloy has been widely employed in automotive, aerospace, and bio implant industries due to its light-weight and biocompatibility properties. However, the equilibrium of ductility and strength of this material and the negativity brought by its poor wear behavior have limited its versatile use. Friction stir processing (FSP) has been commonly used as severe plastic deformation method for improving mechanical and tribological properties of metal sheets. The effect of this method on the biocompatibility of materials is a matter of curiosity that should be emphasized. So, the present study aims to investigate the effect of friction stir process on the mechanical, tribological, and biocompatibility properties of AZ31B magnesium alloy. It is observed that FSP enhanced the tensile properties of the alloy but decreased its elongation. It was determined that the base material exhibited ductile character on the fracture surface of the specimens, and mixed ductile/brittle fracture was evident with the FSP. In the FSP zone, the hardness value was improved by 17% compared to the base material. Also, the wear performance of the alloy enhanced in ambient air and Simulated Body Fluid (SBF) solution. Wear properties in SBF solution were better due to less adhesive bonds between the friction surfaces. This assessment was supported by SEM images of the wear path and surface of counter bodies. On the other hand, FSPed AZ31B alloy materials with improved strength properties were not cytotoxic for human gingival fibroblasts, and these results may suggest that the materials are safe for clinical uses.
Collapse
Affiliation(s)
- Hojjat Ghahramanzadeh Asl
- Department of Mechanical Engineering, Faculty of Engineering, Karadeniz Technical University, Trabzon, Turkey
| | - Selcen Celik-Uzuner
- Department of Molecular Biology and Genetics, Faculty of Science, Karadeniz Technical University, Trabzon, Turkey
| | - Ugur Uzuner
- Department of Molecular Biology and Genetics, Faculty of Science, Karadeniz Technical University, Trabzon, Turkey
| | - Yaşar Sert
- Department of Mechanical Engineering, Faculty of Engineering, Karadeniz Technical University, Trabzon, Turkey
| | - Tevfik Küçükömeroğlu
- Department of Mechanical Engineering, Faculty of Engineering, Karadeniz Technical University, Trabzon, Turkey
| |
Collapse
|
|
20
|
Shan Z, Xie X, Wu X, Zhuang S, Zhang C. Development of degradable magnesium-based metal implants and their function in promoting bone metabolism (A review). J Orthop Translat 2022; 36:184-193. [PMID: 36263386 PMCID: PMC9552026 DOI: 10.1016/j.jot.2022.09.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/05/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022] Open
Abstract
Background Use of degradable magnesium (Mg)-based metal implants in orthopaedic surgeries can avoid drawbacks associated with subsequent removal of the non-degradable metallic implants, reducing cost and trauma of patients. Although Mg has been applied in the clinic for orthopaedic treatment, the use of Mg-based metal implants is largely in the research phase. But its application is potentially beneficial in this context as it has been shown that Mg can promote osteogenesis and inhibit osteoclast activity. Methods A systematic literature search about “degradable magnesium (Mg)-based metal implants” was performed in PubMed and Web of Science. Meanwhile, relevant findings have been reviewed and quoted. Results In this review, we summarize the latest developments in Mg-based metal implants and their role in bone regeneration. We also review the various molecular mechanisms by which Mg ions regulate bone metabolic processes, including osteogenesis, osteoclast activity, angiogenesis, immunity, and neurology. Finally, we discuss the remaining research challenges and opportunities for Mg-based implants and their applications. Conclusion Currently, establishment of the in vitro and in vivo biological evaluation systems and phenotypic modification improvement of Mg-based implants are still needed. Clarifying the functions of Mg-based metal implants in promoting bone metabolism is beneficial for their clinical application. The Translational potential of this article All current reviews on Mg-based implants are mainly concerned with the improvement of Mg alloy properties or the progress of applications. However, there are few reviews that provides a systematic narrative on the effect of Mg on bone metabolism. This review summarized the latest developments in Mg-based metal implants and various molecular mechanisms of Mg ions regulating bone metabolism, which is beneficial to further promote the translation of Mg based implants in the clinic and is able to provide a strong basis for the clinical application of Mg based implants.
Collapse
Affiliation(s)
- Zhengming Shan
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Xinhui Xie
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
- The Department of Orthopaedics, ZhongDa Hospital, Nanjing, Jiangsu, 210009, China
- Corresponding author. The Department of Orthopaedics, ZhongDa hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
| | - Xiaotao Wu
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
- The Department of Orthopaedics, ZhongDa Hospital, Nanjing, Jiangsu, 210009, China
- Corresponding author. The Department of Orthopaedics, ZhongDa hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
| | - Suyang Zhuang
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
- The Department of Orthopaedics, ZhongDa Hospital, Nanjing, Jiangsu, 210009, China
| | - Cong Zhang
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
- The Department of Orthopaedics, ZhongDa Hospital, Nanjing, Jiangsu, 210009, China
| |
Collapse
|
|
21
|
Zhang T, Wang W, Liu J, Wang L, Tang Y, Wang K. A review on magnesium alloys for biomedical applications. Front Bioeng Biotechnol 2022; 10:953344. [PMID: 36051586 PMCID: PMC9424554 DOI: 10.3389/fbioe.2022.953344] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Magnesium (Mg) and Mg alloys are considered as potential candidates for biomedical applications because of their high specific strength, low density, and elastic modulus, degradability, good biocompatibility and biomechanical compatibility. However, the rapid corrosion rate of Mg alloys results in premature loss of mechanical integrity, limiting their clinical application in load-bearing parts. Besides, the low strength of Mg alloys restricts their further application. Thus, it is essential to understand the characteristics and influencing factors of mechanical and corrosion behavior, as well as the methods to improve the mechanical performances and corrosion resistance of Mg alloys. This paper reviews the recent progress in elucidating the corrosion mechanism, optimizing the composition, and microstructure, enhancing the mechanical performances, and controlling the degradation rate of Mg alloys. In particular, the research progress of surface modification technology of Mg alloys is emphasized. Finally, the development direction of biomedical Mg alloys in the future is prospected.
Collapse
Affiliation(s)
- Ting Zhang
- School of Metallurgical Engineering, Xi’an University of Architecture and Technology, Xi’an, China
| | - Wen Wang
- School of Metallurgical Engineering, Xi’an University of Architecture and Technology, Xi’an, China
| | - Jia Liu
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
- *Correspondence: Jia Liu, ; Kuaishe Wang,
| | - Liqiang Wang
- State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yujin Tang
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Kuaishe Wang
- School of Metallurgical Engineering, Xi’an University of Architecture and Technology, Xi’an, China
- *Correspondence: Jia Liu, ; Kuaishe Wang,
| |
Collapse
|