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Jingyue X, Zhiwei Z, Jirui W, Fei F, Jiang W, Yali M. Application and research progress in composite stem cell materials of pelvic floor reconstruction. Eur J Obstet Gynecol Reprod Biol 2025; 307:49-54. [PMID: 39883984 DOI: 10.1016/j.ejogrb.2025.01.018] [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: 01/19/2024] [Revised: 10/05/2024] [Accepted: 01/08/2025] [Indexed: 02/01/2025]
Abstract
As an important tool for the surgical treatment of pelvic floor dysfunction, the safety of mesh must be guaranteed. Although the short-term curative effect of most synthetic mesh is satisfactory, complications often occur due to its material. Planting stem cells on mesh through specific methods may resolve the problems of mesh with poor biocompatibility or an uncontrollable rate o degradation. Based on recent research, this paper summarizes the research progress of stem cells composited with common mesh materials, such as polypropylene, polylactic acid and acellular matrix.
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Affiliation(s)
- Xiao Jingyue
- Department of Obstetrics and Gynaecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China; West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhao Zhiwei
- West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Wen Jirui
- West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Fang Fei
- Deep Underground Space Medical Centre, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Wu Jiang
- Deep Underground Space Medical Centre, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Miao Yali
- Department of Obstetrics and Gynaecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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Chapple CR, Bullock AJ, MacNeil S. Where are we in 2024 in the development of materials for surgical treatment of pelvic organ prolapse and stress urinary incontinence? Curr Opin Urol 2024; 34:433-437. [PMID: 39175404 DOI: 10.1097/mou.0000000000001217] [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: 08/24/2024]
Abstract
PURPOSE OF REVIEW There is a long history of implantation of absorbable and nonabsorbable materials to treat stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The focus of this review is to review the development of new materials for use in the surgical management of both pelvic conditions following an unacceptable level of severe complications in the use of polypropylene mesh (PPM). We discuss current concepts relating to the development of new materials with particular reference to our experience with polyurethane mesh. RECENT FINDINGS Our review highlights the strategies that manufacturers and researchers are employing to improve PPM using collagen gels and stem cells, or to find alternatives. We conclude that current preclinical safety testing is inadequate, and the field requires better in vivo testing. Specifically, we highlight novel techniques demonstrating the degradation of polypropylene potentially elucidating the link between PPM degradation and induction of inflammation leading to adverse side effects. SUMMARY This field badly needs innovation in developing new materials and in testing these to ensure materials will benefit patients. A collaboration between materials scientists and clinicians is needed to facilitate the translation of basic research and preclinical testing into patient benefit for the treatment of SUI and POP.
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Affiliation(s)
| | - Anthony J Bullock
- The University of Sheffield, Kroto Research Institute, Sheffield, UK
| | - Sheila MacNeil
- The University of Sheffield, Kroto Research Institute, Sheffield, UK
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Shiroud Heidari B, Dodda JM, El-Khordagui LK, Focarete ML, Maroti P, Toth L, Pacilio S, El-Habashy SE, Boateng J, Catanzano O, Sahai N, Mou L, Zheng M. Emerging materials and technologies for advancing bioresorbable surgical meshes. Acta Biomater 2024; 184:1-21. [PMID: 38879102 DOI: 10.1016/j.actbio.2024.06.012] [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: 02/05/2024] [Revised: 05/22/2024] [Accepted: 06/10/2024] [Indexed: 06/29/2024]
Abstract
Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.
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Affiliation(s)
- Behzad Shiroud Heidari
- Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, WA, Australia
| | - Jagan Mohan Dodda
- New Technologies - Research Centre (NTC), University of West Bohemia, Univerzitní 8, 301 00 Pilsen, Czech Republic.
| | | | - Maria Letizia Focarete
- Department of Chemistry "Giacomo Ciamician" and INSTM UdR of Bologna, University of Bologna, Italy. Health Sciences & Technologies (HST) CIRI, University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Italy
| | - Peter Maroti
- University of Pecs, Medical School, 3D Printing and Visualization Centre, Hungary, University of Pecs, Medical Skills Education and Innovation Centre, Hungary
| | - Luca Toth
- University of Pecs, Medical School, Institute for Translational Medicine, Hungary, University of Pecs, Medical School, Department of Neurosurgery, Hungary
| | - Serafina Pacilio
- Department of Chemistry "Giacomo Ciamician" and INSTM UdR of Bologna, University of Bologna, Italy. Health Sciences & Technologies (HST) CIRI, University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, Italy; Department of Biomedical and Neuromotor Sciences DIBINEM, Alma Mater Studiorum-University of Bologna, Italy
| | - Salma E El-Habashy
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt
| | - Joshua Boateng
- Faculty of Engineering and Science, University of Greenwich, Medway Campus, UK
| | - Ovidio Catanzano
- Institute for Polymers, Composites and Biomaterials (IPCB-CNR), Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy
| | - Nitin Sahai
- University of Pecs, Medical School, 3D Printing and Visualization Centre, Hungary, University of Pecs, Medical Skills Education and Innovation Centre, Hungary; Department of Biomedical Engineering, North Eastern Hill University, Meghalaya, India
| | - Lingjun Mou
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - Minghao Zheng
- Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, WA, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
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Xu LM, Yu XX, Zhang N, Chen YS. Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse. World J Stem Cells 2024; 16:708-727. [PMID: 38948096 PMCID: PMC11212552 DOI: 10.4252/wjsc.v16.i6.708] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/23/2024] [Accepted: 04/22/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling. AIM To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved. METHODS Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules. RESULTS In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression. CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
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Affiliation(s)
- Lei-Mei Xu
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
- Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China
| | - Xin-Xin Yu
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
| | - Ning Zhang
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
| | - Yi-Song Chen
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
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5
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Xu LM, Yu XX, Zhang N, Chen YS. Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse. World J Stem Cells 2024; 16:707-726. [DOI: 10.4252/wjsc.v16.i6.707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/23/2024] [Accepted: 04/22/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.
AIM To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS Human vaginal wall collagen content was assessed by Masson’s trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
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Affiliation(s)
- Lei-Mei Xu
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
- Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China
| | - Xin-Xin Yu
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
| | - Ning Zhang
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
| | - Yi-Song Chen
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
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Zhang D, Xu D, Huang X, Wei Y, Tang F, Qin X, Liang W, Liang Z, Jin L, Wang H, Wang H. Puerarin-Loaded Electrospun Patches with Anti-Inflammatory and Pro-Collagen Synthesis Properties for Pelvic Floor Reconstruction. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2308590. [PMID: 38509840 DOI: 10.1002/advs.202308590] [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: 11/09/2023] [Revised: 02/02/2024] [Indexed: 03/22/2024]
Abstract
Pelvic organ prolapse (POP) is one of the most common pelvic floor dysfunction disorders worldwide. The weakening of pelvic connective tissues initiated by excessive collagen degradation is a leading cause of POP. However, the patches currently used in the clinic trigger an unfavorable inflammatory response, which often leads to implantation failure and the inability to simultaneously reverse progressive collagen degradation. Therefore, to overcome the present challenges, a new strategy is applied by introducing puerarin (Pue) into poly(l-lactic acid) (PLLA) using electrospinning technology. PLLA improves the mechanical properties of the patch, while Pue offers intrinsic anti-inflammatory and pro-collagen synthesis effects. The results show that Pue is released from PLLA@Pue in a sustained manner for more than 20 days, with a total release rate exceeding 80%. The PLLA@Pue electrospun patches also show good biocompatibility and low cytotoxicity. The excellent anti-inflammatory and pro-collagen synthesis properties of the PLLA@Pue patch are demonstrated both in vitro in H2O2-stimulated mouse fibroblasts and in vivo in rat abdominal wall muscle defects. Therefore, it is believed that this multifunctional electrospun patch integrating anti-inflammatory and pro-collagen synthesis properties can overcome the limitations of traditional patches and has great prospects for efficient pelvic floor reconstruction.
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Affiliation(s)
- Di Zhang
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Dong Xu
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xiaobo Huang
- Department of Ophthalmology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Yingqi Wei
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Fuxin Tang
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xiusen Qin
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Weiwen Liang
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Zhongping Liang
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, China
| | - Lin Jin
- International Joint Research Laboratory for Biomedical Nanomaterials of Henan, Zhoukou Normal University, Zhoukou, 466001, China
| | - Hui Wang
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Huaiming Wang
- Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
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7
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Ghanbari Z, Jelodarian P, Salkisari FH, Sohbati S, Eftekhar T, Hosseini RS, Nezami Z, Pesikhani MD. A 5-year evaluation of quality of life, pelvic discomfort, and sexual function following posterior pericervical repair. J Med Life 2024; 17:392-396. [PMID: 39071513 PMCID: PMC11282904 DOI: 10.25122/jml-2023-0321] [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: 09/24/2023] [Accepted: 12/09/2023] [Indexed: 07/30/2024] Open
Abstract
The aim of this study was to evaluate the quality of life, pelvic discomfort, and sexual function of patients who underwent posterior pericervical repair or level I to III surgical procedures for pelvic organ prolapse (POP) after 5 years of follow-up. This retrospective cohort study enrolled 107 women with POP who were referred to the Imam Khomeini Hospital Complex, an academic center affiliated with the Tehran University of Medical Sciences, Tehran, Iran, from 2014 to 2021. The patients underwent transvaginal surgery using native tissue, in which the rectovaginal fascia was attached to the pericervical ring. The Pelvic Floor Distress Inventory-20 (PFDI-20) and Lower Urinary Tract Symptoms Module (ICIQ-FLUTSsex) questionnaires were completed by each patient before and 5 years after surgery. Of the 107 patients, only 78 completed the 5-year follow-up. The mean PFDI-20 scores before, 12 months, and 5 years after surgery were 141.87 ± 34.48, 100.87 ± 26.48, and 37.49 ± 56.39, respectively, indicating a significant improvement in the patients' symptoms after surgery (P < 0.001). The total mean score of ICIQ-FLUTSsex was 3.67 ± 3.63 (range, 0-10). In total, 22 (28.2%) women had an ICIQ-FLUTSsex score of 0, indicating no problems. The attachment of the rectovaginal fascia to the pericervical rings can be an effective surgical technique for correcting posterior vaginal wall prolapses, without significant morbidity. The PFDI-20 score improved significantly from before surgery to 12 months and 5 years after surgery.
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Affiliation(s)
- Zinat Ghanbari
- Department of Obstetrics and Gynecology, Pelvic Floor Fellowship, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parivash Jelodarian
- Pelvic Floor Fellowship, Department of Obstetrics and Gynecology, Fertility Infertility and Perinatology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fatemeh Hosseini Salkisari
- Pelvic Floor Fellowship, Department of Obstetrics and Gynecology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Samira Sohbati
- Department of Obstetrics and Gynecology, Clinical Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Tahereh Eftekhar
- Department of Obstetrics and Gynecology, Pelvic Floor Fellowship, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reihane Sadat Hosseini
- Department of Obstetrics and Gynecology, Pelvic Floor Fellowship, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Nezami
- Fellowship of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Maryam Deldar Pesikhani
- Department of Obstetrics and Gynecology, Pelvic Floor Fellowship, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Koner S, Mukherjee A, Chandrasekaran N. Elucidating the effects of naturally weathered aged-polypropylene microplastics and newly procured polypropylene microplastics on raw 264.7 macrophages. ENVIRONMENTAL SCIENCE: NANO 2024; 11:983-999. [DOI: 10.1039/d3en00742a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
In this work, we investigated weathered aged-PPMPs and naturally obtained polypropylene microplastics (NP-PPMPs) with raw 264.7 macrophages, which causes cytotoxicity and an imbalance in the intracellular system.
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Affiliation(s)
- Shramana Koner
- Center for Nanobiotechnology, Vellore Institute of Technology, Vellore-632014, Tamil Nadu, India
| | - Amitava Mukherjee
- Center for Nanobiotechnology, Vellore Institute of Technology, Vellore-632014, Tamil Nadu, India
| | - Natarajan Chandrasekaran
- Center for Nanobiotechnology, Vellore Institute of Technology, Vellore-632014, Tamil Nadu, India
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9
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Utomo E, Domínguez-Robles J, Anjani QK, Picco CJ, Korelidou A, Magee E, Donnelly RF, Larrañeta E. Development of 3D-printed vaginal devices containing metronidazole for alternative bacterial vaginosis treatment. Int J Pharm X 2023; 5:100142. [PMID: 36531743 PMCID: PMC9755236 DOI: 10.1016/j.ijpx.2022.100142] [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: 09/14/2022] [Revised: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
Bacterial vaginosis (BV) is an abnormal condition caused by the change of microbiota in the vagina. One of the most common bacteria found in the case of BV is Gardnerella vaginalis, which is categorised as anaerobic facultative bacteria. Currently, the available treatment for BV is the use of antibiotics, such as metronidazole (MTZ), in topical and oral dosage forms. The limitation of the currently available treatment is that multiple administration is required and thus, the patient needs to apply the drug frequently to maintain the drug efficacy. To address these limitations, this research proposed prolonged delivery of MTZ in the form of intravaginal devices made from biodegradable and biocompatible polymers. Semi-solid extrusion (SSE) 3D printing was used to prepare the intravaginal devices. The ratio of high and low molecular weight poly(caprolactone) (PCL) was varied to evaluate the effect of polymer composition on the drug release. The versatility of SSE 3D printer was used to print the intravaginal devices into two different shapes (meshes and discs) and containing two different polymer layers made from PCL and a copolymer of methyl vinyl ether and maleic anhydride (Gantrez™-AN119), which provided mucoadhesive properties. Indeed, this layer made from Gantrez™-AN119 increased ca. 5 times the mucoadhesive properties of the final 3D-printed devices (from 0.52 to 2.57 N). Furthermore, MTZ was homogenously dispersed within the polymer matrix as evidenced by scanning electron microscopy analysis. Additionally, in vitro drug release, and antibacterial activity of the MTZ-loaded intravaginal devices were evaluated. Disc formulations were able to sustain the release of MTZ for 72 h for formulations containing 70/30 and 60/40 ratio of high molecular weight/low molecular weight PCL. On the other hand, the discs containing a 50/50 ratio of high molecular weight/low molecular weight PCL showed up to 9 days of release. However, no significant differences in the MTZ release from the MTZ-loaded meshes (60/40 and 50/50 ratio of high molecular weight/low molecular weight PCL) were found after 24 h. The results showed that the different ratios of high and low molecular weight PCL did not significantly affect the MTZ release. However, the shape of the devices did influence the release of MTZ, showing that larger surface area of the meshes provided a faster MTZ release. Moreover, MTZ loaded 3D-printed discs (5% w/w) were capable of inhibiting the growth of Gardnerella vaginalis. These materials showed clear antimicrobial properties, exhibiting a zone of inhibition of 19.0 ± 1.3 mm. Based on these findings, the manufactured represent a valuable alternative approach to the current available treatment, as they were able to provide sustained release of MTZ, reducing the frequency of administration and thus improving patient compliance.
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Affiliation(s)
| | | | - Qonita Kurnia Anjani
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Camila J. Picco
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Anna Korelidou
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Erin Magee
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Ryan F. Donnelly
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
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10
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Magill E, Demartis S, Gavini E, Permana AD, Thakur RRS, Adrianto MF, Waite D, Glover K, Picco CJ, Korelidou A, Detamornrat U, Vora LK, Li L, Anjani QK, Donnelly RF, Domínguez-Robles J, Larrañeta E. Solid implantable devices for sustained drug delivery. Adv Drug Deliv Rev 2023; 199:114950. [PMID: 37295560 DOI: 10.1016/j.addr.2023.114950] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 06/02/2023] [Accepted: 06/04/2023] [Indexed: 06/12/2023]
Abstract
Implantable drug delivery systems (IDDS) are an attractive alternative to conventional drug administration routes. Oral and injectable drug administration are the most common routes for drug delivery providing peaks of drug concentrations in blood after administration followed by concentration decay after a few hours. Therefore, constant drug administration is required to keep drug levels within the therapeutic window of the drug. Moreover, oral drug delivery presents alternative challenges due to drug degradation within the gastrointestinal tract or first pass metabolism. IDDS can be used to provide sustained drug delivery for prolonged periods of time. The use of this type of systems is especially interesting for the treatment of chronic conditions where patient adherence to conventional treatments can be challenging. These systems are normally used for systemic drug delivery. However, IDDS can be used for localised administration to maximise the amount of drug delivered within the active site while reducing systemic exposure. This review will cover current applications of IDDS focusing on the materials used to prepare this type of systems and the main therapeutic areas of application.
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Affiliation(s)
- Elizabeth Magill
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Sara Demartis
- Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Sassari, 07100, Italy
| | - Elisabetta Gavini
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, 07100, Italy
| | - Andi Dian Permana
- Department of Pharmaceutics, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
| | - Raghu Raj Singh Thakur
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK; Re-Vana Therapeutics, McClay Research Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Muhammad Faris Adrianto
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK; Re-Vana Therapeutics, McClay Research Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Airlangga University, Surabaya, East Java 60115, Indonesia
| | - David Waite
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK; Re-Vana Therapeutics, McClay Research Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Katie Glover
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Camila J Picco
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Anna Korelidou
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Usanee Detamornrat
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Lalitkumar K Vora
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Linlin Li
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Qonita Kurnia Anjani
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK; Fakultas Farmasi, Universitas Megarezky, Jl. Antang Raya No. 43, Makassar 90234, Indonesia
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK
| | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK; Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain.
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, UK.
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11
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Picco CJ, Utomo E, McClean A, Domínguez-Robles J, Anjani QK, Volpe-Zanutto F, McKenna PE, Acheson JG, Malinova D, Donnelly RF, Larrañeta E. Development of 3D-printed subcutaneous implants using concentrated polymer/drug solutions. Int J Pharm 2023; 631:122477. [PMID: 36509226 DOI: 10.1016/j.ijpharm.2022.122477] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022]
Abstract
Implantable drug-eluting devices that provide therapeutic cover over an extended period of time following a single administration have potential to improve the treatment of chronic conditions. These devices eliminate the requirement for regular and frequent drug administration, thus reducing the pill burden experienced by patients. Furthermore, the use of modern technologies, such as 3D printing, during implant development and manufacture renders this approach well-suited for the production of highly tuneable devices that can deliver treatment regimens which are personalised for the individual. The objective of this work was to formulate subcutaneous implants loaded with a model hydrophobic compound, olanzapine (OLZ) using robocasting - a 3D-printing technique. The formulated cylindrical implants were prepared from blends composed of OLZ mixed with either poly(caprolactone) (PCL) or a combination of PCL and poly(ethylene)glycol (PEG). Implants were characterised using scanning electron microscopy (SEM), thermal analysis, infrared spectroscopy, and X-ray diffraction and the crystallinity of OLZ in the formulated devices was confirmed. In vitro release studies demonstrated that all the formulations were capable of maintaining sustained drug release over a period of 200 days, with the maximum percentage drug release observed to be c.a. 60 % in the same period.
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Affiliation(s)
- Camila J Picco
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Emilia Utomo
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Andrea McClean
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Qonita Kurnia Anjani
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Fabiana Volpe-Zanutto
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Peter E McKenna
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Jonathan G Acheson
- Nanotechnology and Integrated Bioengineering Centre (NIBEC), School of Engineering, Ulster University, United Kingdom
| | - Dessislava Malinova
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
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12
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Zhou Q, Lu M, Li GS, Peng GL, Song YF. Knowledge mapping and visualization analysis of pelvic organ prolapse repair with mesh from 2001 to 2021. Front Bioeng Biotechnol 2023; 11:1104724. [PMID: 37091336 PMCID: PMC10113510 DOI: 10.3389/fbioe.2023.1104724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/22/2023] [Indexed: 04/25/2023] Open
Abstract
Aims: In recent decades, extensive attention has been paid to the application of mesh to repair pelvic floor defects. However, a large body of related literature has not been system summarized. The purpose of this study is to summarize and visualize the literature on pelvic organ prolapse (POP) repair with mesh using bibliometrics. Methods: Medical literature regarding POP repair with mesh were searched and obtained in the Web of Science™ Core (WoSCC) database from 2001 to 2021. Microsoft Excel 2020, CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis. Results: In the past 20 years, a total of 2,550 articles and reviews have been published in 35 journals, and the published and cited results show a growing trend. Cosson M and International Urogynecology Journal were the authors and journals with the highest output, respectively. The United States, France and the United Kingdom are among the top three countries/organizations in relevant publications in worldwide. 584 key words in the literature are divided into 8 clusters, which are mainly related to prolapse type, risk factors, surgical methods, imaging, quality of life and bioengineering. Using clinical research and tissue engineering technology to reduce mesh complications is the current hot spot in this field. Conclusion: Reasonable application of mesh and avoiding mesh complications are still the most concerned topics in POP research. Although clinical research, surgical improvement, biological mesh and bioengineering technology have shown promising results, it is still urgent to carry out clinical transformation application research.
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Affiliation(s)
- Quan Zhou
- Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang, China
- Department of Gynecology and Obstetrics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian, China
- *Correspondence: Quan Zhou, ; Yan-Feng Song,
| | - Man Lu
- Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang, China
| | - Guo-Sheng Li
- Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang, China
| | - Gan-Lu Peng
- Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang, China
| | - Yan-Feng Song
- Department of Gynecology and Obstetrics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian, China
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13
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Lin M, Lu Y, Chen J. Tissue-engineered repair material for pelvic floor dysfunction. Front Bioeng Biotechnol 2022; 10:968482. [PMID: 36147522 PMCID: PMC9485870 DOI: 10.3389/fbioe.2022.968482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
Pelvic floor dysfunction (PFD) is a highly prevalent urogynecology disorder affecting many women worldwide, with symptoms including pelvic organ prolapse (POP), stress urinary incontinence (SUI), fecal incontinence, and overactive bladder syndrome (OAB). At present, the clinical treatments of PFD are still conservative and symptom-based, including non-surgical treatment and surgery. Surgical repair is an effective and durable treatment for PFD, and synthetic and biological materials can be used to enforce or reinforce the diseased tissue. However, synthetic materials such as polypropylene patches caused a series of complications such as mesh erosion, exposure, pain, and inflammation. The poor mechanical properties and high degradation speed of the biomaterial meshes resulted in poor anatomical reduction effect and limitation to clinical application. Therefore, the current treatment options are suboptimal. Recently, tissue-engineered repair material (TERM) has been applied to repair PFD and could markedly improve the prognosis of POP and SUI repair surgery in animal models. We review the directions and progression of TERM in POP and SUI repair. Adipose-derived stem cells (ADSCs) and endometrial mesenchymal stem cells (eMSCs) appear to be suitable cell types for scaffold seeding and clinical implantation. The multidisciplinary therapy approach to tissue engineering is a promising direction for tissue repair. More and longer follow-up studies are needed before determining cell types and materials for PFD repair.
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Affiliation(s)
- Meina Lin
- NHC Key Laboratory of Reproductive Health and Medical Genetics (China Medical University) and Liaoning Key Laboratory of Reproductive Health, Liaoning Research Institute of Family Planning (The Affiliated Reproductive Hospital of China Medical University), Shenyang, China
| | - Yongping Lu
- NHC Key Laboratory of Reproductive Health and Medical Genetics (China Medical University) and Liaoning Key Laboratory of Reproductive Health, Liaoning Research Institute of Family Planning (The Affiliated Reproductive Hospital of China Medical University), Shenyang, China
- *Correspondence: Yongping Lu, ; Jing Chen,
| | - Jing Chen
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Yongping Lu, ; Jing Chen,
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14
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Wang J, Xu X, Xu J. Modified laparoscopic high uterosacral ligament suspension for treatment of apical prolapse: A feasibility study. J Obstet Gynaecol Res 2022; 48:2918-2925. [DOI: 10.1111/jog.15393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 07/20/2022] [Accepted: 07/27/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Jing Wang
- Department of Gynecology The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Quzhou China
| | - Xiaomin Xu
- Department of Gynecology The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Quzhou China
| | - Jingui Xu
- Department of Gynecology The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Quzhou China
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15
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Preparation of a Cage-Type Polyglycolic Acid/Collagen Nanofiber Blend with Improved Surface Wettability and Handling Properties for Potential Biomedical Applications. Polymers (Basel) 2021; 13:polym13203458. [PMID: 34685218 PMCID: PMC8541674 DOI: 10.3390/polym13203458] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 11/17/2022] Open
Abstract
Electrospun biobased polymeric nanofiber blends are widely used as biomaterials for different applications, such as tissue engineering and cell adhesion; however, their surface wettability and handling require further improvements for their practical utilization in the assistance of surgical operations. Therefore, Polyglycolic acid (PGA) and collagen-based nanofibers with three different ratios (40:60, 50:50 and 60:40) were prepared using the electrospinning method, and their surface wettability was improved using ozonation and plasma (nitrogen) treatment. The effect on the wettability and the morphology of pristine and blended PGA and collagen nanofibers was assessed using the WCA test and SEM, respectively. It was observed that PGA/collagen with the ratio 60:40 was the optimal blend, which resulted in nanofibers with easy handling and bead-free morphology that could maintain their structural integrity even after the surface treatments, imparting hydrophilicity on the surface, which can be advantageous for cell adhesion applications. Additionally, a cage-type collector was used during the electrospinning process to provide better handling properties to (PGA/collagen 60:40) blend. The resultant nanofiber mat was then incorporated with activated poly (α,β-malic acid) to improve its surface hydrophilicity. The chemical composition of PGA/collagen 60:40 was assessed using FTIR spectroscopy, supported by Raman spectroscopy.
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16
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Domínguez-Robles J, Shen T, Cornelius VA, Corduas F, Mancuso E, Donnelly RF, Margariti A, Lamprou DA, Larrañeta E. Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 129:112375. [PMID: 34579894 PMCID: PMC8505756 DOI: 10.1016/j.msec.2021.112375] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 12/11/2022]
Abstract
Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.
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Affiliation(s)
- Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Tingjun Shen
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Victoria A Cornelius
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK
| | - Francesca Corduas
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Jordanstown Campus, Newtownabbey BT37 0QB, UK
| | - Elena Mancuso
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Jordanstown Campus, Newtownabbey BT37 0QB, UK
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Andriana Margariti
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK
| | - Dimitrios A Lamprou
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
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17
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Cazorla-Luna R, Ruiz-Caro R, Veiga MD, Malcolm RK, Lamprou DA. Recent advances in electrospun nanofiber vaginal formulations for women's sexual and reproductive health. Int J Pharm 2021; 607:121040. [PMID: 34450222 DOI: 10.1016/j.ijpharm.2021.121040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/17/2021] [Accepted: 08/21/2021] [Indexed: 12/22/2022]
Abstract
Electrospinning is an innovative technique that allows production of nanofibers and microfibers by applying a high voltage to polymer solutions of melts. The properties of these fibers - which include high surface area, high drug loading capacity, and ability to be manufactured from mucoadhesive polymers - may be particularly useful in a myriad of drug delivery and tissue engineering applications. The last decade has witnessed a surge of interest in the application of electrospinning technology for the fabrication of vaginal drug delivery systems for the treatment and prevention of diseases associated with women's sexual and reproductive health, including sexually transmitted infections (e.g. infection with human immunodeficiency virus and herpes simplex virus) vaginitis, preterm birth, contraception, multipurpose prevention technology strategies, cervicovaginal cancer, and general maintenance of vaginal health. Due to their excellent mechanical properties, electrospun scaffolds are also being investigated as next-generation materials in the surgical treatment of pelvic organ prolapse. In this article, we review the latest advances in the field.
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Affiliation(s)
- Raúl Cazorla-Luna
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Roberto Ruiz-Caro
- Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - María-Dolores Veiga
- Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - R Karl Malcolm
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
| | - Dimitrios A Lamprou
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
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18
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Stewart SA, Domínguez-Robles J, Utomo E, Picco CJ, Corduas F, Mancuso E, Amir MN, Bahar MA, Sumarheni S, Donnelly RF, Permana AD, Larrañeta E. Poly(caprolactone)-based subcutaneous implant for sustained delivery of levothyroxine. Int J Pharm 2021; 607:121011. [PMID: 34391850 DOI: 10.1016/j.ijpharm.2021.121011] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/21/2021] [Accepted: 08/10/2021] [Indexed: 12/15/2022]
Abstract
This work aimed to develop a subcutaneous implant for prolonged delivery of LEVO to treat hypothyroidism. This could overcome challenges with patient compliance and co-administration and could improve treatment of this condition. For this purpose, implants were produced by solvent casting mixtures of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG) and LEVO sodium. These implants contained mixtures of PCL of differing molecular weight, PEG and different LEVO sodium loadings (20% or 40% w/w). SEM images confirmed that the drug was evenly dispersed throughout the implant. In vitro release rates ranging from 28.37 ± 1.19 - 78.21 ± 19.93 µg/day and 47.39 ± 8.76 - 98.92 ± 4.27 µg/day were achieved for formulations containing 20% and 40% w/w drug loading, respectively. Implants containing higher amounts of low molecular weight PCL and 40% w/w of LEVO showed release profiles governed by zero order kinetics. On the other hand, implants containing higher amounts of high molecular weight PCL showed a release mechanism governed by Fickian diffusion. Finally, two representative formulations were tested in vivo. These implants were capable of providing detectable LEVO levels in plasma during the entire duration of the experiments (4 weeks) with LEVO plasma levels ranging between 5 and 20 ng/mL.
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Affiliation(s)
- Sarah A Stewart
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Emilia Utomo
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Camila J Picco
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Francesca Corduas
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Jordanstown Campus, Newtownabbey BT37 0QB, UK
| | - Elena Mancuso
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Jordanstown Campus, Newtownabbey BT37 0QB, UK
| | - Muh Nur Amir
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
| | - Muh Akbar Bahar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
| | - Sumarheni Sumarheni
- Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Andi Dian Permana
- Department of Pharmaceutics, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia.
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
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19
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Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme. Pharmaceutics 2021; 13:pharmaceutics13040471. [PMID: 33807243 PMCID: PMC8065414 DOI: 10.3390/pharmaceutics13040471] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/23/2021] [Accepted: 03/23/2021] [Indexed: 12/11/2022] Open
Abstract
A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.
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20
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Quarterman JC, Geary SM, Salem AK. Evolution of drug-eluting biomedical implants for sustained drug delivery. Eur J Pharm Biopharm 2021; 159:21-35. [PMID: 33338604 PMCID: PMC7856224 DOI: 10.1016/j.ejpb.2020.12.005] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/19/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023]
Abstract
In the field of drug delivery, the most commonly used treatments have traditionally been systemically delivered using oral or intravenous administration. The problems associated with this type of delivery is that the drug concentration is controlled by first pass metabolism, and therefore may not always remain within the therapeutic window. Implantable drug delivery systems (IDDSs) are an excellent alternative to traditional delivery because they offer the ability to precisely control the drug release, deliver drugs locally to the target tissue, and avoid the toxic side effects often experienced with systemic administration. Since the creation of the first FDA-approved IDDS in 1990, there has been a surge in research devoted to fabricating and testing novel IDDS formulations. The versatility of these systems is evident when looking at the various biomedical applications that utilize IDDSs. This review provides an overview of the history of IDDSs, with examples of the different types of IDDS formulations, as well as looking at current and future biomedical applications for such systems. Though there are still obstacles that need to be overcome, ever-emerging new technologies are making the manufacturing of IDDSs a rewarding therapeutic endeavor with potential for further improvements.
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Affiliation(s)
- Juliana C Quarterman
- University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 180 S. Grand Avenue, Iowa City, IA 52242, United States
| | - Sean M Geary
- University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 180 S. Grand Avenue, Iowa City, IA 52242, United States
| | - Aliasger K Salem
- University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 180 S. Grand Avenue, Iowa City, IA 52242, United States.
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21
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Martin NK, Domínguez-Robles J, Stewart SA, Cornelius VA, Anjani QK, Utomo E, García-Romero I, Donnelly RF, Margariti A, Lamprou DA, Larrañeta E. Fused deposition modelling for the development of drug loaded cardiovascular prosthesis. Int J Pharm 2021; 595:120243. [PMID: 33484923 DOI: 10.1016/j.ijpharm.2021.120243] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/16/2020] [Accepted: 12/17/2020] [Indexed: 01/25/2023]
Abstract
Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared.
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Affiliation(s)
- Niamh K Martin
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Sarah A Stewart
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Victoria A Cornelius
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK
| | - Qonita Kurnia Anjani
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Emilia Utomo
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Inmaculada García-Romero
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK
| | - Andriana Margariti
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK
| | - Dimitrios A Lamprou
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
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22
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Next-generation surgical meshes for drug delivery and tissue engineering applications: materials, design and emerging manufacturing technologies. Biodes Manuf 2021. [DOI: 10.1007/s42242-020-00108-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Abstract
Surgical meshes have been employed in the management of a variety of pathological conditions including hernia, pelvic floor dysfunctions, periodontal guided bone regeneration, wound healing and more recently for breast plastic surgery after mastectomy. These common pathologies affect a wide portion of the worldwide population; therefore, an effective and enhanced treatment is crucial to ameliorate patients’ living conditions both from medical and aesthetic points of view. At present, non-absorbable synthetic polymers are the most widely used class of biomaterials for the manufacturing of mesh implants for hernia, pelvic floor dysfunctions and guided bone regeneration, with polypropylene and poly tetrafluoroethylene being the most common. Biological prostheses, such as surgical grafts, have been employed mainly for breast plastic surgery and wound healing applications. Despite the advantages of mesh implants to the treatment of these conditions, there are still many drawbacks, mainly related to the arising of a huge number of post-operative complications, among which infections are the most common. Developing a mesh that could appropriately integrate with the native tissue, promote its healing and constructive remodelling, is the key aim of ongoing research in the area of surgical mesh implants. To this end, the adoption of new biomaterials including absorbable and natural polymers, the use of drugs and advanced manufacturing technologies, such as 3D printing and electrospinning, are under investigation to address the previously mentioned challenges and improve the outcomes of future clinical practice. The aim of this work is to review the key advantages and disadvantages related to the use of surgical meshes, the main issues characterizing each clinical procedure and the future directions in terms of both novel manufacturing technologies and latest regulatory considerations.
Graphic abstract
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23
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Liu PR, Lu L, Zhang JY, Huo TT, Liu SX, Ye ZW. Application of Artificial Intelligence in Medicine: An Overview. Curr Med Sci 2021; 41:1105-1115. [PMID: 34874486 PMCID: PMC8648557 DOI: 10.1007/s11596-021-2474-3] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/01/2020] [Indexed: 02/06/2023]
Abstract
Artificial intelligence (AI) is a new technical discipline that uses computer technology to research and develop the theory, method, technique, and application system for the simulation, extension, and expansion of human intelligence. With the assistance of new AI technology, the traditional medical environment has changed a lot. For example, a patient's diagnosis based on radiological, pathological, endoscopic, ultrasonographic, and biochemical examinations has been effectively promoted with a higher accuracy and a lower human workload. The medical treatments during the perioperative period, including the preoperative preparation, surgical period, and postoperative recovery period, have been significantly enhanced with better surgical effects. In addition, AI technology has also played a crucial role in medical drug production, medical management, and medical education, taking them into a new direction. The purpose of this review is to introduce the application of AI in medicine and to provide an outlook of future trends.
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Affiliation(s)
- Peng-ran Liu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Lin Lu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Jia-yao Zhang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Tong-tong Huo
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Song-xiang Liu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Zhe-wei Ye
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
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24
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Farmer ZL, Utomo E, Domínguez-Robles J, Mancinelli C, Mathew E, Larrañeta E, Lamprou DA. 3D printed estradiol-eluting urogynecological mesh implants: Influence of material and mesh geometry on their mechanical properties. Int J Pharm 2021; 593:120145. [DOI: 10.1016/j.ijpharm.2020.120145] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/26/2020] [Accepted: 11/28/2020] [Indexed: 12/30/2022]
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