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Aili Y, Wei P, Yu X, Fan G, Maimaitiaili N, Li Y, Liu S, Huang Y, Zhao B, Wang Z, Qin H, Wang Y. Janus adhesive bio-patches with targeted drug delivery enabled anti-bacteria and pro-angiogenesis for dura mater repair. Mater Today Bio 2025; 31:101484. [PMID: 39925716 PMCID: PMC11804716 DOI: 10.1016/j.mtbio.2025.101484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/18/2024] [Accepted: 01/11/2025] [Indexed: 02/11/2025] Open
Abstract
Dural injuries often result in severe complications such as cerebrospinal fluid (CSF) leakage, intracranial infections, and brain herniation, which significantly impact patient recovery and quality of life. Conventional dural repair materials, which rely on suturing to peripheral tissues, fail to promote tissue regeneration and provide sufficient CSF leakage prevention, leading to suboptimal outcomes. To address these limitations, we developed a Janus adhesive bio-patch with both antibacterial and pro-angiogenic properties to enhance dura mater repair. This bio-patch consisted of a polyacrylic acid (PAA) adhesive gel layer loaded with vancomycin and magnesium carbonate (MgCO3), integrated onto a small intestinal submucosa (SIS) extracellular matrix. It exhibited a burst strength of 20.50±2.89kPa, effectively sealing CSF leaks, while demonstrating excellent antibacterial efficacy (∼99%) and significant enhanced angiogenesis (3.47-fold higher than the control). In rat, rabbit, and dog dural injury models, the bio-patch adhered seamlessly to the injury site, successfully preventing leaks and promoting tissue regeneration. These results highlighted the Janus adhesive bio-patch as a promising solution for improving dural repair in neurosurgery, offering a safer and more effective alternative to conventional suturing techniques.
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Affiliation(s)
- Yirizhati Aili
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
- Key Laboratory of Precision Diagnosis and Clinical Transformation of Nervous System Tumors, Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
| | - Pengfei Wei
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Xueqiao Yu
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Guofeng Fan
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
| | - Nuerailijiang Maimaitiaili
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
| | - Yunhuan Li
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Siqi Liu
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Yiqian Huang
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Bo Zhao
- Beijing Biosis Healing Biological Technology Co., Ltd, No.29 Yongda Road, Beijing, 102600, China
| | - Zengliang Wang
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
- Key Laboratory of Precision Diagnosis and Clinical Transformation of Nervous System Tumors, Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
| | - Hu Qin
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
| | - Yongxin Wang
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
- Key Laboratory of Precision Diagnosis and Clinical Transformation of Nervous System Tumors, Xinjiang Medical University, No.393 Xinyi Road, Urumqi, Xinjiang, 830054, China
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Yang Y, Tong T, Li X, Zheng H, Yao S, Deng J, Zhang Q, Liu Z, Huang X, Li H, Mu Y, Ma S. The Phase-Transited Lysozyme Coating Modified Small Intestinal Submucosa Membrane Loaded with Calcium and Zinc Ions for Enhanced Bone Regeneration. Adv Healthc Mater 2025; 14:e2404564. [PMID: 39995373 DOI: 10.1002/adhm.202404564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/03/2025] [Indexed: 02/26/2025]
Abstract
Bone defects caused by severe trauma, tumors, infections and diseases remain a global challenge due to limited natural regeneration capacity of bone tissue in large-scale or complex injuries. Guided bone regeneration (GBR) has emerged as a pivotal technique in addressing these issues, relying on barrier membranes to facilitate osteoprogenitor cell infiltration. Current clinical GBR membranes function solely as physical barriers, lacking antibacterial and osteoinductive properties, which underscores the need for advanced alternatives. This study focuses on resorbable GBR membranes made from small intestinal submucosa (SIS), known for biocompatibility and tissue regeneration but hindered by low mechanical strength and rapid degradation. In addition, SIS lacks both antibacterial properties and strong osteogenic capabilities. Enhancements involve crosslinking treatment and dual incorporation of calcium (Ca2+) and zinc (Zn2+), which address the physical property shortcomings and synergistically boost osteoinductivity by activating osteogenic signaling pathways. Additionally, phase-transited lysozyme (PTL) nanofilm technique enables efficient ion loading and controlled release, while offering antibacterial properties. In this study, a multifunctional SIS membrane is constructed by PTL-ions layers, providing a potential solution to the challenge of clinical bone defects.
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Affiliation(s)
- Yilin Yang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Tianyi Tong
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Xin Li
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Hong Zheng
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Shiyu Yao
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Jiayin Deng
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Qi Zhang
- Department of Quality Control and Management, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital) Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266000, China
| | - Zihao Liu
- Zhongnuo Dental Hospital, Tianjin Nankai District, Tianjin, 300101, China
| | - Xin Huang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
- Department of Oral and Maxillofacial Surgery, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin, 300070, P. R. China
| | - Hongjie Li
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Yuzhu Mu
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University, Tianjin, 300070, China
| | - Shiqing Ma
- Tianjin Medical University, Tianjin, 300070, China
- Department of Oral and Maxillofacial Surgery, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin, 300070, P. R. China
- Department of Stomatology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China
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de Paulo CB, Miglino MA, Castelucci P. Perspectives on the extracellular matrix in inflammatory bowel disease and bowel decellularization protocols. World J Exp Med 2024; 14:97179. [PMID: 39713079 PMCID: PMC11551702 DOI: 10.5493/wjem.v14.i4.97179] [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: 05/24/2024] [Revised: 09/15/2024] [Accepted: 10/15/2024] [Indexed: 10/31/2024] Open
Abstract
The extracellular matrix (ECM) is a non-cellular three-dimensional structure present in all tissues that is essential for the intestinal maintenance, function and structure, as well as for providing physical support for tissue integrity and elasticity. ECM enables the regulation of various processes involved in tissue homeostasis, being vital for healing, growth, migration and cell differentiation. Structurally, ECM is composed of water, polysaccharides and proteins, such as collagen fibers and proteoglycans, which are specifically arranged for each tissue. In pathological scenarios, such as inflammatory bowel disease (IBD), the deposition and remodeling of the ECM can be altered in relation to the homeostatic composition. IBD, such as Ulcerative colitis and Crohn's disease, can be differentiated according to ECM alterations, such as circulating levels of collagen, laminin and vimentin neoepitopes. In this context, ECM presents particularities in both physiological and pathological processes, however, exploring methods of tissue decellularization is emerging as a promising frontier for new therapeutic interventions and clinical protocols, promoting the development of new approaches to intestinal diseases.
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Affiliation(s)
- Caroline Bures de Paulo
- Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo 05508-270, São Paulo, Brazil
| | - Maria Angelica Miglino
- Laboratório de Medicina Regenerativa, Universidade de Marilia, Marilia 00000, São Paulo, Brazil
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张 秀, 王 家, 解 慧. [Application and progress of bio-derived materials in bladder regeneration and repair]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2024; 38:1299-1306. [PMID: 39542618 PMCID: PMC11563737 DOI: 10.7507/1002-1892.202404099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 11/17/2024]
Abstract
Objective To summarize the research progress of bio-derived materials used for bladder regeneration and repair. Methods The recent domestic and foreign sutudies on bio-derived materials used for bladder regeneration and repair, including classification, morphology optimization process, tissue regeneration strategies, and relevant clinical trials, were summarized and analyzed. Results Numerous types of bio-derived materials are employed in bladder regeneration and repair, characterized by their low immunogenicity and high inducible activity. Surface modification, gelation, and other morphology optimization process have significantly broadened the application scope of bio-derived materials. These advancements have effectively addressed complications, such as perforation and urolith formation, that may arise during bladder regeneration and repair. The strategy of tissue regeneration utilizing bio-derived materials, targeting the regeneration of bladder epithelium, smooth muscle, blood vessels, and nerves, offers a novel approach to achieving functional regeneration of bladder. Bio-derived materials show great promise for use in bladder regeneration and repair, yet the results from clinical trials with these materials have been less than satisfactory. Conclusion Bio-derived materials are widely used in bladder regeneration and repair due to the good biocompatibility, low immunogenicity, and degradable properties, yet face a series of problems, and there are no commercialized bladder tissue engineering grafts used in clinical treatment.
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Affiliation(s)
- 秀珍 张
- 四川大学华西医院干细胞与组织工程研究中心（成都 610041）Stem Cell and Tissue Engineering Research Center, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China
| | - 家玮 王
- 四川大学华西医院干细胞与组织工程研究中心（成都 610041）Stem Cell and Tissue Engineering Research Center, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China
| | - 慧琪 解
- 四川大学华西医院干细胞与组织工程研究中心（成都 610041）Stem Cell and Tissue Engineering Research Center, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China
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Clifford AL, Klifto CS, Li NY. Nerve Coaptation in 2023: Adjuncts to Nerve Repair Beyond Suture. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2024; 6:705-710. [PMID: 39381375 PMCID: PMC11456665 DOI: 10.1016/j.jhsg.2024.01.027] [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: 10/15/2023] [Accepted: 01/20/2024] [Indexed: 10/10/2024] Open
Abstract
Effective nerve coaptation entails tensionless repair of healthy fascicles with intact fascicular architecture and a well-vascularized environment, supportive of the regenerative cellular behaviors of neurons, immune cells, and Schwann cells. Suture coaptations have historically been used to ensure that these criteria are met for end-to-end repair, nerve transfers, and allograft or autograft reconstructions; however, unfortunately, overall restoration of function remains poor. As optimal coaptation is required for return of sensorimotor function, adjunct biomaterials are increasingly being enlisted attempting to optimize these suture-based coaptations. The purpose of this review was to discuss the biological, preclinical, and clinical data for the use of fibrin glue and nerve wraps made of type 1 collagen, porcine small intestine submucosa, chitosan, and human amniotic membrane. This study provides available data on each material's ability to optimize the regenerative potential of nerve repair as well as available outcomes data. Although each biomaterial discussed has benefits to nerve regeneration, at large, data remain heterogeneous, and continued investigation is required to fully understand the specific mechanisms involved and the long-term potential clinical impacts each can provide for improvement of sensorimotor outcomes.
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Affiliation(s)
| | | | - Neill Y. Li
- Department of Orthopaedic Surgery, Duke University, Durham, NC
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Zhao J, Zhang H, Ling Z, An Z, Xiao S, Wang P, Fu Z, Shao J, Sun Y, Fu W. A bilayer bioengineered patch with sequential dual-growth factor release to promote vascularization in bladder reconstruction. Regen Biomater 2024; 11:rbae083. [PMID: 39077683 PMCID: PMC11286312 DOI: 10.1093/rb/rbae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 06/15/2024] [Accepted: 06/25/2024] [Indexed: 07/31/2024] Open
Abstract
Bladder tissue engineering holds promise for addressing bladder defects resulting from congenital or acquired bladder diseases. However, inadequate vascularization significantly impacts the survival and function of engineered tissues after transplantation. Herein, a novel bilayer silk fibroin (BSF) scaffold was fabricated with the capability of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) sequential release. The outer layer of the scaffold was composed of compact SF film with waterproofness to mimic the serosa of the bladder. The inner layer was constructed of porous SF matrix incorporated with SF microspheres (MS) loaded with VEGF and PDGF-BB. We found that the 5% (w/v) MS-incorporated scaffold exhibited a rapid release of VEGF, whereas the 0.2% (w/v) MS-incorporated scaffold demonstrated a slow and sustained release of PDGF-BB. The BSF scaffold exhibited good biocompatibility and promoted endothelial cell migration, tube formation and enhanced endothelial differentiation of adipose derived stem cells (ADSCs) in vitro. The BSF patch was constructed by seeding ADSCs on the BSF scaffold. After in vivo transplantation, not only could the BSF patch facilitate the regeneration of urothelium and smooth muscle, but more importantly, stimulate the regeneration of blood vessels. This study demonstrated that the BSF patch exhibited excellent vascularization capability in bladder reconstruction and offered a viable functional bioengineered patch for future clinical studies.
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Affiliation(s)
- Jian Zhao
- Medical School of PLA, Beijing 100853, China
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
- Department of Urology, 960th Hospital of PLA, Jinan 250031, China
| | - Haoqian Zhang
- Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, China
| | - Zhengyun Ling
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Ziyan An
- Medical School of PLA, Beijing 100853, China
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
| | - Shuwei Xiao
- Department of Urology, Air Force Medical Center, Beijing 100142, China
| | - Pengchao Wang
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
| | - Zhouyang Fu
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
| | - Jinpeng Shao
- Medical School of PLA, Beijing 100853, China
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
| | - Yanfeng Sun
- Department of Pediatrics, The Third Medical Center, PLA General Hospital, Beijing 100039, China
| | - Weijun Fu
- Department of Urology, The Third Medical Center, PLA General Hospital, Beijing 100039, China
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Zhao Y, Peng H, Sun L, Tong J, Cui C, Bai Z, Yan J, Qin D, Liu Y, Wang J, Wu X, Li B. The application of small intestinal submucosa in tissue regeneration. Mater Today Bio 2024; 26:101032. [PMID: 38533376 PMCID: PMC10963656 DOI: 10.1016/j.mtbio.2024.101032] [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: 12/13/2023] [Revised: 03/04/2024] [Accepted: 03/15/2024] [Indexed: 03/28/2024] Open
Abstract
The distinctive three-dimensional architecture, biological functionality, minimal immunogenicity, and inherent biodegradability of small intestinal submucosa extracellular matrix materials have attracted considerable interest and found wide-ranging applications in the domain of tissue regeneration engineering. This article presents a comprehensive examination of the structure and role of small intestinal submucosa, delving into diverse preparation techniques and classifications. Additionally, it proposes approaches for evaluating and modifying SIS scaffolds. Moreover, the advancements of SIS in the regeneration of skin, bone, heart valves, blood vessels, bladder, uterus, and urethra are thoroughly explored, accompanied by their respective future prospects. Consequently, this review enhances our understanding of the applications of SIS in tissue and organ repair and keeps researchers up-to-date with the latest research advancements in this area.
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Affiliation(s)
- Yifan Zhao
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Hongyi Peng
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Lingxiang Sun
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jiahui Tong
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Chenying Cui
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Ziyang Bai
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jingyu Yan
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Danlei Qin
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Yingyu Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jue Wang
- The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Xiuping Wu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Bing Li
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
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XiaoMing X, Yan C, JiaMing G, LiTao L, LiJuan Z, Ying S, Lu Y, Qian S, Jian D. Human umbilical cord mesenchymal stem cells combined with porcine small intestinal submucosa promote the healing of full-thickness skin injury in SD rats. Future Sci OA 2024; 10:FSO955. [PMID: 38817375 PMCID: PMC11137796 DOI: 10.2144/fsoa-2023-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 12/13/2023] [Indexed: 06/01/2024] Open
Abstract
Aim: To assess the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with porcine small intestinal submucosa (SIS) on full-thickness skin injuries in rats. Methods: We established full-thickness skin injury models in Sprague-Dawley rats, dividing them into blank control, SIS, hUCMSCs and hUCMSCs combined with SIS. We monitored wound healing, scores and area, and analyzed inflammatory cells, microvessel density and collagen fibers after 12 days. Results: The blank group showed no healing, forming a scar of 0.6 × 0.5 cm2, while SIS and hUCMSCs groups exhibited incomplete healing with 0.4 × 0.5 cm2 scabs. Wound healing was significantly better in the hUCMSCs combined with the SIS group. Conclusion: Local application of hUCMSCs combined with SIS enhances full-thickness skin injury wound healing in rats.
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Affiliation(s)
- Xu XiaoMing
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
| | - Chen Yan
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
| | - Gu JiaMing
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
| | - Liang LiTao
- Department of Obstetrics, The Second Affiliated Hospital of Kunming Medical University,Kunming,Yunnan, 650101, China
| | - Zhang LiJuan
- Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital, Kunming, Yunnan, 650118, China
| | - Song Ying
- Department of Obstetrics, Kunming Maternal & Child Health Hospital, Kunming, Yunnan, 650011, China
| | - Yuan Lu
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
| | - Song Qian
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
| | - Dong Jian
- Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital/Yunnan Cellular Therapy & Quality Control System Engineering Research Center, Kunming, Yunnan, 650118, China
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Nikzad S, Same S, Safiri S, Dolati S, Roushangar Zineh B, Meshgi S, Roshangar L, Şahin F. The effect of Wharton's jelly-derived stem cells seeded/boron-loaded acellular scaffolds on the healing of full-thickness burn wounds in the rat model. Biomed Mater 2024; 19:025042. [PMID: 38364284 DOI: 10.1088/1748-605x/ad2a3e] [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: 06/19/2023] [Accepted: 02/16/2024] [Indexed: 02/18/2024]
Abstract
Burn wounds are the most destructive and complicated type of skin or underlying soft tissue injury that are exacerbated by a prolonged inflammatory response. Several cell-based therapeutic systems through the culturing of potent stem cells on modified scaffolds have been developed to direct the burn healing challenges. In this context, a new regenerative platform based on boron (B) enriched-acellular sheep small intestine submucosa (AOSIS) scaffold was designed and used as a carrier for mesenchymal stem cells derived from Wharton's jelly (WJMSCs) aiming to promote the tissue healing in burn-induced rat models. hWJMSCs have been extracted from human extra-embryonic umbilical cord tissue. Thereafter, 96 third-degree burned Wistar male rats were divided into 4 groups. The animals that did not receive any treatment were considered as group A (control). Then, group B was treated just by AOSIS scaffold, group C was received cell-seeded AOSIS scaffold (hWJMSCs-AOSIS), and group D was covered by boron enriched-cell-AOSIS scaffold (B/hWJMSCs-AOSIS). Inflammatory factors, histopathological parameters, and the expression levels of epitheliogenic and angiogenic proteins were assessed on 5, 14 and 21 d post-wounding. Application of the B/hWJMSCs-AOSIS on full-thickness skin-burned wounds significantly reduced the volume of neutrophils and lymphocytes at day 21 post-burning, whilst the number of fibroblasts and blood vessels enhanced at this time. In addition, molecular and histological analysis of wounds over time further verified that the addition of boron promoted wound healing, with decreased inflammatory factors, stimulated vascularization, accelerated re-epithelialization, and enhanced expression levels of epitheliogenic genes. In addition, the boron incorporation amplified wound closure via increasing collagen deposition and fibroblast volume and activity. Therefore, this newly fabricated hWJMSCs/B-loaded scaffold can be used as a promising system to accelerate burn wound reconstruction through inflammatory regulation and angiogenesis stimulation.
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Affiliation(s)
- Sadeneh Nikzad
- Biology Department, Concordia University, Montreal, Canada
| | - Saeideh Same
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeid Safiri
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sanam Dolati
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Shahla Meshgi
- General Cardiologist, Tabriz Madani Heart Hospital, Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Faculty of Medicine, Department of Anatomical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fikrettin Şahin
- Faculty of Engineering and Architecture, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey
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Liu Z, Du Y, Xu S, Li M, Lu X, Tian G, Ye J, Zhao B, Wei P, Wang Y. Histatin 1-modified SIS hydrogels enhance the sealing of peri-implant mucosa to prevent peri-implantitis. iScience 2023; 26:108212. [PMID: 37965149 PMCID: PMC10641262 DOI: 10.1016/j.isci.2023.108212] [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: 05/27/2023] [Revised: 09/15/2023] [Accepted: 10/11/2023] [Indexed: 11/16/2023] Open
Abstract
Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.
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Affiliation(s)
- Zihao Liu
- Zhongnuo Dental Hospital, Tianjin Nankai District, Tianjin 300101, China
| | - Yaqi Du
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
| | - Shendan Xu
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
| | - Minting Li
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
| | - Xuemei Lu
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
| | - Guangjie Tian
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
| | - Jing Ye
- Department of Stomatology, Tianjin Hospital, Tianjin 300211, China
| | - Bo Zhao
- Beijing Biosis Healing Biological Technology Co., Ltd., Beijing 102600, China
| | - Pengfei Wei
- Beijing Biosis Healing Biological Technology Co., Ltd., Beijing 102600, China
| | - Yonglan Wang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 30070, China
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11
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Cui L, Zhao Y, Zhong Y, Zhang L, Zhang X, Guo Z, Wang F, Chen X, Tong H, Fan J. Combining decellularized adipose tissue with decellularized adventitia extravascular matrix or small intestinal submucosa matrix for the construction of vascularized tissue-engineered adipose. Acta Biomater 2023; 170:567-579. [PMID: 37683968 DOI: 10.1016/j.actbio.2023.08.060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 08/24/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023]
Abstract
Adipose tissue is an endocrine organ. It serves many important functions, such as energy storage, hormones secretion, and providing insulation, cushioning and aesthetics to the body etc. Adipose tissue engineering offers a promising treatment for soft tissue defects. Early adipose tissue production and long-term survival are closely associated with angiogenesis. Decellularized matrix has a natural ECM (extracellular matrix) component, good biocompatibility, and low immunogenicity. Therefore, in this study, the injectable composite hydrogels were developed to construct vascularized tissue-engineered adipose by using the pro-angiogenic effects of aortic adventitia extravascular matrix (Adv) or small intestinal submucosa (SIS), and the pro-adipogenic effects of decellularized adipose tissue (DAT). The composite hydrogels were cross-linked by genipin. The adipogenic and angiogenic abilities of composite hydrogels were investigated in vitro, and in a rat dorsal subcutaneous implant model. The results showed that DAT and SIS or Adv 1:1 composite hydrogel promoted the migration and tube formation of endothelial cells. Furthermore, DAT and SIS or Adv 1:1 composite hydrogel enhanced adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs) through activation of PPARγ and C/EBPα. The in vivo studies further demonstrated that DAT with SIS or Adv in a 1:1 ratio also significantly promoted adipogenesis and angiogenesis. In addition, DAT with SIS or Adv in a 1:1 ratio hydrogel recruited macrophage population with enhanced M2-type macrophage polarization, suggesting a positive effect of inflammatory response on angiogenesis. In conclusion, these data suggest that the composite hydrogels of DAT with SIS or Adv in 1:1 ratio have apparent pro-adiogenic and angiogenic abilities, thus providing a promising cell-free tissue engineering biomaterial with broad clinical applications. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT) has emerged as an important biomaterial in adipose tissue regeneration. Early adipose tissue production and long-term survival is tightly related to the angiogenesis. The revascularization of the DAT is a key issue that needs to be solved in adipose regeneration. In this study, the injectable composite hydrogels were developed by using DAT with Adv (aortic adventitia extravascular matrix) or SIS (small intestinal submucosa) in different ratio. We demonstrated that the combination of DAT with SIS or Adv in 1:1 ratio effectively improved the proliferation of adipose stem cells and endothelial cells, and promoted greater adipose regeneration and tissue vascularization as compared to the DAT scaffold. This study provides the potential biomaterial for clinical soft tissue regeneration.
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Affiliation(s)
- Lu Cui
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Yujia Zhao
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Yuxuan Zhong
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Lanlan Zhang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Xinnan Zhang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Zhenglong Guo
- Second Clinical Medical College, Shengjing Hospital, China Medical University, No.36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, PR China
| | - Fanglin Wang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Xin Chen
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Hao Tong
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China
| | - Jun Fan
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, PR China.
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Zhang N, Huang Y, Wei P, Sun L, Jing W, Xue Y, Zhang Y, Zhao B, Yang Z. Killing two birds with one stone: A therapeutic copper-loaded bio-patch promoted abdominal wall repair via VEGF pathway. Mater Today Bio 2023; 22:100785. [PMID: 37680583 PMCID: PMC10480776 DOI: 10.1016/j.mtbio.2023.100785] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/09/2023] Open
Abstract
Hernia and life-threatening intestinal obstruction often result from abdominal wall injuries, and the regeneration of abdominal wall defects is limited due to the lack of biocompatible, antibacterial and angiogenic scaffolding materials for treating injured tissues. Taking inspiration from the facile preparation of dopamine polymerization and its surface modification technology, in this study, multi-therapeutic copper element was introduced into porcine small intestinal submucosa (SIS) bio-patches through polydopamine (PDA) deposition, in order to regenerate abdominal wall injury. In both in vitro antibacterial assays, cytocompatibility assays and in vivo abdominal wall repair experiments, the SIS/PDA/Cu bio-patches exhibited robust antibacterial efficiency (＞99%), excellent biocompatibility to cells (＞90%), and enhanced neovascularization and improved collagen maturity compared to other commercially available patches (3.0-fold higher than the PP mesh), due to their activation of VEGF pathway. These findings indicated the bio-patch was a promising application for preventing visceral adhesion, bacterial infection, and promoting soft tissue regeneration.
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Affiliation(s)
- Nan Zhang
- Department of General Surgery, Tianjin Nankai Hospital, Tianjin, 300100, China
| | - Yiqian Huang
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
| | - Pengfei Wei
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
- Foshan (Southern China) Institute for New Materials, Foshan, 528220, China
| | - Liya Sun
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
| | - Wei Jing
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
- Foshan (Southern China) Institute for New Materials, Foshan, 528220, China
| | - Yunxia Xue
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
| | - Yan Zhang
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
| | - Bo Zhao
- Beijing Biosis Healing Biological Technology Co., Ltd, Beijing, 102600, China
| | - Ziang Yang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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Luo K, Wang L, Wang MX, Du R, Tang L, Yang KK, Wang YZ. 4D Printing of Biocompatible Scaffolds via In Situ Photo-crosslinking from Shape Memory Copolyesters. ACS APPLIED MATERIALS & INTERFACES 2023; 15:44373-44383. [PMID: 37669475 DOI: 10.1021/acsami.3c10747] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
The complexity of surgical treatments for large-area soft tissue injuries makes placing large implants into injury sites challenging. Aliphatic polyesters are often used for scaffold preparation in tissue engineering owing to their excellent biodegradability and biocompatibility. Scaffolds with shape-memory effect (SME) can also avoid large-volume trauma during the implantation. However, the complexity and diversity of diseases require more adaptable and precise processing methods. Four-dimensional (4D) printing, a booming smart material additive manufacturing technology, provides a new opportunity for developing shape memory scaffolds. With the aim of personalized or patient-adaptable soft tissues such as blood vessels, we developed a feasible strategy for fabricating scaffolds with fine architectures using 4D printing crosslinkable shape memory linear copolyesters using fused deposition modeling (FDM). To overcome the weak bonding strength of each printed layer during FDM, a catalyst-free photo-crosslinkable functional group derived from biocompatible cinnamic acid was embedded into the linear copolyesters as in situ crosslinking points during FDM printing. Under ultraviolet-assisted irradiation, the resulting 4D scaffold models demonstrated excellent SME, desirable mechanical performance, and good stability in a water environment owing to the chemical bonding between each layer. Moreover, the excellent biocompatibility of the scaffold was evaluated in vitro and in vivo. The developed composite scaffolds could be used for minimally invasive soft tissue repair.
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Affiliation(s)
- Kun Luo
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
| | - Li Wang
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
- Department of Biomedical Engineering, School of Big Health and Intelligent Engineering, Chengdu 610500, China
| | - Man-Xi Wang
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
| | - Rui Du
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
| | - Li Tang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ke-Ke Yang
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
| | - Yu-Zhong Wang
- Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials (MoE), State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu 610064, China
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14
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Miao X, Yang S, Zhu J, Gong Z, Wu D, Hong J, Cai K, Wang J, Fang X, Lu J, Jiang G. Bioactive mineralized small intestinal submucosa acellular matrix/PMMA bone cement for vertebral bone regeneration. Regen Biomater 2023; 10:rbad040. [PMID: 37250976 PMCID: PMC10224805 DOI: 10.1093/rb/rbad040] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/30/2023] [Accepted: 04/15/2023] [Indexed: 05/31/2023] Open
Abstract
Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.
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Affiliation(s)
| | | | | | - Zhe Gong
- Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China
- Key Laboratory of Musculoskeletal System, Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
| | - Dongze Wu
- Department of Spinal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang, China
| | - Juncong Hong
- Department of Anesthesiology, The First People’s Hospital of Linping District, Hangzhou 311100, Zhejiang, China
| | - Kaiwen Cai
- Department of Spinal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang, China
| | - Jiying Wang
- Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China
- Key Laboratory of Musculoskeletal System, Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
| | | | - Jiye Lu
- Correspondence address. E-mail: (G.J.); (J.L.); (X.F.)
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15
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Wang L, Liu F, Zhai X, Dong W, Wei W, Hu Z. An adhesive gelatin-coated small intestinal submucosa composite hydrogel dressing aids wound healing. Int J Biol Macromol 2023; 241:124622. [PMID: 37119906 DOI: 10.1016/j.ijbiomac.2023.124622] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/19/2023] [Accepted: 04/23/2023] [Indexed: 05/01/2023]
Abstract
It is a challenging clinical task to determine how to repair large-area skin defects better. Traditional wound dressings (e.g., cotton and gauze) can only be used as a dressing; consequently, there is an increasing demand for wound dressings with additional properties (i.e., antibacterial and pro-repair) in clinical practice. In this study, a composite hydrogel with o-nitrobenzene-modified gelatin-coated decellularized small intestinal submucosa (GelNB@SIS) was designed for the repair of skin injuries. SIS is a natural extracellular matrix with a 3D microporous structure and also contains high levels of growth factors and collagen. GelNB provides this material photo-triggering tissue adhesive property. The structure, tissue adhesion, cytotoxicity, and bioactivity to cells were investigated. Based on in vivo study and histological analysis, we found the combination of GelNB and SIS improved the healing process by promoting vascular renewal, dermal remodeling, and epidermal regeneration. Based on our findings, GelNB@SIS is a promising candidate for tissue repair applications.
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Affiliation(s)
- Lu Wang
- International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China
| | - Fengling Liu
- International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
| | - Xinrang Zhai
- International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
| | - Wei Dong
- School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
| | - Wei Wei
- International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
| | - Zhenhua Hu
- International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China.
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16
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Viet-Nhi NK, Chen YC, Dang LH, Tseng H, Hung SH. Degassing a Decellularized Scaffold Enhances Wound Healing and Reduces Fibrosis during Tracheal Defect Reconstruction: A Preliminary Animal Study. J Funct Biomater 2023; 14:jfb14030147. [PMID: 36976071 PMCID: PMC10051568 DOI: 10.3390/jfb14030147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Few efforts have been made regarding the optimization of porcine small intestinal submucosa (SIS) to improve its biocompatibility. This study aims to evaluate the effect of SIS degassing on the promotion of cell attachment and wound healing. The degassed SIS was evaluated in vitro and in vivo, compared with the nondegassed SIS control. In the cell sheet reattachment model, the reattached cell sheet coverage was significantly higher in the degassed SIS group than in the nondegassed group. Cell sheet viability was also significantly higher in the SIS group than in the control group. In vivo studies showed that the tracheal defect repaired by the degassed SIS patch showed enhanced healing and reductions in fibrosis and luminal stenosis compared to the nondegassed SIS control group, with the thickness of the transplanted grafts in the degassed SIS group significantly lower than those in the control group (346.82 ± 28.02 µm vs. 771.29 ± 20.41 µm, p < 0.05). Degassing the SIS mesh significantly promoted cell sheet attachment and wound healing by reducing luminal fibrosis and stenosis compared to the nondegassed control SIS. The results suggest that the degassing processing might be a simple and effective way to improve the biocompatibility of SIS.
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Affiliation(s)
- Nguyen-Kieu Viet-Nhi
- International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Yen-Chun Chen
- Department of Otolaryngology, Taipei Medical University Hospital, Taipei 110, Taiwan
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Luong Huu Dang
- Department of Otolaryngology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 70000, Vietnam
| | - How Tseng
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Shih-Han Hung
- International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Correspondence:
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Cai F, Ren Y, Dai J, Yang J, Shi X. Effects of Various Cell Surface Engineering Reactions on the Biological Behavior of Mammalian Cells. Macromol Biosci 2023; 23:e2200379. [PMID: 36579789 DOI: 10.1002/mabi.202200379] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 12/15/2022] [Indexed: 12/30/2022]
Abstract
Cell surface engineering technologies can regulate cell function and behavior by modifying the cell surface. Previous studies have mainly focused on investigating the effects of cell surface engineering reactions and materials on cell activity. However, they do not comprehensively analyze other cellular processes. This study exploits covalent bonding, hydrophobic interactions, and electrostatic interactions to modify the macromolecules succinimide ester-methoxy polyethylene glycol (NHS-mPEG), distearoyl phosphoethanolamine-methoxy polyethylene glycol (DSPE-mPEG), and poly-L-lysine (PLL), respectively, on the cell surface. This work systematically investigates the effects of the three surface engineering reactions on the behavior of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts, including viability, growth, proliferation, cell cycle, adhesion, and migration. The results reveals that the PLL modification method notably affects cell viability and G2/M arrest and has a short modification duration. However, the DSPE-mPEG and NHS-mPEG modification methods have little effect on cell viability and proliferation but have a prolonged modification duration. Moreover, the DSPE-mPEG modification method highly affects cell adherence. Further, the NHS-mPEG modification method can significantly improve the migration ability of HUVECs by reducing the area of focal adhesions. The findings of this study will contribute to the application of cell surface engineering technology in the biomedical field.
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Affiliation(s)
- Fengying Cai
- College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China
| | - Yafeng Ren
- College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China
| | - Jiajia Dai
- College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China
| | - Jianmin Yang
- College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China.,Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China
| | - Xianai Shi
- College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China.,Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China
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18
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Liu S, Yao L, Wang Y, Li Y, Jia Y, Yang Y, Li N, Hu Y, Kong D, Dong X, Wang K, Zhu M. Immunomodulatory hybrid micro-nanofiber scaffolds enhance vascular regeneration. Bioact Mater 2023; 21:464-482. [PMID: 36185748 PMCID: PMC9486249 DOI: 10.1016/j.bioactmat.2022.08.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 12/02/2022] Open
Abstract
The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellularized extracellular matrix (dECM) limited their promotive efforts on tissue regeneration. Here, we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix (pECM) nanofibers by co-electrospinning, which was grafted with heparin and further absorbed with IL-4. The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype (increased by 18.1%) and then promoted migration, NO production, tube formation of endothelial cells (ECs), and migration and maturation of vascular smooth muscle cells (VSMCs), and ECM deposition in vitro and in vivo. ECs coverage rate increased by 8.6% and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks. Our study realized the complementary advantages of synthetic polymer materials and dECM materials, and opened intriguing perspectives for the design and construction of small-diameter vascular grafts (SDVGs) and immune-regulated materials for other tissue regeneration.
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Affiliation(s)
- Siyang Liu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Liying Yao
- Tianjin Central Hospital of Obstetrics and Gynecology/ Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300199, China
| | - Yumeng Wang
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Yi Li
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Yanju Jia
- Tianjin Central Hospital of Obstetrics and Gynecology/ Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300199, China
| | - Yueyue Yang
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Na Li
- Tianjin Central Hospital of Obstetrics and Gynecology/ Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300199, China
| | - Yuanjing Hu
- Tianjin Central Hospital of Obstetrics and Gynecology/ Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300199, China
| | - Deling Kong
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
- Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, 300192, China
| | - Xianhao Dong
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Kai Wang
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
| | - Meifeng Zhu
- College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China
- Tianjin Central Hospital of Obstetrics and Gynecology/ Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300199, China
- Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, 300192, China
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Song Z, Yang D, Hu Q, Wang Y, Zhang H, Dong W, Yang J, Gu Y. Reconstruction of Abdominal Wall Defect with Composite Scaffold of 3D Printed ADM/PLA in a Rat Model. Macromol Biosci 2023; 23:e2200521. [PMID: 36746773 DOI: 10.1002/mabi.202200521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/15/2023] [Indexed: 02/08/2023]
Abstract
Abdominal wall defects are a frequently occurring condition in surgical practice. The most important are material structure and biocompatibility. In this study, PLA mesh composited with a 3D printing of acellular dermal matrix (ADM) material is used to repair abdominal wall defects. The results show that the adhesion score of ADM/PLA composite scaffolds is smaller than PLA meshes. Immunohistochemical assessment reveals that the ADM/PLA composite scaffold can effectively reduce the inflammatory response at the contact surface between the meshes and the abdominal organs. And the ADM/PLA composite scaffold can effectively reduce the expression levels of the inflammation-related factors IL-6 and IL-10. In addition, the ADM/PLA composite scaffold repair is rich in the expression levels of tissue regeneration-related factors vascular endothelial growth factor and transforming growth factor β. Thus, ADM/PLA composite scaffolds can effectively reduce surrounding inflammation to effectively promote the repair of abdominal wall defects.
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Affiliation(s)
- Zhicheng Song
- General Surgery, Huadong Hospital Affiliated to Fudan University, 221 Yan 'an West Road, Jing 'an District, Shanghai, Shanghai, 200040, China
| | - Dongchao Yang
- General Surgery, Huadong Hospital Affiliated to Fudan University, 221 Yan 'an West Road, Jing 'an District, Shanghai, Shanghai, 200040, China
| | - Qingxi Hu
- Rapid Manufacturing Engineering Center, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai, Shanghai, 200444, China
| | - Yiming Wang
- Administrative office, Tenth People's Hospital of Tongji University, 301 Yanchang Zhong Lu, Jing 'an District, Shanghai, Shanghai, 200072, China
| | - Haiguang Zhang
- Rapid Manufacturing Engineering Center, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai, Shanghai, 200444, China
| | - Wenpei Dong
- General Surgery, Huadong Hospital Affiliated to Fudan University, 221 Yan 'an West Road, Jing 'an District, Shanghai, Shanghai, 200040, China
| | - Jianjun Yang
- General Surgery, Huadong Hospital Affiliated to Fudan University, 221 Yan 'an West Road, Jing 'an District, Shanghai, Shanghai, 200040, China
| | - Yan Gu
- General Surgery, Huadong Hospital Affiliated to Fudan University, 221 Yan 'an West Road, Jing 'an District, Shanghai, Shanghai, 200040, China
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Li Y, Zhou Y, Qiao W, Shi J, Qiu X, Dong N. Application of decellularized vascular matrix in small-diameter vascular grafts. Front Bioeng Biotechnol 2023; 10:1081233. [PMID: 36686240 PMCID: PMC9852870 DOI: 10.3389/fbioe.2022.1081233] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023] Open
Abstract
Coronary artery bypass grafting (CABG) remains the most common procedure used in cardiovascular surgery for the treatment of severe coronary atherosclerotic heart disease. In coronary artery bypass grafting, small-diameter vascular grafts can potentially replace the vessels of the patient. The complete retention of the extracellular matrix, superior biocompatibility, and non-immunogenicity of the decellularized vascular matrix are unique advantages of small-diameter tissue-engineered vascular grafts. However, after vascular implantation, the decellularized vascular matrix is also subject to thrombosis and neoplastic endothelial hyperplasia, the two major problems that hinder its clinical application. The keys to improving the long-term patency of the decellularized matrix as vascular grafts include facilitating early endothelialization and avoiding intravascular thrombosis. This review article sequentially introduces six aspects of the decellularized vascular matrix as follows: design criteria of vascular grafts, components of the decellularized vascular matrix, the changing sources of the decellularized vascular matrix, the advantages and shortcomings of decellularization technologies, modification methods and the commercialization progress as well as the application prospects in small-diameter vascular grafts.
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Affiliation(s)
| | | | | | | | - Xuefeng Qiu
- *Correspondence: Xuefeng Qiu, ; Nianguo Dong,
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21
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Cao D, Ding J. Recent advances in regenerative biomaterials. Regen Biomater 2022; 9:rbac098. [PMID: 36518879 PMCID: PMC9745784 DOI: 10.1093/rb/rbac098] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/23/2022] [Accepted: 12/01/2022] [Indexed: 07/22/2023] Open
Abstract
Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of 'biomaterials', and a typical new insight is the concept of tissue induction biomaterials. The term 'regenerative biomaterials' and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field-regenerative biomaterials.
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Affiliation(s)
- Dinglingge Cao
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Jiandong Ding
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
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22
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Peng L, Jin X, He Q, Gao X, Wang W, Zeng X, Shen H, Luo D. Remodelling landscape of tissue-engineered bladder with porcine small intestine submucosa using single-cell RNA sequencing. Cell Prolif 2022; 56:e13343. [PMID: 36177893 PMCID: PMC9816928 DOI: 10.1111/cpr.13343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/01/2022] [Accepted: 09/16/2022] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE Bioscaffolds are widely used for tissue engineering, but failed and inconsistent preclinical results have hampered the clinical use of bioscaffolds for tissue engineering. We aimed to construct a cellular remodelling landscape and to identify the key cell subpopulations and important genes driving bladder remodelling. METHODS Twenty-four reconstructed mouse bladders using porcine small intestinal submucosa (PSIS) were harvested at 1, 3, and 6 weeks to perform single-cell RNA sequencing. Cell types were identified and their differentially expressed genes (DEGs) at each stage were used for functional analysis. Immunofluorescence was used to validate the specific cell type. RESULTS The remodelling landscape included 13 cell types. Among them, fibroblasts, smooth muscle cells (SMCs), endothelial cells, and macrophages had the most communications with other cells. In the process of regeneration, DEGs of fibroblasts at 1, 3, and 6 weeks were mainly involved in wound healing, extracellular matrix organization, and regulation of development growth, respectively. Among these cells, Saa3+ fibroblasts might mediate tissue remodelling. The DEGs of SMCs at 1, 3, and 6 weeks were mainly involved in the inflammatory response, muscle cell proliferation, and mesenchyme development, respectively. Moreover, we found that Notch3+ SMCs potentially modulated contractility. From 1 to 6 weeks, synchronous development of endothelial cells was observed by trajectory analysis. CONCLUSIONS A remoulding landscape was successfully constructed and findings might help surficial modifications of PSIS and find a better alternative. However, more in vivo and in vitro studies are needed to further validate these results.
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Affiliation(s)
- Liao Peng
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - Xi Jin
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - Qing He
- Department of UrologyThe Third People's Hospital of ChengduChengduPR China
| | - Xiao‐shuai Gao
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - Wei Wang
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - Xiao Zeng
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - Hong Shen
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
| | - De‐yi Luo
- Department of UrologyInstitute of Urology, West China Hospital, Sichuan UniversityChengduPR China
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23
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Shen X, Zhang H, Li X, Li P, Zhao Y, Wang Y, Wang J. A hydrophobic layer prepared by cyclic grafting of polydimethylsiloxane on magnesium: improved corrosion resistance and biocompatibility. Regen Biomater 2022; 9:rbac068. [PMID: 36267153 PMCID: PMC9566967 DOI: 10.1093/rb/rbac068] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/17/2022] [Accepted: 09/04/2022] [Indexed: 02/07/2024] Open
Abstract
Magnesium and its alloys have been widely studied as absorbable coronary stent materials. However, the rapid corrosion rate in the intravascular environment inhibits the application of magnesium-based stents. In order to endow magnesium-based stent with appropriate degradation rate and biocompatibility, a hydrophobic layer was constructed by in situ cyclic grafting 4,4'-diphenylmethane diisocyanate and aminopropyl-terminated polydimethylsiloxane on pure magnesium. SEM-EDS, X-ray photoelectron spectroscopy and water contact angle were detected to analyze the chemical composition of the layer. The amino groups were confirmed to be introduced on the surface which provide a platform for subsequent modification. The contact angle value of the modified surface is 132.1°, indicating a hydrophilic surface. The electrochemical measurements and immersion tests demonstrated that the hydrophobic layer significantly improved the anti-corrosion ability of the substrate. Besides, the biocompatibility of the hydrophobic surface was examined by platelet adhesion, cytocompatibility in vitro and subcutaneous implantation in vivo. Immunological and histological results indicated that the hydrophobic layer had excellent biocompatibility. Therefore, the presented study might be a promising method for the surface modification of biomedical magnesium-based stent.
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Affiliation(s)
| | - Hao Zhang
- Panzhihua University, Panzhihua 617000, China
| | - Xin Li
- Third People’s Hospital of Chengdu, Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Peichuang Li
- School of Material Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Yuancong Zhao
- School of Material Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Yunbing Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China
| | - Jin Wang
- School of Material Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China
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Tian X, Zhao K, Teng A, Li Y, Wang W. A rethinking of collagen as tough biomaterials in meat packaging: assembly from native to synthetic. Crit Rev Food Sci Nutr 2022; 64:957-977. [PMID: 35997287 DOI: 10.1080/10408398.2022.2111401] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Due to the high moisture-associated typical rheology and the changeable and harsh processing conditions in the production process, packaging materials for meat products have higher requirements including a sufficient mechanical strength and proper ductility. Collagen, a highly conserved structural protein consisting of a triple helix of Gly-X-Y repeats, has been proved to be suitable packaging material for meat products. The treated animal digestive tract (i.e. the casing) is the perfect natural packaging material for wrapping meat into sausage. Its thin walls, strong toughness and impact resistance make it the oldest and best edible meat packaging. Collagen casing is another wisdom of meat packaging, which is made by collagen fibers from hide skin, presenting a rapid growth in casing market. To strengthen mechanical strength and barrier behaviors of collagen-based packaging materials, different physical, chemical, and biological cross-linking methods are springing up exuberantly, as well as a variety of reinforcement approaches including nanotechnology. In addition, the rapid development of biomimetic technology also provides a good research idea and means for the promotion of collagen's assembly and relevant mechanical properties. This review can offer some reference on fundamental theory and practical application of collagenous materials in meat products.
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Affiliation(s)
- Xiaojing Tian
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - KaiXuan Zhao
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Anguo Teng
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Yu Li
- College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China
| | - Wenhang Wang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
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Small Intestinal Submucosa Biomimetic Periosteum Promotes Bone Regeneration. MEMBRANES 2022; 12:membranes12070719. [PMID: 35877922 PMCID: PMC9323854 DOI: 10.3390/membranes12070719] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/10/2022] [Accepted: 07/14/2022] [Indexed: 11/30/2022]
Abstract
Background: Critical bone defects are a significant problem in clinics. The periosteum plays a vital role in bone regeneration. A tissue-engineered periosteum (TEP) has received increasing attention as a novel strategy for bone defect repairs. Methods: In this experiment, a biomimetic periosteum was fabricated by using coaxial electrospinning technology with decellularized porcine small intestinal submucosa (SIS) as the shell and polycaprolactone (PCL) as the core. In vitro, the effects of the biomimetic periosteum on Schwann cells, vascular endothelial cells, and bone marrow mesenchymal stem cells were detected by a scratch test, an EdU, a tube-forming test, and an osteogenesis test. In vivo, we used HE staining to evaluate the effect of the biomimetic periosteum on bone regeneration. Results: In vitro experiments showed that the biomimetic periosteum could significantly promote the formation of angiogenesis, osteogenesis, and repaired Schwann cells (SCs). In vivo experiments showed that the biomimetic periosteum could promote the repair of bone defects. Conclusions: The biomimetic periosteum could simulate the structural function of the periosteum and promote bone repair. This strategy may provide a promising method for the clinical treatment of skull bone defects.
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Zhou J, Wu X, Zhao C. Optimization of decellularized liver matrix-modified chitosan fibrous scaffold for C3A hepatocyte culture. J Biomater Appl 2022; 37:903-917. [PMID: 35834434 DOI: 10.1177/08853282221115367] [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: 11/15/2022]
Abstract
Hepatocyte scaffold is an essential part in bioartificial liver device. We have designed a novel hepatocyte scaffold based on porcine liver extracellular matrix (ECM) and chitosan (CTS) fabrics. This CTS-ECM scaffold can improve cell adhesion and proliferation. In the present study, an orthogonal test was designed to optimize the CTS/ECM composite scaffold, in which ECM concentration, EDC concentration and EDC to NHS ratio were taken as factors, proportion of nitrogen element and hydroxyproline content as indicators. The cytocompatibility of the novel scaffold for C3A hepatocytes was analyzed in vitro. The orthogonal test demonstrated that the optimal scaffold should be based on ECM concentration of 5 mg/mL, EDC concentration of 5 mg/mL, and EDC to NHS ratio 1:1. C3A hepatocytes cultured on the optimized CTS-ECM scaffolds showed stronger proliferation and functionality than those on Cytodex3 microcarriers (p < 0.05). The CTS/ECM composite scaffold may be widely used as a promising hepatocyte culture carrier, especially in bioartificial liver support systems.
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Affiliation(s)
- Junjing Zhou
- Department of Hepatobiliary Surgery, 199193Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Xinglian Wu
- Department of pharmacy, 117969The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Chaochen Zhao
- Department of Hepatobiliary Surgery, 117969The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
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27
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Lei X, Cheng L, Yang Y, Pang M, Dong Y, Zhu X, Chen C, Yao Z, Wu G, Cheng B, Forouzanfar T. Co-administration of platelet-rich plasma and small intestinal submucosa is more beneficial than their individual use in promoting acute skin wound healing. BURNS & TRAUMA 2022; 9:tkab033. [PMID: 35464804 DOI: 10.1093/burnst/tkab033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 07/14/2021] [Indexed: 01/13/2023]
Abstract
Background Acute skin wounds may compromise the skin barrier, posing a risk of infection. Small intestinal submucosa (SIS) is widely used to treat acute and chronic wounds. However, the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands. To tackle this problem, platelet-rich plasma (PRP) is used due to its potency to promote proliferation, migration and adhesion of target cells. In this study, we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization, collagen production, angiogenesis and the inflammatory response. Methods A 1 × 1-cm full-thickness skin defect was established in mice. Sixty mice were divided into four treatment groups: PRP + SIS, PRP, SIS and control. On days 3, 5, 7, 10 and 14 post-surgery, tissue specimens were harvested. Haematoxylin and eosin, Masson's trichrome, immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness, collagen and vascular regeneration and inflammation. Results Wound contraction in the PRP and PRP + SIS groups was significantly greater, compared with the other groups, on days 3 and 5 post-surgery. A histological analysis showed higher collagen expression in the PRP and PRP + SIS groups on day 7, which was associated with a thicker epidermal layer on day 14. In addition, immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP + SIS and PRP groups were significantly higher, compared with the control group. Furthermore, immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP + SIS and PRP groups was higher, compared with the control and SIS groups alone, on day 3. However, on day 7, the number of M1 macrophages dramatically decreased in the PRP + SIS and PRP groups. The ratio of M2 to M1 macrophages in the PRP + SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group, respectively. Conclusion Co-administration of SIS and PRP has a better effect on promoting angiogenesis, re-epithelialization and collagen regeneration in managing acute wound healing than either agent alone.
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Affiliation(s)
- Xiaoxuan Lei
- Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, 1081HV, The Netherlands
| | - Liuhanghang Cheng
- Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, 1081HV, The Netherlands
| | - Yu Yang
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Mengru Pang
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Yunqing Dong
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Xuanru Zhu
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Caihong Chen
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Zexin Yao
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Gang Wu
- Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, 1081HV, The Netherlands
| | - Biao Cheng
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510030, China
| | - Tymour Forouzanfar
- Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, 1081HV, The Netherlands
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He S, Walimbe T, Chen H, Gao K, Kumar P, Wei Y, Hao D, Liu R, Farmer DL, Lam KS, Zhou J, Panitch A, Wang A. Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing. Bioact Mater 2022; 10:460-473. [PMID: 34901560 PMCID: PMC8636679 DOI: 10.1016/j.bioactmat.2021.08.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 08/13/2021] [Accepted: 08/13/2021] [Indexed: 02/07/2023] Open
Abstract
Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment. When applied in an established Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model, LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients.
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Affiliation(s)
- Siqi He
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, China
- Department of Surgery, UC Davis, United States
| | - Tanaya Walimbe
- Department of Biomedical Engineering, UC Davis, United States
| | | | - Kewa Gao
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, China
- Department of Surgery, UC Davis, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, United States
| | - Priyadarsini Kumar
- Department of Surgery, UC Davis, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, United States
| | - Yifan Wei
- Department of Surgery, UC Davis, United States
| | - Dake Hao
- Department of Surgery, UC Davis, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, United States
| | - Ruiwu Liu
- Department of Biochemistry and Molecular Medicine, UC Davis, United States
| | - Diana L. Farmer
- Department of Surgery, UC Davis, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, United States
| | - Kit S. Lam
- Department of Biochemistry and Molecular Medicine, UC Davis, United States
| | - Jianda Zhou
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, China
| | - Alyssa Panitch
- Department of Surgery, UC Davis, United States
- Department of Biomedical Engineering, UC Davis, United States
| | - Aijun Wang
- Department of Surgery, UC Davis, United States
- Department of Biomedical Engineering, UC Davis, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, United States
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Marei I, Abu Samaan T, Al-Quradaghi MA, Farah AA, Mahmud SH, Ding H, Triggle CR. 3D Tissue-Engineered Vascular Drug Screening Platforms: Promise and Considerations. Front Cardiovasc Med 2022; 9:847554. [PMID: 35310996 PMCID: PMC8931492 DOI: 10.3389/fcvm.2022.847554] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 02/03/2022] [Indexed: 12/12/2022] Open
Abstract
Despite the efforts devoted to drug discovery and development, the number of new drug approvals have been decreasing. Specifically, cardiovascular developments have been showing amongst the lowest levels of approvals. In addition, concerns over the adverse effects of drugs to the cardiovascular system have been increasing and resulting in failure at the preclinical level as well as withdrawal of drugs post-marketing. Besides factors such as the increased cost of clinical trials and increases in the requirements and the complexity of the regulatory processes, there is also a gap between the currently existing pre-clinical screening methods and the clinical studies in humans. This gap is mainly caused by the lack of complexity in the currently used 2D cell culture-based screening systems, which do not accurately reflect human physiological conditions. Cell-based drug screening is widely accepted and extensively used and can provide an initial indication of the drugs' therapeutic efficacy and potential cytotoxicity. However, in vitro cell-based evaluation could in many instances provide contradictory findings to the in vivo testing in animal models and clinical trials. This drawback is related to the failure of these 2D cell culture systems to recapitulate the human physiological microenvironment in which the cells reside. In the body, cells reside within a complex physiological setting, where they interact with and respond to neighboring cells, extracellular matrix, mechanical stress, blood shear stress, and many other factors. These factors in sum affect the cellular response and the specific pathways that regulate variable vital functions such as proliferation, apoptosis, and differentiation. Although pre-clinical in vivo animal models provide this level of complexity, cross species differences can also cause contradictory results from that seen when the drug enters clinical trials. Thus, there is a need to better mimic human physiological conditions in pre-clinical studies to improve the efficiency of drug screening. A novel approach is to develop 3D tissue engineered miniaturized constructs in vitro that are based on human cells. In this review, we discuss the factors that should be considered to produce a successful vascular construct that is derived from human cells and is both reliable and reproducible.
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Affiliation(s)
- Isra Marei
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- *Correspondence: Isra Marei
| | - Tala Abu Samaan
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | | | - Asmaa A. Farah
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | | | - Hong Ding
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Chris R. Triggle
- Department of Pharmacology, Weill Cornell Medicine-Qatar, Doha, Qatar
- Chris R. Triggle
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Heparin Immobilization of Tissue Engineered Xenogeneic Small Diameter Arterial Scaffold Improve Endothelialization. Tissue Eng Regen Med 2022; 19:505-523. [PMID: 35092597 PMCID: PMC9130405 DOI: 10.1007/s13770-021-00411-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/24/2021] [Accepted: 11/01/2021] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Autologous vessels graft (Inner diameter < 6 mm) harvesting always challenged during bypass grafting surgery and its complication shows poor outcome. Tissue engineered vascular graft allow to generate biological graft without any immunogenic complication. The approach presented in this study is to induce graft remodeling through heparin coating in luminal surface of small diameter (Inner diameter < 1 mm) decellularized arterial graft. METHODS Decellularization of graft was done using SDS, combination of 0.5% sodium dodecyl sulfate and 0.5% sodium deoxycholate and only sodium deoxycholate. Decellularization was confirmed on basis of histology, and DAPI. Characterization of extracellular matrix was analyzed using histology and scanning electron microscopy. Surface modification of decellularized vascular graft was done with heparin coating. Heparin immobilization was evaluated by toluidine blue stain. Heparin-coated graft was transplanted end to end anastomosis in femoral artery in rat. RESULTS Combination of 0.5% sodium dodecyl sulfate and 0.5% Sodium deoxycholate showed complete removal of xenogeneic cells. The heparin coating on luminal surface showed anti-thrombogenicity and endothelialization. Mechanical testing revealed no significant differences in strain characteristics and modulus between native tissues, decellularized scaffolds and transplanted scaffold. Collectively, this study proposed a heparin-immobilized ECM coating to surface modification offering functionalize biomaterials for developing small-diameter vascular grafts. CONCLUSION We conclude that xenogeneic decellularized arterial scaffold with heparin surface modification can be fabricated and successfully transplanted small diameter (inner diameter < 1 mm) decellularized arterial graft.
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Zhang C, Xia D, Li J, Zheng Y, Weng B, Mao H, Mei J, Wu T, Li M, Zhao J. BMSCs and Osteoblast-Engineered ECM Synergetically Promotes Osteogenesis and Angiogenesis in an Ectopic Bone Formation Model. Front Bioeng Biotechnol 2022; 10:818191. [PMID: 35127662 PMCID: PMC8814575 DOI: 10.3389/fbioe.2022.818191] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/04/2022] [Indexed: 12/16/2022] Open
Abstract
Bone mesenchymal stem cells (BMSCs) have been extensively used in bone tissue engineering because of their potential to differentiate into multiple cells, secrete paracrine factors, and attenuate immune responses. Biomaterials are essential for the residence and activities of BMSCs after implantation in vivo. Recently, extracellular matrix (ECM) modification with a favorable regenerative microenvironment has been demonstrated to be a promising approach for cellular activities and bone regeneration. The aim of the present study was to evaluate the effects of BMSCs combined with cell-engineered ECM scaffolds on osteogenesis and angiogenesis in vivo. The ECM scaffolds were generated by osteoblasts on the small intestinal submucosa (SIS) under treatment with calcium (Ca)-enriched medium and icariin (Ic) after decellularization. In a mouse ectopic bone formation model, the SIS scaffolds were demonstrated to reduce the immune response, and lower the levels of immune cells compared with those in the sham group. Ca/Ic-ECM modification inhibited the degradation of the SIS scaffolds in vivo. The generated Ca/Ic-SIS scaffolds ectopically promoted osteogenesis according to the results of micro-CT and histological staining. Moreover, BMSCs on Ca/Ic-SIS further increased the bone volume percentage (BV/TV) and bone density. Moreover, angiogenesis was also enhanced by the Ca/Ic-SIS scaffolds, resulting in the highest levels of neovascularization according to the data ofCD31 staining. In conclusion, osteoblast-engineered ECM under directional induction is a promising strategy to modify biomaterials for osteogenesis and angiogenesis. BMSCs synergetically improve the properties of ECM constructs, which may contribute to the repair of large bone defects.
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Affiliation(s)
- Chi Zhang
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Medical Research Center, Ningbo City First Hospital, Ningbo, China
| | - Dongdong Xia
- Orthopedic Department, Ningbo City First Hospital, Ningbo, China
| | - Jiajing Li
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
| | - Yanan Zheng
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
| | - Bowen Weng
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
| | - Haijiao Mao
- Department of Orthopaedic Surgery, the Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
| | - Jing Mei
- Medical Research Center, Ningbo City First Hospital, Ningbo, China
| | - Tao Wu
- Cardiovascular Center, the Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
| | - Mei Li
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Ningbo Institute of Medical Sciences, Ningbo, China
- *Correspondence: Mei Li, ; Jiyuan Zhao,
| | - Jiyuan Zhao
- Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- *Correspondence: Mei Li, ; Jiyuan Zhao,
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Zhao P, Fang Q, Gao D, Wang Q, Cheng Y, Ao Q, Wang X, Tian X, Zhang Y, Tong H, Yan N, Hu X, Fan J. Klotho functionalization on vascular graft for improved patency and endothelialization. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2022; 133:112630. [DOI: 10.1016/j.msec.2021.112630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 12/13/2021] [Accepted: 12/19/2021] [Indexed: 10/19/2022]
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Wang M, Li B, Liu Y, Tang L, Zhang Y, Xie Q. A Novel Bionic Extracellular Matrix Polymer Scaffold Enhanced by Calcium Silicate for Bone Tissue Engineering. ACS OMEGA 2021; 6:35727-35737. [PMID: 34984303 PMCID: PMC8717537 DOI: 10.1021/acsomega.1c05623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/02/2021] [Indexed: 06/14/2023]
Abstract
A novel porous calcium silicate (CS)-enhanced small intestinal submucosa (SIS) scaffold was prepared by freeze-drying to mimic the natural extracellular matrix environment for bone tissue engineering. The micro-morphology, physicochemical properties, biological characteristics, and effects on osteogenic differentiation in vitro were explored; the effects on promoting bone formation in vivo were evaluated. The composite scaffold had an ideal three-dimensional porous structure. The amount of calcium silicate played a significant role in improving mechanical properties and promoting osteogenic differentiation. The SIS/2CS scaffold promoted proliferation and osteogenic differentiation in human bone marrow mesenchymal stem cells; it also significantly increased osteogenesis in vivo. This novel composite polymer scaffold has potential applications in bone tissue engineering.
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Affiliation(s)
- Mei Wang
- Department
of Prosthodontics, Peking University School
and Hospital of Stomatology & National Center of Stomatology &National
Clinical Research Center for Oral Diseases & National Engineering
Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
| | - Bowen Li
- Department
of Prosthodontics, Peking University School
and Hospital of Stomatology & National Center of Stomatology &National
Clinical Research Center for Oral Diseases & National Engineering
Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
| | - Yuhua Liu
- Department
of Prosthodontics, Peking University School
and Hospital of Stomatology & National Center of Stomatology &National
Clinical Research Center for Oral Diseases & National Engineering
Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
| | - Lin Tang
- Department
of Prosthodontics, Peking University School
and Hospital of Stomatology & National Center of Stomatology &National
Clinical Research Center for Oral Diseases & National Engineering
Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
| | - Yi Zhang
- Department
of General Dentistry II, Peking University
School and Hospital of Stomatology & National Center of Stomatology
&National Clinical Research Center for Oral Diseases & National
Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
| | - Qiufei Xie
- Department
of Prosthodontics, Peking University School
and Hospital of Stomatology & National Center of Stomatology &National
Clinical Research Center for Oral Diseases & National Engineering
Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
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Jing L, Fan S, Yao X, Zhang Y. Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis. Regen Biomater 2021; 8:rbab066. [PMID: 34868635 PMCID: PMC8634505 DOI: 10.1093/rb/rbab066] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/27/2021] [Accepted: 11/05/2021] [Indexed: 12/13/2022] Open
Abstract
Bone tissue with strong adaptability is often in a complex dynamical microenvironment in vivo, which is associated with the pathogenesis and treatment of orthopedic diseases. Therefore, it is of great significance to investigate the effects of corresponding compound stimulation on cell behaviors. Herein, a fluid shear stress (FSS) plus ultrasound stimulation platform suitable for cell studies based on a microfluidic chip was constructed and bone marrow mesenchymal stem cell (BMSC) was chosen as a model cell. The proliferation and osteogenesis of BMSCs under the compound stimulation of FSS plus ultrasound in growth medium without any soluble induction factors were firstly investigated. Single FSS stimulation and static culture conditions were also examined. Results illustrated that suitable single FSS stimulation (about 0.06 dyn/cm2) could significantly enhance cell proliferation and osteogenesis simultaneously when compared to the static control, while greater FSS mitigated or even restricted these enhancing effects. Interestingly, ultrasound stimulation combined with this suitable FSS stimulation further accelerated cell proliferation as the intensity of ultrasound increasing. As for the osteogenesis under compound stimulation, it was relatively restricted under lower ultrasound intensity (about 0.075 W/cm2), while promoted when the intensity became higher (about 1.75 W/cm2). This study suggests that both the cell proliferation and osteogenesis are very responsive to the magnitudes of FSS and ultrasound stimulations and can be both significantly enhanced by proper combination strategies. Moreover, these findings will provide valuable references for the construction of effective cell bioreactors and also the treatment of orthopedic diseases.
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Affiliation(s)
- Lingzhi Jing
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P.R. China
| | - Suna Fan
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P.R. China.,Jinan Jinquan Bio-Technology Co. Ltd, Jinan 250101, P.R. China
| | - Xiang Yao
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P.R. China
| | - Yaopeng Zhang
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P.R. China.,Jinan Jinquan Bio-Technology Co. Ltd, Jinan 250101, P.R. China
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Ma J, Zhan H, Li W, Zhang L, Yun F, Wu R, Lin J, Li Y. Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion. Biomater Res 2021; 25:40. [PMID: 34819167 PMCID: PMC8611984 DOI: 10.1186/s40824-021-00242-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/31/2021] [Indexed: 12/25/2022] Open
Abstract
Intrauterine adhesion (IUA) is a common gynaecological disease that develops from infection or trauma. IUA disease may seriously affect the physical and mental health of women of childbearing age, which may lead to symptoms such as hypomenorrhea or infertility. Presently, hysteroscopic transcervical resection of adhesion (TCRA) is the principal therapy for IUAs, although its function in preventing the recurrence of adhesion and preserving fertility is limited. Pharmaceuticals such as hormones and vasoactive agents and the placement of nondegradable stents are the most common postoperative adjuvant therapy methods. However, the repair of injured endometrium is relatively restricted due to the different anatomical structures of the endometrium. Recently, the treatment outcome of IUAs has improved with the advancement of hysteroscopic techniques. In particular, the application of bioactive scaffolds combined with tissue engineering technology has proven to have high therapeutic potential or endometrial repair in IUA treatment. Herein, this review has summarized past therapeutic strategies, including postoperative adjuvant therapy, cell or therapeutic molecular delivery therapy methods and bioactive scaffold-based tissue engineering methods. Therefore, this review presented the recent therapeutic strategies for repairing endometrium treatment and pointed out the issues of clinical concern to provide alternative methods for the management of IUAs.
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Affiliation(s)
- Junyan Ma
- Zhejiang Provincial Key Laboratory for Precision Diagnosis & Treatment of Major Gynecological Diseases, Hangzhou, 310006, Zhejiang Province, China
| | - Hong Zhan
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Wen Li
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Liqi Zhang
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Feng Yun
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Ruijin Wu
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.
| | - Jun Lin
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.
| | - Yangyang Li
- Zhejiang Provincial Key Laboratory for Precision Diagnosis & Treatment of Major Gynecological Diseases, Hangzhou, 310006, Zhejiang Province, China.
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He J, Liu Q, Zheng S, Shen R, Wang X, Gao J, Wang Q, Huang J, Ding J. Enlargement, Reduction, and Even Reversal of Relative Migration Speeds of Endothelial and Smooth Muscle Cells on Biomaterials Simply by Adjusting RGD Nanospacing. ACS APPLIED MATERIALS & INTERFACES 2021; 13:42344-42356. [PMID: 34469116 DOI: 10.1021/acsami.1c08559] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Although many tissue regeneration processes after biomaterial implantation are related to migrations of multiple cell types on material surfaces, available tools to adjust relative migration speeds are very limited. Herein, we put forward a nanomaterial strategy to employ surface modification with arginine-glycine-aspartate (RGD) nanoarrays to tune in vitro cell migration using endothelial cells (ECs) and smooth muscle cells (SMCs) as demonstrated cell types. We found that migrations of both cell types exhibited a nonmonotonic trend with the increase of RGD nanospacing, yet with different peaks-74 nm for SMCs but 95 nm for ECs. The varied sensitivities afford a facile way to regulate the relative migration speeds. Although ECs migrated at a speed similar to SMCs on a non-nano surface, the migration of ECs could be controlled to be significantly faster or slower than SMCs simply by adjusting the RGD nanospacing. This study suggests a potential application of surface modification of biomaterials on a nanoscale level.
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Affiliation(s)
- Junhao He
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Qiong Liu
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
- Navy Medical Center, The Second Military Medical University, Shanghai 200433, China
| | - Shuang Zheng
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Runjia Shen
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Xinlei Wang
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Jingming Gao
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Qunsong Wang
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Jiale Huang
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
| | - Jiandong Ding
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China
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Zheng S, Liu Q, He J, Wang X, Ye K, Wang X, Yan C, Liu P, Ding J. Critical adhesion areas of cells on micro-nanopatterns. NANO RESEARCH 2021; 15:1623-1635. [PMID: 34405038 PMCID: PMC8359768 DOI: 10.1007/s12274-021-3711-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/19/2021] [Accepted: 06/24/2021] [Indexed: 06/13/2023]
Abstract
UNLABELLED Cell adhesion to extracellular matrices (ECM) is critical to physiological and pathological processes as well as biomedical and biotechnological applications. It has been known that a cell can adhere on an adhesive microisland only over a critical size. But no publication has concerned critical adhesion areas of cells on microislands with nanoarray decoration. Herein, we fabricated a series of micro-nanopatterns with different microisland sizes and arginine-glycine-aspartate (RGD) nanospacings on a nonfouling poly(ethylene glycol) background. Besides reproducing that nanospacing of RGD, a ligand of its receptor integrin (a membrane protein), significantly influences specific cell adhesion on bioactive nanoarrays, we confirmed that the concept of critical adhesion area originally suggested in studies of cells on micropatterns was justified also on the micro-nanopatterns, yet the latter exhibited more characteristic behaviors of cell adhesion. We found increased critical adhesion areas of human mesenchymal stem cells (hMSCs) on nanoarrayed microislands with increased RGD nanospacings. However, the numbers of nanodots with respect to the critical adhesion areas were not a constant. A unified interpretation was then put forward after combining nonspecific background adhesion and specific cell adhesion. We further carried out the asymptotic analysis of a series of micro-nanopatterned surfaces to obtain the effective RGD nanospacing on unpatterned free surfaces with densely grafted RGD, which could be estimated nonzero but has never been revealed previously without the assistance of the micro-nanopatterning techniques and the corresponding analysis. ELECTRONIC SUPPLEMENTARY MATERIAL Supplementary materials and methods (details of fabrication of micro-nanopatterns), and supplementary results (selective adhesion or localization of hMSCs on nanoarrayed microislands with non-fouling background, calculation of critical number of integrin-ligand binding N*, etc.) are available in the online version of this article at 10.1007/s12274-021-3711-6.
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Affiliation(s)
- Shuang Zheng
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Qiong Liu
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
- Navy Characteristic Medical Center, the Second Military Medical University, Shanghai, 200433 China
| | - Junhao He
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Xinlei Wang
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Kai Ye
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Xuan Wang
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Ce Yan
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
| | - Peng Liu
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
- College of Bioengineering, Chongqing University, Chongqing, 400044 China
| | - Jiandong Ding
- State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 China
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Shen Z, Wang S, Shen Z, Tang Y, Xu J, Lin C, Chen X, Huang Q. Deciphering controversial results of cell proliferation on TiO 2 nanotubes using machine learning. Regen Biomater 2021; 8:rbab025. [PMID: 34168893 PMCID: PMC8218935 DOI: 10.1093/rb/rbab025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/19/2021] [Accepted: 05/09/2021] [Indexed: 12/27/2022] Open
Abstract
With the rapid development of biomedical sciences, contradictory results on the relationships between biological responses and material properties emerge continuously, adding to the challenge of interpreting the incomprehensible interfacial process. In the present paper, we use cell proliferation on titanium dioxide nanotubes (TNTs) as a case study and apply machine learning methodologies to decipher contradictory results in the literature. The gradient boosting decision tree model demonstrates that cell density has a higher impact on cell proliferation than other obtainable experimental features in most publications. Together with the variation of other essential features, the controversy of cell proliferation trends on various TNTs is understandable. By traversing all combinational experimental features and the corresponding forecast using an exhausted grid search strategy, we find that adjusting cell density and sterilization methods can simultaneously induce opposite cell proliferation trends on various TNTs diameter, which is further validated by experiments. This case study reveals that machine learning is a burgeoning tool in deciphering controversial results in biomedical researches, opening up an avenue to explore the structure-property relationships of biomaterials.
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Affiliation(s)
- Ziao Shen
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
| | - Si Wang
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
| | - Zhenyu Shen
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
| | - Yufei Tang
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
| | - Junbin Xu
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
| | - Changjian Lin
- State Key Laboratory for Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen 361005, China
| | - Xun Chen
- Wenzhou Institute, University of Chinese Academy of Sciences, No.16 Xinsan Road, Hi-tech Industrial Park, Wenzhou, Zhejiang, 325000, China
| | - Qiaoling Huang
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Zengcuoan West Road, Siming District, Xiamen 361005, China
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Biodegradable polymeric occluder for closure of atrial septal defect with interventional treatment of cardiovascular disease. Biomaterials 2021; 274:120851. [PMID: 33965798 DOI: 10.1016/j.biomaterials.2021.120851] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 04/22/2021] [Indexed: 02/07/2023]
Abstract
The next-generation closure device for interventional treatment of congenital heart disease is regarded to be biodegradable, yet the corresponding biomaterial technique is still challenging. Herein, we report the first fully biodegradable atrial septal defect (ASD) occluder finally coming into clinical use, which is made of biodegradable poly(l-lactic acid) (PLLA). We characterized the physico-chemical properties of PLLA fibers as well as the raw polymer and the operability of the as-fabricated occluders. Cell behaviors on material were observed, and in vivo fiber degradation and inflammatory responses were examined. ASD models in piglets were created, and 44 PLLA ASD occluders were implanted via catheter successfully. After 36 months, the PLLA ASD occluders almost degraded without any complications. The mechanical properties and thickness between newborn and normal atrial septum showed no significant difference. We further accomplished the first clinical implantation of the PLLA ASD occluder in a four-year boy, and the two-year follow-up up to date preliminarily indicated safety and feasibility of such new-generation fully biodegradable occluder made of synthetic polymers.
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Agarwal T, Onesto V, Lamboni L, Ansari A, Maiti TK, Makvandi P, Vosough M, Yang G. Engineering biomimetic intestinal topological features in 3D tissue models: retrospects and prospects. Biodes Manuf 2021. [DOI: 10.1007/s42242-020-00120-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Mallis P, Kostakis A, Stavropoulos-Giokas C, Michalopoulos E. Future Perspectives in Small-Diameter Vascular Graft Engineering. Bioengineering (Basel) 2020; 7:160. [PMID: 33321830 PMCID: PMC7763104 DOI: 10.3390/bioengineering7040160] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 12/04/2020] [Accepted: 12/09/2020] [Indexed: 02/07/2023] Open
Abstract
The increased demands of small-diameter vascular grafts (SDVGs) globally has forced the scientific society to explore alternative strategies utilizing the tissue engineering approaches. Cardiovascular disease (CVD) comprises one of the most lethal groups of non-communicable disorders worldwide. It has been estimated that in Europe, the healthcare cost for the administration of CVD is more than 169 billion €. Common manifestations involve the narrowing or occlusion of blood vessels. The replacement of damaged vessels with autologous grafts represents one of the applied therapeutic approaches in CVD. However, significant drawbacks are accompanying the above procedure; therefore, the exploration of alternative vessel sources must be performed. Engineered SDVGs can be produced through the utilization of non-degradable/degradable and naturally derived materials. Decellularized vessels represent also an alternative valuable source for the development of SDVGs. In this review, a great number of SDVG engineering approaches will be highlighted. Importantly, the state-of-the-art methodologies, which are currently employed, will be comprehensively presented. A discussion summarizing the key marks and the future perspectives of SDVG engineering will be included in this review. Taking into consideration the increased number of patients with CVD, SDVG engineering may assist significantly in cardiovascular reconstructive surgery and, therefore, the overall improvement of patients' life.
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Affiliation(s)
- Panagiotis Mallis
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (C.S.-G.); (E.M.)
| | - Alkiviadis Kostakis
- Center of Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece;
| | - Catherine Stavropoulos-Giokas
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (C.S.-G.); (E.M.)
| | - Efstathios Michalopoulos
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (C.S.-G.); (E.M.)
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Magden GK, Vural C, Bayrak BY, Ozdogan CY, Kenar H. Composite sponges from sheep decellularized small intestinal submucosa for treatment of diabetic wounds. J Biomater Appl 2020; 36:113-127. [PMID: 33023379 DOI: 10.1177/0885328220963897] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Despite the fast development of technology in the world, diabetic foot wounds cause deaths and massive economical losses. Diabetes comes first among the reasons of non traumatic foot amputations. To reduce the healing time of these fast progressing wounds, effective wound dressings are in high demand. In our study, sheep small intestinal submucosa (SIS) based biocompatible sponges were prepared after SIS decellularization and their wound healing potential was investigated on full thickness skin defects in a diabetic rat model. The decellularized SIS membranes had no cytotoxic effects on human fibroblasts and supported capillary formation by HUVECs in a fibroblast-HUVEC co-culture. Glutaraldehyde crosslinked sponges of three different compositions were prepared to test in a diabetic rat model: gelatin (GS), gelatin: hyaluronic acid (GS:HA) and gelatin: hyaluronic acid: SIS (GS:HA:SIS). The GS:HA:SIS sponges underwent a 24.8 ± 5.4% weight loss in a 7-day in vitro erosion test. All sponges had a similar Young's modulus under compression but GS:HA:SIS had the highest (5.00 ± 0.04 kPa). Statistical analyses of histopathological results of a 12-day in vivo experiment revealed no significant difference among the control, GS, GS:HA, and GS:HA:SIS transplanted groups in terms of granulation tissue thickness, collagen deposition, capillary vessel formation, and foreign body reaction (P > 0.05). On the other hand, in the GS:HA:SIS transplanted group 80% of the animals had a complete epidermal regeneration and this was significantly different than the control group (30%, P < 0.05). Preclinical studies revealed that the ECM of sheep small intestinal submucosa can be used as an effective biomaterial in diabetic wound healing.
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Affiliation(s)
- Gamze Kara Magden
- Polymer Science and Technology Dept., Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey
| | - Cigdem Vural
- Polymer Science and Technology Dept., Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey
| | - Busra Yaprak Bayrak
- Polymer Science and Technology Dept., Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey
| | - Candan Yilmaz Ozdogan
- Polymer Science and Technology Dept., Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey
| | - Halime Kenar
- Experimental and Clinical Research Center, Diabetes and Obesity Research Laboratory, Kocaeli University, Turkey
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