Pub Date : 2024-06-28eCollection Date: 2024-01-01DOI: 10.12336/biomatertransl.2024.02.002
Qiushi Liang, Zhiliang Cheng, Ling Qin
Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.
骨关节炎(OA)是最普遍的退行性关节疾病,影响着全球数亿人。目前的临床方法仅限于缓解症状。过去二十年的研究证实,OA 不仅仅是关节软骨的磨损过程,还涉及所有关节组织的异常重塑。尽管在过去几十年中已经发现了许多新的疾病机制,但如何高效、可持续地在关节组织中输送针对这些机制的药物仍然是一项重大挑战。最近,纳米颗粒成为治疗 OA 的首选给药载体,它能延长药物保留时间、增强药物靶向性、提高药物稳定性和溶解性。在本综述中,我们将 OA 视为一种影响整个关节的疾病,并初步探讨了 OA 在关节软骨、滑膜、脂肪垫、骨和半月板等多个关节组织中的病理生理学。然后,我们根据纳米颗粒的组成和结构对其进行分类,如脂类、聚合物、无机材料、肽/蛋白质和细胞外囊泡。我们总结了纳米粒子用于治疗和诊断 OA 的最新进展。最后,我们讨论了该领域当前面临的挑战和未来的发展方向。总之,基于纳米粒子的纳米系统是推进 OA 治疗和诊断的有前途的载体。
{"title":"Advanced nanoparticles in osteoarthritis treatment.","authors":"Qiushi Liang, Zhiliang Cheng, Ling Qin","doi":"10.12336/biomatertransl.2024.02.002","DOIUrl":"10.12336/biomatertransl.2024.02.002","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"95-113"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.
{"title":"Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications.","authors":"Wan-Ying Guo, Wei-Huang Wang, Pei-Yao Xu, Ranjith Kumar Kankala, Ai-Zheng Chen","doi":"10.12336/biomatertransl.2024.02.003","DOIUrl":"10.12336/biomatertransl.2024.02.003","url":null,"abstract":"<p><p>Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"114-128"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28eCollection Date: 2024-01-01DOI: 10.12336/biomatertransl.2024.02.005
Yanwen Ai, Yuan Tian, Jiaming Qiao, Changnan Wang, Huafei Li
Understanding the in vivo transport process provides guidelines for designing ideal nanoparticles (NPs) with higher efficacy and fewer off-target effects. Many factors, such as particle size, morphology, surface potential, structural stability, and etc., may influence the delivering process of NPs due to the existence of various physiological barriers within the body. Herein, we summarise the distinct influences of NP physicochemical properties on the four consecutive in vivo transport steps: (1) navigating with bloodstream within blood vessels, (2) transport across vasculature walls into tumour tissues, (3) intratumoural transport through the interstitial space, and (4) cellular uptake & intracellular delivery by cancerous cells. We found that the philosophy behind the current consensus for NP design has certain similarities to the "Yin-Yang" theory in traditional Chinese culture. Almost all physicochemical properties, regardless of big or small sizes, long or short length, positive or negative zeta potentials, are double-edged swords. The balance of potential benefits and side effects, drug selectivity and accessibility should be fully considered when optimising particle design, similar to the "Yin-Yang harmony". This paper presents a comprehensive review of the advancements in NPs research, focusing on their distinct features in tumour targeting, drug delivery, and cell uptake. Additionally, it deliberates on future developmental trends and potential obstacles, thereby aiming to uncover the ways these characteristics influence the NPs' biological activity and provide theoretical guidance for the targeted delivery of NPs.
{"title":"\"<i>Yin-Yang</i> philosophy\" for the design of anticancer drug delivery nanoparticles.","authors":"Yanwen Ai, Yuan Tian, Jiaming Qiao, Changnan Wang, Huafei Li","doi":"10.12336/biomatertransl.2024.02.005","DOIUrl":"10.12336/biomatertransl.2024.02.005","url":null,"abstract":"<p><p>Understanding the in vivo transport process provides guidelines for designing ideal nanoparticles (NPs) with higher efficacy and fewer off-target effects. Many factors, such as particle size, morphology, surface potential, structural stability, and etc., may influence the delivering process of NPs due to the existence of various physiological barriers within the body. Herein, we summarise the distinct influences of NP physicochemical properties on the four consecutive in vivo transport steps: (1) navigating with bloodstream within blood vessels, (2) transport across vasculature walls into tumour tissues, (3) intratumoural transport through the interstitial space, and (4) cellular uptake & intracellular delivery by cancerous cells. We found that the philosophy behind the current consensus for NP design has certain similarities to the \"Yin-Yang\" theory in traditional Chinese culture. Almost all physicochemical properties, regardless of big or small sizes, long or short length, positive or negative zeta potentials, are double-edged swords. The balance of potential benefits and side effects, drug selectivity and accessibility should be fully considered when optimising particle design, similar to the \"Yin-Yang harmony\". This paper presents a comprehensive review of the advancements in NPs research, focusing on their distinct features in tumour targeting, drug delivery, and cell uptake. Additionally, it deliberates on future developmental trends and potential obstacles, thereby aiming to uncover the ways these characteristics influence the NPs' biological activity and provide theoretical guidance for the targeted delivery of NPs.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"144-156"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28eCollection Date: 2024-01-01DOI: 10.12336/biomatertransl.2024.02.001
Han Liu, James T Triffitt, Zhidao Xia, Jiacan Su
{"title":"Artificial intelligence-enabled studies on organoid and organoid extracellular vesicles.","authors":"Han Liu, James T Triffitt, Zhidao Xia, Jiacan Su","doi":"10.12336/biomatertransl.2024.02.001","DOIUrl":"10.12336/biomatertransl.2024.02.001","url":null,"abstract":"","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"93-94"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Exosomes, a specialised type of extracellular vesicle, have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic tool. While the competence of key substances responsible for the delivery function was gradually elucidated, series of shortcomings exemplified by the limited stability still need to be improved. Therefore, how to take maximum advantage of the biological characteristics of exosomes is of great importance. Recently, the comprehensive exploration and application of biomedical engineering has improved the availability of exosomes and revealed the future direction of exosomes combined with biomaterials. This review delves into the present application of biomaterials such as nanomaterials, hydrogels, and electrospun scaffolds, serving as the carriers of exosomes in tendon/ligament repair. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way the future direction of biomaterials in the application of exosomes in tendon/ligament repair in this field.
{"title":"Exosome-loaded biomaterials for tendon/ligament repair.","authors":"Haohan Wang, Yonglin Guo, Yiwen Jiang, Yingyu Ge, Hanyi Wang, Dingyi Shi, Guoyang Zhang, Jinzhong Zhao, Yuhao Kang, Liren Wang","doi":"10.12336/biomatertransl.2024.02.004","DOIUrl":"10.12336/biomatertransl.2024.02.004","url":null,"abstract":"<p><p>Exosomes, a specialised type of extracellular vesicle, have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic tool. While the competence of key substances responsible for the delivery function was gradually elucidated, series of shortcomings exemplified by the limited stability still need to be improved. Therefore, how to take maximum advantage of the biological characteristics of exosomes is of great importance. Recently, the comprehensive exploration and application of biomedical engineering has improved the availability of exosomes and revealed the future direction of exosomes combined with biomaterials. This review delves into the present application of biomaterials such as nanomaterials, hydrogels, and electrospun scaffolds, serving as the carriers of exosomes in tendon/ligament repair. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way the future direction of biomaterials in the application of exosomes in tendon/ligament repair in this field.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"129-143"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg2+ is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg2+-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg2+/ icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg2+ doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg2+ substitution or coordination in the HAP lattice. At 30% Mg2+ doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg2+ release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.
{"title":"Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells.","authors":"Kaihua Liu, Meiqi Cheng, Hao Huang, Hui Yu, Shiyao Zhao, Jinnuo Zhou, Dan Tie, Jianhua Wang, Panpan Pan, Jingdi Chen","doi":"10.12336/biomatertransl.2024.02.008","DOIUrl":"10.12336/biomatertransl.2024.02.008","url":null,"abstract":"<p><p>Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg<sup>2+</sup> is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg<sup>2+</sup>-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg<sup>2+</sup>/ icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg<sup>2+</sup> doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg<sup>2+</sup> substitution or coordination in the HAP lattice. At 30% Mg<sup>2+</sup> doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg<sup>2+</sup> release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"185-196"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peripheral nerve injury poses a great threat to neurosurgery and limits the regenerative potential of sacral nerves in the neurogenic bladder. It remains unknown whether electrical stimulation can facilitate sacral nerve regeneration in addition to modulate bladder function. The objective of this study was to utilise electrical stimulation in sacra nerve crush injury with newly constructed electroconductive scaffold and explore the role of macrophages in electrical stimulation with crushed nerves. As a result, we generated a polypyrrole-coated polycaprolactone/silk fibroin scaffold through which we applied electrical stimulation. The electrical stimulation boosted nerve regeneration and polarised the macrophages towards the M2 phenotype. An in vitro test using bone marrow derived macrophages revealed that the pro-regenerative polarisation of M2 were significantly enhanced by electrical stimulation. Bioinformatics analysis showed that the expression of signal transducer and activator of transcriptions (STATs) was differentially regulated in a way that promoted M2-related genes expression. Our work indicated the feasibility of electricals stimulation used for sacral nerve regeneration and provided a firm demonstration of a pivotal role which macrophages played in electrical stimulation.
{"title":"Electrical stimulation with polypyrrole-coated polycaprolactone/silk fibroin scaffold promotes sacral nerve regeneration by modulating macrophage polarisation.","authors":"Haofeng Cheng, Jun Bai, Xingyu Zhou, Nantian Chen, Qingyu Jiang, Zhiqi Ren, Xiangling Li, Tianqi Su, Lijing Liang, Wenli Jiang, Yu Wang, Jiang Peng, Aijia Shang","doi":"10.12336/biomatertransl.2024.02.006","DOIUrl":"10.12336/biomatertransl.2024.02.006","url":null,"abstract":"<p><p>Peripheral nerve injury poses a great threat to neurosurgery and limits the regenerative potential of sacral nerves in the neurogenic bladder. It remains unknown whether electrical stimulation can facilitate sacral nerve regeneration in addition to modulate bladder function. The objective of this study was to utilise electrical stimulation in sacra nerve crush injury with newly constructed electroconductive scaffold and explore the role of macrophages in electrical stimulation with crushed nerves. As a result, we generated a polypyrrole-coated polycaprolactone/silk fibroin scaffold through which we applied electrical stimulation. The electrical stimulation boosted nerve regeneration and polarised the macrophages towards the M2 phenotype. An in vitro test using bone marrow derived macrophages revealed that the pro-regenerative polarisation of M2 were significantly enhanced by electrical stimulation. Bioinformatics analysis showed that the expression of signal transducer and activator of transcriptions (STATs) was differentially regulated in a way that promoted M2-related genes expression. Our work indicated the feasibility of electricals stimulation used for sacral nerve regeneration and provided a firm demonstration of a pivotal role which macrophages played in electrical stimulation.</p>","PeriodicalId":58820,"journal":{"name":"Biomaterials Translational","volume":"5 2","pages":"157-174"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}