{"title":"β-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis.","authors":"Weihong Ji, Yuanxing Zhang, Weichen Shao, Ranjith Kumar Kankala, Aizheng Chen","doi":"10.1093/rb/rbae071","DOIUrl":"10.1093/rb/rbae071","url":null,"abstract":"<p><p>Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of β-cyclodextrin (β-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of β-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, β-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of β-CD-based nanoassemblies, including β-CD derivatives-based, β-CD/polymer conjugates-based and polymer β-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These β-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of β-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing angiogenesis in peri-implant soft tissue with bioactive silk fibroin microgroove coatings on zirconia surfaces.","authors":"Zhihan Wang, Palati Tuerxun, Takkun Ng, Yinuo Yan, Ke Zhao, Yutao Jian, Xiaoshi Jia","doi":"10.1093/rb/rbae068","DOIUrl":"10.1093/rb/rbae068","url":null,"abstract":"<p><p>Zirconia abutments and restorations have improved the aesthetic appeal of implant restoration, yet peri-implantitis poses a significant threat to long-term success. The soft tissue surrounding implants is a crucial biological barrier against inflammation and subsequent bone loss. Peri-implantitis, akin to periodontitis, progresses rapidly and causes extensive tissue damage. Variations in tissue structure significantly influence disease progression, particularly the lower vascular density in peri-implant connective tissue, compromising its ability to combat infection and provide essential nutrients. Blood vessels within this tissue are vital for healing, with angiogenesis playing a key role in immune defense and tissue repair. Enhancing peri-implant soft tissue angiogenesis holds promise for tissue integration and inflammation control. Microgroove surfaces have shown potential in guiding vessel growth, but using subtractive technologies to carve microgrooves on zirconia surfaces may compromise mechanical integrity. In this study, we utilized inkjet printing to prepare bioactive silk fibroin microgrooves (SFMG) coating with different sizes on zirconia surfaces. SFMG coating, particularly with 90 µm width and 10 µm depth, effectively directed human umbilical vein endothelial cells (HUVECs) along microgrooves, promoting their proliferation, migration, and tube formation. The expression of vascular endothelial growth factor A and fibroblast growth factor in HUVECs growing on SFMG coating was upregulated. Additionally, the SFMG coating activated the PI3K-AKT pathway and increased glycolytic enzyme gene expression in HUVECs. In conclusion, SFMG coating enhances HUVEC growth and angiogenesis potential by activating the PI3K-AKT pathway and glycolysis, showing promise for improving tissue integration and mitigating inflammation in zirconia abutments and restorations.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multifunctional surface of the nano-morphic PEEK implant with enhanced angiogenic, osteogenic and antibacterial properties.","authors":"Jiajia Zhang, Tongtong Ma, Xueye Liu, Xiaoran Zhang, Wenqing Meng, Junling Wu","doi":"10.1093/rb/rbae067","DOIUrl":"10.1093/rb/rbae067","url":null,"abstract":"<p><p>Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co<sup>2+</sup> notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co<sup>2+</sup> and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dae Hyung Lee, Yeji Choi, Mi Hee Lee, Jong-Chul Park
{"title":"Comparison of tissue response and lifting effect induced by non-absorbable elastic thread and commercialized threads in rat model.","authors":"Dae Hyung Lee, Yeji Choi, Mi Hee Lee, Jong-Chul Park","doi":"10.1093/rb/rbae069","DOIUrl":"10.1093/rb/rbae069","url":null,"abstract":"<p><p>As we age, our skin loses elasticity and wrinkles form. To prevent this, most people try to improve skin wrinkles by performing procedures such as fillers, and absorbable lifting threads. Another way to solve this structural problem is to use an elastic thread. Although elastic sutures made of polymer materials (such as silicone) are widely used, data regarding their properties and potential effectiveness are lacking. This study aimed to investigate the effects of inserting non-absorbable elastic threads, with different manufacturing requirements and methods, on the skin and subcutaneous tissue. In this study, non-absorbable elastic threads ELATENS and Elasticum using different manufacturing methods were compared. Each thread was transplanted into the subcutaneous layer of the back of a rat to induce wrinkles. After inducing wrinkles in the skin of rat, the degree of skin maintenance by each thread and the thickness of the capsule formed around the suture were measured. Through <i>ex-vivo</i> experiments on each thread, the fixation force in the tissue was confirmed. In a comparison of inflammatory response and collagen formation through histological analysis, it was confirmed that there was no significant difference from the equivalent comparative product. In conclusion, the degree of encapsulation between tissues and collagen fiber formation for improving skin wrinkles was superior in elastic threads compared to non-elastic threads. It is believed that this provides certain elasticity to the skin layer and can induce cell influx to improve wrinkles.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yang, Siwen Huang, Qing Ma, Ning Li, Runchu Li, Yongjun Wang, Hongzhuo Liu
{"title":"Combined therapeutic strategy based on blocking the deleterious effects of AGEs for accelerating diabetic wound healing","authors":"Yang Yang, Siwen Huang, Qing Ma, Ning Li, Runchu Li, Yongjun Wang, Hongzhuo Liu","doi":"10.1093/rb/rbae062","DOIUrl":"https://doi.org/10.1093/rb/rbae062","url":null,"abstract":"\u0000 Diabetic foot ulcer is a serious complication of diabetes. Excessive accumulation of advanced glycation end products (AGEs) is one of the critical pathogenic factors in postponing diabetic wound healing. The main pathogenic mechanisms of AGEs include inducing cellular dysfunction, prolonging inflammatory response, increasing oxidative stress, and reducing endogenous nitric oxide (NO) production. Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing. Here, we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed. The designed co-delivery system augmented the survival of fibroblasts, reduced oxidative stress levels, reversed the change of mitochondrial membrane potential, and decreased the proinflammatory cytokine expression. Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate, alleviating inflammation, promoting collagen fiber production and angiogenesis. Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanqing Liu, Yuqing Meng, Y. Zhu, L. Gu, Ang Ma, Rui Liu, Dandan Liu, Shengnan Shen, Shujie Zhang, Chengchao Xu, Junzhe Zhang, Jigang Wang
{"title":"Comparative time-dependent proteomics reveal the tolerance of cancer cells to magnetic iron oxide nanoparticles","authors":"Yanqing Liu, Yuqing Meng, Y. Zhu, L. Gu, Ang Ma, Rui Liu, Dandan Liu, Shengnan Shen, Shujie Zhang, Chengchao Xu, Junzhe Zhang, Jigang Wang","doi":"10.1093/rb/rbae065","DOIUrl":"https://doi.org/10.1093/rb/rbae065","url":null,"abstract":"\u0000 Cancer is one of the most common diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation, and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death, and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiuyu Wang, Sai Zhang, Jiayi Jiang, Shaojuan Chen, Seeram Ramakrishna, Wenwen Zhao, Fan Yang, Shaohua Wu
{"title":"Electrospun radially oriented berberine-PHBV nanofiber dressing patches for accelerating diabetic wound healing.","authors":"Qiuyu Wang, Sai Zhang, Jiayi Jiang, Shaojuan Chen, Seeram Ramakrishna, Wenwen Zhao, Fan Yang, Shaohua Wu","doi":"10.1093/rb/rbae063","DOIUrl":"10.1093/rb/rbae063","url":null,"abstract":"<p><p>A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning strategy. The as-electrospun PHBV radially oriented nanofiber dressing patch exhibited uniform and bead-free nanofibrous morphology and innovative radially oriented arrangement, which was demonstrated to possess obviously improved mechanical property, increased surface hydrophilicity and enhanced biological properties compared to the PHBV nanofiber dressing patch control with traditionally randomly oriented pattern. Interestingly, it was found that the radially oriented pattern could induce the cell migration from the periphery to the center along the radially oriented nanofibers in a rapid manner. To further improve the biofunction of PHBV radially oriented nanofiber dressing patch, berberine (Beri, an isoquinoline alkaloid) with two different concentrations were encapsulated into PHBV nanofibers during electrospinning, which were found to present a sustained drug release behavior for nearly one month. Importantly, the addition of Beri could impart the dressing patch with excellent anti-inflammatory property by significantly inhibiting the secretion of pro-inflammatory factors of M1 macrophages, and also showed an additive influence on promoting the proliferation of human dermal fibroblasts (HDFs), as well as inhibiting the growth of <i>E. coli</i>, <i>S. aureus</i> and <i>C. albicans,</i> compared with the Beri-free dressing patch. In the animal studies, the electrospun PHBV radially oriented nanofiber dressing patch loading with high Beri content was found to obviously accelerate the healing process of diabetic mouse full-thickness skin wound with shortened healing time (100% wound closure rate after 18 days' treatment) and improved healing quality (improved collagen deposition, enhanced re-epithelialization and neovascularization and increased hair follicles). In all, this study reported an innovative therapeutic strategy integrating the excellent physical cues of electrospun PHBV radially oriented nanofiber dressing patch with the multiple biological cues of Beri for the effective treatment of hard-to-heal diabetic wounds.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Zhu, Qiuchen Luo, Tiefeng Cao, Guang Yang, Lin Xiao
{"title":"Injectable cartilage microtissues based on 3D culture using porous gelatin microcarriers for cartilage defect treatment.","authors":"Jing Zhu, Qiuchen Luo, Tiefeng Cao, Guang Yang, Lin Xiao","doi":"10.1093/rb/rbae064","DOIUrl":"10.1093/rb/rbae064","url":null,"abstract":"<p><p>Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects <i>in vivo</i>, via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dewei Zhao, Liangliang Cheng, Faqiang Lu, Xiuzhi Zhang, Jiawei Ying, Xiaowei Wei, Fang Cao, Chunxiao Ran, Guoshuang Zheng, Ge Liu, Pinqiao Yi, Haiyao Wang, Liqun Song, Bin Wu, Lingpeng Liu, Lu Li, Xiaohu Wang, Junlei Li
{"title":"Design, fabrication, and clinical characterization of additively manufactured tantalum hip joint prosthesis","authors":"Dewei Zhao, Liangliang Cheng, Faqiang Lu, Xiuzhi Zhang, Jiawei Ying, Xiaowei Wei, Fang Cao, Chunxiao Ran, Guoshuang Zheng, Ge Liu, Pinqiao Yi, Haiyao Wang, Liqun Song, Bin Wu, Lingpeng Liu, Lu Li, Xiaohu Wang, Junlei Li","doi":"10.1093/rb/rbae057","DOIUrl":"https://doi.org/10.1093/rb/rbae057","url":null,"abstract":"\u0000 The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials used and the structural design of the prosthesis. This study aimed to fabricate a porous tantalum (Ta) hip prosthesis using selective laser melting (SLM) technology. The feasibility of SLM Ta use in hip prosthesis was verified by studying its chemical composition, metallographic structure, and mechanical properties. In vitro experiments proved that SLM Ta exhibited better biological activities in promoting osteogenesis and inhibiting inflammation than SLM Ti6Al4V. Then, the topological optimization design of the femoral stem of the SLM Ta hip prosthesis was carried out by finite element simulation, and the fatigue performance of the optimized prosthesis was tested to verify the biomechanical safety of the prosthesis. A porous Ta acetabulum cup was also designed and fabricated using SLM. Its mechanical properties were then studied. Finally, clinical trials were conducted to verify the clinical efficacy of the SLM Ta hip prosthesis. The porous structure could reduce the weight of the prosthesis and stress shielding and avoid bone resorption around the prosthesis. In addition, anti-infection drugs can also be loaded into the pores for infection treatment. The acetabular cup can be custom-designed based on the severity of bone loss on the acetabular side, and the integrated acetabular cup can repair the acetabular bone defect while achieving the function of the acetabular cup.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141269485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Woo-Jin Kim, Jeong-Hyun Ryu, Ji Won Kim, Ki-Tae Kim, Hye-rim Shin, H. Yoon, Hyun-Mo Ryoo, Young-Dan Cho
{"title":"Bone targeted lipoplex loaded Three-Dimensional bioprinting bilayer scaffold enhanced bone regeneration","authors":"Woo-Jin Kim, Jeong-Hyun Ryu, Ji Won Kim, Ki-Tae Kim, Hye-rim Shin, H. Yoon, Hyun-Mo Ryoo, Young-Dan Cho","doi":"10.1093/rb/rbae055","DOIUrl":"https://doi.org/10.1093/rb/rbae055","url":null,"abstract":"\u0000 Clinical bone-morphogenetic protein 2 (BMP2) treatment for bone regeneration, often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems, necessitates research into improved biomaterials for better BMP2 stability and retention. To tackle this challenge, we introduced a groundbreaking bone-targeted, lipoplex-loaded, three-dimensional bioprinted bilayer scaffold, termed the polycaprolactone-bioink-nanoparticle (PBN) scaffold, aimed at boosting bone regeneration. We encapsulated BMP2 within the fibroin nanoparticle based lipoplex (Fibroplex) and functionalized it with DSS6 for bone tissue-specific targeting. 3D printing technology enables customized, porous PCL scaffolds for bone healing and soft tissue growth, with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex, shown to support effective nutrient exchange and cell growth at specific pore sizes. The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue, a finding validated by in vitro osteogenic differentiation assays. The PBN scaffold was evaluated for critical calvarial defects, focusing on sustained BMP2 delivery, prevention of soft tissue cell infiltration, and controlled fiber membrane pore size in vivo. The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge, promoting osteogenic differentiation and bone regeneration in a calvarial defect animal. Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation, thereby reducing the risk of heterotopic ossification.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141271279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}