{"title":"Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair","authors":"Jiaxin Chen, Xing Cheng, Zhengran Yu, Rongli Deng, Rui Cui, Jing Zhou, Houqing Long, Yong Hu, Daping Quan, Ying Bai","doi":"10.1093/rb/rbae039","DOIUrl":"https://doi.org/10.1093/rb/rbae039","url":null,"abstract":"\u0000 Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 hours, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in-situ injected DSCM+NT3+Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM+NT3+Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719548","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}
{"title":"Correction to: Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan–indocyanine green/luteolin nanocomposites for wound healing","authors":"","doi":"10.1093/rb/rbae037","DOIUrl":"https://doi.org/10.1093/rb/rbae037","url":null,"abstract":"[This corrects the article DOI: 10.1093/rb/rbac072.].","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140721474","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}
{"title":"Correction to: Chitin nanocrystal-assisted 3D bioprinting of gelatin methacrylate scaffolds","authors":"","doi":"10.1093/rb/rbae026","DOIUrl":"https://doi.org/10.1093/rb/rbae026","url":null,"abstract":"[This corrects the article DOI: 10.1093/rb/rbad058.].","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140729382","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}
Nan Zhang, Qiqi Sun, Junhua Li, Jing Li, Lei Tang, Q. Zhao, Yujie Pu, Gaofeng Liang, Bin He, Wenxia Gao, Jianlin Chen
{"title":"A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for Colon cancer therapy","authors":"Nan Zhang, Qiqi Sun, Junhua Li, Jing Li, Lei Tang, Q. Zhao, Yujie Pu, Gaofeng Liang, Bin He, Wenxia Gao, Jianlin Chen","doi":"10.1093/rb/rbae036","DOIUrl":"https://doi.org/10.1093/rb/rbae036","url":null,"abstract":"\u0000 Immune checkpoint blockade therapy provides a new strategy for tumor treatment, however, the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects. Herein, we reported a lipid/PLGA nanocomplex (RDCM) co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1MT to improve immunotherapy of colon cancer. Arginine-glycine-aspartic acid (RGD) as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via PEG, and programmed cell death-ligand 1 (PD-L1) peptide inhibitor DPPA was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker. The Ce6 and 1MT were encapsulated in PLGA nanoparticles. The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes. When the nanocomplexes were delivered to tumor, DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding. RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin. Strong immunogenic cell death was induced by 1O2 generated from Ce6 irradiation under 660 nm laser. 1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment. The RDCM facilitated the maturation of dendritic cells, inhibited the activity of IDO, and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice, triggering a robust immunological memory effect, thus effectively preventing tumor metastasis. The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140372966","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}
Ying Wang, Katrina Vizely, Chen Yu Li, Karen Shen, Amid Shakeri, Ramak Khosravi, James Ryan Smith, Eugene Alfonzo, A. Alteza, Yimu Zhao, M. Radisic
{"title":"Biomaterials for immunomodulation in wound healing","authors":"Ying Wang, Katrina Vizely, Chen Yu Li, Karen Shen, Amid Shakeri, Ramak Khosravi, James Ryan Smith, Eugene Alfonzo, A. Alteza, Yimu Zhao, M. Radisic","doi":"10.1093/rb/rbae032","DOIUrl":"https://doi.org/10.1093/rb/rbae032","url":null,"abstract":"\u0000 The substantial economic impact of nonhealing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients and the healthcare system. This review paper provides an overview of the skin's vital role in guarding against various environmental challenges as the body's largest protective organ and associated developments in biomaterials for wound healing. We first introduce the composition of skin tissue and intricate processes of wound healing, with special attention to the crucial role of immunomodulation in both acute and chronic wounds. This highlights how the imbalance in the immune response, particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression, hinders normal healing stages. Then, this review distinguishes between traditional wound healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune response to facilitate wound closure. Additionally, we highlight the importance of considering the stages of wounds in the healing process. By integrating advanced materials engineering with an in-depth understanding of wound biology, this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140374487","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}
Yu Cheng, Yini Huangfu, Tingyuan Zhao, Linxian Wang, Jing Yang, Jie Liu, Zujian Feng, Kehua Que
{"title":"Thermosensitive hydrogel with programmed Dual-Octenidine release combating biofilm for the treatment of apical periodontitis","authors":"Yu Cheng, Yini Huangfu, Tingyuan Zhao, Linxian Wang, Jing Yang, Jie Liu, Zujian Feng, Kehua Que","doi":"10.1093/rb/rbae031","DOIUrl":"https://doi.org/10.1093/rb/rbae031","url":null,"abstract":"\u0000 The utilization of intracanal medicaments is an indispensable procedure in root canal treatment(RCT). However, the conventional intracanal medicaments still need improvement regarding antimicrobial efficacy and ease of clinical operation. To address the above issues, OCT/PECT@OCT+ALK composite hydrogel characterized by programming sequential release of dual antimicrobial agents has been proposed. Thanks to the self-assemble ability of amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro -9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9- undecanone) (PECT), dual hydrophilic and hydrophobic antimicrobial agents could be easily encapsulated in the hydrogel system, and tailored for sequential drug release for a better antibiofilm effect. The hydrophilic octenidine (Octenidine dihydrochloride, OCT-HCl) is encapsulated in the hydrophilic part of hydrogel for instantaneous elevating the drug concentration through bursting release, and the hydrophobic octenidine(Octenidine, OCT) is further loaded into the PECT nanoparticles to achieve a slower and sustained release profile. Additionally, calcium hydroxide (Ca(OH)2) was incorporated into the system and evenly dispersed among PECT nanoparticles to create an alkaline (ALK) environment, synergistically enhancing the antibiofilm effect with higher efficiency and prolonged duration. The antibiofilm effect has been demonstrated in root-canal models and apical periodontitis rats, exhibiting superior performance compared to clinically used Ca(OH)2 paste. This study demonstrates that OCT/PECT@OCT+ALK composite thermosensitive hydrogel is a potential intracanal medicament with excellent antibiofilm effect and clinical operability.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140379096","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}
Konstantinos Loukelis, Nikos Koutsomarkos, A. Mikos, M. Chatzinikolaidou
{"title":"Advances in 3D bioprinting for regenerative medicine applications","authors":"Konstantinos Loukelis, Nikos Koutsomarkos, A. Mikos, M. Chatzinikolaidou","doi":"10.1093/rb/rbae033","DOIUrl":"https://doi.org/10.1093/rb/rbae033","url":null,"abstract":"\u0000 Biofabrication techniques allow for the construction of biocompatible and biofunctional structures composed from biomaterials, cells and biomolecules. Bioprinting is an emerging 3D printing method which utilizes biomaterial-based mixtures with cells and other biological constituents into printable suspensions known as bioinks. Coupled with automated design protocols and based on different modes for droplet deposition, 3D bioprinters are able to fabricate hydrogel-based objects with specific architecture and geometrical properties, providing the necessary environment that promotes cell growth and directs cell differentiation towards application-related lineages. For the preparation of such bioinks, various water-soluble biomaterials have been employed, including natural and synthetic biopolymers, and inorganic materials. Bioprinted constructs are considered to be one of the most promising avenues in regenerative medicine due to their native organ biomimicry. For successful application, the bioprinted constructs should meet particular criteria such as optimal biological response, mechanical properties similar to the target tissue, high levels of reproducibility and printing fidelity, but also increased upscaling capability. In this review, we highlight the most recent advances in bioprinting, focusing on the regeneration of various tissues including bone, cartilage, cardiovascular, neural, skin, and other organs such as liver, kidney, pancreas, and lungs. We discuss the rapidly developing co-culture bioprinting systems used to resemble the complexity of tissues and organs and the crosstalk between various cell populations towards regeneration. Moreover, we report on the basic physical principles governing 3D bioprinting, and the ideal bioink properties based on the biomaterials’ regenerative potential. We examine and critically discuss the present status of 3D bioprinting regarding its applicability and current limitations that need to be overcome to establish it at the forefront of artificial organ production and transplantation.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140379263","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}
Delong Zhu, Ying Hu, Xiangkai Kong, Yuansen Luo, Yi Zhang, Yu Wu, Jiameng Tan, Jianwei Chen, Tao Xu, Lei Zhu
{"title":"Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel.","authors":"Delong Zhu, Ying Hu, Xiangkai Kong, Yuansen Luo, Yi Zhang, Yu Wu, Jiameng Tan, Jianwei Chen, Tao Xu, Lei Zhu","doi":"10.1093/rb/rbae035","DOIUrl":"https://doi.org/10.1093/rb/rbae035","url":null,"abstract":"<p><p>Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions <i>in vitro</i> and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870144","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":"Triple-layered core-shell fiber dressings with enduring platelet conservation and sustained growth factor release abilities for chronic wound healing.","authors":"Simin Lai, Tingbin Wu, Chenxi Shi, Xiaojing Wang, Pengbi Liu, Lihuan Wang, Hui Yu","doi":"10.1093/rb/rbae034","DOIUrl":"https://doi.org/10.1093/rb/rbae034","url":null,"abstract":"<p><p>Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11004556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852599","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":"In vitro and in vivo degradation, biocompatibility and bone repair performance of strontium doped montmorillonite coating on Mg-Ca alloy","authors":"Wenxin Sun, Kaining Yang, Yuhong Zou, Yande Ren, Lin Zhang, Fen Zhang, Rongchang Zeng","doi":"10.1093/rb/rbae027","DOIUrl":"https://doi.org/10.1093/rb/rbae027","url":null,"abstract":"\u0000 Poor bone growth remains a challenge for degradable bone implants. Montmorillonite and strontium were selected as the carrier and bone growth promoting elements to prepare strontium doped montmorillonite coating on magnesium-calcium alloy. The surface morphology and composition were characterized by SEM, EDS, XPS, FT-IR and XRD. The hydrogen evolution experiment and electrochemical test results showed that the magnesium calcium alloy coated with Sr-MMT coating possessed optimal corrosion resistance performance. Furthermore, in vitro studies on cell activity, ALP activity, and cell morphology confirmed that Sr-MMT coating had satisfactory biocompatibility, which can significantly avail the proliferation, differentiation, and adhesion of osteoblasts. Moreover, the results of the 90 days implantation experiment in rats indicated that, the preparation of Sr-MMT coating effectively advanced the biocompatibility and bone repair performance of magnesium calcium alloy. In addition, The Osteogenic ability of Sr-MMT coating may be due to the combined effect of the precipitation of Si4+ and Sr2+ in Sr-MMT coating and the dissolution of Mg2+ and Ca2+ during the degradation of Mg-Ca alloy. By using coating technology, this study provides a late-model strategy for biodegradable Mg alloys with good corrosion resistance, biocompatibility. This new material will bring more possibilities in bone repair.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140220383","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}