Hyaluronic acid hydrogels: Establishing a sustained delivery system for extracellular vesicles DOI Creative Commons
Yashna Chabria, Joanne O’Dwyer, Emma McDermott

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Extracellular vesicles (EVs) are versatile transporters of genetic cargo with enormous potential in the therapeutic setting. Scalable production EVs, and routes to overcome rapid clearance required. Biocompatible hydrogels may support precise, localized delivery EVs target sites. This study aimed establish sustained a scalable 3D dynamic bioreactor fabricate using tyramine-modified hyaluronic acid (HA-TA) EV integration release patterns. MDA-MB-231 cells transduced lentiviral GFP fused CD63, were cultured 20kD hollow fiber GFP-EVs harvested over five weeks. characterized by Nanoparticle Tracking Analysis(NTA), Western Blot(WB) Transmission Electron Microscopy(TEM). Tyramine modified acid(HA-TA) formulated via enzymatic crosslinking hydrogen peroxide horseradish peroxidase, investigate patterns static conditions. Hydrogel swelling was recorded at 1-72 hrs loaded assess distribution Scanning Microscopy(SEM) NTA respectively. GFP-EV uptake assessed confocal microscopy. Longitudinal expression demonstrated released throughout culture. TEM successful isolation 30-200 nm size intact lipid bilayers (average 4×10 9 EVs/harvest). Initial harvests exhibited subpopulations larger which disappeared upon serum withdrawal. WB verified presence markers TSG101, CD81. HA-TA successfully formed assays revealed requirement for higher concentrations crosslinkers scaffold stability continued swelling. incorporated into variable observed time, depending on concentration hydrogel formulation. clusters visualized SEM. Investigation under conditions highlighted significant increase fluid flow Efficient transfer recipient also vitro . The data demonstrate engineered free subsequent incorporation release. These biocompatible hold promise tuneable variety disease settings.

Language: Английский

GelMA-based bioactive hydrogel scaffolds with multiple bone defect repair functions: therapeutic strategies and recent advances DOI Creative Commons

Bixia Zhou,

Xulei Jiang, Xinxin Zhou

et al.

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these with synthetic substitutes is most common strategy. In general, tissue engineering materials that mimic structural, mechanical biological properties natural have been extensively applied fill promote in situ regeneration. Hydrogels extracellular matrix (ECM)-like are materials, among which methacrylate-based gelatin (GelMA) hydrogels widely used because their tunable properties, excellent photocrosslinking capability good biocompatibility. Owing lack osteogenic activity, however, GelMA combined other types activities improve current composites. There three main aspects consider when enhancing regenerative performance composite materials: osteoconductivity, vascularization osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors two-dimensional (2D) nanomaterials combinations achieve enhanced regeneration activities. Three-dimensional (3D)-bioprinted scaffolds popular research topic (BTE), printed customized suitable for restoring large irregular due shape structural tunability, Herein, recent progress on GelMA-based hydrogel as multifunctional platforms plastic or orthopedic clinics systematically reviewed summarized. These strategies pave way design effective reconstruction biosafety. This review provides novel insights into development trends (BTE) correcting defects, contents summarized emphasized from perspectives (osteoconductivity, vascularization, osteoinduction 3D-bioprinting). addition, advantages deficiencies put forward, corresponding improvement measures presented prior application near future (created BioRender.com).

Language: Английский

Citations

78

Current Knowledge and Future Perspectives of Exosomes as Nanocarriers in Diagnosis and Treatment of Diseases DOI Creative Commons
Zaijun Zou, Li Han, Gang Xu

et al.

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 4751 - 4778

Published: Aug. 1, 2023

Abstract: Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes shown great potential diagnostic markers for diseases are also considered a promising cell-free therapy. Engineered significantly enhanced the efficacy precision of delivering therapeutic agents, currently being extensively employed in investigations various ailments, including oncology, inflammatory disorders, degenerative conditions. Particularly, engineered enable agent loading, modification, evasion MPS phagocytosis, intelligent control, bioimaging, been developed multifunctional nano-delivery platforms recent years. The utilization bioactive scaffolds that loaded exosome has to substantially augment retention, extend release, enhance efficacy. This approach advanced from conventional hydrogels nanocomposite hydrogels, nanofiber 3D printing, resulting superior physical biological properties effectively address limitations scaffolds. Additionally, plant-derived exosomes, can participate gut flora remodeling via oral administration, an ideal platform treatment intestinal diseases. Consequently, there is interest nanocarriers applications. comprehensive review provides overview biogenesis, composition, isolation methods exosomes. it examines pathological mechanisms diseases, tumors, Furthermore, this highlights significance microbial-derived Strategies specific applications scaffold-loaded further summarized, especially some new techniques such large-scale loading technique, macromolecular development nano-scaffold-loaded delivery. benefits using gut-related discussed. challenges, opportunities, prospects exosome-based disease diagnosis summarized both preclinical clinical viewpoints. Keywords: diagnosis,

Language: Английский

Citations

43

Extracellular vesicles and their engineering strategies, delivery systems, and biomedical applications DOI
Chunhao Yang,

Yunxin Xue,

Yu Duan

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 365, P. 1089 - 1123

Published: Jan. 1, 2024

Language: Английский

Citations

43

The role and applications of extracellular vesicles in osteoporosis DOI Creative Commons
Fei Fang, Jie Yang, Jiahe Wang

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 23, 2024

Abstract Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture, which increases patient susceptibility to fragile fractures. The intricate mechanisms governing homeostasis are substantially impacted extracellular vesicles (EVs), play crucial roles in both pathological physiological contexts. EVs derived from various sources exert distinct effects on osteoporosis. Specifically, released osteoblasts, endothelial cells, myocytes, mesenchymal stem cells contribute formation due their unique cargo proteins, miRNAs, cytokines. Conversely, secreted osteoclasts immune promote resorption inhibit formation. Furthermore, use as therapeutic modalities or biomaterials for diagnosing managing osteoporosis promising. Here, we review current understanding impact homeostasis, including classification biogenesis regulatory present an overview latest research progress treating using EVs. Finally, discuss challenges prospects translational

Language: Английский

Citations

27

Engineered exosomes and composite biomaterials for tissue regeneration DOI Creative Commons
Weikang Hu, Wang Wang, Zesheng Chen

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 2099 - 2126

Published: Jan. 1, 2024

Exosomes, which are small vesicles enclosed by a lipid bilayer and released many cell types, widely dispersed have garnered increased attention in the field of regenerative medicine due to their ability serve as indicators diseases agents with therapeutic potential. Exosomes play crucial role mediating intercellular communication through transfer biomolecules, including proteins, lipids, RNA, other molecular constituents, between cells. The targeted transport proteins nucleic acids specific cells has potential enhance or impair biological functions. applications, they can be used alone combination approaches. examination unique attributes functions these factors emerged prominent study realm biomedical research. This manuscript summarizes origins properties exosomes, structural, biological, physical, chemical aspects. paper offers complete recent progress tissue repair medicine, emphasizing possible implications methods forthcoming regeneration attempts.

Language: Английский

Citations

20

Engineered extracellular vesicles with sequential cell recruitment and osteogenic functions to effectively promote senescent bone repair DOI Creative Commons

Lei Qi,

Jing Wang,

Jinge Yan

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 12, 2025

Senescent mandibular bone repair poses a formidable challenge without completely satisfactory strategy. Endogenous cell recruitment and osteogenic differentiation are two sequential stages in regeneration, disruptions these processes present significant obstacles to senescent repair. To address issues, engineered extracellular vesicles (EV) with stem functions were developed. This study demonstrated that Apt19s-engineered (Apt19s-EV) recognize recruit marrow mesenchymal cells derived from old rats (O-BMSCs) specifically effectively. MiR-376b-5p, identified by RNA sequencing transfection, was significantly decreased O-BMSCs, it selected construct miR-376b-5p-engineered (376b-EV). 376b-EV could promote osteogenesis alleviate senescence of O-BMSCs targeting Camsap1. combine the advantages Apt19s miR-376b-5p, dual (Apt-376b-EV) comprising both miR-376b-5p modifications constructed. further validate its function, Gelatin methacryloyl (GelMA) hydrogel used as carrier Apt-376b-EV@GelMA delivery system. The vitro results have sequentially. Notably, vivo also showed sequentially endogenous enhance new formation fracture critical-sized defect models. In summary, vesicles, Apt-376b-EV, offer an appealing solution for recruiting promoting microenvironment, which may broaden clinical applications EV provide valuable strategies treating bone-related diseases future work.

Language: Английский

Citations

2

Advancements and Applications of Injectable Hydrogel Composites in Biomedical Research and Therapy DOI Creative Commons
Hossein Omidian,

Sumana Dey Chowdhury

Gels, Journal Year: 2023, Volume and Issue: 9(7), P. 533 - 533

Published: June 30, 2023

Injectable hydrogels have gained popularity for their controlled release, targeted delivery, and enhanced mechanical properties. They hold promise in cardiac regeneration, joint diseases, postoperative analgesia, ocular disorder treatment. Hydrogels enriched with nano-hydroxyapatite show potential bone addressing challenges of defects, osteoporosis, tumor-associated regeneration. In wound management cancer therapy, they enable accelerated closure, drug delivery. also find applications ischemic brain injury, tissue cardiovascular personalized immunotherapy. This manuscript highlights the versatility injectable hydrogel nanocomposites biomedical research. Moreover, it includes a perspective section that explores future prospects, emphasizes interdisciplinary collaboration, underscores promising research applications.

Language: Английский

Citations

38

Engineering preparation and sustained delivery of bone functional exosomes-laden biodegradable hydrogel for in situ bone regeneration DOI

Jinru Sun,

Guangfeng Li,

Shunli Wu

et al.

Composites Part B Engineering, Journal Year: 2023, Volume and Issue: 261, P. 110803 - 110803

Published: May 15, 2023

Language: Английский

Citations

33

Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis DOI Creative Commons

Futing Shu,

Hongchao Huang, Shichu Xiao

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 39, P. 302 - 316

Published: May 24, 2024

Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design gelatin methacrylate (GelMA) hydrogel for the sustained release netrin-1 evaluate its potential as scaffold promote diabetic wound healing. The results showed that was highly expressed during proliferation phases normal whereas it synchronously exhibited aberrantly low expression in wounds. Neutralization inhibited healing, topical application accelerated Mechanistic studies demonstrated regulated macrophage heterogeneity via A2bR/STAT/PPARγ signaling pathway promoted function endothelial cells, thus accelerating These data suggest is therapeutic target

Language: Английский

Citations

12

Stem Cells and Bone Tissue Engineering DOI Creative Commons
Xueqin Gao, Joseph J. Ruzbarsky, Jonathan E. Layne

et al.

Life, Journal Year: 2024, Volume and Issue: 14(3), P. 287 - 287

Published: Feb. 21, 2024

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host autograft is considered the gold standard for restoring function but comes with cost of harvest site comorbidity. Allograft a secondary option has its own limitations in incorporation host as well cost. Therefore, developing new tissue engineering strategies to treat critically needed. In past three decades, use stem cells delivered different scaffolds growth factors made tremendous progress. Many varieties have been isolated from tissues engineering. This review summarizes progress using postnatal cells, including marrow mesenchymal muscle-derived adipose-derived dental pulp cells/periodontal ligament periosteum umbilical cord-derived peripheral blood urine-derived apical papilla, and induced pluripotent repair. also exosomes extracellular vesicles various The advantages disadvantages each type cell discussed explained detail. It hoped future, these preclinical results will translate into regenerative therapies defect

Language: Английский

Citations

11