Is it snowing in your city Anext Chromosome-based Diagnosis and Engineering Strategies for Oral and Maxillofacial Diseases (III) Continued from Part I: Exosome-Based Diagnosis and Engineering Strategies for Oral and Maxillofacial Diseases (II).2. Engineering strategies for exosomes
Although natural exosomes have been widely used for oral and maxillofacial diseases, their disadvantages are still obvious, including low yield, high impurities, easy removal, and lack of targeting, resulting in the limited effectiveness of natural exosomes. In recent years, it has been discovered that the use of exosomes to precisely** oral and maxillofacial diseases is expected to be achieved through engineering means. The preparation methods of engineered exosomes include pretreatment of mother cells, direct treatment of exosomes, and biomaterials bound to exosomes, which can make exosome-related functions have obvious relevance.
, pretreatment of mother cells
Common pretreatment methods for maternal cells include transfection of maternal organisms by permeabilization virus or plasmid to obtain exosomes carrying specific genes, pretreatment of inflammatory factors, and pretreatment of environmental conditions. It was found that synovial mesenchymal stem cells (SMSCs) could only promote fibroblast proliferation, but could not promote endothelial cell angiogenesis. Up-regulating the expression level of the exosome miR-126-3p produced by SMSCS by lentiviral transfection technology can promote collagen production and angiogenesis, thereby leading to long-term diabetic wounds. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophage activity in rheumatoid arthritis (RA) induces synovial inflammation and autoimmunity. The researchers encapsulated plasmid DNA in exosomes extracted from M2-type macrophages encoding the anti-inflammatory cytokine interleukin-10 (IL-10 PDNA) and the chemotherapy drug-mezon-sodium phosphate (BSP), and found that the M2 exo PDNA BSP co-transport system promotes M2 macrophage polarity, which can be used as a promising biocompatible drug carrier and anti-inflammatory agent in RA**. Melatonin (MT)-pretreated MSCS-derived exosomes, MT-EXO can promote diabetic wound healing by inhibiting inflammatory responses and increase M2 polarization versus M1 polarization rates by activating the PTEN AKT signaling pathway. MT pretreatment has proven to be a promising method for diabetic wound healing. Artuvastatin (ATV), an HMG-Coa reductase inhibitor, is used to lower blood lipids clinically. Exosomes of bone marrow mesenchymal stem cells (BMSCs) pretreated with ATV (ATV-EXO) accelerate diabetic wound healing by enhancing angiogenesis. Some experts have found that human umbilical cord-derived mesenchymal stem cells (HUCMSCs) treated with 3,3-diindiindimethane can accelerate the healing of deep secondary burn wounds by increasing the autocrine signal of exosome WNT11 to promote the proliferation of HUCMSCs. After induction of hypoxia, the survival and proliferation of adipose stem cells are significantly enhanced, and the exosomes they produce can be activated by the PI3K AKT pathway to promote high-quality healing of diabetic wounds.
Mechanism of macrophage repolarization in rheumatoid arthritis.
Molecularly engineered M2 macrophage-derived exosomes with inflammatory anti-contagious and anti-inflammatory abilities that co-deliver IL-10 PDNA and GCS to achieve Ra** by M1 to M2 macrophage repolarization.
, direct modification of exosomes
Compared to the pretreatment of parental cells, exosome modification has a more direct and beneficial effect. Exosome loading methods include co-incubation, sonication, and electroporation. Co-incubation is a common method for direct modification of exosomes. Monocyte-derived myeloid cells play a crucial role in inflammation-related autoimmune inflammatory diseases and cancers, and EL-4 (murine lymphoma cells)-derived exosomes are co-cultured with curcumin, which in turn enhances the ** effect of exosomes on inflammation. Early studies have reported that exogenous cargo can be loaded into exosomes by ultrasound. Sonication can maintain the stability of the outer structure and may facilitate cargo loading better than co-hatching. Due to the lack of antimicrobial effect, exosomes are rarely used in infected wounds. A study conferred antimicrobial activity on exosomes from human umbilical cord mesenchymal stem cells (HUCMSCs) by sonicating exosomes carrying silver nanoparticles (AGNPS). An asymmetrical wet dressing composed of exosomes and a silver nanoparticle complex, the TS-SF SA AG-EXO dressing has multifunctional properties, including broad-spectrum antimicrobial activity, promoting wound healing, water retention, and maintaining electrolyte homeostasis. Electropores are another common method used to load exosomes with high cargo loading rates. At the same time, electroporation increases the number of RNA and small hydrophilic molecules loaded in exosomes, thereby reducing RNA degradation in the wound microenvironment. The researchers loaded the Cas9 ribonucleic acid protein (RNP) into purified exosomes isolated from hepatic stellate cells via electrical pore, and found that this promoted efficient cytoplasmic delivery of RNPs while allowing for a specific accumulation of RNPs in liver tissue in vivo, which in turn promoted tissue-specific genes for liver disease**.
Schematic diagram of exosomes used for in vivo delivery of Cas9 RNP** liver disease.
, biomaterial loading exosomes
Recent studies have reported satisfactory** results have been achieved by using various types of biomaterial examples such as hydrogel scaffolds or dressings to provide structural support and deliver exosomes. One study resulted in Oxoband, an exosome-rich, oxygen-releasing antioxidant wound dressing consisting of antioxidant polyurethane (PUAO), a highly porous cryogel with sustained oxygen-releasing properties containing adipose-derived stem cell (ADSC) exosomes. Experimental results showed that oxoband promoted faster wound closure, enhanced collagen deposition, faster re-epithelialization, increased angiogenesis and decreased oxidative stress within 2 weeks to enhance diabetic wound healing and may lead to **new diabetic ulcers**. The researchers developed a bioreactive polyethylene glycol (PEG) DNA hybrid hydrogel loaded with human papillary stem cell-derived exosomes (scap-exo) and found that the system was effective in promoting bone regeneration under both normal and diabetic conditions. Researchers have encapsulated umbilical cord mesenchymal stem cell (UCMSC) exosomes (UCMSC-EXO) in thiol hyaluronic acid microgels and shown that they can promote osteoarthritis (OA) cartilage repair and softened chondrocyte rejuvenation.
Schematic diagram of the formation and application of Oxoband.
Next: Exosome-based diagnosis and engineering strategies for oral and maxillofacial diseases (IV).