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Antibody Conjugate Assembly on Ultrasound-Confined Microcarrier Particles.

ABSTRACT: Bioconjugates are important next-generation drugs and imaging agents. Assembly of these increasingly complex constructs requires precise control over processing conditions, which is a challenge for conventional manual synthesis. This inadequacy has motivated the pursuit of new approaches for efficient, controlled modification of high-molecular-weight biologics such as proteins, carbohydrates, and nucleic acids. We report a novel, hands-free, semiautomated platform for synthetic manipulation of biomolecules using acoustically responsive microparticles as three-dimensional reaction substrates. The microfluidic reactor incorporates a longitudinal acoustic trap that controls the chemical reactions within a localized acoustic field. Forces generated by this field immobilize the microscale substrates against the continuous flow of participating chemical reagents. Thus, the motion of substrates and reactants is decoupled, enabling exquisite control over multistep reaction conditions and providing high-yield, high-purity products with minimal user input. We demonstrate these capabilities by conjugating clinically relevant antibodies with a small molecule. The on-bead synthesis comprises capture of the antibody, coupling of a fluorescent tag, product purification, and product release. Successful capture and modification of a fluorescently labeled antibody are confirmed via fold increases of 49 and 11 in the green (antibody)- and red (small-molecule dye)-channel median intensities determined using flow cytometry. Antibody conjugates assembled on acoustically responsive, ultrasound-confined microparticles exhibit similar quality and quantity to those prepared manually by a skilled technician.

SUBMITTER: Binkley MM

PROVIDER: S-EPMC8221231 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

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Antibody Conjugate Assembly on Ultrasound-Confined Microcarrier Particles.

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