title: An orthopedic tissue adhesive for targeted delivery of intraoperative biologics.
abstract: Tissue adhesives can bind together damaged tissues and serve as tools to deliver and localize therapeutics to facilitate regeneration. One emerging therapeutic trend in orthopedics is the use of intraoperative biologics (IOB), such as bone marrow (BM) and platelet-rich plasma (PRP), to stimulate healing. Here, we introduce the application of the biomaterial chondroitin sulfate succinimidyl succinate (CS-NHS) to deliver IOB in a hydrogel adhesive. We demonstrate the biomaterial's ability to bind various tissue types and its cellular biocompatibility with encapsulated human mesenchymal stem cells (hMSCs). Further, we examine in detail the CS-NHS adhesive combined with BM aspirate for use in bone applications. hMSCs were encapsulated in CS-BM and cultured for 5 weeks in osteogenic medium. Quantitative RT-PCR demonstrated osteogenesis via upregulation of the osteogenic transcription factor Runx2 and bone markers alkaline phosphatase and osteocalcin. Significant deposition of calcium and osteocalcin was detected using biochemical, histological, and immunohistochemical techniques. Shear testing demonstrated that the CS-BM adhesive exhibited an adhesive strength approximately an order of magnitude stronger than fibrin glue and approaching that of a cyanoacrylate adhesive. These results indicate that CS-NHS is a promising delivery tool for IOB in orthopedic applications requiring a strong, degradable, and biocompatible adhesive that supports bone growth.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simson
authors.forename: Joshua
authors.initials: J
authors.lastname: Crist
authors.forename: Iossif
authors.initials: I
authors.lastname: Strehin
authors.forename: Qiaozhi
authors.initials: Q
authors.lastname: Lu
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000138:chemical synthesis* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000378:metabolism; D007432:Intraoperative Period; D008422:Materials Testing; D053657:Platelet-Rich Plasma / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D013388:Succinimides / Q000138:chemical synthesis* / Q000378:metabolism; D014014:Tissue Adhesives / Q000138:chemical synthesis* / Q000378:metabolism; D023822:Tissue Engineering
chemical_list: D013388:Succinimides; D014014:Tissue Adhesives; C579126:chondroitin sulfate succinimidyl succinate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002809:Chondroitin Sulfates