Absorbable hemostatic agents with a high hemostatic efficacy play an important role in surgical and severely traumatic hemostasis. In the present study, by applying polyelectrolyte assembly, polyelectrolyte complexes (PECs), using carboxymethyl starch (CMS) and chitosan oligosaccharide (COS), with controllable physicochemical properties were prepared and optimized for hemorrhage control. Particle size, zeta potential, morphology and water absorption of the PECs with different CMS/COS ratios were systematically evaluated. The results of in vitro degradation in PBS suggested that CMS/COS PECs were degradable and their degradation rates, which decreased with the increase of the COS content, were suitable for absorbable hemostatic agents. The in vivo hemostatic efficacy of the PECs with 10 wt% COS content (PEC 10), which was evaluated in a rabbit hepatic hemorrhage model, was better than CMS but decreased with the increase of the COS content. The plasma coagulation evaluation revealed that the PECs could significantly activate and accelerate the coagulation cascade through both the intrinsic and extrinsic pathways but could not directly affect the common pathway. CMS/COS PECs also showed antimicrobial activity against S. aureus, which enhanced with the increase of the COS content, but failed against E. coli. Moreover, PEC 10 displayed excellent cytocompatibility with MC3T3-L1 and good tissue compatibility in a rabbit liver model. These findings not only suggest that CMS/COS PECs with a suitable COS content were promising absorbable hemostatic agents for internal use but they are also useful to understand the underlying principles for designing PEC based hemostatic agents.
Degradable bone cement has superior osteoconductivity and plasticity and is commonly used to treat defects greater than the critical-size. Magnesium gallate metal–organic frameworks (MOFs) (Mg-MOF), with antibacterial and anti-inflammatory properties, are doped into a composite cement composed of calcium sulfate, calcium citrate, and dicalcium hydrogen phosphate anhydrous (CS/CC/DCPA). The doping of the Mg-MOF slightly influences the microstructure and curing properties of the composite cement, with the mechanical strength of the cement displaying a significant increase from 27 to 32 MPa. Antibacterial tests reveal that the Mg-MOF bone cement has excellent antibacterial characteristics and can effectively inhibit bacterial growth in 4 h (Staphyloccocus aureus survival rate <10%). Herein, lipopolysaccharide (LPS)-induced macrophage models are used to investigate the anti-inflammatory characteristics of composite cement. The Mg-MOF bone cement can regulate the inflammatory factors and polarization of macrophages (M1 and M2). In addition, the composite cement promotes cell proliferation and osteo-differentiation of mBMSCs, and the activity of alkaline phosphatase and calcium nodules are increased. The bone related transcription factor and specific proteins, such as runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2, osteocalcin (OCN), osteopontin (OPN), and collagen type 1 (COL1), were highly expressed by the Mg-MOF bone cements. Therefore, Mg-MOF doped CS/CC/DCPA bone cement is multifunctional for bone repair, which will promote bone formation and avoid the infection of wounds, and it is suitable for use with non-load-bearing bone defects.
9 November 2012 in Journal of Applied Polymer Science