Isabella Laurén

Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young's modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

Cationically modified chitosan derivatives exhibit a range of appealing characteristics, with a particular emphasis on their antimicrobial potential across a broad spectrum of biomedical applications. This study aimed to delve deeper into quaternary chitosan (QC) derivatives. Through the synthesis of both homogeneously and heterogeneously dual-quaternized chitosan (DQC), utilizing AETMAC ([2-(acryloyloxy)ethyl]-trimethylammonium chloride) and GTMAC (glycidyl trimethylammonium chloride), a permanent charge was established, spanning a wide pH range. We assessed structural differences, the type of quaternary functional group, molecular weight (M_w), and charge density. Intriguingly, an upper critical solution temperature (UCST) behavior was observed in AETMAC-functionalized QC. To our knowledge, it is a novel discovery in cationically functionalized chitosan. These materials demonstrated excellent antimicrobial efficacy against model test organisms E. coli and P. syringae. Furthermore, we detected concentration-dependent cytotoxicity in NIH-3T3 fibroblasts. Striking a balance between antimicrobial activity and cytotoxicity becomes a crucial factor in application feasibility. AETMAC-functionalized chitosan emerges as the top performer in terms of overall antibacterial effectiveness, possibly owing to factors like molecular weight, charge characteristics, and variations in the quaternary linker. Quaternary chitosan derivatives, with their excellent antibacterial attributes, hold significant promise as antibacterial or sanitizing agents, as well as across a broad spectrum of biomedical and environmental contexts.