Bilayer osteochondral graft in rabbit xenogeneic transplantation model comprising sintered 3D-printed bioceramic and human adipose-derived stem cells laden biohydrogel.

Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D ß-tricalcium phosphate (ß-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D ß-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D ß-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D ß-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D ß-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D ß-TCP bioceramic scaffold.

Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models.

Simvastatin (SIM) is a lipid-lowering drug that also promotes bone formation, but its high liver specificity may cause muscle damage, and the low solubility of lipophilic drugs limits the systemic administration of SIM, especially in osteoporosis (OP) studies. In this study, we utilized the bone-targeting moiety of dendritic oligopeptides consisting of three aspartic acid moieties (dAsp3) and amphiphilic polymers (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid); PEG-PLGA) to create dAsp3-PEG-PLGA (APP) nanoparticles (NPs), which can carry SIM to treat OP. An in vivo imaging system showed that gold nanocluster (GNC)-PLGA/APP NPs had a significantly higher accumulation rate in representative bone tissues. In vivo experiments comparing low-dose SIM treatment (0.25 mg/kg per time, 2 times per week) showed that bone-targeting SIM/APP NPs could increase the bone formation effect compared with non-bone-targeting SIM/PP NPs in a local bone loss of hindlimb suspension (disuse) model, but did not demonstrate good bone formation in a postmenopausal (ovariectomized) model of systemic bone loss. The APP NPs could effectively target high mineral levels in bone tissue and were expected to reduce side effects in other organs affected by SIM. However, in vivo OP model testing showed that the same lower dose could not be used to treat different types of OP.

Generating adipose stem cell-laden hyaluronic acid-based scaffolds using 3D bioprinting via the double crosslinked strategy for chondrogenesis.

Bioprinting of most cell-laden hydrogel scaffolds with the required structural integrity, mechanical modulus, cell adhesion, cell compatibility, and chondrogenic differentiation are still significant issues that affect the application of bioinks in cartilage tissue engineering. This study focuses on constructing printable bioinks by combining adipose-derived stem cells (ADSCs), hyaluronic acid (HA)-based hydrogels and analyzing their ability to induce chondrogenesis using 3D bioprinting technology. First, biotinylated hyaluronic acid was synthesized via an adipic acid dihydrazide (ADH) linker with amide bond formation to form HA-biotin (HAB). Both HAB and the as-received streptavidin were mixed to form a partially cross-linked HA-biotin-streptavidin (HBS) hydrogel through noncovalent bonding. After that, the partially cross-linked HBS hydrogel was mixed with sodium alginate and subsequently printed to form the HBSA hydrogel 3D scaffolds using a bioprinter. Finally, the 3D scaffolds of the HBSA (HBS + alginate) hydrogel were submerged into CaCl2 solution to achieve a stable 3D HBSAC (HBSA + Ca2+) hydrogel scaffold through ion transfer crosslinking. The physical-chemical characteristics of the hybrid bioink compositions have been evaluated to determine the desired 3D bioprinting structure. Cytotoxicity and chondrogenic differentiation were also assessed to confirm that the double cross-linked HBSAC hydrogel scaffold was useful for chondrogenic formation. The results showed that partially crosslinking the biotinylated HA-based hydrogel with streptavidin has a significant effect on printability and structural integrity. Morphological analysis of a suitable 3D printed HBSAC hydrogel scaffold showed visible pores with the desired shape and geometry. We have concluded that the HBSAC hydrogel possesses a favorable biocompatibility profile. The HBSAC hydrogel can also secrete significantly higher amounts of chondrogenic marker genes at day 5 and sulfated glycosaminoglycans (sGAGs) from days 7 to 14 compared to the HA hydrogel, as determined via quantitative real-time PCR assay and Alcian blue staining and the DMMB assay.