Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering.

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.

Injectable macro-porous chitosan/polyethylene glycol-silicotungstic acid double-network hydrogels based on "smashed gels recombination" strategy for cartilage tissue engineering.

The lack of interconnected macro-porous structure of most injectable hydrogels lead to poor cell and tissue infiltration. Herein, we present the fabrication of injectable macro-porous hydrogels based on "smashed gels recombination" strategy. Chitosan/polyethylene glycol-silicotungstic acid (CS/PEG-SiW) double-network hydrogels were prepared via dual dynamic interactions. The bulk CS/PEG-SiW hydrogels were then smashed into micro-hydrogels with average sizes ranging from 47.6 to 63.8 µm by mechanical fragmentation. The CS/PEG-SiW micro-hydrogels could be continuously injected and rapidly recombined into a stable porous hydrogel based on the dual dynamic interactions between micro-hydrogels. The average pore size of the recombined porous CS/PEG-SiW hydrogels ranged from 52 to 184 µm. The storage modulus, compress modulus and maximum compressive strain of the recombined porous CS/PEG-SiW1.0 hydrogels reached about 47.2 %, 28.2 % and 127.6 % of the values for their corresponding bulk hydrogels, respectively. The recombined porous hydrogels were cytocompatible and could effectively support proliferation and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In a rat cartilage defect model, recombined porous CS/PEG-SiW hydrogels could promote cartilage regeneration. Hematoxylin and eosin (H&E), Safranin-O/Fast green and immunohistochemical staining confirmed the accumulation of glycosaminoglycans (GAG) and type II collagen (Col II) in regenerated cartilage.

Treatment of thoracolumbar fractures by temporary posterior instrumentation with selective fusion schemes.

OBJECTIVE: This retrospective study investigated the clinical and radiographic outcomes following temporary transpedicular posterior instrumentation between two cohorts of patients with thoracolumbar fractures (TLF) who underwent selective or bi-segments intervertebral articular process fusion. METHODS: Patients with TLF who underwent the temporary posterior fixation with selective fusion (Group SF), or bi-segments fusion (Group BF) were studied. Superior intervertebral articular process and interlaminar fusion were performed in Group SF, whereas in Group BF, the patients underwent bi-segments fusion in both superior and inferior articular processes, as well as interlaminar fusion. We measured the distal and proximal intervertebral mobility, regional kyphotic angle, and vertebral height before and after surgery in both groups. Greenough Low-Back Outcome Score was used to assess the clinical outcomes. RESULTS: Sixty-five patients with TLF from T12 to L2 fractures were enrolled in the study period: 33 patients in the Group SF and 32 patients in the Group BF. All the patients experienced fracture healing (mean follow-up time: 19.7 months). The mean postoperative functional outcomes were 65.0 ± 2.0 points for the Low-Back Outcome Score in the Group SF and 65.2 ± 1.8 for the Group BF. A progressive regional kyphotic angle was observed with time regardless of fusion but was not significantly different between the two groups. There was a statistical difference between unfused inferior proximal adjacent and inferior distal adjacent segment regardless of fracture segments. CONCLUSIONS: The strategy of selective fusion is reported to be useful for the treatment of patients with TLF. The motion in the un-fused and adjacent segment could be better regained after instrumentation removal in the selective fusion group. LEVEL OF EVIDENCE: Level 3.

Mussel-Inspired Bisphosphonated Injectable Nanocomposite Hydrogels with Adhesive, Self-Healing, and Osteogenic Properties for Bone Regeneration.

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.