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A great interest has been shown in the injectable scaffolds for cartilage tissue regeneration because it can fill irregularly shaped defects easily through minimally invasive surgical treatments. Herein, we developed a new injectable three-dimensional (3D) alginate hydrogel loaded with biodegradable porous poly(ε-caprolactone)–b-poly(ethylene glycol)–b-poly(ε-caprolactone) microspheres (MPs/Alg) as the calcium gluconate container to cross-link alginate. Suspensions of chondrocytes/alginate and porous microspheres turned into a gel because of the release of calcium gluconate; thus, the injectable composite hydrogels give a 3D scaffold to fit the defects perfectly and integrate the extracellular-matrix-mimicking architecture to efficiently accommodate cartilage cells in situ. Tissue repair in a full-thickness cartilage defect model was controlled at 6, 12, and 18 weeks after the implant by micro-CT and immunohistochemistry to evaluate the healing status. The defect in the MPs/Alg+ cells group achieved an almost complete repair at 18 weeks, and the repaired chondrocytes regained a normal tissue structure. Moreover, the MPs/Alg+ cells-treated group increased the quality of tissue formed, including the accumulated glycosaminoglycan and the uniformly deposited type II collagen. The results point out the promising application of the injectable MPs/Alg-chondrocytes system for cartilage tissue engineering.

Spinal fusion is the classic treatment to achieve spinal stability for the treatment of the spinal disease. Generally, spinal fusion still has to combine a certain of bone matrix for promoting bone formation to achieve the desired fusion effect based on the surgery, including the traditional bone matrix, such as the autologous bone, allografts and xenografts. Nevertheless, some problems still existed such as the immunogenic problems, the secondary wound, and pathogenic transfer and so on. Here the injectable thermosensitive hydrogel could substitute to avoid the problems as a potential biological scaffold for tissue engineering. Once injected, they could fill in the irregular-shaped cavity and change to a gel state at physiological temperature. We wanted to design the collagen/n-HA/BMP-2@PCEC/PECE hydrogel composites based on previous work about collagen/n-HA/PECE hydrogel to exhibit better performance in guiding spinal fusion because of the addition of BMP-2@PCEC nanoparticles (PCEC, PCL-PEG-PCL). However, when the hydrogels were injected, one of the surfaces was in contact with the spine, but others were in contact with soft tissue like muscles and fascia. The release behavior was the same at the different surfaces, so the factors could be released into the soft tissue, and it may then be consumed or lead to ectopic bone formation. The hydrogel composites should be improved to adjust the direction of the releaser behavior. In consequence, we wrapped an electrostatic spinning nanofiber membrane possessing hydrophobicity around the hydrogels. In this study, we developed a system that the collagen/n-HA/BMP-2@PCEC/PECE hydrogels were wrapped with the hydrophobicity PDLLA electrospun nanofiber membrane, setting up a barrier between the hydrogels and the soft tissue. The system could exhibit biocompatibility, preventing the factors from escaping to keep their retention in the needed places of osteogenesis; the results demonstrated that it showed an excellent effect on spinal fusion.

In our study, a hybrid alginate hydrogel cross-linked by calcium gluconate crystals deposited in poly­(ε-caprolactone)-b-poly­(ethylene glycol)-b-poly­(ε-caprolactone) (PCL-PEG-PCL, abbreviated as PCEC) porous microspheres was developed for skin engineering. The diameter of microspheres was ∼212 μm, and the pore size was ∼8 μm. The PCEC porous microspheres supplied different functions in the hydrogel: (1) Calcium gluconate crystals were loaded in the inner pores of the microspheres, which can induce alginate hydrogel to cross-link in a few minutes once they were mixed. (2) The porous structure of the microspheres provided more anchor points for fibroblast attachment and growth, resulting in the enhancement of cell growth in the hybrid hydrogel. The PCEC microspheres/Alg hydrogel (MPs/Alg hydrogel) possessed excellent compatibility, because cell viability remained around 100% even at a concentration of 500 μg/mL. Meanwhile, the morphology of 3T3 and L929 cells attached on both PCEC porous microspheres and MPs/Alg hydrogel were confirmed by confocal laser spectrometry (CLSM). What’s more, MPs/Alg hydrogel promoted wound regeneration in a full-thickness skin defect model of rats. The mild inflammation reaction existed at the early stage of wound repair and gradually disappeared. These findings suggested that MPs/Alg hydrogel may possess great potential in the application of skin tissue engineering.