Stem cell-laden injectable hydrogel microspheres for cancellous bone regeneration

Self Cite

163

The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.

Section: Methodsmentioning

confidence: 99%

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

Han

Yang

Zhao

et al. 2021

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163

“…A variety of techniques such as 3D printing, electrospinning, and microfluidics have been employed to manufacture artificial bone scaffolds [ [7] , [8] , [9] , [10] ]. Microfluidics enables precise manipulation of fluids in a low-cost, fast-processing, high-throughput, and mass-production manner for creating high-quality products [ [11] , [12] , [13] , [14] , [15] , [57] ] and has attracted increasing attention for the synthesis of artificial bone scaffolds [ 16 ]. The feasibility of the mass-production of high-quality artificial bone scaffolds is extremely important for success in the clinical treatment of bone defects.…”

Section: Introductionmentioning

confidence: 99%

Ca2+-supplying black phosphorus-based scaffolds fabricated with microfluidic technology for osteogenesis

Zhang

Ouyang

et al. 2021

Effective osteogenesis remains a challenge in the treatment of bone defects. The emergence of artificial bone scaffolds provides an attractive solution. In this work, a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus (P), calcium (Ca), and silicon (Si). We developed black phosphorus (BP)-based, three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment. The fibrous scaffolds were fabricated from 3D poly ( l -lactic acid) (PLLA) nanofibers (3D NFs), BP nanosheets, and hydroxyapatite (HA)-porous SiO 2 nanoparticles. The 3D BP@HA NFs possess three advantages: i) stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells (BMSCs) into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis; ii) plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area; iii) the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation, thus achieving accelerated osteogenesis. Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs, with the assistance of NIR laser, exhibited good performance in promoting bone regeneration. Furthermore, microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs, rapid processing, high throughput and mass production, greatly improving the prospects for clinical application. This is also the first BP-based bone scaffold platform that can self-supply Ca 2+ , which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.

“…Fragmented chitosan microgels injected into a rat spinal cord injury model were similarly found to enhance spinal tissue repair [ 30 ]. Granular hydrogel systems have also been used for cell delivery, drug delivery and other tissue engineering applications [ [31] , [32] , [33] , [34] , [35] ], including bone and cartilage regeneration [ [36] , [37] , [38] , [39] ], as well as the growth of skin [ 24 , 40 ] and heart tissue [ [41] , [42] , [43] ].…”

Section: Introductionmentioning

confidence: 99%

Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds

Hsu

George

Waller

et al. 2022

To reflect human development, it is critical to create a substrate that can support long-term cell survival, differentiation, and maturation. Hydrogels are promising materials for 3D cultures. However, a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction. Herein, granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell (hiPSC)-derived neural networks. A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules. Cells and hydrogel granules were combined using a weaker secondary gelation step, forming self-supporting cell laden scaffolds. At three and seven days, granular scaffolds supported higher cell viability compared to bulk hydrogels, whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions (65.52 ± 11.59 μm) after seven days compared to bulk hydrogels (22.90 ± 4.70 μm). Long-term (three-month) cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold. This approach is significant as it provides a simple, rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.