Growth differentiation factor-5–gelatin methacryloyl injectable microspheres laden with adipose-derived stem cells for repair of disc degeneration

Abstract

Nucleus pulposus (NP) degeneration is the major cause of degenerative disc disease (DDD). This condition cannot be treated or attenuated by traditional open or minimally invasive surgical options. However, a combination of stem cells, growth factors (GFs) and biomaterials present a viable option for regeneration. Injectable biomaterials act as carriers for controlled release of GFs and deliver stem cells to target tissues through a minimally invasive approach. In this study, injectable gelatin methacryloyl microspheres (GMs) with controllable, uniform particle sizes were rapidly biosynthesized through a low-cost electrospraying method. The GMs were used as delivery vehicles for cells and GFs, and they exhibited good mechanical properties and biocompatibility and enhanced the in vitro differentiation of laden cells into NP-like phenotypes. Furthermore, this integrated system attenuated the in vivo degeneration of rat intervertebral discs, maintained NP tissue integrity and accelerated the synthesis of extracellular matrix. Therefore, this novel therapeutic system is a promising option for the treatment of DDD.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

“…NP repair restores the motion characteristics and physical properties of the target segments by NP tissue rehydration or NP replacement [ 6 ]. Biomaterials for NP replacement have focused mainly on injectable synthetic or biologically based hydrogels [ [7] , [8] , [9] ]. These hydrogels are mainly derived from non-degradable polyacrylates and polyacrylamides [ 10 , 11 ] and degradable hyaluronic acid, collagen in the extracellular matrix and chitosan [ 8 , 12 ].…”

The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

“…These matrices preserve the NP ECM biological components and microstructure and, therefore, should perfectly mimic the NP microenvironment (Yu et al, 2020;Yuan et al, 2013). A protocol for the decellularisation of porcine NP tissue has been developed, which results in a decrease in IVD degeneration following in vivo implantation (Xu et al, 2019). This, naturally derived, bioactive ECM material could serve as a potential treatment option for degenerated discs (Borrelli and Buckley, 2020).…”

3D Cell Culture—Can It Be As Popular as 2D Cell Culture?

“…[ 119 ] The use of GelMA hydrogel microspheres to load growth differentiation factor‐5 and rat ADSCs has a slow drug release effect and can treat degenerative disc disease. [ 120 ]…”

“…Mixed in bioink to improve manufacturability [120,219,220] HA Nonimmunogenicity, with hydroxyl group, carboxyl group, acetylamino groups Low strength, fast degradation Chemical cross-linking Chondrogenesis [221][222][223] Corning Matrigel With Contains growth factor Low strength Temperature Stem cell culture [224,225] Corning human type-I collagen Good cell adhesion, bioactivity Low strength Temperature and pH Bone, [226] stem cell culture [227] Collagen Good cell adhesion, stypticity Immunogenicity Temperature and pH Bone, [228] skin, [229,230] angiogenesis [231] Synthetic Polyvinyl alcohol With Contains hydroxyl group, can be modified easily Undegradable Temperature Skin, [232] chondrogenesis [233] PEG With Contains terminal hydroxyl group, can be modified easily, controllable mechanical properties…”

“…[119] The use of GelMA hydrogel microspheres to load growth differentiation factor-5 and rat ADSCs has a slow drug release effect and can treat degenerative disc disease. [120] Utilize the advantage that the terminals of the hydrogel can be modified with functional groups. Hydrogels are very suitable as carriers for drug delivery and controlled release.…”