Gelatin hydrolysis test on xray film12/4/2023 ![]() ![]() Moreover, the physical properties of GMPs can also be modified for controlled and sequential release of TGF-β1 and BMP-2 for osteochondral tissue regeneration 21. ![]() Proteins such as TGF-β1 have been conjugated to GMPs to facilitate cartilage tissue regeneration 20. GMPs are biocompatible and biofunctionalizable. In our previous study, we showed that gelatin microparticles (GMPs) can be incorporated in adipose-derived MSC (ASC) spheroids without compromising cell viability 19. To address these issues, microcapsules in the form of hydrogel microparticles may be incorporated into the cell spheroids to deliver important proteins or supply oxygen in the core of the spheroids 18. However, due to the 3D conformation of cell spheroids, the efficient transfer of nutrients, differential oxygen concentrations, and diffusivity of growth factors into the core have remained major concerns 16, 17. Moreover, these cells show improved survivability and thus offer greater regenerative capacity in transplantation procedures 16. Although a 2D culture system is fast and easy, 3D cell aggregates called spheroids have been proven to be superior since the cells cultured in spheroids show increased expression of angiogenic, antiinflammatory, and chondrogenic markers. Many studies on DDD that attempted transplantation of MSCs and MSC-derived chondrocytes into the injury site have shown promising results and significant improvements in patients’ condition 14.Ĭhondrogenic differentiation of MSCs in vitro has been attempted with both 2-D and 3-D cultures incubated in differentiation media supplemented with various chondrogenic induction molecules, such as transforming growth factor beta (TGF-β3) and fibroblast growth factors (FGFs) 15. MSCs have long been used in tissue engineering and regenerative medicine for their ability to differentiate into different progenitor cells such as chondrocytes, osteocytes, and adipocytes. Cell-based therapies range from the use of disc-derived and non-disc-derived chondrocytes to treatments with stem cells such as the mesenchymal stem cells (MSCs) 13. Treatment for DDD includes nonsurgical (occupational therapy, physical therapy, and medications like steroids, opiates, and nonsteroidal antiinflammatory drugs ) and surgical interventions such as gene therapy, prosthetic total disc replacement (TDR), and cell-based therapy 11, 12. DDD is the leading cause of excruciating lower back pain in adults worldwide and is often characterized by several morphological (bulging, herniation, and thinning) and molecular (tissue dehydration, cellular senescence, oxidative stress, and proteolytic damage) changes that ultimately lead to tissue collapse, structural failure, and loss of function 5, 8, 10. However, aging, coupled with other contributing factors such as injury, smoking, diet, obesity, and extreme physical activity, inevitably causes progressive disintegration of IVDs, resulting in a condition commonly known as degenerative disc disease (DDD) 4, 5, 6, 7, 8, 9. These disks are primarily composed of a central nucleus pulposus (NP), concentric rings of annulus fibrosus (AF), and endplate, and they are rich in proteoglycans and various collagen proteins (collagen I and collagen II) 3. They are the key component of the spine that absorbs mechanical shock, imparts mobility, permits flexibility, and provides efficient support for the body 1, 2. Intervertebral disks (IVDs) are fibro-cartilaginous tissues that lie between adjacent vertebrae of the spinal column. Finally, injections of these composite spheroids in a rat model of intervertebral disc disease promoted restoration of the chondrogenic properties of the cells, thereby allowing regeneration of the chondrogenic tissue in vivo. Moreover, these composite spheroids induced the release of chondrogenic cytokines that, in turn, promoted regeneration of degenerative chondrocytes in vitro. Here, we report that the incorporation of gelatin microparticles coloaded with transforming growth factor beta 3 and matrilin 3 promoted chondrogenic differentiation of adipose-derived mesenchymal stem cell spheroids while preventing hypertrophy and terminal differentiation of cells. However, further advancement of these therapies is required to not only ensure a supply of healthy chondrocytes but also to promote regeneration of the defective cells in the injury site. Among the current treatments for DDD, cell-based therapies such as the injection of both disc- and non-disc-derived chondrocytes have shown significant improvements in the patients’ condition. Degenerative disc disease (DDD) is the leading cause of excruciating lower back pain and disability in adults worldwide. ![]()
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