More Like this

1. Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells

   https://doi.org/10.1155/2019/5654324  

   Winston, Tackla S.; Suddhapas, Kantaphon; Wang, Chenyan; Ramos, Rafael; Soman, Pranav; Ma, Zhen (January 2019, Stem Cells International)

   Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications. 

   more » « less
2. Biodegradable zinc oxide composite scaffolds promote osteochondral differentiation of mesenchymal stem cells

   https://doi.org/10.1002/bit.27173  

   Khader, Ateka; Arinzeh, Treena_Livingston (October 2019, Biotechnology and Bioengineering)

   Abstract Osteoarthritis (OA) involves the degeneration of articular cartilage and subchondral bone. The capacity of articular cartilage to repair and regenerate is limited. A biodegradable, fibrous scaffold containing zinc oxide (ZnO) was fabricated and evaluated for osteochondral tissue engineering applications. ZnO has shown promise for a variety of biomedical applications but has had limited use in tissue engineering. Composite scaffolds consisted of ZnO nanoparticles embedded in slow degrading, polycaprolactone to allow for dissolution of zinc ions over time. Zinc has well‐known insulin‐mimetic properties and can be beneficial for cartilage and bone regeneration. Fibrous ZnO composite scaffolds, having varying concentrations of 1–10 wt.% ZnO, were fabricated using the electrospinning technique and evaluated for human mesenchymal stem cell (MSC) differentiation along chondrocyte and osteoblast lineages. Slow release of the zinc was observed for all ZnO composite scaffolds. MSC chondrogenic differentiation was promoted on low percentage ZnO composite scaffolds as indicated by the highest collagen type II production and expression of cartilage‐specific genes, while osteogenic differentiation was promoted on high percentage ZnO composite scaffolds as indicated by the highest alkaline phosphatase activity, collagen production, and expression of bone‐specific genes. This study demonstrates the feasibility of ZnO‐containing composites as a potential scaffold for osteochondral tissue engineering. 

   more » « less
3. Microtopography-induced changes in cell nucleus morphology enhance bone regeneration by modulating the cellular secretome

   https://doi.org/10.1038/s41467-025-60760-y  

   Wang, Xinlong; Li, Yiming; Lin, Zitong; Pla, Indira; Gajjela, Raju; Mattamana, Basil Baby; Joshi, Maya; Liu, Yugang; Wang, Huifeng; Zun, Amy B; et al (December 2025, Nature Communications)

   Nuclear morphology plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored. In this study, we fabricate implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell secretome for osteogenesis and cranial bone regeneration. In vitro, cells with deformed nuclei show enhanced secretion of proteins that support extracellular matrix (ECM) organization, which promotes osteogenic differentiation in neighboring mesenchymal stromal cells (MSCs). In a female mouse model with critical-size cranial defects, nuclear-deformed MSCs on micropillar mPOC/HA implants elevate Col1a2 expression, contributing to bone matrix formation, and drive cell differentiation toward osteogenic progenitor cells. These findings indicate that micropillars modulate the secretome of hMSCs, thereby influencing the fate of surrounding cells through matricrine effects. 

   more » « less
4. Bioactive Cellulose Acetate Electrospun Mats as Scaffolds for Bone Tissue Regeneration

   https://doi.org/10.1155/2022/3255039  

   Laboy-López, Simara; Méndez Fernández, Pedro O.; Padilla-Zayas, Jorge G.; Nicolau, Eduardo (February 2022, International Journal of Biomaterials)

   Galli, Carlo (Ed.)

   In the last decades, cell-based approaches for bone tissue engineering (BTE) have relied on using models that cannot replicate the complexity of the bone microenvironment. There is an ongoing amount of research on scaffold development responding to the need for feasible materials that can mimic the bone extracellular matrix (ECM) and aid bone tissue regeneration (BTR). In this work, a porous cellulose acetate (CA) fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface and promote osteoconduction and osteoinduction. The mats were characterized using FTIR and SEM/EDS to validate the chemical modifications and assess their structural integrity. By coupling adhesive peptides KRSR, RGD, and growth factor BMP-2, the fiber mats were bioactivated, and their induced biological responses were evaluated by employing immunocytochemical (ICC) techniques to study the adhesion, proliferation, and differentiation of premature osteoblast cells (hFOB 1.19). The biological assessment revealed that at short culturing periods of 48 hours and 7 days, the presence of the peptides was significant for proliferation and adhesion, whereas at longer culture times of 14 days, it had no significant effect on differentiation and maturation of the osteogenic progenitor cells. Based on the obtained results, it is thus concluded that the CA porous fiber mats provide a promising surface morphology that is both biocompatible and can be rendered bioactive upon the addition of osteogenic peptides to favor osteoconduction leading to new tissue formation. 

   more » « less
5. Notch signaling and fluid shear stress in regulating osteogenic differentiation

   https://doi.org/10.3389/fbioe.2022.1007430  

   Zhao, Yuwen; Richardson, Kiarra; Yang, Rui; Bousraou, Zoe; Lee, Yoo Kyoung; Fasciano, Samantha; Wang, Shue (October 2022, Frontiers in Bioengineering and Biotechnology)

   Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, a locked nucleic acid (LNA)/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation. 

   more » « less