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Background: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture., Methods: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DW-MSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts., Results: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring., Conclusion: Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no commercial or financial conflicts of interest in conducting this research. Ethical statement: All animal study procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Gyeongsang National University (GNU-191015-D0053) and conducted in strict compliance with the Guidelines for Care and Use of Laboratory Animals at the School of Medicine, Gyeongsang National University., (© 2024. Korean Tissue Engineering and Regenerative Medicine Society.)

Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

Hypoxia and limited vascularization inhibit bone growth and recovery after surgical debridement to treat osteomyelitis. Similarly, despite significant efforts to create functional tissue-engineered organs, clinical success is often hindered by insufficient oxygen diffusion and poor vascularization. To overcome these shortcomings, we previously used the oxygen carrier perfluorooctane (PFO) to develop PFO emulsion-loaded hollow microparticles (PFO-HPs). PFO-HPs act as a local oxygen source that increase cell viability and maintains the osteogenic differentiation potency of human periosteum-derived cells (hPDCs) under hypoxic conditions. In the present study, we used a miniature pig model of mandibular osteomyelitis to investigate bone regeneration using hPDCs seeded on PFO-HPs (hPDCs/PFO-HP) or hPDCs seeded on phosphate-buffered saline (PBS)-HPs (hPDCs/PBS-HP). Osteomyelitis is characterized by a series of microbial invasion, vascular disruption, bony necrosis, and sequestrum formation due to impaired host defense response. Sequential plain radiography, computed tomography (CT), and 3D reconstructed CT images revealed new bone formation was more advanced in defects that had been implanted with the hPDCs/PFO-HPs than in defects implanted with the hPDCs/PBS-HP. Thus, PFO-HPs are a promising tissue engineering approach to repair challenging bone defects and regenerate structurally organized bone tissue with 3D architecture., (© 2019 Wiley Periodicals, Inc.)

Sufficient oxygen delivery into tissue-engineered three-dimensional (3D) scaffolds to produce clinically applicable tissues/organs remains a challenge for researchers and clinicians. One potential strategy to overcome this limitation is the use of an oxygen releasing scaffold. In the present study, we prepared hollow microparticles (HPs) loaded with an emulsion of the oxygen carrier perfluorooctane (PFO; PFO-HPs) for the timely supply of oxygen to surrounding cells. These PFO-HPs prolonged the survival and preserved the osteogenic differentiation potency of human periosteal-derived cells ( hPDCs) under hypoxia. hPDCs seeded onto PFO-HPs formed new bone at a faster rate and with a higher bone density than hPDCs seeded onto phosphate buffered saline-loaded control HPs. These findings suggest that PFO-HPs provide a suitable environment for the survival and maintenance of differentiation ability of hPDCs at bony defects without vascular networks until new blood vessel ingrowth occurs, thus enhancing bone regeneration. PFO-HPs are a promising system for effective delivery of various functional cells, including stem cells and progenitor cells, to regenerate damaged tissues/organs.

It is commonly accepted that the sustained release of bone morphogenetic protein-2 (BMP-2) can enhance bone regeneration and minimize its safety issues. However, little is known regarding the appropriate duration of BMP-2 stimulation for sufficient osteogenic differentiation and new bone formation because of the short half-life of BMP-2 in the physiological environment and the lack of a well-defined delivery matrix that can regulate the release period of BMP-2. In this study, we prepared porous poly(lactic-co-glycolic acid) (PLGA) beads with different surface pore sizes that can regulate the release period of BMP-2 (i.e., 7, 17, and 30 days) while providing the BMP-2 concentration required for bone regeneration. Our findings in both in vitro cell culture and in vivo animal studies using these BMP-2-loaded beads demonstrate that release of BMP-2 within 7 days affects only the initial differentiation of human periosteum-derived cells (hPDCs) and does not significantly enhance their subsequent differentiation into mature functional cells. However, extending the duration of BMP-2 stimulation over 17 days can provide a suitable environment for osteogenic differentiation of hPDCs and new bone formation.

In our previous study, dental follicle tissues from extracted wisdom teeth were successfully cryopreserved for use as a source of stem cells. The goals of the present study were to investigate the immunomodulatory properties of stem cells from fresh and cryopreserved dental follicles (fDFCs and cDFCs, respectively) and to analyze in vivo osteogenesis after transplantation of these DFCs into experimental animals. Third passage fDFCs and cDFCs showed similar expression levels of interferon-γ receptor (CD119) and major histocompatibility complex class I and II (MHC I and MHC II, respectively), with high levels of CD119 and MHC I and nearly no expression of MHC II. Both fresh and cryopreserved human DFCs (hDFCs) were in vivo transplanted along with a demineralized bone matrix scaffold into mandibular defects in miniature pigs and subcutaneous tissues of mice. Radiological and histological evaluations of in vivo osteogenesis in hDFC-transplanted sites revealed significantly enhanced new bone formation activities compared with those in scaffold-only implanted control sites. Interestingly, at 8 weeks post-hDFC transplantation, the newly generated bones were overgrown compared to the original size of the mandibular defects, and strong expression of osteocalcin and vascular endothelial growth factor were detected in the hDFCs-transplanted tissues of both animals. Immunohistochemical analysis of CD3, CD4, and CD8 in the ectopic bone formation sites of mice showed significantly decreased CD4 expression in DFCs-implanted tissues compared with those in control sites. These findings indicate that hDFCs possess immunomodulatory properties that involved inhibition of the adaptive immune response mediated by CD4 and MHC II, which highlights the usefulness of hDFCs in tissue engineering. In particular, long-term preserved dental follicles could serve as an excellent autologous or allogenic stem cell source for bone tissue regeneration as well as a valuable therapeutic agent for immune diseases., (Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)