Tissue Engineering Part A最新文献

{"title":"Optimized Biomanufacturing for Treatment of Volumetric Muscle Loss Enables Physiomimetic Recovery.","authors":"Rachel K Bour, Gavin T Garner, Shayn M Peirce, George J Christ","doi":"10.1089/ten.TEA.2023.0315","DOIUrl":"10.1089/ten.TEA.2023.0315","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) injuries are defined by loss of sufficient skeletal muscle to produce persistent deficits in muscle form and function, with devastating lifelong consequences to both soldiers and civilians. There are currently no satisfactory treatments for VML injuries. The work described herein details the implementation of a fully enclosed bioreactor environment (FEBE) system that efficiently interfaces with our existing automated bioprinting and advanced biomanufacturing methods for cell deposition on sheet-based scaffolds for our previously described tissue-engineered muscle repair (TEMR) technology platform. Briefly, the TEMR technology consists of a porcine bladder acellular matrix seeded with skeletal muscle progenitor cells and preconditioned via 10% uniaxial cyclic stretch in a bioreactor. Overall, TEMR implantation in an established rat tibialis anterior (TA) VML injury model can result in 60 to ∼90% functional recovery. However, our original study documented >50% failure rate. That is, more than half of the implanted TEMR constructs produced no functional improvement beyond no treatment/repair. The high failure rate was attributed to the untoward mechanical disruption of TEMR during surgical implantation. In a follow-up study, adjustments were made to the geometry of both the VML injury and the TEMR construct, and the \"nonresponder\" group was reduced from over half the TEMR-treated animals to just 33%. Nonetheless, additional improvement is needed for clinical applicability. The main objectives of the current study were twofold: (1) explore the use of advanced biomanufacturing methods (i.e., FEBE bioreactor) to further improve TEMR reliability (i.e., increase functional response rate), (2) determine if previously established bioprinting methods, when coupled to the customized FEBE system would further improve the rate, magnitude or amplitude of functional outcomes following TEMR implantation in the same rat TA VML injury model. The current study demonstrates the unequivocal benefits of a customized bioreactor system that reduces manipulation of TEMR during cell seeding and maturation via bioprinting while simultaneously maximizing TEMR stability throughout the biofabrication process. This new biomanufacturing strategy not only accelerated the rate of functional recovery, but also eliminated all TEMR failures. In addition, implementation of bioprinting resulted in more physiomimetic skeletal muscle characteristics of repaired muscle tissue.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"373-386"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascularization of Human Acellular Dermal Matrices: A Comparative Study in a Nonhuman Primate Model.","authors":"Victoria Stefanelli, Jared Lombardi, Joselito Ferrer, Maryellen Gardocki-Sandor","doi":"10.1089/ten.TEA.2024.0059","DOIUrl":"10.1089/ten.TEA.2024.0059","url":null,"abstract":"<p><p>Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates (<i>n</i> = 3 animals/time point, <i>n</i> = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10^-5 ± 3.96 × 10^-5 vessels/µm², and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"419-432"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bi-layered Adipose Mesenchymal Cell Sheets Improve Bladder Compliance in Spinal Cord-Injured Rats.","authors":"Yuki Matsumoto, Tetsuya Imamura, Ryo Kitahara, Yoshihiro Inoue, Tetsuichi Saito, Manabu Ueno, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka","doi":"10.1089/ten.TEA.2024.0115","DOIUrl":"10.1089/ten.TEA.2024.0115","url":null,"abstract":"<p><p>To improve bladder compliance in patients with low-compliance bladders, augmentation cystoplasty with the intestinal tract is performed. However, the use of the intestinal tract often leads to serious surgical complications. Tissue engineering technologies have the potential to improve bladder compliance without using the intestinal tract. In this study, we fabricated bi-layered adipose-derived mesenchymal cell (AMC) sheets and then determined whether the bi-layered AMC sheets could improve bladder compliance in rats with spinal cord injury (SCI). The abdominal adipose tissues of green fluorescence protein (GFP)-transfected Sprague-Dawley (SD) rats were harvested, and the attached and proliferating cells on type I collagen were used as AMCs. The AMCs were then cultured on temperature-responsive culture dishes. After reaching over-confluence, the AMCs that maintained cell-cell contacts were detached from the dishes and applied to a gelatin hydrogel sheet. Then, another detached AMC monolayer was accumulated on the AMC monolayer-applied gelatin. Prior to 4 weeks of transplantation, the levels of T8-9 in the spinal cords of recipient SD rats were partially transected. After producing the bi-layered AMC sheets and the rats with SCI, the detrusor muscles of the anterior bladder walls of the rats with SCI were incised, and the bi-layered AMC sheet was patch-transplanted onto the exposed bladder epithelium (<i>n</i> = 8). As a control, the sham operation was performed (<i>n</i> = 7). Four weeks after the transplantation, bladder capacity and bladder compliance in AMC sheet-transplanted SCI rats were significantly higher than those in sham-operated control SCI rats. The smooth muscle layers in AMC sheet-transplanted bladders were significantly larger than those in control bladders. In addition, the collagen fibers in the AMC sheet-transplanted bladders were significantly smaller than those in the control bladders. Some GFP-positive transplanted AMCs differentiated into smooth muscle actin- or desmin-positive cells. Furthermore, GFP-positive cells secreted transforming growth factor-β1 or vascular endothelial growth factor. Therefore, this study showed that bi-layered AMC sheets could improve bladder compliance and bladder tissues in SCI rats.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"409-418"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating Microbial Stimuli for Osteogenesis in a Rabbit Posterolateral Spinal Fusion Model.","authors":"Nada Ristya Rahmani, Anneli Duits, Michiel Croes, Olivia Lock, Debby Gawlitta, Harrie Weinans, Moyo C Kruyt","doi":"10.1089/ten.TEA.2024.0064","DOIUrl":"10.1089/ten.TEA.2024.0064","url":null,"abstract":"<p><p>Autologous bone grafts are commonly used to repair defects in skeletal tissue, however, due to their limited supply there is a clinical need for alternatives. Synthetic ceramics present a promising option but currently lack biological activity to stimulate bone regeneration. One potential approach to address this limitation is the incorporation of immunomodulatory agents. In this study, we investigate the application of microbial stimuli to stimulate bone formation. Three different microbial stimuli were incorporated in a biphasic calcium phosphate (BCP) ceramic: Bacille Calmette-Guérin (BCG), gamma-irradiated <i>Staphylococcus aureus (</i>γi-<i>S. aureus)</i>, or γi<i>-Candida albicans</i> (γi<i>-C. Albicans</i>). The constructs were then implanted in both a rabbit posterolateral spinal fusion (PLF) and an intramuscular implant model for 10 weeks and compared to a nonstimulated control construct. For the PLF model, the formation of a bony bridge was evaluated by manual palpation, micro computed tomography, and histology. While complete fusion was not observed, the BCG condition was most promising with higher manual stiffness and almost twice as much bone volume in the central fusion mass compared to the control (9 ± 4.4% bone area vs. 4.6 ± 2.3%, respectively). Conversely, the γi-<i>S. aureus</i> or <i>γi-C. albicans</i> appeared to inhibit bone formation (1.4 ± 1.4% and 1.2 ± 0.6% bone area). Bone induction was not observed in any of the intramuscular implants. This study indicates that incorporating immunomodulatory agents in ceramic bone substitutes can affect bone formation, which can be positive when selected carefully. The readily available and clinically approved BCG showed promising results, which warrants further research for clinical translation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"387-397"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modular, Vascularized Hypertrophic Cartilage Constructs for Bone Tissue Engineering Applications.","authors":"Nicholas G Schott, Gurcharan Kaur, Rhima M Coleman, Jan P Stegemann","doi":"10.1089/ten.tea.2024.0367","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0367","url":null,"abstract":"<p><p>Insufficient vascularization is the main barrier to creating engineered bone grafts for treating large and ischemic defects. Modular tissue engineering approaches have promise in this application because of the ability to combine tissue types and localize microenvironmental cues to drive desired cell function. In direct bone formation approaches, it is challenging to maintain sustained osteogenic activity, since vasculogenic cues can inhibit tissue mineralization. This study harnessed the physiological process of endochondral ossification to create multiphase tissues that allowed concomitant mineralization and vessel formation. Mesenchymal stromal cells in pellet culture were differentiated toward a cartilage phenotype, followed by induction to chondrocyte hypertrophy. Hypertrophic pellets (HPs) exhibited increased alkaline phosphatase activity, calcium deposition, and osteogenic gene expression relative to chondrogenic pellets. In addition, HPs secreted and sequestered angiogenic factors, and supported new blood vessel formation by cocultured endothelial cells and undifferentiated stromal cells. Multiphase constructs created by combining HPs and vascularizing microtissues and maintained in an unsupplemented basal culture medium were shown to support robust vascularization and sustained tissue mineralization. These results demonstrate a promising <i>in vitro</i> strategy to produce multiphase-engineered constructs that concomitantly support the generation of mineralized and vascularized tissue in the absence of exogenous osteogenic or vasculogenic medium supplements.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface-Patterned Silicon Oxynitride for Aligned Myotubes and Neurite Outgrowth <i>In Vitro</i>.","authors":"Kamal Awad, Matthew Fiedler, Ahmed S Yacoub, Leticia Brotto, Pranesh B Aswath, Marco Brotto, Venu Varanasi","doi":"10.1089/ten.tea.2024.0358","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0358","url":null,"abstract":"<p><p>Traumatic injuries lead to volumetric muscle loss (VML) and nerve damage that cause chronic functional deficits. Due to the inability of mammalian skeletal muscle to regenerate after VML damage, engineered scaffolds have been explored to address this challenge, but with limited success in functional restoration. We introduce novel bioactive amorphous silicon oxynitride (SiONx) biomaterials with surface properties and Si ion release to accelerate muscle and nerve cell differentiation for functional tissue regeneration. Micropatterned scaffolds were designed and developed on Si-wafer to test the effect of SiONx on myogenesis and neurogenesis. The scaffolds were created using UV photolithography to first pattern their surface, followed by the deposition of SiONx through plasma enhanced chemical vapor deposition (PECVD). X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) confirmed the uniform chemical structure of an amorphous SiONx film on the patterned surfaces. Atomic force microscopy and scanning electron microscopy (SEM) elucidated the surface morphology with a uniform 2 μm grating microstructure. The 2 µm pattern size is within the range of cellular dimensions, allowing for effective cell-surface interactions. Further, 2 µm features provide sufficient contact points for cell adhesion without overwhelming the cell's ability to interact with the surface. Two separate studies were conducted with SiONx biomaterials and Si ions alone. This was done to understand how Si ions impact cell response separate from the surfaces. C2C12 mouse myoblasts and NG108 neuronal cells were cultured on SiONx biomaterials. In separate studies, we tested the effect of Si ion treatments with these cells (cultured on tissue culture plastic). Cell culture studies demonstrated enhanced C2C12 myoblast attachment and proliferation on SiONx surfaces. High-resolution SEM and fluorescence images revealed highly aligned myotubes (from C2C12 cells) and axons (from NG108 cells) in a parallel direction to the micropatterned SiONx scaffolds. GAP43 expression, neurite outgrowth, and alignment were significantly increased with the Si-ions and SiONx biomaterials. These findings suggest that SiONx scaffolds enhance muscle and nerve cell adhesion and growth and promote the formation of aligned myotubes and axons on the pattern surfaces.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Bioprinting of Astrocytes and Endothelial Cells to Direct Retinal Axon Growth and Vascularization.","authors":"Fatima E Abukunna, Afnan M Aladdad, Kiran J McLoughlin, Khyathi Thallapureddy, Michael Vierra, Zoya Siddiqui, Karl E Kador","doi":"10.1089/ten.tea.2024.0326","DOIUrl":"10.1089/ten.tea.2024.0326","url":null,"abstract":"<p><p>Retinal organoids (ROs) are currently used to study retinal development and diseases but cannot model glaucoma because they fail to form a nerve fiber layer (NFL) and optic nerve (ON). Utilizing three-dimensional bioprinting, ON head astrocytes (ONHAs) and vascular endothelial cells, both of which contribute to NFL development <i>in vivo</i> but are absent in ROs, were positioned at the center of scaffolds seeded with retinal ganglion cells (RGCs). In experiments using ONHAs isolated from developing retinas, polarization of RGC neurite growth increased by 43% while ONHA from adult retinas or astrocytes from the developing peripheral retina or developing cortex did not increase polarization above controls. Furthermore, RGC-seeded scaffolds increased both the number and rate of ONHAs migrating out from the printed center compared to scaffolds lacking RGCs, mimicking the migration pattern observed during retinal development. Finally, in scaffolds containing both ONHAs and endothelial cells, the endothelial cells preferentially migrate on and only form vascular tube structures on scaffolds also containing RGCs. These results suggest that recreating the developmental organization of the retina can recapitulate the mechanism of NFL development and retinal vascularization <i>in vitro.</i> This step is not only necessary for the development of retinal models of glaucoma but has the potential for translation to other parts of the central nervous system.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microencapsulation of Liver Spheroids with Poly(Vinyl Alcohol) Enhances Function Compared with Alginate.","authors":"Stephen Harrington, Edward Larson, Aldyn Wildey, Vincent Ling, Lisa Stehno-Bittel, Francis Karanu","doi":"10.1089/ten.tea.2024.0312","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0312","url":null,"abstract":"<p><p><b><i>Background and Aims:</i></b> Cell therapy approaches to treating chronic liver disease provide only transient improvements, mainly due to loss of hepatocytes after infusion. Microencapsulation in alginate has been shown to protect transplanted cells from physical stress and rejection, but the poor biocompatibility of alginate can lead to graft failure. This study aimed to evaluate a biocompatible poly(vinyl alcohol) (PVA)-based microcapsule against standard alginate for improved transplantation outcome of liver spheroids. <b><i>Materials and Methods:</i></b> Human hepatocyte spheroids were microencapsulated in alginate or PVA hydrogel microspheres. Viability and function (albumin secretion and CYP activity) of the encapsulated spheroids were assessed <i>in vitro</i> at 3, 10, and 30 days postencapsulation and compared with unencapsulated spheroids. Spheroids were implanted intraperitoneally into immunodeficient mice, and human albumin levels in serum were monitored over 30 days. Cell-free microspheres were implanted in immune-competent mice to assess material biocompatibility. <b><i>Results:</i></b> Unencapsulated spheroids aggregated extensively beyond 10 days, precluding day 30 assessment. At day 30, PVA spheroids showed significantly higher CYP1A1 induction, albumin secretion, and metabolic activity compared with alginate. Mice receiving PVA spheroids had significantly higher serum albumin after 30 days compared with alginate and unencapsulated spheroids. Empty PVA microspheres showed less evidence of foreign body response <i>in vivo</i>, whereas thicker regions of inflamed tissue were observed in the alginate group. <b><i>Conclusions:</i></b> PVA-encapsulated hepatocyte spheroids maintained better overall viability, metabolic activity, and function compared with alginate-encapsulated cells both <i>in vitro</i> and <i>in vivo</i>. Both encapsulated groups demonstrated substantially improved outcomes compared with unencapsulated cells.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoblast-Mesenchymal Stem Cell Coculture Drives <i>In Vitro</i> Osteogenesis in 3D Bioprinted Periosteum.","authors":"Shannon T McLoughlin, Paige Wilcox, John F Caccamese, John P Fisher","doi":"10.1089/ten.tea.2025.0038","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0038","url":null,"abstract":"<p><p>The periosteum serves as a local source of osteoprogenitor cells and vasculature, therefore influencing the key processes of osteogenesis and neovascularization during bone healing. However, it is often not considered in traditional bone tissue engineering strategies. The periosteum consists of two stratified cell layers, including an inner cambium layer, which serves as a local source of osteoblasts (OBs) and osteoprogenitor cells, and an outer fibrous layer, which hosts vasculature, collagen fibers, and support cells. While several studies have investigated different methodologies to produce tissue-engineered periosteum (TEP) substitutes, few have evaluated the roles of specific cell types within the inner cambium layer and their patterning in 3D environments on underlying bone tissue development. Therefore, we sought to investigate whether mesenchymal stem cells (MSCs) alone, OBs alone, or a 1:1 mixture of the two would result in increased osteogenic differentiation of bone layer MSCs in a 3D bioprinted periosteum-bone coculture model <i>in vitro</i>. We first evaluated these effects in a 2D transwell model, demonstrating that OB-containing cultures, either alone or in a mixed population with MSCs, upregulated alkaline phosphatase activity and runt-related transcription factor 2 (<i>RUNX2</i>) expression. In the 3D bioprinted model, the mixed population showed higher levels of <i>RUNX2</i> expression and calcium deposition, indicating increased osteogenic differentiation within the bone layer. Results obtained from this study provide evidence that a mixed population of MSCs and OBs within the inner cambium layer of TEP can increase bone regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging Impairs Implant Osseointegration Through a Novel Reactive Oxygen Species-Hypoxia-Inducible Factor 1α/p53 Axis.","authors":"Jingjing Shao, Shibo Liu, Chenfeng Chen, Wenchuan Chen, Zhimin Zhu, Lei Li","doi":"10.1089/ten.tea.2024.0355","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0355","url":null,"abstract":"<p><p>Enhancing bone-vessel coupling to form high-quality vascular-rich peri-implant bone is crucial for improving implant prognosis in elder patients. Notably, hypoxia-inducible factor 1α (HIF1α) is known to promote osteogenesis-angiogenesis coupling; however, this effect remains to be investigated in aged bone owing to the dual effect of HIF1α in different aged organs. In this study, HIF1α inhibitor or activator was applied to aged mice and their bone mesenchymal stem cells (BMSCs) to investigate the effects and inner mechanism of HIF1α on the peri-implant osteogenesis and angiogenesis in senescent status. Cell senescence, along with osteogenic and angiogenic abilities of aged BMSCs, was detected, respectively. Meanwhile, a femur implant implantation model was constructed on aged mice, and the bone-vessel coupling of peri-implant bone was observed. Mandibular bone morphology was also detected to further provide evidence for clinical oral implantation. Furthermore, p53 expression was examined <i>in vivo</i> and <i>in vitro</i> following HIF1α intervention. A reactive oxygen species (ROS) scavenger was also adopted to further investigate the roles of ROS in the HIF1α-p53 axis. Results showed that the suppression of HIF1α alleviated senescence and osteogenesis-angiogenesis coupling of aged BMSCs, while its activation aggravated these effects. The mandible phenotype and bone-vessel coupling in aged peri-implant bone also changed accordingly upon regulation of HIF1α. Mechanistically, p53 changed in the same direction as HIF1α <i>in vivo</i> and <i>in vitro</i>. Moreover, the ROS scavenger reversed the HIF1α-p53 relationship and weakened the effect of HIF1α inhibitor on peri-implant bone improvement. In conclusion, in aged mice, highly expressed HIF1α impaired peri-implant bone-vessel coupling and implant osseointegration through p53, and accumulated ROS was a prerequisite for HIF1α to positively regulate p53. These findings provide new insights into the role of HIF1α and the ROS-HIF1α/p53 signaling axis, offering potential therapeutic targets to improve implant outcomes in elderly patients.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}