Tissue Engineering Part A最新文献

{"title":"Comparison of Chondrocytes in Knee Osteoarthritis and Regulation by Scaffold Pore Size and Stiffness.","authors":"Yu Zhao,&nbsp;Zhifeng You,&nbsp;Dan Xing,&nbsp;Jiao Jiao Li,&nbsp;Qingxi Zhang,&nbsp;Hesuyuan Huang,&nbsp;Zhikun Li,&nbsp;Shumeng Jiang,&nbsp;Zhaozhao Wu,&nbsp;Yuying Zhang,&nbsp;Wenjing Li,&nbsp;Lin Zhang,&nbsp;Yanan Du,&nbsp;Jianhao Lin","doi":"10.1089/ten.TEA.2020.0085","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0085","url":null,"abstract":"<p><p>In knee osteoarthritis (OA), there is more pronounced cartilage damage in the medial compartment (\"lesion zone\") than the lateral compartment (\"remote zone\"). This study fills a gap in the literature by conducting a systematic comparison of cartilage and chondrocyte characteristics from these two zones. It also investigates whether chondrocytes from the different zones respond distinctly to changes in the physical and mechanical microenvironment using three-dimensional porous scaffolds by changing stiffness and pore size. Cartilage was harvested from patients with end-stage varus knee OA. Cartilage from the lesion and remote zones were compared through histological and biomechanical assessments, and through proteomic and gene transcription analyses of chondrocytes. Gelatin scaffolds with varied pore sizes and stiffness were used to investigate <i>in vitro</i> microenvironmental regulation of chondrocytes from the two zones. Cartilage from the lesion and remote zones differed significantly (<i>p</i> < 0.05) in histological and biomechanical characteristics, as well as phenotype, protein, and gene expression of chondrocytes. Chondrocytes from both zones were sensitive to changes in the structural and mechanical properties of gelatin scaffolds. Of interest, although all chondrocytes better retained chondrocyte phenotype in stiffer scaffolds, those from the lesion and remote zones, respectively, preferred scaffolds with larger and smaller pores. Distinct variations exist in cartilage and chondrocyte characteristics in the lesion and remote zones of knee OA. Cells in these two zones respond differently to variations in the physical and mechanical microenvironment. Understanding and manipulating these differences will facilitate the development of more efficient and precise diagnostic and therapeutic approaches for knee OA.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"223-236"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38049334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized Media Volumes Enable Homogeneous Growth of Mesenchymal Stem Cell-Based Engineered Cartilage Constructs.","authors":"Hannah M Zlotnick,&nbsp;Brendan D Stoeckl,&nbsp;Elizabeth A Henning,&nbsp;David R Steinberg,&nbsp;Robert L Mauck","doi":"10.1089/ten.TEA.2020.0123","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0123","url":null,"abstract":"<p><p>Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time <i>in vitro</i>. We assessed the MSC-laden constructs after 4 and 8 weeks of chondrogenic culture using bulk mechanical, histological, and biochemical measures. These assays were performed on both the intact total constructs and the construct cores to elucidate region-dependent differences. In addition, local strain transfer was assessed to quantify depth-dependent mechanical properties throughout the constructs. Our findings suggest that increased media volume enhances matrix deposition early in culture and ameliorates unwanted regional heterogeneities at later time points. Taken together, these data support the use of higher media volumes during <i>in vitro</i> culture to hasten tissue maturation and increase the core strength of tissue constructs. These findings will forward the field of cartilage tissue engineering and the translation of tissue engineered constructs.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"214-222"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38058383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells.","authors":"Rachel A Heuer,&nbsp;Kevin T Nella,&nbsp;Hsiang-Tsun Chang,&nbsp;Kyle S Coots,&nbsp;Andrew M Oleksijew,&nbsp;Christian B Roque,&nbsp;Luisa H A Silva,&nbsp;Tammy L McGuire,&nbsp;Kazuaki Homma,&nbsp;Akihiro J Matsuoka","doi":"10.1089/ten.TEA.2020.0078","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0078","url":null,"abstract":"<p><p>Stem cell-replacement therapies have been proposed as a potential tool to treat sensorineural hearing loss by aiding the regeneration of spiral ganglion neurons (SGNs) in the inner ear. However, transplantation procedures have yet to be explored thoroughly to ensure proper cell differentiation and optimal transplant procedures. We hypothesized that the aggregation of human embryonic stem cell (hESC)-derived otic neuronal progenitor (ONP) cells into a multicellular form would improve their function and their survival <i>in vivo</i> post-transplantation. We generated hESC-derived ONP spheroids-an aggregate form conducive to differentiation, transplantation, and prolonged cell survival-to optimize conditions for their transplantation. Our findings indicate that these cell spheroids maintain the molecular and functional characteristics similar to those of ONP cells, which are upstream in the SGN lineage. Moreover, our phenotypical, electrophysiological, and mechanical data suggest an optimal spheroid transplantation point after 7 days of <i>in vitro</i> three-dimensional (3D) culture. We have also developed a feasible transplantation protocol for these spheroids using a micropipette aided by a digital microinjection system. In summary, the present work demonstrates that the transplantation of ONP cells in spheroid form into the inner ear through micropipette 7 days after seeding for 3D spheroid culture is an expedient and viable method for stem cell replacement therapies in the inner ear.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"256-269"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38086202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coral-Derived Collagen Fibers for Engineering Aligned Tissues.","authors":"Ortal Shelah,&nbsp;Shir Wertheimer,&nbsp;Rami Haj-Ali,&nbsp;Ayelet Lesman","doi":"10.1089/ten.TEA.2020.0116","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0116","url":null,"abstract":"<p><p>There is a growing need for biomaterial scaffolds that support engineering of soft tissue substitutes featuring structure and mechanical properties similar to those of the native tissue. This work introduces a new biomaterial system that is based on centimeter-long collagen fibers extracted from <i>Sarcophyton</i> soft corals, wrapped around frames to create aligned fiber arrays. The collagen arrays displayed hyperelastic and viscoelastic mechanical properties that resembled those of collagenous-rich tissues. Cytotoxicity tests demonstrated that the collagen arrays were nontoxic to fibroblast cells. In addition, fibroblast cells seeded on the collagen arrays demonstrated spreading and increased growth for up to 40 days, and their orientation followed that of the aligned fibers. The possibility to combine the collagen cellular arrays with poly(ethylene glycol) diacrylate (PEG-DA) hydrogel, to create integrated biocomposites, was also demonstrated. This study showed that coral collagen fibers in combination with a hydrogel can support biological tissue-like growth, with predefined orientation over a long period of time in culture. As such, it is an attractive scaffold for the construction of various engineered tissues to match their native oriented morphology.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"187-200"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38032460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticytokine Activity Enhances Osteogenesis of Bioactive Implants.","authors":"Fan Yang,&nbsp;Xin Zhang,&nbsp;Hairong Huang,&nbsp;Gang Wu,&nbsp;Kurt Lippuner,&nbsp;Ernst B Hunziker","doi":"10.1089/ten.TEA.2020.0067","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0067","url":null,"abstract":"<p><p>In dental clinical practice, systemic steroids are often applied at the end of implant surgeries to reduce postsurgical inflammation (tissue swelling, etc.) and to reduce patient discomfort. However, the use of systemic steroids is associated with generalized catabolic effects and with a temporarily reduced immunological competence. We hypothesize that by applying locally anticytokine antibodies (antitumor necrosis factor alpha and anti-interleukin-1 beta) together with a bioactive osteogenic implant at the time of the surgical intervention for the placement of a construct, we will be able to achieve the same beneficial effects as those using systemic steroids but are able to avoid the generalized antianabolic effects and the reduced immunocompetence effects, associated with the systemic use of steroids. In an adult rat model, a collagen sponge, soaked with the osteogenic agent bone morphogenetic protein-2, was used as an example for a bioactive implant material and was surgically placed subcutaneously. In the acute inflammatory phase after implantation (2 days after surgery) we investigated the local inflammatory tissue response, and 18 days postsurgically the efficiency of local osteogenesis (to assess possible antianabolic effects). We found that the negative control groups, treated postsurgically with systemic steroids, showed a significant suppression of both the inflammatory response and the osteogenetic activity, that is, they were associated with significant general antianabolic effects, even when steroids were used only at a low dose level. The local anticytokine treatment, however, was able to significantly enhance new bone formation activity, that is, the anabolic activity, over positive control values with BMP-2 only. However, the anticytokine treatment was unable to reduce the local inflammatory and swelling responses.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"177-186"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38047255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondrogenic Predifferentiation Inhibits Vascular Endothelial Growth Factor Angiogenic Effect in Pericranium-Derived Spheroids.","authors":"Serban San-Marina,&nbsp;Christopher M Prummer,&nbsp;Stephen G Voss,&nbsp;Danielle E Hunter,&nbsp;Benjamin J Madden,&nbsp;Mary Cristine Charlesworth,&nbsp;Dale C Ekbom,&nbsp;Jeffrey R Janus","doi":"10.1089/ten.TEA.2020.0117","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0117","url":null,"abstract":"<p><p>Craniofacial reconstruction of critical bone defects typically requires a bone graft. As graft availability may be restricted by disease or comorbidities, tissue engineering approaches are actively sought. The pericranium could provide new bone graft material. During development and repair, bone transitions through a chondrogenic phase. However, with tissue engineering, pluripotent cells can differentiate directly into bone cells. Does ability to recapitulate bone formation <i>in vitro</i> affect osteogenesis and vascularization of pericranium grafts? To answer this, we obtained tissue from nine patients with preplanned craniotomy surgery and studied three-dimensional osteogenesis and angiogenesis of pericranium-derived spheroids. First, we established growth and differentiation conditions on Matrigel. For each spheroid sample, we investigated (i) continuous osteogenic differentiation (COD) and (ii) osteogenic differentiation preceded by chondrogenesis (CD → OD). The effect of vascular endothelial growth factor (VEGF) was compared to VEGF supplemented with fibroblast growth factor, interleukin (IL)-1, IL-6, platelet-derived growth factor, and tumor necrosis factor-α, a growth factor mix (GFM) with possible synergistic effects. In this limited sample, we observed no age- or sex-related differences in cell expansion. Similarly, no statistically significant differences in osteogenic or angiogenic scores between COD or CD → OD spheroids were noted with regular media. In COD, however, VEGF statistically significantly increased angiogenesis compared to control media (<i>p</i> = 0.007). Also, in COD, both VEGF and VEGF + GFM increased osteogenesis (<i>p</i> = 0.047 and <i>p</i> = 0.038, respectively). By contrast, in CD → OD, neither VEGF nor VEGF + GFM yielded statistically significant angiogenesis or osteogenesis scores compared to control media. To understand these results, we characterized spheroid protein expression by nanoliquid chromatography coupled to tandem mass spectrometry. Nine angiogenic proteins were either uniquely expressed or upregulated in COD compared to CD → OD: (i) endothelial markers JUP, PTGIS, PTGS2, and TYMP, (ii) tissue remodeling factors CHI3L1 and MMP14, and (iii) metabolic pathways modulators ANGPTL4, ITGA5, and WNT5A. ANGPTL4, ITGA5, PTGIS, PTGS2, and WNT5A define a conserved angiogenic network and were >2-fold increased in VEGF compared to VEGF + GFM. Finally, we examined bone formation on printable poly-(propylene-fumarate) (PPF) scaffolds for individualized grafting. Under COD + VEGF conditions, PPF scaffolds loaded with pericranium-derived cells displayed hallmarks of spongiform-like bone formation. Thus, the human pericranium may be a potential repository for bone-generating cells with applications in craniofacial bone repair using tissue printing.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"237-245"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38132123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Release Kinetics on Efficacy of Locally Delivered Parathyroid Hormone for Bone Regeneration Applications.","authors":"Samantha J Wojda,&nbsp;Ian A Marozas,&nbsp;Kristi S Anseth,&nbsp;Michael J Yaszemski,&nbsp;Seth W Donahue","doi":"10.1089/ten.TEA.2020.0119","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0119","url":null,"abstract":"<p><p>Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. This study examined the local delivery of parathyroid hormone (PTH) using a thiol-ene hydrogel embedded in a porous poly(propylene fumarate) (PPF) scaffold for bone regeneration applications. The aim of this study was to characterize the degradation-controlled <i>in vitro</i> release kinetics of PTH from the thiol-ene hydrogels, <i>in vivo</i> hydrogel degradation in a subcutaneous implant model, and bone healing in a rat critical size bone defect. Tethering PTH to the hydrogel matrix eliminated the early timepoint burst release that was observed in previous <i>in vitro</i> work where PTH was free to diffuse out of the matrix. Only 8% of the tethered PTH was released from the hydrogel during the first 2 weeks, but by day 21, 80% of the PTH was released, and complete release was achieved by day 28. <i>In vivo</i> implantation revealed that complete degradation of the hydrogel alone occurred by day 21; however, when incorporated in a three-dimensional printed osteoconductive PPF scaffold, the hydrogel persisted for >56 days. Treatment of bone defects with the composite thiol-ene hydrogel-PPF scaffold, delivering either 3 or 10 μg of tethered PTH 1-84, was found to increase bridging of critical size bone defects, whereas treatment with 30 μg of tethered PTH resulted in less bone ingrowth into the defect area. Continued development of this biomaterial delivery system for PTH could lead to improved therapies for treatment of nonunion fractures and critical size bone defects.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"246-255"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38113262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Topographic Micropatterning on Endothelial Colony-Forming Cells.","authors":"Matthew W Hagen,&nbsp;Monica T Hinds","doi":"10.1089/ten.TEA.2020.0066","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0066","url":null,"abstract":"<p><p>Artificial small-diameter vascular grafts remain an unmet need in modern medicine, due to the thrombosis and neointimal hyperplasia that plague currently available synthetic devices. Tissue engineering techniques, including <i>in vitro</i> endothelialization, could offer a solution to this problem. A potential minimally invasive source of patient autologous endothelium is endothelial colony-forming cells (ECFCs), endothelial-like outgrowth products of circulating progenitors. While ECFCs respond to shear stress similar to mature endothelial cells (ECs), their response to luminal topographic micropatterning (TMP), a biomaterial modification with the potential to flow-independently, enhance the attachment, migration, gene expression, and function of mature ECs, remains unstudied. In this study, case-matched carotid endothelial cells (CaECs) and blood-derived ECFCs are statically cultured on polyurethane substrates with micropatterned pitches (pitch = peak to peak distance) ranging from 3-to 14 μm. On all pattern pitches tested, both CaECs and ECFCs showed significant and robust alignment to the angle of the micropatterns. Using a novel cell-by-cell image analysis technique, it was found that actin fibers similarly and significantly aligned to the angle of micropatterned features on all pitches tested. Microtubules analyzed through the same novel approach showed significant alignment on most pitches examined, with a greater variation in fiber angle overall. Interestingly, only CaECs showed significant cellular elongation, and notably to a lower degree than previously seen either <i>in vivo</i> due to flow or <i>in vitro</i> due to spatial growth restriction micropatterning, but consistent with earlier studies of TMP. Neither cell type displayed any significant micropattern-driven changes in the expression of KLF-2 or the downstream adhesion molecules it regulates. These results demonstrate that TMP flow-independently affects ECFC morphology, but that alignment alone is insufficient to drive protective changes in EC and ECFC function.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"270-281"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38103630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Evaluation of Osteochondral-Like Tissue Using Chondrocyte Sheet and Cancellous Bone.","authors":"Sopita Wongin,&nbsp;Rapeepat Narkbunnam,&nbsp;Saranatra Waikakul,&nbsp;Pojchong Chotiyarnwong,&nbsp;Thanyawan Aresanasuwan,&nbsp;Sittiruk Roytrakul,&nbsp;Kwanchanok Viravaidya-Pasuwat","doi":"10.1089/ten.TEA.2020.0107","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0107","url":null,"abstract":"<p><p>The manipulation of human chondrocyte sheets in target areas frequently results in their tearing because they are thin and fragile. In this study, human cancellous bones were used as a supporting material to create chondrocyte sheet-cancellous bone tissues, and their properties were evaluated. Using cell sheet technology, human chondrocytes were constructed into triple-layered chondrocyte sheets that displayed chondrogenic properties. After transferring the chondrocyte sheets onto cancellous bones, the top area of the chondrocyte sheet-cancellous bone tissues exhibited a smooth surface topography without cell sheet floating within 7 days of culture. The immunofluorescence staining of collagen type II (COL2A1) and fibronectin (FN1) was also performed and examined. Using the shotgun proteomic analysis, the proteins associated with cell adhesion, extracellular matrix (ECM) organization, cell-substrate junction assembly, and cell adhesion mediated by integrin were observed in the chondrocyte sheets, cancellous bones, and chondrocyte sheet-cancellous bone tissues. Three integrin members, including integrin β4 (ITGB4), ITGB6, and ITGB8, were found in the chondrocyte sheets. Only ITGB8 was found in the chondrocyte sheets and chondrocyte sheet-cancellous bone tissues. During 48 h, the mean velocity of the individual cell migration was low, which did not affect the structure and chondrogenic properties of the chondrocyte sheets. Staining of the filamentous actin (F-actin) cytoskeleton in the migratory cells also provided a better understanding of the dynamic communication between the cell cytoskeleton and adhesion molecules through ITGB8, which may play a key role in the attachment of the chondrocyte sheets and the synthesis of the cartilage ECM. Therefore, we suggest that cancellous bone could be used as a supporting material to construct chondrocyte sheet-cancellous bone tissues for potential treatment of osteochondral lesions. Impact Statement We proposed a method to construct an osteochondral-like tissue by placing human chondrocyte sheets onto cancellous bone. The stationary chondrocyte sheets and the low mean velocity of the individual cell migration on the cancellous bone with the expression of COL2A1 indicated that the cancellous bone served as an appropriate supporting material. Moreover, the cellular mechanism for the adhesion of the chondrocyte sheets on the cancellous bone based on ITGB8-mediated adhesion through the rearrangement of filamentous actin provided a better understanding to improve the construction of osteochondral-like tissues, and to predict the repair mechanism in osteoarthritis therapy.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"282-295"},"PeriodicalIF":4.1,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38206155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Geometry and Architecture on the <i>In Vivo</i> Success of 3D-Printed Scaffolds for Spinal Fusion.","authors":"Mitchell Hallman,&nbsp;J Adam Driscoll,&nbsp;Ryan Lubbe,&nbsp;Soyeon Jeong,&nbsp;Kevin Chang,&nbsp;Meraaj Haleem,&nbsp;Adam Jakus,&nbsp;Richard Pahapill,&nbsp;Chawon Yun,&nbsp;Ramille Shah,&nbsp;Wellington K Hsu,&nbsp;Stuart R Stock,&nbsp;Erin L Hsu","doi":"10.1089/ten.TEA.2020.0004","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0004","url":null,"abstract":"&lt;p&gt;&lt;p&gt;We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model. Inks containing HA and DBM particles in a poly(lactide-co-glycolide) elastomer were 3D-printed into scaffolds with varying relative strut angles (90° vs. 45° advancing angle), macropore size (0 μm vs. 500 μm vs. 1000 μm), and strut alignment (aligned vs. offset). The following configurations were compared with scaffolds containing no macropores: 90°/500 μm/aligned, 45°/500 μm/aligned, 90°/1000 μm/aligned, 45°/1000 μm/aligned, 90°/1000 μm/offset, and 45°/1000 μm/offset. Eighty-four female Sprague-Dawley rats underwent spine fusion with bilateral placement of the various scaffold configurations (&lt;i&gt;n&lt;/i&gt; = 12/configuration). Osteointegration and vascularization were assessed by using microComputed Tomography and histology, and spine fusion was assessed via blinded manual palpation. The 45°/1000 μm scaffolds with aligned struts achieved the highest average fusion score (1.61/2) as well as the highest osteointegration score. Both the 45°/1000 μm/aligned and 90°/1000 μm/aligned scaffolds elicited fusion rates of 100%, which was significantly greater than the 45°/500 μm/aligned iteration (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). All porous scaffolds were fully vascularized, with blood vessels present in every macropore. Vessels were also observed extending from the native transverse process bone, through the protrusions of new bone, and into the macropores of the scaffolds. When viewed independently, scaffolds printed with relative strut angles of 45° and 90° each allowed for osteointegration sufficient to stabilize the spine at L4-L5. Within those parameters, a pore size of 500 μm or greater was generally sufficient to achieve unilateral fusion. However, our results suggest that scaffolds printed with the larger pore size and with aligned struts at an advancing angle of 45° may represent the optimal configuration to maximize osteointegration and fusion capacity. Overall, this work suggests that the HA/DBM composite scaffolds provide a conducive environment for bone regeneration as well as vascular infiltration. This technology, therefore, represents a novel, growth-factor-free biomaterial with significant potential as a bone graft substitute for use in spinal surgery. Impact statement We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed composite material comprising hydroxyapatite and demineralized bone matrix for bone regeneration. Here, we identify a range of 3D geometric and architectural parameters that support the prec","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"26-36"},"PeriodicalIF":4.1,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37678114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}