Tianyi Tang, Ping Kang, Fiona Verisqa, Linh Nguyen, Jonathan C. Knowles
{"title":"Zinc phosphate glass microspheres promoted mineralization and expression of BMP2 in MC3T3-E1 cells","authors":"Tianyi Tang, Ping Kang, Fiona Verisqa, Linh Nguyen, Jonathan C. Knowles","doi":"10.1002/jbm.a.37781","DOIUrl":"10.1002/jbm.a.37781","url":null,"abstract":"<p>Degradable phosphate glasses have shown favorable properties for tissue engineering. By changing the composition of the glasses, the degradation rate, and ion release are controllable. Zinc oxide can function as a glass network modifier and has been shown to play a positive role in bone formation. Also, phosphate glasses can easily be processed into microspheres, which can be used as microcarriers. This study aims to develop zinc phosphate glasses microspheres and explore the optimized size and composition for applications in bone tissue engineering. Zinc–titanium–calcium–sodium phosphate glasses with 0, 1, 3, 5, or 10 mol % zinc oxide were prepared and processed into microspheres. The smaller microspheres ranged in size from 50 to 106 μm, while the larger ones ranged from 106 to 150 μm. The characteristics of glasses were examined. The osteoblastic cell line MC3T3-E1 was cultured on the surface of microspheres and the cell viability was examined. To evaluate osteogenic differentiation, Alizarin Red S staining, quantitative reverse transcription polymerase chain reaction, and western blot analysis were performed after 14 days. Different sizes of zinc phosphate glass microspheres were successfully made. The glass microspheres with <10 mol % zinc oxide were able to support the adhesion and proliferation of MC3T3-E1 cell lines. The relative gene expression of BMP2 was significantly upregulated in the smaller glass microspheres containing 3 mol % zinc oxide (26-fold, <i>p</i> < .001) and both sizes of microspheres containing 5 mol % zinc oxide (smaller: 27-fold, <i>p</i> < .001; larger: 35-fold, <i>p</i> < .001). Additionally, cluster formation was observed in glass microspheres after 14 days, and the mineralization of MC3T3-E1 cell lines was promoted. Based on these findings, the glass microspheres containing 3–5 mol % of zinc oxide can promote osteogenic differentiation for MC3T3-E1 cells.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2314-2328"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiangqiang Zhou, Zhaocheng Shi, Liyao Xia, Jing Mi, Yuejiao Zhang, Xiaobo Xu, Jie Pan
{"title":"Breaking the boundaries of wound closure: A novel polyurethane tissue adhesive with enhanced healing properties","authors":"Qiangqiang Zhou, Zhaocheng Shi, Liyao Xia, Jing Mi, Yuejiao Zhang, Xiaobo Xu, Jie Pan","doi":"10.1002/jbm.a.37770","DOIUrl":"10.1002/jbm.a.37770","url":null,"abstract":"<p>Over the past few decades, there have been advancements in the development of high-performance tissue adhesives as alternatives to traditional sutures and staples for rapid and effective wound closure post-surgery. While tissue adhesives offer advantages such as ease of use, short application time, and minimal tissue damage, they also face challenges related to biocompatibility, biodegradability, and adhesive strength. In this study, <span>L</span>-lysine diisocyanate (LDI) and trimethylolpropane (TMP) were utilized as the primary raw materials to produce a prepolymer terminated with <span></span>NCO, resulting in the development of a new biocompatible polyurethane tissue adhesive (TMP-LDI). Additionally, SiO<sub>2</sub> nanoparticles were incorporated into the prepolymer, significantly enhancing the adhesive strength of the TMP-LDI tissue adhesive through the “nanobridging effect,” achieving a strength of 170.4 kPa. Furthermore, the SiO<sub>2</sub>/TMP-LDI tissue adhesive exhibited satisfactory temperature change during curing and degradation performance. In vitro and in vivo studies demonstrated that SiO<sub>2</sub>/TMP-LDI exhibited good biocompatibility, efficient hemostasis, antimicrobial properties, and the ability to promote wound healing. This research presents a novel approach for the development of tissue adhesives with superior adhesive performance.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2301-2313"},"PeriodicalIF":3.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753669","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}
Isabela Sanches Pompeo da Silva, Ester Alves Ferreira Bordini, Erika Soares Bronze-Uhle, Vitor de Stuani, Matheus Castro Costa, Letícia Alves Martins de Carvalho, Fernanda Balestrero Cassiano, Lucas José de Azevedo Silva, Ana Flávia Sanches Borges, Diana Gabriela Soares
{"title":"Photo-crosslinkable hydrogel incorporated with bone matrix particles for advancements in dentin tissue engineering","authors":"Isabela Sanches Pompeo da Silva, Ester Alves Ferreira Bordini, Erika Soares Bronze-Uhle, Vitor de Stuani, Matheus Castro Costa, Letícia Alves Martins de Carvalho, Fernanda Balestrero Cassiano, Lucas José de Azevedo Silva, Ana Flávia Sanches Borges, Diana Gabriela Soares","doi":"10.1002/jbm.a.37777","DOIUrl":"10.1002/jbm.a.37777","url":null,"abstract":"<p>The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2273-2288"},"PeriodicalIF":3.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629553","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}
Niloofar Aldaghi, Mohammad Kamalabadi-Farahani, Morteza Alizadeh, Majid Salehi
{"title":"Doxycycline-loaded carboxymethyl cellulose/sodium alginate/gelatin hydrogel: An approach for enhancing pressure ulcer healing in a rat model","authors":"Niloofar Aldaghi, Mohammad Kamalabadi-Farahani, Morteza Alizadeh, Majid Salehi","doi":"10.1002/jbm.a.37778","DOIUrl":"10.1002/jbm.a.37778","url":null,"abstract":"<p>Pressure ulcers, or bedsores, are created by areas of the skin under prolonged pressure and can lead to skin and underlying tissue damage. The present study evaluated the effects of carboxymethyl cellulose/sodium alginate/gelatin (CMC/Alg/Gel) hydrogel containing doxycycline (DOX) on improving the healing process of pressure ulcers. The magnet was used to apply pressure on the dorsum skin rat to induce a pressure ulcer model. Then sterile gauze, CMC/Alg/Gel, and CMC/Alg/Gel/1% w/v DOX hydrogels were used to cover the wounds. Blood compatibility, weight loss, cytocompatibility, drug release rate, cell viability, wound closure, and re-epithelialization were evaluated in all animals on the 14th day after treatment. In vivo results and histopathological evaluation showed 56.66% wound closure and the highest re-epithelialization in the CMC/Alg/Gel/1% w/v DOX hydrogel group (14 days after treatment). Furthermore, real-time PCR results indicated that the hydrogel containing DOX significantly decreased the expression of the <i>MMP</i> family consisting of <i>MMP2</i> and <i>MMP9</i> mRNA and also increased the expression of vascular endothelial growth factor <i>VEGF</i> mRNA. This study suggested that the addition of DOX, an antibiotic and <i>MMP</i> inhibitor, to hydrogels may be effective in the healing process of pressure ulcers.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2289-2300"},"PeriodicalIF":3.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636258","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}
Pengcheng Yang, Fang Xie, Lihang Zhu, Jonathan Nimal Selvaraj, Donghui Zhang, Jie Cai
{"title":"Fabrication of chitin-fibrin hydrogels to construct the 3D artificial extracellular matrix scaffold for vascular regeneration and cardiac tissue engineering","authors":"Pengcheng Yang, Fang Xie, Lihang Zhu, Jonathan Nimal Selvaraj, Donghui Zhang, Jie Cai","doi":"10.1002/jbm.a.37774","DOIUrl":"10.1002/jbm.a.37774","url":null,"abstract":"<p>As the cornerstone of tissue engineering and regeneration medicine research, developing a cost-effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized <i>β</i>-chitin derivative (QC) and fibrin-matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human-engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220–1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring-shaped and patch-shaped hEHT. These QCFM1 hydrogels-based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin-derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2257-2272"},"PeriodicalIF":3.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617878","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}
Aishwarya V. Menon, Amelia A. Putnam-Neeb, Caitlin E. Brown, Christa J. Crain, Gert J. Breur, Sanjeev K. Narayanan, Jonathan J. Wilker, Julie C. Liu
{"title":"Biocompatibility of mussel-inspired water-soluble tissue adhesives","authors":"Aishwarya V. Menon, Amelia A. Putnam-Neeb, Caitlin E. Brown, Christa J. Crain, Gert J. Breur, Sanjeev K. Narayanan, Jonathan J. Wilker, Julie C. Liu","doi":"10.1002/jbm.a.37775","DOIUrl":"10.1002/jbm.a.37775","url":null,"abstract":"<p>Wound closure in surgeries is traditionally achieved using invasive methods such as sutures and staples. Adhesion-based wound closure methods such as tissue adhesives, sealants, and hemostats are slowly replacing these methods due to their ease of application. Although several chemistries have been developed and used commercially for wound closure, there is still a need for better tissue adhesives from the point of view of toxicity, wet-adhesion strength, and long-term bonding. Catechol chemistry has shown great promise in developing wet-set adhesives that meet these criteria. Herein, we have studied the biocompatibility of a catechol-based copolymer adhesive, poly([dopamine methacrylamide]-co-[methyl methacrylate]-co-[poly(ethylene glycol) methyl ether methacrylate]) or poly(catechol-MMA-OEG), which is soluble in water. The adhesive was injected subcutaneously in a mouse model on its own and in combination with a sodium periodate crosslinker. After 72 h, 4 weeks, and 12 weeks, the mice were euthanized and subjected to histopathological analysis. Both adhesives were present and still palpable at the end of 12 weeks. The moderate inflammation observed for the poly(catechol-MMA-OEG) cohort at 72 h had reduced to mild inflammation at the end of 12 weeks. However, the moderate inflammatory response observed for the poly(catechol-MMA-OEG) + crosslinker cohort at 72 h had not subsided at 12 weeks.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2243-2256"},"PeriodicalIF":3.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to the first corrigendum to “Design and fabrication of clinoptilolite–nanohydroxyapatite/chitosan–gelatin composite scaffold and evaluation of its effects on bone tissue engineering”","authors":"","doi":"10.1002/jbm.a.37759","DOIUrl":"10.1002/jbm.a.37759","url":null,"abstract":"<p>Sadeghinia A, Soltani S, Aghazadeh M, Khalilifard J, Davaran S. Design and fabrication of clinoptilolite–nanohydroxyapatite/chitosan–gelatin composite scaffold and evaluation of its effects on bone tissue engineering. <i>J Biomed Mater Res A</i>. 2020;108(2):221–233. doi:10.1002/jbm.a.36806</p><p>Figure 2: Cln-nHA/CS-Gel.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2374-2377"},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parmida Ghiasi Tabari, Amirmohammad Sattari, Mohsen Mashhadi Keshtiban, Nushin Karkuki Osguei, John G. Hardy, Ali Samadikuchaksaraei
{"title":"Injectable hydrogel scaffold incorporating microspheres containing cobalt-doped bioactive glass for bone healing","authors":"Parmida Ghiasi Tabari, Amirmohammad Sattari, Mohsen Mashhadi Keshtiban, Nushin Karkuki Osguei, John G. Hardy, Ali Samadikuchaksaraei","doi":"10.1002/jbm.a.37773","DOIUrl":"10.1002/jbm.a.37773","url":null,"abstract":"<p>Injectable in situ-forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt-doped bioactive glass (BG)-loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl<sub>2</sub>. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast-like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well-dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear-thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A-S-G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of <i>COL1A1</i>, <i>ALPL</i>, <i>OCN</i>, and <i>RUNX2</i> and angiogenic genes of <i>HIF1A</i> and <i>VEGF</i> at different time points in the cells cultured with the A-S-G5Co. Finally, the in vivo study demonstrated that A-S-G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow-up. These results show that incorporation of SF/gelatin microspheres containing cobalt-doped BG in an injectable in situ-forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2225-2242"},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565425","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":"Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation","authors":"Premchirakorn Phewchan, Artit Laoruengthana, Supaporn Lamlertthon, Waree Tiyaboonchai","doi":"10.1002/jbm.a.37772","DOIUrl":"10.1002/jbm.a.37772","url":null,"abstract":"<p>The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas–Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against <i>Staphylococcus aureus</i> for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2210-2224"},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565426","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}
Masatoshi Murayama, Issei Shinohara, Masakazu Toya, Yosuke Susuki, Max L. Lee, Bill Young, Qi Gao, Simon Kwoon-Ho Chow, Stuart B. Goodman
{"title":"T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells","authors":"Masatoshi Murayama, Issei Shinohara, Masakazu Toya, Yosuke Susuki, Max L. Lee, Bill Young, Qi Gao, Simon Kwoon-Ho Chow, Stuart B. Goodman","doi":"10.1002/jbm.a.37771","DOIUrl":"10.1002/jbm.a.37771","url":null,"abstract":"<p>Approximately 5%–10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"112 12","pages":"2202-2209"},"PeriodicalIF":3.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499956","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}