Title: Editorial: Modulation of the Immune System to Improve Tissue Regeneration Strategies
Abstract: Tissue Engineering Part AAhead of Print Free AccessEditorial: Modulation of the Immune System to Improve Tissue Regeneration StrategiesLaura G. Bracaglia and Themis R. KyriakidesLaura G. BracagliaAddress correspondence to: Laura G. Bracaglia, PhD, Department of Chemical and Biological Engineering, Villanova University, 800 Lancaster Avenue, White Hall, Room 315, Villanova, PA 19085, USA E-mail Address: [email protected]Department of Chemical and Biological Engineering, Villanova University, Villanova, Pennsylvania, USA.Search for more papers by this author and Themis R. KyriakidesThemis R. Kyriakides, PhD, Department of Pathology, Yale University School of Medicine, New Haven, CT 06519, USA E-mail Address: [email protected]Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.Search for more papers by this authorPublished Online:6 Mar 2024https://doi.org/10.1089/ten.tea.2024.29055.editorialAboutSectionsPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail A wide range of implanted biomaterials, tissue engineered scaffolds, and devices interact with the immune system via complex and not well-understood mechanisms. This is due, in part, to the diversity of tissue- and cell-specific elicited responses that are broadly characterized as the foreign body response (FBR). In general, FBR leads to encapsulation by a collagenous and largely avascular capsule that limits functions and lifespan of implants. This outcome is especially at odds with tissue engineering and regenerative medicine strategies that intend to integrate with or recruit cells from the native tissue environment to build or restore functional tissue. The FBR and other unwanted inflammatory processes may also add further damage to the already injured or diseased environment.It is appreciated that biomaterial sources such as native or synthetic, and properties including porosity, topography, stiffness, charge, and wettability can impact the FBR.1 Interactions between implant surfaces and other components and proteins and cells in tissues involve the innate immune system with macrophages playing a central role in mediating FBR outcomes. Polarization of macrophages and acquisition of activation states unique to the FBR have attracted extensive interest and numerous studies have shed light on this process.2 Moreover, many investigators have developed strategies to modulate macrophage polarization toward attenuation of the FBR in the context of tissue engineered constructs.3 In some cases, balanced macrophage activity between prohealing and proinflammatory phenotypes is essential to tissue repair.4–6 Collectively, findings from these studies highlight the importance of this cell type and innate immunity in general. Importantly, it is recognized that the successful employment of tissue-engineered constructs relies on enhancement of tissue remodeling and overall growth without excessive fibrosis or other unwanted reactions.Engagement of components of adaptive immunity in the FBR, including T and B cells, has also been demonstrated,7 specifically, the participation of these cell types in pro- or anti-fibrotic responses toward natural or synthetic biomaterials. Therefore, it is important to consider communication between the innate and adaptive arms of immunity and their cross-talk with cells of mesenchymal origin responsible for extracellular matrix deposition and remodeling. These processes can be altered in many pathological conditions such as diabetes or autoimmune diseases, suggesting that FBR outcomes can be influenced by the overall status of the immune system. For example, implant studies in diabetic animals showed an exacerbated FBR.Interestingly, distinct approaches targeting either components of the immune system or employing biomaterial modifications have resulted in almost complete amelioration of the FBR in experimental systems. For example, biomechanical stimulation, inhibition of inflammatory signals, and controlling scaffold porosity, or surface chemistry have been shown to limit encapsulation and, in some cases, improve implant/cell functions.8–11 Collectively, these studies highlight the importance of both immunity and biomaterial properties in driving the FBR or beneficial healing and should inform the development of strategies with clinical potential.The focus of this special issue is centered on the above themes and aims to contribute to our understanding of the immune response in the context of the FBR and how it might hinder or enhance tissue-engineering goals. It contains descriptions of approaches involving modulations and modifications of immune reactions and biomaterial properties, respectively. These include immunomodulatory strategies and exploration of biomechanical and other inputs in cell- and tissue-specific approaches.References1. Chen Y, Luo Z, Meng W, et al. Decoding the "Fingerprint" of implant materials: Insights into the foreign body reaction. Small 2024;e2310325; doi: 10.1002/smll.202310325 Crossref, Google Scholar2. Doloff JC, Ma M, Sadraei A, et al. Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response. Sci Adv 2023;9(24):eade9488; doi: 10.1126/sciadv.ade9488 Crossref, Medline, Google Scholar3. Elisseeff J, Badylak SF, Boeke JD. Immune and genome engineering as the future of transplantable tissue. N Engl J Med 2021;385(26):2451–2462; doi: 10.1056/NEJMra1913421 Crossref, Medline, Google Scholar4. Anderson LE, Tellier LE, Shah KR, et al. Bone marrow mobilization and local stromal cell-derived factor-1alpha delivery enhances nascent supraspinatus muscle fiber growth. Tissue Eng Part A 2024;30(1–2):45–60; doi: 10.1089/ten.TEA.2023.0128 Link, Google Scholar5. Dziki JL, Huleihel L, Scarritt ME, et al. Extracellular matrix bioscaffolds as immunomodulatory biomaterials. Tissue Eng Part A 2017;23(19–20):1152–1159; doi: 10.1089/ten.TEA.2016.0538 Link, Google Scholar6. Wei F, Zhou Y, Wang J, et al. The immunomodulatory role of BMP-2 on macrophages to accelerate osteogenesis. Tissue Eng Part A 2018;24(7–8):584–594; doi: 10.1089/ten.TEA.2017.0232 Link, Google Scholar7. Yang B, Rutkowski N, Elisseeff J. The foreign body response: Emerging cell types and considerations for targeted therapeutics. Biomater Sci 2023;11(24):7730–7747; doi: 10.1039/d3bm00629h Crossref, Medline, Google Scholar8. Chan AHP, Moore MJ, Grant AJ, et al. Selective immunosuppression targeting the NLRP3 inflammasome mitigates the foreign body response to implanted biomaterials while preserving angiogenesis. Adv Healthc Mater 2023;12(32):e2301571; doi: 10.1002/adhm.202301571 Crossref, Medline, Google Scholar9. Moore LB, Sawyer AJ, Charokopos A, et al. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFkappaB activation in the foreign body response. Acta Biomater 2015;11:37–47; doi: 10.1016/j.actbio.2014.09.022 Crossref, Medline, Google Scholar10. Zhang L, Cao Z, Bai T, et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat Biotechnol 2013;31(6):553–556; doi: 10.1038/nbt.2580 Crossref, Medline, Google Scholar11. Vegas AJ, Veiseh O, Doloff JC, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 2016;34(3):345–352; doi: 10.1038/nbt.3462 Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Volume 0Issue 0 InformationCopyright 2024, Mary Ann Liebert, Inc., publishersTo cite this article:Laura G. Bracaglia and Themis R. Kyriakides.Editorial: Modulation of the Immune System to Improve Tissue Regeneration Strategies.Tissue Engineering Part A.ahead of printhttp://doi.org/10.1089/ten.tea.2024.29055.editorialOnline Ahead of Print:March 6, 2024 TopicsRegenerative medicineT lymphocytesTissue engineeringWound healing PDF download
Publication Year: 2024
Publication Date: 2024-04-01
Language: en
Type: editorial
Indexed In: ['crossref', 'pubmed']
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