Effects of aging upon the host response to implants.

Macrophage polarization during the host response is now a well-accepted predictor of outcomes following material implantation. Immunosenescence, dysregulation of macrophage function, and delayed resolution of immune responses in aged individuals have all been demonstrated, suggesting that host responses to materials in aged individuals should differ from those in younger individuals. However, few studies examining the effects of aging upon the host response have been performed. The present work sought to elucidate the impacts of aging upon the host response to polypropylene mesh implanted into 8-week-old and 18-month-old mice. The results showed that there are significant differences in macrophage surface marker expression, migration, and polarization during the early host macrophage response and delayed resolution of the host response in 18-month-old versus 8-week-old mice. These differences could not be attributed to cell-intrinsic defects alone, suggesting that the host macrophage response to implants is likely also dictated to a significant degree by the local tissue microenvironment. These results raise important questions about the design and testing of materials and devices often intended to treat aged individuals and suggest that an improved understanding of patient- and context-dependent macrophage responses has the potential to improve outcomes in aged individuals. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1281-1292, 2017.

[1]  Stephen F. Badylak,et al.  Rethinking Regenerative Medicine: A Macrophage-Centered Approach , 2014, Front. Immunol..

[2]  P. Kingshott,et al.  Surfaces that resist bioadhesion , 1999 .

[3]  Gordana Vunjak-Novakovic,et al.  Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. , 2015, Biomaterials.

[4]  P. Sacerdote,et al.  Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses , 2004, Pain.

[5]  S. Shono,et al.  Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. , 2010, Journal of hepatology.

[6]  Ansuman T. Satpathy,et al.  Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. , 2014, Immunity.

[7]  G. Ashcroft,et al.  Ageing and wound healing , 2004, Biogerontology.

[8]  P. Sacerdote.  Opioids and the immune system , 2006, Palliative medicine.

[9]  P. Campos,et al.  Diabetes alters inflammation, angiogenesis, and fibrogenesis in intraperitoneal implants in rats. , 2014, Microvascular research.

[10]  S. Gordon,et al.  Monocyte and macrophage heterogeneity , 2005, Nature Reviews Immunology.

[11]  B. Brown,et al.  Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. , 2012, Biomaterials.

[12]  P. Kubes,et al.  A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair , 2016, Cell.

[13]  R. C. Johnson,et al.  Neovascularization of synthetic membranes directed by membrane microarchitecture. , 1995, Journal of biomedical materials research.

[14]  Molecular and Cellular Aspects of Macrophage Aging , 2009 .

[15]  Tom C. Freeman,et al.  Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation , 2014, Immunity.

[16]  J. Suttles,et al.  Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age‐associated microenvironmental changes , 2005, Immunological reviews.

[17]  J M Anderson,et al.  Influence of biomaterial surface chemistry on the apoptosis of adherent cells. , 2001, Journal of biomedical materials research.

[18]  Shaoyi Jiang,et al.  Blood compatibility of surfaces with superlow protein adsorption. , 2008, Biomaterials.

[19]  Arundhati Rao,et al.  Long-term histologic response to synthetic and biologic graft materials implanted in the vagina and abdomen of a rabbit model. , 2009, American journal of obstetrics and gynecology.

[20]  K. Brand,et al.  Tumorigenesis by Millipore filters in mice: histology and ultrastructure of tissue reactions as related to pore size. , 1973, Journal of the National Cancer Institute.

[21]  Christian R. Gomez,et al.  Innate immunity and aging , 2008, Experimental Gerontology.

[22]  Charles D Mills,et al.  M1 and M2 Macrophages: Oracles of Health and Disease. , 2012, Critical reviews in immunology.

[23]  Y. S. Bakhle,et al.  Host response to sponge implants differs between subcutaneous and intraperitoneal sites in mice. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[24]  J. Olerud,et al.  Cutaneous and inflammatory response to long-term percutaneous implants of sphere-templated porous/solid poly(HEMA) and silicone in mice. , 2012, Journal of biomedical materials research. Part A.

[25]  D. Grainger,et al.  Aging and the Host Response to Implanted Biomaterials , 2015 .

[26]  Shaoyi Jiang,et al.  Zwitterionic hydrogels implanted in mice resist the foreign-body reaction , 2013, Nature Biotechnology.

[27]  D. Klee,et al.  Topographical control of human macrophages by a regularly microstructured polyvinylidene fluoride surface. , 2008, Biomaterials.

[28]  A. Khademhosseini,et al.  Delivery strategies to control inflammatory response: Modulating M1-M2 polarization in tissue engineering applications. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Elazer R. Edelman,et al.  Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia , 2015, Science Translational Medicine.

[30]  David M. Mosser,et al.  Exploring the full spectrum of macrophage activation , 2010, Nature Reviews Immunology.

[31]  M. Finley,et al.  Intracellular signaling mechanisms associated with CD47 modified surfaces. , 2013, Biomaterials.

[32]  George P McCabe,et al.  Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. , 2009, Biomaterials.

[33]  S. Guelcher,et al.  Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling. , 2015, Biomaterials.

[34]  D. Mann,et al.  Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart , 2014, Proceedings of the National Academy of Sciences.

[35]  E. Kovacs,et al.  Advanced age impairs macrophage polarization. , 2012, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[36]  J. Olerud,et al.  Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice. , 2010, Journal of biomedical materials research. Part A.

[37]  K. Spiller,et al.  Drug delivery strategies to control macrophages for tissue repair and regeneration , 2016, Experimental biology and medicine.

[38]  Fan Yang,et al.  Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response. , 2013, Biomaterials.

[39]  P. Campos,et al.  Alterations in the dynamics of inflammation, proliferation and apoptosis in subcutaneous implants of lupus-prone mice. , 2011, Histology and histopathology.

[40]  Julie Gold,et al.  Quantitative assessment of the response of primary derived human osteoblasts and macrophages to a range of nanotopography surfaces in a single culture model in vitro. , 2003, Biomaterials.

[41]  A. Kissenpfennig,et al.  Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis , 2014, Aging cell.

[42]  Cameron J Wilson,et al.  Mediation of biomaterial-cell interactions by adsorbed proteins: a review. , 2005, Tissue engineering.

[43]  Silvano Sozzani,et al.  The chemokine system in diverse forms of macrophage activation and polarization. , 2004, Trends in immunology.

[44]  R. Cabrini,et al.  In vitro age dependent response of macrophages to micro and nano titanium dioxide particles. , 2015, Journal of biomedical materials research. Part A.

[45]  D. Grainger,et al.  Senescence and quiescence induced compromised function in cultured macrophages. , 2012, Biomaterials.

[46]  Michael Thompson,et al.  Surface chemistry to minimize fouling from blood-based fluids. , 2012, Chemical Society reviews.

[47]  R. Maier,et al.  Differential monocyte/macrophage interleukin-1β production due to biomaterial topography requires the β2 integrin signaling pathway. , 2011, Journal of biomedical materials research. Part A.

[48]  N. Rosenthal,et al.  Progressive replacement of embryo-derived cardiac macrophages with age , 2014, The Journal of experimental medicine.

[49]  Marc M. Takeno,et al.  Quantifying the effect of pore size and surface treatment on epidermal incorporation into percutaneously implanted sphere-templated porous biomaterials in mice. , 2011, Journal of biomedical materials research. Part A.

[50]  Buddy D. Ratner,et al.  Porous Implants Modulate Healing and Induce Shifts in Local Macrophage Polarization in the Foreign Body Reaction , 2013, Annals of Biomedical Engineering.

[51]  M. Horan,et al.  Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[52]  T. Matsuda,et al.  Student Research Award in the Undergraduate Degree Candidate category, 30th Annual Meeting of the Society for Biomaterials, Memphis, Tennessee, April 27-30, 2005. Monocyte/lymphocyte interactions and the foreign body response: in vitro effects of biomaterial surface chemistry. , 2005, Journal of biomedical materials research. Part A.

[53]  Kerry A. Daly,et al.  The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. , 2012, Biomaterials.

[54]  N. Rosenthal,et al.  Age-related changes in tissue macrophages precede cardiac functional impairment , 2014, Aging.

[55]  Buddy D. Ratner,et al.  Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro. , 2010, Journal of biomedical materials research. Part A.

[56]  Buddy D Ratner,et al.  Engineering biomaterials to integrate and heal: The biocompatibility paradigm shifts , 2012, Biotechnology and bioengineering.

[57]  B. Brown,et al.  Cell Therapy Strategies to Combat Immunosenescence , 2015, Organogenesis.

[58]  B. Brown,et al.  Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration. , 2017, Biomaterials.

[59]  M. Finley,et al.  Diminished adhesion and activation of platelets and neutrophils with CD47 functionalized blood contacting surfaces. , 2012, Biomaterials.

[60]  Thomas A. Wynn,et al.  Macrophage biology in development, homeostasis and disease , 2013, Nature.

[61]  Ali Khademhosseini,et al.  Engineering Immunomodulatory Biomaterials To Tune the Inflammatory Response. , 2016, Trends in biotechnology.

[62]  M. Nakashima,et al.  Distinct development and functions of resident and recruited liver Kupffer cells/macrophages , 2013, Journal of leukocyte biology.

[63]  David L Cochran,et al.  Osteoblast maturation and new bone formation in response to titanium implant surface features are reduced with age , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[64]  B. Ratner.  Healing with medical implants: The body battles back , 2015, Science Translational Medicine.

[65]  B. Boyan,et al.  Titanium surface characteristics, including topography and wettability, alter macrophage activation. , 2016, Acta biomaterialia.

[66]  Kerry A. Daly,et al.  Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. , 2012, Acta biomaterialia.

[67]  R. Bellamkonda,et al.  Effect of modulating macrophage phenotype on peripheral nerve repair. , 2012, Biomaterials.

[68]  Jillian E Tengood,et al.  The use of CD47-modified biomaterials to mitigate the immune response , 2016, Experimental biology and medicine.

[69]  R. Miron,et al.  OsteoMacs: Key players around bone biomaterials. , 2016, Biomaterials.