Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing.

The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch + RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018.

[1]  A. M. Marcaccini,et al.  Local delivery of strontium ranelate promotes regeneration of critical size bone defects filled with collagen sponge. , 2018, Journal of biomedical materials research. Part A.

[2]  H. Lee,et al.  A novel calcium-accumulating peptide/gelatin in situ forming hydrogel for enhanced bone regeneration. , 2018, Journal of biomedical materials research. Part A.

[3]  T. Kaur,et al.  Chitosan composite three dimensional macrospheric scaffolds for bone tissue engineering. , 2017, International journal of biological macromolecules.

[4]  A. M. Gil,et al.  Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regeneration. , 2016, Biomaterials.

[5]  A. C. Jayasuriya,et al.  Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect. , 2016, Materials science & engineering. C, Materials for biological applications.

[6]  M. Hasanzadeh,et al.  Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances. , 2016, Journal of biomedical materials research. Part A.

[7]  H. Fahmi,et al.  The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis , 2016, Inflammation Research.

[8]  C. Serhan,et al.  Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. , 2015, Journal of molecular and cellular cardiology.

[9]  M. Barbosa,et al.  Development of an immunomodulatory biomaterial: using resolvin D1 to modulate inflammation. , 2015, Biomaterials.

[10]  G. Garlet,et al.  Intramembranous Bone Healing Process Subsequent to Tooth Extraction in Mice: Micro-Computed Tomography, Histomorphometric and Molecular Characterization , 2015, PloS one.

[11]  N. Rosenthal,et al.  Preparing the ground for tissue regeneration: from mechanism to therapy , 2014, Nature Medicine.

[12]  U. Klinge,et al.  Skin as marker for collagen type I/III ratio in abdominal wall fascia , 2014, Hernia.

[13]  Samira M. Azarin,et al.  Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression. , 2014, Biomaterials.

[14]  B. Matthews,et al.  Remodeling characteristics and collagen distribution in synthetic mesh materials explanted from human subjects after abdominal wall reconstruction: an analysis of remodeling characteristics by patient risk factors and surgical site classifications , 2014, Surgical Endoscopy.

[15]  C. Serhan,et al.  Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. , 2014, Cell metabolism.

[16]  M. Barbosa,et al.  Macrophage polarization following chitosan implantation. , 2013, Biomaterials.

[17]  T. V. Van Dyke,et al.  Natural resolution of inflammation. , 2013, Periodontology 2000.

[18]  M. Lamghari,et al.  Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response. , 2013, Acta biomaterialia.

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

[20]  Milan Raska,et al.  Particle disease: Biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty , 2013, Innate immunity.

[21]  C. Serhan,et al.  A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation , 2013, PloS one.

[22]  Yunan Tang,et al.  Proresolution Therapy for the Treatment of Delayed Healing of Diabetic Wounds , 2013, Diabetes.

[23]  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.

[24]  J. Smolen,et al.  Inflammatory bone loss: pathogenesis and therapeutic intervention , 2012, Nature Reviews Drug Discovery.

[25]  Lutz Claes,et al.  Fracture healing under healthy and inflammatory conditions , 2012, Nature Reviews Rheumatology.

[26]  V. Arroyo,et al.  Resolvin D1 and Its Precursor Docosahexaenoic Acid Promote Resolution of Adipose Tissue Inflammation by Eliciting Macrophage Polarization toward an M2-Like Phenotype , 2011, The Journal of Immunology.

[27]  J. Simon,et al.  Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. , 2011, Biomaterials.

[28]  Jeffrey A. Hubbell,et al.  Materials engineering for immunomodulation , 2009, Nature.

[29]  C. Godson,et al.  Lipoxins: resolutionary road , 2009, British journal of pharmacology.

[30]  T. Krieg,et al.  Interrelation of immunity and tissue repair or regeneration. , 2009, Seminars in cell & developmental biology.

[31]  C. Cooper,et al.  Epidemiology of osteoporosis. , 2008, Best practice & research. Clinical endocrinology & metabolism.

[32]  T. Krieg,et al.  Inflammation in wound repair: molecular and cellular mechanisms. , 2007, The Journal of investigative dermatology.

[33]  G. Daculsi,et al.  Small-animal models for testing macroporous ceramic bone substitutes. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[34]  C. Serhan,et al.  Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells , 2003, The Journal of Biological Chemistry.

[35]  C. Serhan,et al.  Resolvins , 2002, The Journal of experimental medicine.

[36]  C. M. Agrawal,et al.  The role of collagen in determining bone mechanical properties , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  L. Junqueira,et al.  Reduced collagen content and fibre bundle disorganization in skin biopsies of patients with Ehlers-Danlos syndrome , 1985, The Histochemical Journal.

[38]  R. Brentani,et al.  Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections , 1979, The Histochemical Journal.

[39]  W. Świȩszkowski,et al.  Gelatin methacrylate scaffold for bone tissue engineering: The influence of polymer concentration. , 2018, Journal of biomedical materials research. Part A.

[40]  M. Barbosa,et al.  Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators. , 2015, Biomaterials.

[41]  Louis C. Gerstenfeld,et al.  Fracture healing: mechanisms and interventions , 2015, Nature Reviews Rheumatology.

[42]  P. Delmas,et al.  The role of collagen in bone strength , 2005, Osteoporosis International.

[43]  L. Junqueira,et al.  The use of the Picrosirius-polarization method for the study of the biopathology of collagen. , 1991, Memorias do Instituto Oswaldo Cruz.