{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:06:37Z","timestamp":1787673997186,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant\/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan\/gelatin-coated titan implants over chitosan\/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan\/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.<\/jats:p>","DOI":"10.3390\/ijms23010374","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Osteocytes Influence on Bone Matrix Integrity Affects Biomechanical Competence at Bone-Implant Interface of Bioactive-Coated Titanium Implants in Rat Tibiae"],"prefix":"10.3390","volume":"23","author":[{"given":"Sabine","family":"Stoetzel","sequence":"first","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeksha","family":"Malhan","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Wild","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Helbing","sequence":"additional","affiliation":[{"name":"Chair of Materials Science (CMS), Otto Schott Institute of Materials Research (OSIM), Faculty of Physics and Astronomy, Friedrich Schiller University Jena, L\u00f6bdergraben 32, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-0691","authenticated-orcid":false,"given":"Fathi","family":"Hassan","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9174-6435","authenticated-orcid":false,"given":"Sameh","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Justus-Liebig University of Giessen, Klinikstrasse 33, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus D.","family":"Jandt","sequence":"additional","affiliation":[{"name":"Chair of Materials Science (CMS), Otto Schott Institute of Materials Research (OSIM), Faculty of Physics and Astronomy, Friedrich Schiller University Jena, L\u00f6bdergraben 32, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Heiss","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"},{"name":"Department of Trauma, Hand and Reconstructive Surgery, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1187-8578","authenticated-orcid":false,"given":"Thaqif","family":"El Khassawna","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery, Faculty of Medicine, Justus-Liebig-University, Aulweg 128, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.colsurfb.2003.12.002","article-title":"Biomaterials in total joint replacement","volume":"39","author":"Katti","year":"2004","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"El Khassawna, T., Knapp, G., Scheibler, N., Malhan, D., Walter, N., Biehl, C., Alt, V., Heiss, C., and Rupp, M. (2021). Mortality, Risk Factors and Risk Assessment after Periprosthetic Femoral Fractures\u2014A Retrospective Cohort Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194324"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40824-018-0144-8","article-title":"Recent updates for biomaterials used in total hip arthroplasty","volume":"22","author":"Hu","year":"2018","journal-title":"Biomater. Res"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.jcms.2018.12.017","article-title":"Functional and aesthetic treatment outcomes after immediate jaw reconstruction using a fibula flap and dental implants","volume":"47","author":"Attia","year":"2019","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000381700","article-title":"Biomaterials in the Reconstruction of the Oral and Maxillofacial Region","volume":"17","author":"Ayoub","year":"2015","journal-title":"Front. Oral. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Alkhasawnah, Q., Elmas, S., Sohrabi, K., Attia, S., Heinemann, S., El Khassawna, T., and Heiss, C. (2021). Confirmation of Calcium Phosphate Cement Biodegradation after Jawbone Augmentation around Dental Implants Using Three-Dimensional Visualization and Segmentation Software. Materials, 14.","DOI":"10.3390\/ma14227084"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113","DOI":"10.59566\/IJBS.2015.11113","article-title":"A Review on Biomaterials in Dental Implantology","volume":"11","author":"Ananth","year":"2015","journal-title":"Int. J. Biomed. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Attia, S., Schaaf, H., El Khassawna, T., Malhan, D., Mausbach, K., Howaldt, H.-P., and Streckbein, P. (2019). Oral Rehabilitation of Hypodontia Patients Using an Endosseous Dental Implant: Functional and Aesthetic Results. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101687"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.actbio.2018.10.036","article-title":"Review of titanium surface modification techniques and coatings for antibacterial applications","volume":"83","author":"Chouirfa","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_10","first-page":"261","article-title":"Bioactive glass coatings on metallic implants for biomedical applications","volume":"4","author":"Oliver","year":"2019","journal-title":"Bioact. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jeurceramsoc.2006.04.015","article-title":"Titania-based bioactive materials","volume":"27","author":"Kokubo","year":"2007","journal-title":"J. Eur. Ceram. Soc."},{"key":"ref_12","first-page":"S37","article-title":"Foreign body reactions, marginal bone loss and allergies in relation to titanium implants","volume":"11","author":"Albrektsson","year":"2018","journal-title":"Eur. J. Oral Implantol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1016\/j.biomaterials.2007.04.007","article-title":"Effects of calcium ion incorporation on bone healing of Ti6Al4V alloy implants in rabbit tibiae","volume":"28","author":"Park","year":"2007","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1016\/S0142-9612(99)00161-1","article-title":"RGD-coated titanium implants stimulate increased bone formation in vivo","volume":"20","author":"Ferris","year":"1999","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.1016\/j.biomaterials.2006.06.034","article-title":"Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate","volume":"27","author":"Rammelt","year":"2006","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/jbm.a.34372","article-title":"A novel composite porous coating approach for bioactive titanium-based orthopedic implants","volume":"101","author":"Qiu","year":"2013","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3103\/S1068375517050027","article-title":"Recent development of calcium phosphate-based coatings on titanium alloy implants","volume":"53","author":"Adeleke","year":"2017","journal-title":"Surf. Eng. Appl. Electrochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.orthres.2004.02.011","article-title":"Coating of titanium implants with type-I collagen","volume":"22","author":"Rammelt","year":"2004","journal-title":"J. Orthop. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.msec.2014.05.048","article-title":"Gelatin functionalised porous titanium alloy implants for orthopaedic applications","volume":"42","author":"Vanderleyden","year":"2014","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"D\u2019Almeida, M., Attik, N., Amalric, J., Brunon, C., Renaud, F., Abouelleil, H., Toury, B., and Grosgogeat, B. (2017). Chitosan coating as an antibacterial surface for biomedical applications. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189537"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"730693","DOI":"10.1155\/2012\/730693","article-title":"Hydroxyapatite coating of titanium implants using hydroprocessing and evaluation of their osteoconductivity","volume":"2012","author":"Kuroda","year":"2012","journal-title":"Bioinorg. Chem. Appl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5960","DOI":"10.1016\/j.biomaterials.2005.03.020","article-title":"Polysaccharide-protein surface modification of titanium via a layer-by-layer technique: Characterization and cell behaviour aspects","volume":"26","author":"Cai","year":"2005","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4926","DOI":"10.1016\/j.actbio.2012.08.013","article-title":"The effect of polyelectrolyte multilayer coated titanium alloy surfaces on implant anchorage in rats","volume":"9","author":"Zankovych","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1902\/jop.2009.080484","article-title":"Osteocyte density in the peri-implant bone of immediately loaded and submerged dental implants","volume":"80","author":"Barros","year":"2009","journal-title":"J. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/jbm.b.33000","article-title":"Osteocyte density in the peri-implant bone of implants retrieved after different time periods (4 weeks to 27 years)","volume":"102","author":"Piattelli","year":"2014","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1007\/BF01133326","article-title":"Titanium: The implant material of today","volume":"22","year":"1987","journal-title":"J. Mater. Sci."},{"key":"ref_27","first-page":"523","article-title":"Nonalloyed titanium as a bioinert metal\u2014A review","volume":"36","author":"Tschernitschek","year":"2005","journal-title":"Quintessence Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4103\/0019-5154.143526","article-title":"Titanium allergy: A literature review","volume":"59","author":"Goutam","year":"2014","journal-title":"Indian J. Dermatol."},{"key":"ref_29","first-page":"171","article-title":"Titanium Corrosion: Implications for Dental Implants","volume":"24","author":"Shah","year":"2016","journal-title":"Eur. J. Prosthodont. Restor. Dent."},{"key":"ref_30","first-page":"534","article-title":"Mandibular overdentures with immediate loading: Satisfaction and quality of life","volume":"24","author":"Mendes","year":"2011","journal-title":"Int. J. Prosthodont."},{"key":"ref_31","first-page":"356","article-title":"Patient satisfaction following dental implant treatment with immediate loading in the edentulous atrophic maxilla","volume":"26","author":"Erkapers","year":"2011","journal-title":"Int. J. Oral Maxillofac. Implant"},{"key":"ref_32","first-page":"706","article-title":"Resting injured limbs delays recovery: A systematic review","volume":"53","author":"Nash","year":"2004","journal-title":"J. Fam. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"B454","DOI":"10.1002\/adem.201180020","article-title":"Selectively Promoting or Preventing Osteoblast Growth on Titanium Functionalized with Polyelectrolyte Multilayers","volume":"13","author":"Zankovych","year":"2011","journal-title":"Adv. Eng. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0076-6879(82)82058-2","article-title":"Collagen: An overview","volume":"82 Pt A","author":"Miller","year":"1982","journal-title":"Methods Enzym."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.semcdb.2008.07.004","article-title":"Bone remodeling during fracture repair: The cellular picture","volume":"19","author":"Schindeler","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11154-010-9153-1","article-title":"Cellular mechanisms of bone remodeling","volume":"11","author":"Eriksen","year":"2010","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s11914-012-0105-4","article-title":"Osteocyte signaling in bone","volume":"10","author":"Schaffler","year":"2012","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s00223-015-9985-5","article-title":"Effects of Collagen Crosslinking on Bone Material Properties in Health and Disease","volume":"97","author":"Saito","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_40","first-page":"675","article-title":"Implant materials, designs, and surface topographies: Their effect on osseointegration. A literature review","volume":"15","author":"Sykaras","year":"2000","journal-title":"Int. J. Oral Maxillofac. Implants"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2018.11.018","article-title":"Osseointegration and current interpretations of the bone-implant interface","volume":"84","author":"Shah","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1600-0501.2005.01135.x","article-title":"Effect of three distinct treatments of titanium surface on osteoblast attachment, proliferation, and differentiation","volume":"16","author":"Sader","year":"2005","journal-title":"Clin. Oral Implants Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1600-0501.2004.01054.x","article-title":"A systematic review of the influence of different titanium surfaces on proliferation, differentiation and protein synthesis of osteoblast-like MG63 cells","volume":"15","author":"Bachle","year":"2004","journal-title":"Clin. Oral Implants Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36652","DOI":"10.1021\/acsami.8b10992","article-title":"Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis","volume":"10","author":"Zhang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/08959374990130011401","article-title":"Role of the osteoclast at the bone-implant interface","volume":"13","author":"Minkin","year":"1999","journal-title":"Adv. Dent. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"171305","DOI":"10.1155\/2014\/171305","article-title":"The effect of hydroxyapatite nanocrystals on osseointegration of titanium implants: An in vivo rabbit study","volume":"2014","author":"Breding","year":"2014","journal-title":"Int. J. Dent."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s13758-012-0034-x","article-title":"Response of osteoclasts to titanium surfaces with increasing surface roughness: An in vitro study","volume":"7","author":"Brinkmann","year":"2012","journal-title":"Biointerphases"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1002\/jbmr.1628","article-title":"Osteoblast maturation and new bone formation in response to titanium implant surface features are reduced with age","volume":"27","author":"Raines","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","first-page":"1697","article-title":"The role of osteocytes in bone remodeling","volume":"27","author":"Nishida","year":"2017","journal-title":"Clin. Calcium"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/cid.12257","article-title":"The Ultrastructural Relationship Between Osteocytes and Dental Implants Following Osseointegration","volume":"18","author":"Du","year":"2016","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1016\/j.jbiomech.2015.10.025","article-title":"Ultrastructural alterations of osteocyte morphology via loaded implants in rabbit tibiae","volume":"48","author":"Sasaki","year":"2015","journal-title":"J. Biomech."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11914-015-0256-1","article-title":"Osteocyte shape and mechanical loading","volume":"13","author":"Wang","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/PL00012192","article-title":"A back-scattered electron microscopy (BSEM) study of the tight apposition between bone and hydroxyapatite coating","volume":"1","author":"Merolli","year":"2000","journal-title":"J. Orthop. Traumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1021\/ab500127y","article-title":"High-Resolution Visualization of the Osteocyte Lacuno-Canalicular Network Juxtaposed to the Surface of Nanotextured Titanium Implants in Human","volume":"1","author":"Shah","year":"2015","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1002\/jbm.a.36060","article-title":"Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss","volume":"105","author":"Insua","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3390\/polym3010114","article-title":"Gelatin functionalization of biomaterial surfaces: Strategies for immobilization and visualization","volume":"3","author":"Vanderleyden","year":"2011","journal-title":"Polymers"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nmat1545","article-title":"From brittle to ductile fracture of bone","volume":"5","author":"Peterlik","year":"2006","journal-title":"Nat. Mater."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0021-9290(71)90004-2","article-title":"Relations among mechanical properties, collagen fibers, and calcification in adult human cortical bone","volume":"4","author":"Vincentelli","year":"1971","journal-title":"J. Biomech."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1002\/anie.200800908","article-title":"The nucleation mechanism of fluorapatite-collagen composites: Ion association and motif control by collagen proteins","volume":"47","author":"Kawska","year":"2008","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/adma.200901365","article-title":"Mesocrystals\u2014Ordered nanoparticle superstructures","volume":"22","author":"Song","year":"2010","journal-title":"Adv. Mater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6159","DOI":"10.18632\/oncotarget.6740","article-title":"A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers","volume":"7","author":"Hanley","year":"2016","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00774-017-0844-5","article-title":"Computational segmentation of collagen fibers in bone matrix indicates bone quality in ovariectomized rat spine","volume":"36","author":"Daghma","year":"2018","journal-title":"J. Bone Miner. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1097\/00003086-199810001-00003","article-title":"The cell and molecular biology of fracture healing","volume":"355","author":"Einhorn","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrrheum.2014.164","article-title":"Fracture healing: Mechanisms and interventions","volume":"11","author":"Einhorn","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20563","DOI":"10.1038\/srep20563","article-title":"Self-healing Characteristics of Collagen Coatings with Respect to Surface Abrasion","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108608","DOI":"10.1016\/j.matdes.2020.108608","article-title":"Anisotropy characteristics of microstructures for bone substitutes and porous implants with application of additive manufacturing in orthopaedic","volume":"191","author":"Kang","year":"2020","journal-title":"Mater. Des."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/cnm.2633","article-title":"A comparative study of orthotropic and isotropic bone adaptation in the femur","volume":"30","author":"Geraldes","year":"2014","journal-title":"Int. J. Numer. Methods Biomed. Eng."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1177\/0300985815593124","article-title":"Animal Models for Evaluation of Bone Implants and Devices: Comparative Bone Structure and Common Model Uses","volume":"52","author":"Wancket","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1359\/jbmr.2003.18.1.150","article-title":"The structural and hormonal basis of sex differences in peak appendicular bone strength in rats","volume":"18","author":"Kim","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.ajpath.2017.04.005","article-title":"Osteocyte Regulation of Receptor Activator of NF-kappaB Ligand\/Osteoprotegerin in a Sheep Model of Osteoporosis","volume":"187","author":"Merboth","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1679\/aohc1950.41.267","article-title":"Differential staining of collagens type I, II and III by Sirius Red and polarization microscopy","volume":"41","author":"Junqueira","year":"1978","journal-title":"Arch. Histol. Jpn."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"16007","DOI":"10.1117\/1.JBO.19.1.016007","article-title":"Computational segmentation of collagen fibers from second-harmonic generation images of breast cancer","volume":"19","author":"Bredfeldt","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/modpathol.2015.97","article-title":"Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis","volume":"28","author":"Drifka","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"20417314211047100","DOI":"10.1177\/20417314211047100","article-title":"Early osteoimmunomodulatory effects of magnesium-calcium-zinc alloys","volume":"12","author":"Rahmati","year":"2021","journal-title":"J. Tissue Eng."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3389\/fpsyg.2015.01171","article-title":"To transform or not to transform: Using generalized linear mixed models to analyse reaction time data","volume":"6","author":"Lo","year":"2015","journal-title":"Front. Psychol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:55:45Z","timestamp":1760169345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,29]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010374"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010374","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,29]]}}}