Hydrogels are suitable for osteochondral defect regeneration as they mimic the viscoelastic environment of cartilage. However, their biomechanical properties are not sufficient to withstand high mechanical forces. Therefore, we have prepared electrospun poly-ε-caprolactone-chitosan (PCL-chit) and poly(ethylene oxide)-chitosan (PEO-chit) nanofibers, and FTIR analysis confirmed successful blending of chitosan with other polymers. The biocompatibility of PCL-chit and PEO-chit scaffolds was tested; fibrochondrocytes and chondrocytes seeded on PCL-chit showed superior metabolic activity. The PCL-chit nanofibers were cryogenically grinded into microparticles (mean size of about 500 µm) and further modified by polyethylene glycol-biotin in order to bind the anti-CD44 antibody, a glycoprotein interacting with hyaluronic acid (PCL-chit-PEGb-antiCD44). The PCL-chit or PCL-chit-PEGb-antiCD44 microparticles were mixed with a composite gel (collagen/fibrin/platelet rich plasma) to improve its biomechanical properties. The storage modulus was higher in the composite gel with microparticles compared to fibrin. The Eloss of the composite gel and fibrin was higher than that of the composite gel with microparticles. The composite gel either with or without microparticles was further tested in vivo in a model of osteochondral defects in rabbits. PCL-chit-PEGb-antiCD44 significantly enhanced osteogenic regeneration, mainly by desmogenous ossification, but decreased chondrogenic differentiation in the defects. PCL-chit-PEGb showed a more homogeneous distribution of hyaline cartilage and enhanced hyaline cartilage differentiation.

Department of Organic Chemistry Faculty of Science Palacky University 17 listopadu 12 771 46 Olomouc Czech Republic

Department of Tissue Engineering Institute of Experimental Medicine of the Czech Academy of Science Videnska 1083 142 20 Prague 4 Czech Republic

Faculty of Textile Engineering Technical University of Liberec Studentská 2 461 17 Liberec Czech Republic

Hospital of Rudolfa and Stefanie a s Máchova 400 256 30 Benešov Czech Republic

Institute of Biophysics 2nd Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague 5 Czech Republic

Institute of Histology and Embryology and Biomedical Center Faculty of Medicine in Pilsen Charles University Prague Husova 3 305 06 Pilsen Czech Republic

Student Science s r o Národních Hrdinů 279 Dolní Počernice 190 12 Prague Czech Republic

Zobrazit více v PubMed

Buckwalter J.A., Mankin H.J. Instructional Course Lectures, the American Academy of Orthopaedic Surgeons-Articular Cartilage. Part I: Tissue Design and Chondrocyte-Matrix Interactions*†. Jbjs. 1997;79:600–611. doi: 10.2106/00004623-199704000-00021. PubMed DOI

Mithoefer K., Mcadams T., Williams R.J., Kreuz P.C., Mandelbaum B.R. Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee: An Evidence-Based Systematic Analysis. Am. J. Sports Med. 2009;37:2053–2063. doi: 10.1177/0363546508328414. PubMed DOI

Dewan A.K., Gibson M.A., Elisseeff J.H., Trice M.E. Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques. Biomed. Res. Int. 2014;2014:272481. doi: 10.1155/2014/272481. PubMed DOI PMC

Gille J., Behrens P., Schulz A.P., Oheim R., Kienast B. Matrix-Associated Autologous Chondrocyte Implantation: A Clinical Follow-Up at 15 Years. Cartilage. 2016;7:309–315. doi: 10.1177/1947603516638901. PubMed DOI PMC

Filová E., Rampichová M., Handl M., Lytvynets A., Halouzka R., Usvald D., Hlucilová J., Procházka R., Dezortová M., Rolencová E., et al. Composite Hyaluronate-Type I Collagen-Fibrin Scaffold in the Therapy of Osteochondral Defects in Miniature Pigs. Physiol. Res. 2007;56:5–16. PubMed

Sherwood J.K., Riley S.L., Palazzolo R., Brown S.C., Monkhouse D.C., Coates M., Griffith L.G., Landeen L.K., Ratcliffe A. A Three-Dimensional Osteochondral Composite Scaffold for Articular Cartilage Repair. Biomaterials. 2002;23:4739–4751. doi: 10.1016/S0142-9612(02)00223-5. PubMed DOI

Kandel R.A., Grynpas M., Pilliar R., Lee J., Wang J., Waldman S., Zalzal P., Hurtig M. Repair of Osteochondral Defects With Biphasic Cartilage-Calcium Polyphosphate Constructs in a Sheep Model. Biomaterials. 2006;27:4120–4131. doi: 10.1016/j.biomaterials.2006.03.005. PubMed DOI

Brocher J., Janicki P., Voltz P., Seebach E., Neumann E., Mueller-Ladner U., Richter W. Inferior Ectopic Bone Formation of Mesenchymal Stromal Cells from Adipose Tissue Compared to Bone Marrow: Rescue By Chondrogenic Pre-Induction. Stem Cell Res. 2013;11:1393–1406. doi: 10.1016/j.scr.2013.07.008. PubMed DOI

De Girolamo L., Niada S., Arrigoni E., Di Giancamillo A., Domeneghini C., Dadsetan M., Yaszemski M.J., Gastaldi D., Vena P., Taffetani M., et al. Repair of Osteochondral Defects in the Minipig Model By Opf Hydrogel Loaded with Adipose-Derived Mesenchymal Stem Cells. Regen Med. 2015;10:135–151. doi: 10.2217/rme.14.77. PubMed DOI

Hopper N., Wardale J., Brooks R., Power J., Rushton N., Henson F. Peripheral Blood Mononuclear Cells Enhance Cartilage Repair in In Vivo Osteochondral Defect Model. PLoS ONE. 2015;10:e0133937. doi: 10.1371/journal.pone.0133937. PubMed DOI PMC

Jurgens W.J.F.M., Kroeze R.J., Zandieh-Doulabi B., Dijk A.V., Renders G.A.P., Smit T.H., Milligen F.J.V., Ritt M.J.P.F., Helder M.N. One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study. Biores. Open Access. 2013;2:315–325. doi: 10.1089/biores.2013.0024. PubMed DOI PMC

Kim Y.S., Choi Y.J., Suh D.S., Heo D.B., Kim Y.I., Ryu J.-S., Koh Y.G. Mesenchymal Stem Cell Implantation in Osteoarthritic Knees: Is Fibrin Glue Effective as a Scaffold? Am. J. Sports Med. 2015;43:176–185. doi: 10.1177/0363546514554190. PubMed DOI

Filová E., Jelínek F., Handl M., Lytvynets A., Rampichová M., Varga F., Cinátl J., Soukup T., Trc T., Amler E. Novel Composite Hyaluronan/Type I Collagen/Fibrin Scaffold Enhances Repair of Osteochondral Defect in Rabbit Knee. J. Biomed. Mater. Res. B Appl. Biomater. 2008;87:415–424. doi: 10.1002/jbm.b.31119. PubMed DOI

Kayakabe M., Tsutsumi S., Watanabe H., Kato Y., Takagishi K. Transplantation of Autologous Rabbit Bm-Derived Mesenchymal Stromal Cells Embedded in Hyaluronic Acid Gel Sponge into Osteochondral Defects of the Knee. Cytotherapy. 2006;8:343–353. doi: 10.1080/14653240600845070. PubMed DOI

Prosecká E., Rampichová M., Litvinec A., Tonar Z., Králíčková M., Vojtová L., Kochová P., Plencner M., Buzgo M., Míčková A., et al. Collagen/Hydroxyapatite Scaffold Enriched with Polycaprolactone Nanofibers, Thrombocyte-Rich Solution and Mesenchymal Stem Cells Promotes Regeneration in Large Bone Defect In Vivo. J. Biomed. Mater. Res. A. 2015;103:671–682. doi: 10.1002/jbm.a.35216. PubMed DOI

Wang W., Sun L., Zhang P., Song J., Liu W. An Anti-Inflammatory Cell-Free Collagen/Resveratrol Scaffold for Repairing Osteochondral Defects in Rabbits. Acta Biomater. 2014;10:4983–4995. doi: 10.1016/j.actbio.2014.08.022. PubMed DOI

Filová E., Rampichová M., Litvinec A., Držík M., Míčková A., Buzgo M., Košťáková E., Martinová L., Usvald D., Prosecká E., et al. A Cell-Free Nanofiber Composite Scaffold Regenerated Osteochondral Defects in Miniature Pigs. Int. J. Pharm. 2013;447:139–149. doi: 10.1016/j.ijpharm.2013.02.056. PubMed DOI

Levingstone T.J., Ramesh A., Brady R.T., Brama P.A.J., Kearney C., Gleeson J.P., O’brien F.J. Cell-Free Multi-Layered Collagen-Based Scaffolds Demonstrate Layer Specific Regeneration of Functional Osteochondral Tissue in Caprine Joints. Biomaterials. 2016;87:69–81. doi: 10.1016/j.biomaterials.2016.02.006. PubMed DOI

Cremer M.A., Rosloniec E.F., Kang A.H. The Cartilage Collagens: A Review of Their Structure, Organization, and Role in the Pathogenesis of Experimental Arthritis in Animals and in Human Rheumatic Disease. Int. J. Mol. Med. 1998;76:275–288. doi: 10.1007/s001090050217. PubMed DOI

Van Susante J.L.C., Buma P., Schuman L., Homminga G.N., Van Den Berg W.B., Veth R.P.H. Resurfacing Potential of Heterologous Chondrocytes Suspended in Fibrin Glue in Large Full-Thickness Defects of Femoral Articular Cartilage: An Experimental Study in the Goat. Biomaterials. 1999;20:1167–1175. doi: 10.1016/S0142-9612(97)00190-7. PubMed DOI

Breinan H.A., Minas T., Hsu H.-P., Nehrer S., Shortkroff S., Spector M. Autologous Chondrocyte Implantation in a Canine Model: Change in Composition of Reparative Tissue with Time. J. Orthop. Res. 2001;19:482–492. doi: 10.1016/S0736-0266(00)90015-9. PubMed DOI

Jakubova R., Mickova A., Buzgo M., Rampichova M., Prosecka E., Tvrdik D., Amler E. Immobilization of Thrombocytes on Pcl Nanofibres Enhances Chondrocyte Proliferation In Vitro. Cell Prolif. 2011;44:183–191. doi: 10.1111/j.1365-2184.2011.00737.x. PubMed DOI PMC

Baenziger N.L., Brodie G.N., Majerus P.W. A Thrombin-Sensitive Protein of Human Platelet Membranes. Proc. Natl. Acad. Sci. USA. 1971;68:240–243. doi: 10.1073/pnas.68.1.240. PubMed DOI PMC

Filová E., Jakubcová B., Danilová I., Kuželová Košťáková E., Jarošíková T., Chernyavskiy O., Hejda J., Handl M., Beznoska J., Nečas A., et al. Polycaprolactone Foam Functionalized with Chitosan Microparticles—A Suitable Scaffold for Cartilage Regeneration. Physiol. Res. 2016;65:121–131. doi: 10.33549/physiolres.932998. PubMed DOI

Kuchařová M., Ďoubal S., Klemera P., Rejchrt P., Navrátil M. Viscoelasticity of Biological Materials—Measurement and Practical Impact on Biomedicine. Physiol. Res. 2007;56:S33–S37. PubMed

Kocová J. Overall Staining of Connective Tissue and the Muscular Layer of Vessels. Folia Morphol. (Praha) 1970;18:293–295. PubMed

Rieppo L., Janssen L., Rahunen K., Lehenkari P., Finnilä M.A.J., Saarakkala S. Histochemical Quantification of Collagen Content in Articular Cartilage. PLoS ONE. 2019;14:e0224839. doi: 10.1371/journal.pone.0224839. PubMed DOI PMC

Vermeulen A.H., Vermeer C., Bosman F.T. Histochemical Detection of Osteocalcin in Normal and Pathological Human Bone. J. Histochem. Cytochem. 1989;37:1503–1508. doi: 10.1177/37.10.2789247. PubMed DOI

Conklin J.L. Staining Properties of Hyaline Cartilage. Am. J. Anat. 1963;112:259–267. doi: 10.1002/aja.1001120209. PubMed DOI

Kiernan J.A. Histological and Histochemical Methods. Theory and Practice. 4th ed. Scion Publishing Ltd.; Banbury, UK: 2008. pp. 304–306.

Mouton P.R. Principles and Practices of Unbiased Stereology: An Introduction for Bioscientists. 1st ed. Johns Hopkins University Press; Baltimore, MD, USA: 2002.

Buzgo M., Greplová J., Soural M., Bezděková D., Míčková A., Kofroňová O., Benada O., Hlaváč J., Amler E. Pva Immunonanofibers with Controlled Decay. Polymer. 2015;77:387–398. doi: 10.1016/j.polymer.2015.09.018. DOI

Knotek P., Pouzar M., Buzgo M., Krizkova B., Vlcek M., Mickova A., Plencner M., Navesnik J., Amler E., Belina P. Cryogenic Grinding of Electrospun Poly-Ε-Caprolactone Mesh Submerged in Liquid Media. Mater. Sci. Eng. C. 2012;32:1366–1374. doi: 10.1016/j.msec.2012.04.012. PubMed DOI

Goldenberg D.M., Chang C.-H., Sharkey R.M., Rossi E.A., Karacay H., Mcbride W., Hansen H.J., Chatal J.-F., Barbet J. Radioimmunotherapy: Is Avidin-Biotin Pretargeting the Preferred Choice Among Pretargeting Methods? Eur. J. Nucl. Med. Mol. Imaging. 2003;30:777–780. doi: 10.1007/s00259-002-1089-6. PubMed DOI

Yang I.H., Kim S.H., Kim Y.H., Sun H.J., Kim S.J., Lee J.W. Comparison of Phenotypic Characterization Between “Alginate Bead” and “Pellet” Culture Systems as Chondrogenic Differentiation Models for Human Mesenchymal Stem Cells. Yonsei Med. J. 2004;45:891–900. doi: 10.3349/ymj.2004.45.5.891. PubMed DOI

Uchio Y., Ochi M., Matsusaki M., Kurioka H., Katsube K. Human Chondrocyte Proliferation and Matrix Synthesis Cultured in Atelocollagen® Gel. J. Biomed. Mater. Res. 2000;50:138–143. doi: 10.1002/(SICI)1097-4636(200005)50:2<138::AID-JBM7>3.0.CO;2-K. PubMed DOI

Bosnakovski D., Mizuno M., Kim G., Takagi S., Okumura M., Fujinaga T. Chondrogenic Differentiation of Bovine Bone Marrow Mesenchymal Stem Cells (Mscs) in Different Hydrogels: Influence of Collagen Type Ii Extracellular Matrix on Msc Chondrogenesis. Biotechnol. Bioeng. 2006;93:1152–1163. doi: 10.1002/bit.20828. PubMed DOI

Kim J., Cho H., Young K., Park J., Lee J., Suh D. In Vivo Animal Study and Clinical Outcomes of Autologous Atelocollagen-Induced Chondrogenesis for Osteochondral Lesion Treatment. J. Orthop. Surg. Res. 2015;10:82. doi: 10.1186/s13018-015-0212-x. PubMed DOI PMC

Ponticiello M.S., Schinagl R.M., Kadiyala S., Barry F.P. Gelatin-Based Resorbable Sponge as a Carrier Matrix for Human Mesenchymal Stem Cells in Cartilage Regeneration Therapy. J. Biomed. Mater. Res. 2000;52:246–255. doi: 10.1002/1097-4636(200011)52:2<246::AID-JBM2>3.0.CO;2-W. PubMed DOI

Ishida K., Kuroda R., Miwa M., Tabata Y., Hokugo A., Kawamoto T., Sasaki K., Doita M., Kurosaka M. The Regenerative Effects of Platelet-Rich Plasma on Meniscal Cells In Vitro and Its In Vivo Application with Biodegradable Gelatin Hydrogel. Tissue Eng. 2007;13:1103–1112. doi: 10.1089/ten.2006.0193. PubMed DOI

Fragonas E., Valente M., Pozzi-Mucelli M., Toffanin R., Rizzo R., Silvestri F., Vittur F. Articular Cartilage Repair in Rabbits by Using Suspensions of Allogenic Chondrocytes in Alginate. Biomaterials. 2000;21:795–801. doi: 10.1016/S0142-9612(99)00241-0. PubMed DOI

Hao T., Wen N., Cao J.K., Wang H.B., Lü S.H., Liu T., Lin Q.X., Duan C.M., Wang C.Y. The Support of Matrix Accumulation and the Promotion of Sheep Articular Cartilage Defects Repair In Vivo by Chitosan Hydrogels. Osteoarthr. Cartil. 2010;18:257–265. doi: 10.1016/j.joca.2009.08.007. PubMed DOI

Tan H., Chu C.R., Payne K.A., Marra K.G. Injectable In Situ Forming Biodegradable Chitosan–Hyaluronic Acid Based Hydrogels for Cartilage Tissue Engineering. Biomaterials. 2009;30:2499–2506. doi: 10.1016/j.biomaterials.2008.12.080. PubMed DOI PMC

Plánka L., Nečas A., Gál P., Kecová H., Filová E., Křen L., Krupa P. Prevention of Bone Bridge Formation Using Transplantation of the Autogenous Mesenchymal Stem Cells to Physeal Defects: An Experimental Study in Rabbits. Acta Vet. Brno. 2007;76:253–263. doi: 10.2754/avb200776020253. DOI

Moutos F.T., Freed L.E., Guilak F. A Biomimetic Three-Dimensional Woven Composite Scaffold for Functional Tissue Engineering of Cartilage. Nat. Mater. 2007;6:162. doi: 10.1038/nmat1822. PubMed DOI

Coburn J., Gibson M., Bandalini P.A., Laird C., Mao H.-Q., Moroni L., Seliktar D., Elisseeff J. Biomimetics of the Extracellular Matrix: An Integrated Three-Dimensional Fiber-Hydrogel Composite for Cartilage Tissue Engineering. Smart Struct. Syst. 2011;7:213–222. doi: 10.12989/sss.2011.7.3.213. PubMed DOI PMC

Rampichová M., Buzgo M., Křížková B., Prosecká E., Pouzar M., Štrajtová L. Injectable Hydrogel Functionalised with Thrombocyte-Rich Solution and Microparticles for Accelerated Cartilage Regeneration. Acta Chir. Orthop. Traumatol. Cechoslov. 2013;80:82–88. PubMed

Marijnissen W.J.C.M., Van Osch G.J.V.M., Aigner J., Van Der Veen S.W., Hollander A.P., Verwoerd-Verhoef H.L., Verhaar J.A.N. Alginate as a Chondrocyte-Delivery Substance in Combination with a Non-Woven Scaffold for Cartilage Tissue Engineering. Biomaterials. 2002;23:1511–1517. doi: 10.1016/S0142-9612(01)00281-2. PubMed DOI

Peniche C., Argüelles-Monal W., Peniche H., Acosta N. Chitosan: An Attractive Biocompatible Polymer for Microencapsulation. Macromol. Biosci. 2003;3:511–520. doi: 10.1002/mabi.200300019. DOI

Ohkawa K., Cha D., Kim H., Nishida A., Yamamoto H. Electrospinning of Chitosan. Macromol. Rapid Commun. 2004;25:1600–1605. doi: 10.1002/marc.200400253. DOI

Ohkawa K., Minato K., Kumagai G., Hayashi S., Yamamoto H. Chitosan Nanofiber. Biomacromolecules. 2006;7:3291–3294. doi: 10.1021/bm0604395. PubMed DOI

Yang D., Jin Y., Ma G., Chen X., Lu F., Nie J. Fabrication and Characterization of Chitosan/Pva with Hydroxyapatite Biocomposite Nanoscaffolds. J. Appl. Polym. Sci. 2008;110:3328–3335. doi: 10.1002/app.28829. DOI

Klossner R.R., Queen H.A., Coughlin A.J., Krause W.E. Correlation of Chitosan’s Rheological Properties and Its Ability to Electrospin. Biomacromolecules. 2008;9:2947–2953. doi: 10.1021/bm800738u. PubMed DOI

Kriegel C., Kit K.M., Mcclements D.J., Weiss J. Influence of Surfactant Type and Concentration on Electrospinning of Chitosan–Poly(Ethylene Oxide) Blend Nanofibers. Food Biophys. 2009;4:213–228. doi: 10.1007/s11483-009-9119-6. DOI

Zhang Y.Z., Su B., Ramakrishna S., Lim C.T. Chitosan Nanofibers from an Easily Electrospinnable Uhmwpeo-Doped Chitosan Solution System. Biomacromolecules. 2008;9:136–141. doi: 10.1021/bm701130e. PubMed DOI

Nirmala R., Navamathavan R., Kang H.-S., El-Newehy M.H., Kim H.Y. Preparation of Polyamide-6/Chitosan Composite Nanofibers by a Single Solvent System Via Electrospinning for Biomedical Applications. Colloid Surf. B. 2011;83:173–178. doi: 10.1016/j.colsurfb.2010.11.026. PubMed DOI

Yang M.R., Chen K.S., Tsai J.C., Tseng C.C., Lin S.F. The Antibacterial Activities of Hydrophilic-Modified Nonwoven Pet. Mater. Sci. Eng. C. 2002;20:167–173. doi: 10.1016/S0928-4931(02)00028-0. DOI

Chen H., Fan X., Xia J., Chen P., Zhou X., Huang J., Yu J., Gu P. Electrospun Chitosan-Graft-Poly (Ɛ-Caprolactone)/Poly(Ɛ-Caprolactone) Nanofibrous Scaffolds for Retinal Tissue Engineering. Int. J. Nanomed. 2011;6:453–461. PubMed PMC

Zivanovic S., Li J., Davidson P.M., Kit K. Physical, Mechanical, and Antibacterial Properties of Chitosan/Peo Blend Films. Biomacromolecules. 2007;8:1505–1510. doi: 10.1021/bm061140p. PubMed DOI

Zhou F.-L., Gong R.-H., Porat I. Mass Production of Nanofibre Assemblies by Electrostatic Spinning. Polym. Int. 2009;58:331–342. doi: 10.1002/pi.2521. DOI

Jin J., Song M., Hourston D.J. Novel Chitosan-Based Films Cross-Linked by Genipin with Improved Physical Properties. Biomacromolecules. 2004;5:162–168. doi: 10.1021/bm034286m. PubMed DOI

Van Der Schueren L., Steyaert I., De Schoenmaker B., De Clerck K. Polycaprolactone/Chitosan Blend Nanofibres Electrospun from an Acetic Acid/Formic Acid Solvent System. Carbohydr. Polym. 2012;88:1221–1226. doi: 10.1016/j.carbpol.2012.01.085. DOI

Noriega S.E., Hasanova G.I., Schneider M.J., Larsen G.F., Subramanian A. Effect of Fiber Diameter on the Spreading, Proliferation and Differentiation of Chondrocytes on Electrospun Chitosan Matrices. Cells Tissues Organs. 2012;195:207–221. doi: 10.1159/000325144. PubMed DOI PMC

Lukasova V., Buzgo M., Vocetkova K., Kubíková T., Tonar Z., Doupník M., Blahnová V., Litvinec A., Sovková V., Voltrová B., et al. Osteoinductive 3d Scaffolds Prepared by Blend Centrifugal Spinning for Long-Term Delivery of Osteogenic Supplements. Rsc Adv. 2018;8:21889–21904. PubMed PMC

Bolaina-Lorenzo E., Martínez-Ramos C., Monleón-Pradas M., Herrera-Kao W., Cauich-Rodríguez J.V., Cervantes-Uc J.M. Electrospun Polycaprolactone/Chitosan Scaffolds for Nerve Tissue Engineering: Physicochemical Characterization and Schwann Cell Biocompatibility. Biomed. Mater. 2016;12:015008. doi: 10.1088/1748-605X/12/1/015008. PubMed DOI

Schexnailder P.J., Gaharwar A.K., Bartlett Ii R.L., Seal B.L., Schmidt G. Tuning Cell Adhesion by Incorporation of Charged Silicate Nanoparticles as Cross-Linkers to Polyethylene Oxide. Macromol. Biosci. 2010;10:1416–1423. doi: 10.1002/mabi.201000053. PubMed DOI

Anamelechi C.C., Truskey G.A., Reichert W.M. Mylar™ and Teflon-Af™ as Cell Culture Substrates for Studying Endothelial Cell Adhesion. Biomaterials. 2005;26:6887–6896. doi: 10.1016/j.biomaterials.2005.04.027. PubMed DOI

Tsai W.B., Wang M.C. Effect of an Avidin-Biotin Binding System on Chondrocyte Adhesion, Growth and Gene Expression. Biomaterials. 2005;26:3141–3151. doi: 10.1016/j.biomaterials.2004.08.014. PubMed DOI

Tsai W.B., Wang M.C. Effects of an Avidin-Biotin Binding System on Chondrocyte Adhesion and Growth on Biodegradable Polymers. Macromol. Biosci. 2005;5:214–221. doi: 10.1002/mabi.200400144. PubMed DOI

Feng S., Yan Z., Guo C., Chen Z., Zhang K., Mo X., Gu Y. Effects of an Avidin-Biotin Binding System on Schwann Cells Attachment, Proliferation, and Gene Expressions onto Electrospun Scaffolds. J. Biomed. Mater. Res. A. 2011;97:321–329. doi: 10.1002/jbm.a.33063. PubMed DOI

Chow G., Nietfeld J.J., Knudson C.B., Knudson W. Antisense Inhibition of Chondrocyte Cd44 Expression Leading to Cartilage Chondrolysis. Arthritis Rheumatol. 1998;41:1411–1419. doi: 10.1002/1529-0131(199808)41:8<1411::AID-ART10>3.0.CO;2-Z. PubMed DOI

Knudson W., Casey B., Nishida Y., Eger W., Kuettner K.E., Knudson C.B. Hyaluronan Oligosaccharides Perturb Cartilage Matrix Homeostasis and Induce Chondrocytic Chondrolysis. Arthritis Rheumatol. 2000;43:1165–1174. doi: 10.1002/1529-0131(200005)43:5<1165::AID-ANR27>3.0.CO;2-H. PubMed DOI

Goodison S., Urquidi V., Tarin D. Cd44 Cell Adhesion Molecules. Mol. Pathol. 1999;52:189–196. doi: 10.1136/mp.52.4.189. PubMed DOI PMC

Thorne R.F., Legg J.W., Isacke C.M. The Role of the Cd44 Transmembrane and Cytoplasmic Domains in Co-Ordinating Adhesive and Signalling Events. J. Cell Sci. 2004;117:373. doi: 10.1242/jcs.00954. PubMed DOI

Zhu H., Mitsuhashi N., Klein A., Barsky L.W., Weinberg K., Barr M.L., Demetriou A., Wu G.D. The Role of the Hyaluronan Receptor Cd44 in Mesenchymal Stem Cell Migration in the Extracellular Matrix. Stem Cells. 2006;24:928–935. doi: 10.1634/stemcells.2005-0186. PubMed DOI

Julovi S.M., Ito H., Nishitani K., Jackson C.J., Nakamura T. Hyaluronan Inhibits Matrix Metalloproteinase-13 in Human Arthritic Chondrocytes Via Cd44 and P38. Joredr. 2011;29:258–264. doi: 10.1002/jor.21216. PubMed DOI

Yatabe T., Mochizuki S., Takizawa M., Chijiiwa M., Okada A., Kimura T., Fujita Y., Matsumoto H., Toyama Y., Okada Y. Hyaluronan Inhibits Expression of Adamts4 (Aggrecanase-1) in Human Osteoarthritic Chondrocytes. Ann. Rheum. Dis. 2009;68:1051–1058. doi: 10.1136/ard.2007.086884. PubMed DOI PMC

Galandrini R., Galluzzo E., Albi N., Grossi C.E., Velardi A. Hyaluronate Is Costimulatory for Human T Cell Effector Functions and Binds to Cd44 on Activated T Cells. J. Immunol. 1994;153:21–31. PubMed

Ye X., Zhao Q., Sun X., Li H. Enhancement of Mesenchymal Stem Cell Attachment to Decellularized Porcine Aortic Valve Scaffold by In Vitro Coating with Antibody against Cd90: A Preliminary Study on Antibody-Modified Tissue-Engineered Heart Valve. Tissue Eng. Part A. 2009;15:1–11. doi: 10.1089/ten.tea.2008.0001. PubMed DOI

Yanada S., Ochi M., Adachi N., Nobuto H., Agung M., Kawamata S. Effects of Cd44 Antibody-- or Rgds Peptide--Immobilized Magnetic Beads on Cell Proliferation and Chondrogenesis of Mesenchymal Stem Cells. J. Biomed. Mater. Res. A. 2006;77:773–784. doi: 10.1002/jbm.a.30635. PubMed DOI

Lin H., Zhou J., Shen L., Ruan Y., Dong J., Guo C., Chen Z. Biotin-Conjugated Anti-Cd44 Antibody-Avidin Binding System for the Improvement of Chondrocyte Adhesion to Scaffolds. J. Biomed. Mater. Res. A. 2014;102:1140–1148. doi: 10.1002/jbm.a.34770. PubMed DOI

Jalani G., Rosenzweig D.H., Makhoul G., Abdalla S., Cecere R., Vetrone F., Haglund L., Cerruti M. Tough, In-Situ Thermogelling, Injectable Hydrogels for Biomedical Applications. Macromol. Biosci. 2015;15:473–480. doi: 10.1002/mabi.201400406. PubMed DOI

Wang W., Li B., Yang J., Xin L., Li Y., Yin H., Qi Y., Jiang Y., Ouyang H., Gao C. The Restoration of Full-Thickness Cartilage Defects with Bmscs and Tgf-Beta 1 Loaded Plga/Fibrin Gel Constructs. Biomaterials. 2010;31:8964–8973. doi: 10.1016/j.biomaterials.2010.08.018. PubMed DOI

Almeida H.V., Eswaramoorthy R., Cunniffe G.M., Buckley C.T., O’brien F.J., Kelly D.J. Fibrin Hydrogels Functionalized with Cartilage Extracellular Matrix and Incorporating Freshly Isolated Stromal Cells as an Injectable for Cartilage Regeneration. Acta Biomater. 2016;36:55–62. doi: 10.1016/j.actbio.2016.03.008. PubMed DOI

Mccarrel T., Fortier L. Temporal Growth Factor Release from Platelet-Rich Plasma, Trehalose Lyophilized Platelets, and Bone Marrow Aspirate and Their Effect on Tendon and Ligament Gene Expression. J. Orthop. Res. 2009;27:1033–1042. doi: 10.1002/jor.20853. PubMed DOI

Lukášová V., Buzgo M., Vocetková K., Sovková V., Doupník M., Himawanf E., Staffa A., Sedláček R., Chlup H., Rustichelli F., et al. Needleless Electrospun and Centrifugal Spun Poly-Ε-Caprolactone Scaffolds as a Carrier for Platelets in Tissue Engineering Applications: A Comparative Study with Hmscs. Mater. Sci. Eng. C. 2019;97:567–575. doi: 10.1016/j.msec.2018.12.069. PubMed DOI

Camargo P.M., Lekovic V., Weinlaender M., Vasilic N., Madzarevic M., Kenney E.B. Platelet-Rich Plasma and Bovine Porous Bone Mineral Combined with Guided Tissue Regeneration in the Treatment of Intrabony Defects in Humans. J. Periodontal Res. 2002;37:300–306. doi: 10.1034/j.1600-0765.2002.01001.x. PubMed DOI

Kon E., Mandelbaum B., Buda R., Filardo G., Delcogliano M., Timoncini A., Fornasari P.M., Giannini S., Marcacci M. Platelet-Rich Plasma Intra-Articular Injection Versus Hyaluronic Acid Viscosupplementation as Treatments for Cartilage Pathology: From Early Degeneration to Osteoarthritis. Arthroscopy. 2011;27:1490–1501. doi: 10.1016/j.arthro.2011.05.011. PubMed DOI

Yausep O.E., Madhi I., Trigkilidas D. Platelet Rich Plasma for Treatment of osteochondral Lesions of the Talus: A Systematic Review of Clinical Trials. J. Orthop. 2020;18:218–225. doi: 10.1016/j.jor.2020.01.046. PubMed DOI PMC

Fortier L.A., Hackett C.H., Cole B.J. The Effects of Platelet-Rich Plasma on Cartilage: Basic Science and Clinical Application. Oper. Tech. Sports Med. 2011;19:154–159. doi: 10.1053/j.otsm.2011.03.004. DOI

Chanda M., Roy S. Plastics Technology Handbook. 4th ed. Crc Press; Boca Raton, FL, USA: 2007. pp. 3–28.

Babrnáková J., Pavliňáková V., Brtníková J., Sedláček P., Prosecká E., Rampichová M., Filová E., Hearnden V., Vojtová L. Synergistic Effect of Bovine Platelet Lysate and Various Polysaccharides on the Biological Properties of Collagen-Based Scaffolds for Tissue Engineering: Scaffold Preparation, Chemo-Physical Characterization, In Vitro and Ex Ovo Evaluation. Mater. Sci. Eng. C. 2019;100:236–246. doi: 10.1016/j.msec.2019.02.092. PubMed DOI

He X., Fan X., Feng W., Chen Y., Guo T., Wang F., Liu J., Tang K. Incorporation of Microfibrillated Cellulose into Collagen-Hydroxyapatite Scaffold for Bone Tissue Engineering. Int. J. Biol. Macromol. 2018;115:385–392. doi: 10.1016/j.ijbiomac.2018.04.085. PubMed DOI

Mckee M.D., Cole W.G. Chapter 2—Bone Matrix and Mineralization. In: Glorieux F.H., Pettifor J.M., Jüppner H., editors. Pediatric Bone. 2nd ed. Academic Press; San Diego, CA, USA: 2012. pp. 9–37.

Price P.A., Otsuka A.A., Poser J.W., Kristaponis J., Raman N. Characterization of a Gamma-Carboxyglutamic Acid-Containing Protein from Bone. Proc. Natl. Acad. Sci. USA. 1976;73:1447–1451. doi: 10.1073/pnas.73.5.1447. PubMed DOI PMC

Eastell R., Hannon R.A. Chapter 27—Biochemical Markers of Bone Turnover. In: Lobo R.A., editor. Treatment of the Postmenopausal Woman. 3rd ed. Academic Press; St. Louis, MO, USA: 2007. pp. 337–349.

Sovkova V., Vocetkova K., Rampichova M., Mickova A., Buzgo M., Lukasova V., Dankova J., Filova E., Necas A., Amler E. Platelet Lysate as a Serum Replacement for Skin Cell Culture on Biomimetic Pcl Nanofibers. Platelets. 2018;29:395–405. doi: 10.1080/09537104.2017.1316838. PubMed DOI

Sarban S., Tabur H., Baba Z.F., Işıkan U.E. The Positive Impact of Platelet-Derived Growth Factor on the Repair of Full-Thickness Defects of Articular Cartilage. Eklem Hast. Cerrahisi. 2019;30:91–96. doi: 10.5606/ehc.2019.64018. PubMed DOI

Huang R.Y., Tai W.C., Ho M.H., Chang P.C. Combination of a Biomolecule-Aided Biphasic Cryogel Scaffold with a Barrier Membrane Adhering Pdgf-Encapsulated Nanofibers to Promote Periodontal Regeneration. J. Periodontal Res. 2020 doi: 10.1111/jre.12740. PubMed DOI

Wang S., Li Y., Li S., Yang J., Tang R., Li X., Li L., Fei J. Platelet-Rich Plasma Loaded with Antibiotics as an Affiliated Treatment for Infected Bone Defect by Combining Wound Healing Property and Antibacterial Activity. Platelets. 2020:1–13. doi: 10.1080/09537104.2020.1759792. PubMed DOI

Rampichová M., Buzgo M., Míčková A., Vocetková K., Sovková V., Lukášová V., Filová E., Rustichelli F., Amler E. Platelet-Functionalized Three-Dimensional Poly-Ε-Caprolactone Fibrous Scaffold Prepared Using Centrifugal Spinning for Delivery of Growth Factors. Int. J. Nanomed. 2017;12:347–361. doi: 10.2147/IJN.S120206. PubMed DOI PMC

Xie X., Wang Y., Zhao C., Guo S., Liu S., Jia W., Tuan R.S., Zhang C. Comparative Evaluation of Mscs from Bone Marrow and Adipose Tissue Seeded in Prp-Derived Scaffold for Cartilage Regeneration. Biomaterials. 2012;33:7008–7018. doi: 10.1016/j.biomaterials.2012.06.058. PubMed DOI

Shimizu Y., Van Seventer G.A., Siraganian R., Wahl L., Shaw S. Dual Role of the Cd44 Molecule in T Cell Adhesion and Activation. J. Immunol. 1989;143:2457–2463. PubMed

Krishnan V., Bryant H.U., Macdougald O.A. Regulation of Bone Mass by Wnt Signaling. J. Clin. Investig. 2006;116:1202–1209. doi: 10.1172/JCI28551. PubMed DOI PMC

Majidinia M., Sadeghpour A., Yousefi B. The Roles of Signaling Pathways in Bone Repair and Regeneration. J. Cell. Physiol. 2018;233:2937–2948. doi: 10.1002/jcp.26042. PubMed DOI

El Bialy I., Jiskoot W., Reza Nejadnik M. Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration. Pharm. Res. 2017;34:1152–1170. doi: 10.1007/s11095-017-2147-x. PubMed DOI PMC

Zheng A.Q., Xiao J., Xie J., Lu P.P., Ding X.I.A.E.P. Bfgf Enhances Activation of Osteoblast Differentiation and Osteogenesis on Titanium Surfaces Via Pi3k/Akt Signaling Pathway. Int. J. Clin. Exp. Pathol. 2016;9:4680–4692.

Feng X., Huang D., Lu X., Feng G., Xing J., Lu J., Xu K., Xia W., Meng Y., Tao T., et al. Insulin-Like Growth Factor 1 Can Promote Proliferation and Osteogenic Differentiation of Human Dental Pulp Stem Cells Via Mtor Pathway. Dev. Growth Differ. 2014;56:615–624. doi: 10.1111/dgd.12179. PubMed DOI

Autologous Mesenchymal Stromal Cells Immobilized in Plasma-Based Hydrogel for the Repair of Articular Cartilage Defects in a Large Animal Model

Advances in Electrospun Hybrid Nanofibers for Biomedical Applications