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New-generation osteoplastic materials based on biological and synthetic matrices

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Objectives. The purpose of this analytical review is to evaluate the market for osteoplastic materials and surgical implants, as well as study the features of new-generation materials and the results of clinical applications.

Methods. This review summarizes the volumes of research articles presented in the electronic database PubMed and eLIBRARY. A total of 129 scientific articles related to biological systems, calcium phosphate, polymer, and biocomposite matrices as carriers of pharmaceutical substances, primary recombinant protein osteoinductors, antibiotics, and biologically active chemical reagents were analyzed and summarized. The search depth was 10 years.

Results. Demineralized bone matrix constitutes 26% of all types of osteoplastic matrices used globally in surgical osteology, which includes neurosurgery, traumatology and orthopedics, dentistry, and maxillofacial and pediatric surgery. Among the matrices, polymer and biocomposite matrices are outstanding. Special attention is paid to the possibility of immobilizing osteogenic factors and target pharmaceutical substances on the scaffold material to achieve controlled and prolonged release at the site of surgical implantation. Polymeric and biocomposite materials can retard the release of pharmaceutical substances at the implantation site, promoting a decrease in the toxicity and an improvement in the therapeutic effect. The use of composite scaffolds of different compositions in vivo results in high osteogenesis, promotes the initialization of biomineralization, and enables the tuning of the degradation rate of the material.

Conclusions. Osteoplastic materials of various compositions in combination with drugs showed accelerated regeneration and mineralization of bone tissue in vivo, excluding systemic side reactions. Furthermore, although some materials have already been registered as commercial drugs, a plethora of unresolved problems remain. Due to the limited clinical studies of materials for use on humans, there is still an insufficient understanding of the toxicity of materials, time of their resorption, speed of drug delivery, and the possible long-term adverse effects of using implants of different compositions.

About the Authors

D. D. Lykoshin
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Dmitry D. Lykoshin, Engineer, Laboratory of Biopharmaceutical Technologies. Scopus Author ID 57219992166, ResearcherID AAB-1166-2021

16/10, Miklukho-Maklaya ul., Moscow, 117997

V. V. Zaitsev
N.N. Priorov National Medical Research Center of Traumatology and Orthopedics, Ministry of Health of the Russian Federation
Russian Federation

Vladimir V. Zaitsev, Cand. Sci. (Med.), Leading Researcher, Team Leader of osteoplastic materials. Scopus Author ID 56648236900, ResearcherID AAI-4110-2020

10, Priorova ul., Moscow, 127299

M. A. Kostromina
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Maria A. Kostromina, Junior Researcher, Laboratory of Biopharmaceutical Technologies. Scopus Author ID 55123242300 ResearcherID R-9418-2016

16/10, Miklukho-Maklaya ul., Moscow, 117997

R. S. Esipov
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Roman S. Esipov, Dr. Sci. (Chem.), Senior Reseacher, Laboratory of Biopharmaceutical Technologies. Scopus Author ID 6701850033, Researcher ID G-4950-2017

16/10, Miklukho-Maklaya ul., Moscow, 117997


1. Henkel J., Woodruff M.A., Epari D.R., Steck R., Glatt V., Dickinson I.C., Choong P.F., Schuetz M.A., Hutmacher D.W. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective Bone Res. 2013;1(3):216–248.

2. Barabaschi G.D., Manoharan V., Li Q., Bertassoni L.E. Engineering Pre-vascularized Scaffolds for Bone Regeneration. Adv. Exp. Med. Biol. 2015;881:79–94.

3. O’Brien F.J. Biomaterials & scaffolds for tissue engineering. Mat. Today. 2011;14(3):88–95.

4. García-Gareta E., Coathup M.J., Blunn G.W. Osteoinduction of bone grafting materials for bone repair and regeneration. Bone. 2015; 81:112–121.

5. Vorobyоv K.A., Bozhkova S.A., Tikhilov R.M., Cherny A.Zh. Current methods of processing and sterilization of bone allografts (review of literature). Travmatologiya i ortopediya Rossii = Traumatology and Orthopedics of Russia. 2017;23(3):134–147 (in Russ.).

6. Baldwin P., Li D.J., Auston D.A., Mir H.S., Yoon R.S., Koval K.J. Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. J. Orthop. Trauma. 2019;33(4):203–213.

7. Islam A., Chapin K., Moore E., Ford J., Rimnac C., Akkus O. Gamma Radiation Sterilization Reduces the Highcycle Fatigue Life of Allograft Bone. Clin. Orthop. Relat. Res. 2016;474(3):827–835.

8. Zamborsky R., Svec A., Bohac M., Kilian M., Kokavec M. Infection in Bone Allograft Transplants. Exp. Clin. Transplant. 2016;14(5):484–490.

9. Reddi A.H., Iwasa K. Morphogenesis, Bone Morphogenetic Proteins, and Regeneration of Bone and Articular Cartilage. In: Principles of Regenerative Medicine (Third Edition). Academic Press; 2019. Chapter 25. P. 405–416.

10. Boerckel J.D., Kolambkar Y.M., Dupont K.M., Uhrig B.A., Phelps E.A., Stevens H.Y., García A.J., Guldberg R.E. Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials. 2011;32(22):5241–5251.

11. Damlar I., Erdoğan Ö., Tatli U., Arpağ O.F., Görmez U., Üstün Y. Comparison of osteoconductive properties of three different β-tricalcium phosphate graft materials: a pilot histomorphometric study in a pig model. J. Craniomaxillofac. Surg. 2015;43(1):175–180.

12. Tite T., Popa A.C., Balescu L.M., Bogdan I.M., Pasuk I., Ferreira J., Stan G.E. Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods. Materials. 2018;11(11):2081.

13. Basirun W.J., Nasiri-Tabrizi B., Baradaran S. Overview of Hydroxyapatite–Graphene Nanoplatelets Composite as Bone Graft Substitute: Mechanical Behavior and In-vitro Biofunctionality. Critical reviews in solid state and material sciences. 2018;43(3):177–212.

14. Sheikh Z., Abdallah M.N., Hanafi A.A., Misbahuddin S., Rashid H., Glogauer M. Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials. Materials. 2015;8(11):7913–7925.

15. Raynaud S., Champion E., Bernache-Assollant D., Thomas P. Calcium phosphate apatites with variable Ca/P atomic ratio I. Synthesis, characterisation and thermal stability of powders. Biomaterials. 2002;23(4):1065–1072.

16. Bose S., Tarafder S. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review. Acta Biomater. 2012;8(4):1401-1421.

17. Parsamehr P.S., Zahed M., Tofighy M.A., Mohammadi T., Rezakazemi M. Preparation of novel cross-linked graphene oxide membrane for desalination applications using (EDC and NHS)-activated graphene oxide and PEI. Desalination. 2019;418(15):114079.

18. Poddar S., Agarwal P.S., Sahi A.K., Vajanthri K.Y., Pallawi Singh K.N., Mahto S.K. Fabrication and Cytocompatibility Evaluation of Psyllium Husk (Isabgol)/Gelatin Composite Scaffolds. Appl. Biochem. Biotechnol. 2019;188(3):750–768.

19. Nam K., Kimura T., Funamoto S., Kishida A. Preparation of a collagen/polymer hybrid gel designed for tissue membranes. Part I: Controlling the polymer-collagen cross-linking process using an ethanol/water co-solvent. Acta Biomater. 2010;6(2):403–408.

20. Teixeira S., Yang L., Dijkstra P.J., Ferraz M.P., Monteiro F.J. Heparinized hydroxyapatite/collagen three-dimensional scaffolds for tissue engineering. J. Mater. Sci. Mater. Med. 2010;21(8):2385–2392.

21. Hernigou P., Dubory A., Pariat J., Potage D., Roubineau F., Jammal S., Flouzat Lachaniette C.H. Beta-tricalcium phosphate for orthopedic reconstructions as an alternative to autogenous bone graft. Morphologie. 2017;101(334):173–179.

22. Owen G.Rh., Dard M., Larjava H. Hydoxyapatite/ beta-tricalcium phosphate biphasic ceramics as regenerative material for the repair of complex bone defects. J. Biomed. Mater. Res. B Appl. Biomater. 2018;106(6):2493–2512.

23. Zhang L., Zhang Ch., Zhang R., Jiang D., Zhu Q., Wang S. Extraction and characterization of HA/β-TCP biphasic calcium phosphate from marine fish. Mat. Letters. 2019;236(1):680–682.

24. Tanaka T., Komaki H., Chazono M., Kitasato S., Kakuta A., Akiyama S., Marumo K. Basic research and clinical application of beta-tricalcium phosphate (β-TCP). Morphologie. 2017;101(334):164–172.

25. Shishido A., Yokogawa Y. TEM Observation of Heat-Treated β-Tricalcium Phosphate Powder and its Precursor Obtained by Mechanochemical Reaction. Key Eng. Mat. 2017;758:184–188.

26. Wen J., Kim I.Y., Kikuta K., Ohtsuki C. Optimization of Sintering Conditions for Improvement of Mechanical Property of a-Tricalcium Phosphate Blocks. Glob. J. Biotechnol. Biomater. Sci. 2016;1(1):010–016.

27. Zhang E., Yang L., Xu J., Chen H. Microstructure, mechanical properties and bio-corrosion properties of Mg–Si(–Ca, Zn) alloy for biomedical application. Acta Biomater. 2010;6(5):1756–1762.

28. Chou J., Hao J., Kuroda S., Bishop D., Ben-Nissan B., Milthorpe B., Otsuka M. Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP) Synthesized from Porous Foraminifera Carbonate Macrospheres. Mar. Drugs. 2013;11(12):5148–5158.

29. Hirota M., Hayakawa T., Shima T., Ametani A., Tohnai I. High porous titanium scaffolds showed higher compatibility than lower porous beta-tricalcium phosphate scaffolds for regulating human osteoblast and osteoclast differentiation. Mater. Sci. Eng. C.: Mate. Biol. Appl. 2015;49:623–631.

30. Kaur G., Pandey O.P., Singh K., Homa D., Scott B., Pickrell G. A review of bioactive glasses: Their structure, properties, fabrication and apatite formation. J. Biomed. Mater. Res. A. 2014;102(1):254–274.

31. Fiume E., Barberi J., Verné E., Baino F. Bioactive Glasses: From Parent 45S5 Composition to Scaffold-Assisted Tissue-Healing Therapies. J. Funct. Biomater. 2018;9(1):24.

32. Dittler M.L., Unalan I., Grünewald A., Beltrán A.M., Grillo C.A., Destch R., Gonzalez M.C., Boccaccini A.R. Bioactive glass (45S5)-based 3D scaffolds coated with magnesium and zinc-loaded hydroxyapatite nanoparticles for tissue engineering applications. Colloids. Surf. B: Biointerfaces. 2019;182:110346.

33. Ferraris S, Yamaguchi S, Barbani N, Cazzola M., Cristallini C., Miola M., Vernè E., Spriano S. Bioactive materials: In vitro investigation of different mechanisms of hydroxyapatite precipitation. Acta Biomater. 2020;102:468–480.

34. O’Donnell M.D. Melt‐Derived Bioactive Glass. In: Bio-glasses: An introduction. New Jersey, USA: John Wiley & Sons; 2012. P. 13–28.

35. Höland W., Beall G. H. Glass-Ceramics. In: Handbook of Advanced Ceramics: Materials, Applications, Processing and Properties. New York, USA: Academic Press; 2013. Chapter 5.1. P. 371–381.

36. Nandi S.K., Mahato A., Kundu B., Mukherjee P. Doped Bioactive Glass Materials in Bone Regeneration. In: Advanced Techniques in Bone Regeneration. Norderstedt, Germany: BoD – Books on Demand; 2016. P. 275–328.

37. Zhang X., Zeng D., Li N., Wen J., Jiang X., Liu C., Li Y. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration. Sci Rep. 2016;6:19361.

38. El-Rashidy A.A., Roether J.A., Harhaus L., Kneser U., Boccaccini A.R. Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models. Acta Biomater. 2017;62:1–28.

39. Bossard C., Granel H., Wittrant Y., Jallot É., Lao J., Vial C., Tiainen H. Polycaprolactone/bioactive glass hybrid scaffolds for bone regeneration. Biomed. Glasses. 2018;4(1):108–122.

40. Ding Y., Souza M.T., Li W., Schubert D.W., Boccaccini A.R., Roether J.A. Bioactive Glass-Biopolymer Composites for Applications in Tissue Engineering. In: Handbook of Bioceramics and Biocomposites. Switzerland: Springer International Publishing; 2016. Р. 325–356.

41. Meretoja V.V., Tirri T., Malin M., Seppälä J.V., Närhi T.O. Ectopic bone formation in and soft-tissue response to P(CL/DLLA)/bioactive glass composite scaffolds. Clin. Oral. Implants Res. 2014;25(2):159–164.

42. Iqbal N., Khan A.S., Asif A., Yar M., Haycock J.W., Rehman I.U. Recent concepts in biodegradable polymers for tissue engineering paradigms: A critical review. International Materials Reviews. 2018. 64(2):91–126.

43. Shen Y., Tu T., Yi B., Wang X., Tang H., Liu W., Zhang Y. Electrospun acid-neutralizing fibers for the amelioration of inflammatory response. Acta Biomater. 2019;97:200–215.

44. Luo H., Xiong G., Li Q., Ma C., Zhu Y., Guo R. Preparation and properties of a novel porous poly(lactic acid) composite reinforced with bacterial cellulose nanowhiskers. Fibers and Polym. 2014;15(12):2591–2596.

45. Gentile P., Chiono V., Carmagnola I., Hatton P. V. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)Based Biomaterials for Bone Tissue Engineering. Int. J. Mol. Sci. 2014;15(3):3640–3659.

46. Elmowafy E.M., Tiboni M., Soliman M.E. Biocompatibility, biodegradation and biomedical applications of poly (lactic acid)/poly (lactic-co-glycolic acid) micro and nanoparticles. J. Pharm. Investig. 2019;49:347–380.

47. Anderson J.M, Shive M.S. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv. Drug Deliv. Rev. 2012;64:72–82.

48. Yang F., Wang J., Hou J., Guo H., Liu C. Bone regeneration using cell-mediated responsive degradable PEG-based scaffolds incorporating with rhBMP-2. Biomaterials. 2013;34(5):1514–1528.

49. Ni P., Ding Q., Fan M., Liao J., Qian Z., Luo J. Injectable thermosensitive PEG-PCL-PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects. Biomaterials. 2014;35(1):236–248.

50. Dorati R., DeTrizio A., Modena T., Conti B., Benazzo F., Gastaldi G. Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy. Pharmaceuticals (Basel). 2017;10(4):96.

51. Buyuksungur S., Endogan Tanir T., Buyuksungur A., Bektas E.I., Torun Kose G., Yucel D. 3D printed poly(ε-caprolactone) scaffolds modified with hydroxyapatite and poly(propylene fumarate) and their effects on the healing of rabbit femur defects. Biomater Sci. 2017;5(10):2144-2158.

52. Volkmer E., Leicht U., Moritz M., Schwarz C., Wiese H., Milz S. Poloxamer-based hydrogels hardening at body core temperature as carriers for cell based therapies: in vitro and in vivo analysis. J. Mater. Sci. Mater. Med. 2013;24(9):2223-2234.

53. Amiryaghoubi N., Fathi M., Pesyan N.N., Samiei M., Barar J., Omidi Y. Bioactive polymeric scaffolds for osteogenic repair and bone regenerative medicine. Med. Res. Rev. 2020;40(5):1833–1870.

54. Eğri S., Eczacıoğlu N. Sequential VEGF and BMP-2 releasing PLA-PEG-PLA scaffolds for bone tissue engineering: I. Design and in vitro tests. Artif. Cells. Nanomed. Biotechnol. 2017;45(2):321–329.

55. Schliephake H., Weich H., Dullin C., Gruber R., Frahse S. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid—An experimental study in rats. Biomaterials. 2008;29(1):103–110.

56. Facca S., Ferrand A., Mendoza-Palomares C., PerrinSchmitt F., Netter P., Mainard D. Bone Formation Induced by Growth Factors Embedded into the Nanostructured Particles. J. Biomed. Nanotechnol. 2011;7(3):482–485.

57. Wink J.D., Gerety P.A., Sherif R.D., Lim Y., Clarke N.A., Rajapakse C.S. Sustained Delivery of rhBMP-2 by Means of Poly(Lactic-co-Glycolic Acid) Microspheres: Cranial Bone Regeneration without Heterotopic Ossification or Craniosynostosis. Plast. Reconstr. Surg. 2014;134(1):51–59.

58. Machatschek R., Schulz B., Lendlein A. The influence of pH on the molecular degradation mechanism of PLGA. MRS Advances. 2018;3(63):3883–3889.

59. Liu Y., Ghassemi A.H., Hennink W.E., Schwendeman S.P. The microclimate pH in poly(D,Llactide-co-hydroxymethyl glycolide) microspheres during biodegradation. Biomaterials. 2012;33(30):7584–7593.

60. Hines D.J., Kaplan D.L. Poly(lactic-co-glycolic) AcidControlled-Release Systems: Experimental and Modeling Insights. Crit. Rev. Ther. Drug Carrier. Syst. 2013;30(3):257–276.

61. Kutikov A.B., Song J. Biodegradable PEG-Based Amphiphilic Block Copolymers for Tissue Engineering Applications. ACS Biomater. Sci. Eng. 2015;1(7):463–480.

62. Pan H., Zheng Q., Guo X., Wu Y., Wu B. Polydopamineassisted BMP-2-derived peptides immobilization on biomimetic copolymer scaffold for enhanced bone induction in vitro and in vivo. Colloids Surf. B Biointerfaces. 2016;142:1–9.

63. Majchrowicz A., Roguska A., Krawczyńska A., Lewandowska M., Martí-Muñoz J., Engel E. In vitro evaluation of degradable electrospun polylactic acid/bioactive calcium phosphate ormoglass scaffolds. Archiv. Civ. Mech. Eng. 2020;20:1–11.

64. Amini A.R., Laurencin C.T., Nukavarapu S.P. Bone Tissue Engineering: Recent Advances and Challenges. Crit. Rev. Biomed. Eng. 2012;40(5):363–408.

65. Park S.H., Park S.A., Kang Y.G., Shin J.W., Park Y.S., Gu S.R. PCL/β-TCP Composite Scaffolds Exhibit Positive Osteogenic Differentiation with Mechanical Stimulation. Tissue Eng. Regen Med. 2017;14(4):349–358.

66. Shin D.Y., Kang M.H., Kang I.G., Kim H.E., Jeong S.H. In vitro and in vivo evaluation of polylactic acidbased composite with tricalcium phosphate microsphere for enhanced biodegradability and osseointegration. J. Biomater. Appl. 2018;32(10):1360–1370.

67. Wang Y., Zhao Q., Han N., Bai L., Li J., Liu J., Che E., Hu L., Zhang Q., Jiang T., Wang S. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine. 2015;11(2):313–327.

68. Cheng H., Chawla A., Yang Y., Li Y., Zhang J., Jang H.L., Khademhosseini A. Development of nanomaterials for bonetargeted drug delivery. Drug Discov. Today. 2017;22(9):1336-1350.

69. Zhou Y., Quan G., Wu Q., Zhang X., Niu B., Wu B., Huang Y., Pan X., Wu C. Mesoporous silica nanoparticles for drug and gene delivery. Acta Pharm. Sin. B. 2017;8(2):165–177.

70. Vallet-Regí M. Ordered Mesoporous Materials in the Context of Drug Delivery Systems and Bone Tissue Engineering. Chemistry. 2006;12(23):5934–5943.

71. Ma M., Zheng S., Chen H., Yao M., Zhang K., Jia X., Mou J., Xu H.,Wu R., Shi J. A combined “RAFT” and “Graft From” polymerization strategy for surface modification of mesoporous silica nanoparticles: towards enhanced tumor accumulation and cancer therapy efficacy. J. Mater. Chem. B. 2014;2(35):5828–5836.

72. Motealleh A., Kehr N. S. Nanocomposite Hydrogels and Their Applications in Tissue Engineering. Adv. Healthc. Mater. 2017;6(1):10.1002/adhm.201600938.

73. Xin T., Mao J., Liu L., Tang J., Wu L., Yu X., Gu Y., Cui W., Chen L. Programmed Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 and Inorganic Ion Composite Hydrogel as Artificial Periosteum. ACS Appl. Mater. Interfaces. 2020;12(6):6840–6851.

74. Zhang D., Liu X., Wu G. Forming CNT-guided stereocomplex networks in polylactide-based nanocomposites. Compos. Sci. Technol. 2016;128:8–16.

75. Kumar S.K., Jouault N., Benicewicz B., Neely T. Nanocomposites with Polymer Grafted Nanoparticles. Macromolecules. 2013;46(9):3199–3214.

76. Mikael P.E., Amini A.R., Basu J., Josefina Arellano-Jimenez M., Laurencin C.T., Sanders M.M., Barry Carter C., Nukavarapu S.P. Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication, in vitro and in vivo evaluation. Biomed. Mater. 2014;9(3):035001.

77. Shrestha B., DeLuna F., Anastasio M.A., Yong Ye J., Brey E.M. Photoacoustic Imaging in Tissue Engineering and Regenerative Medicine. Tissue Eng. Part B Rev. 2020;26(1):79–102.

78. Lorite G.S., Pitkänen O., Mohl M., Kordas K., Koivisto J.T., Kellomäki M., Monique Mendonça C.P., Jesus M.B. Carbon nanotube-based matrices for tissue engineering. In: Materials for Biomedical Engineering. Bioactive Materials, Properties, and Applications. Elsevier; 2019. Chapter 10. P. 323–353.

79. Zhu S., Jing W., Hu X., Huang Z., Cai Q., Ao Y., Yang X. Time-dependent effect of electrical stimulation on osteogenic differentiation of bone mesenchymal stromal cells cultured on conductive nanofibers. J. Biomed. Mater. Res. A. 2017;105(12):3369–3383.

80. Andrade V.B., Sá M.A., Mendes R.M., Martins-Júnior P.A., Silva G., Sousa B.R. Enhancement of Bone Healing by Local Administration of Carbon Nanotubes Functionalized with Sodium Hyaluronate in Rat Tibiae. Cells Tissues Organs. 2017;204(3–4):137–149.

81. Sá M.A., Andrade V.B., Mendes R.M., Caliari M.V., Ladeira L.O., Silva E.E., Silva G.A., Corrêa-Júnior J.D., Ferreira A.J. Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets. Oral Dis. 2013;19(5):484–493.

82. Wang X., Huang Z., Wei M.., Lu T., Nong D., Zhao J., Gao X., Teng L. Catalytic effect of nanosized ZnO and TiO 2 on thermal degradation of poly(lactic acid) and isoconversional kinetic analysis. Thermochimica Acta. 2019;672:14–24.

83. Lebedev S.M. Manufacturing poly(lactic acid)/metal composites and their characterization. Int. J. Adv. Manuf. Technol. 2019;102:3213–3216.

84. Glenske K., Donkiewicz P., Köwitsch A., Milosevic-Oljaca N., Rider P., Rofall S., Franke J., Jung O., Smeets R., Schnettler R., Wenisch S., Barbeck M. Applications of Metals for Bone Regeneration. Int. J. Mol. Sci. 2018;19(3):826.

85. Trujillo S., Lizundia E., Vilas J.L., SalmeronSanchez M. PLLA/ZnO nanocomposites: Dynamic surfaces to harness cell differentiation. Colloids Surf. B Biointerfaces. 2016;144:152–160.

86. Pérez‐Álvarez L., Lizundia E., Ruiz-Rubio L., Benito V., Moreno I., Luis J., Vilas-Vilela J.S. Hydrolysis of poly(L‐lactide)/ZnO nanocomposites with antimicrobial activity. J. Appl. Polym. Sci.2019;136(28):47786.

87. Zhao Y., Liang H., Zhang S., Qu S., Jiang Y., Chen M. Effects of Magnesium Oxide (MgO) Shapes on In Vitro and In Vivo Degradation Behaviors of PLA/MgO Composites in Long Term. Polymers. 2020;12(5):E1074.

88. Brown A., Zaky S., Ray H. J., Sfeir C. Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction. Acta Biomater. 2015;11:543–553.

89. Urdzíková L., Jendelová P., Glogarová K., Burian M., Hájek M., Syková E. Transplantation of Bone Marrow Stem Cells as well as Mobilization by Granulocyte-Colony Stimulating Factor Promotes Recovery after Spinal Cord Injury in Rats. J. Neurotrauma. 2016;24(9):1379–1391.

90. Li Y., Ye D., Li M., Ma M., Gu N. Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration. ChemPhysChem. 2018;19(16):1965–1979.

91. Sharifi S., Seyednejad H., Laurent S., Atyabi F., Saei A.A., Mahmoudi M. Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging. Contrast Media Mol. Imaging. 2015;10(5):329–355.

92. Kremen T. J., Bez M., Sheyn D., Ben-David S., Da X., Tawackoli W., Wagner S., Gazit D., Pelled G. In Vivo Imaging of Exogenous Progenitor Cells in Tendon Regeneration via Superparamagnetic Iron Oxide Particles. Am. J. Sports Med. 2019;47(11):2737–2744.

93. Meng J., Xiao B., Zhang Y., Liu J., Xue H., Lei J., Kong H., Huang Y., Jin Z., Gu N., Xu H. Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo. Sci. Rep. 2013;3:2655.

94. Ghassemi T., Shahroodi A., Ebrahimzadeh M.H., Mousavian A., Movaffagh J., Moradi A. Current Concepts in Scaffolding for Bone Tissue Engineering. Arch. Bone Jt. Surg. 2018;6(2):90–99.

95. Akilbekova D., Shaimerdenova M., Adilov S., Berillo D. Biocompatible scaffolds based on natural polymers for regenerative medicine. Int. J. Biol. Macromol. 2018;114:324–333.

96. Sofi H.S., Ashraf R., Beigh M.A., Sheikh F.A. Scaffolds Fabricated from Natural Polymers/Composites by Electrospinning for Bone Tissue Regeneration. Adv. Exp. Med. Biol. 2018;1078:49–78.

97. Islam S., Rahman Bhuiyan M.A., Islam M.N. Chitin and Chitosan: Structure, Properties and Applications in Biomedical Engineering. J. Polym. Environ. 2017;25:854–866.

98. Ahsan S.M., Thomas M., Reddy K.K., Sooraparaju S.G., Asthana A., Bhatnagar I. Chitosan as biomaterial in drug delivery and tissue engineering. Int. J. Biol. Macromol. 2018;110:97–109.

99. Lei B., Guo B., Rambhia K.J., Ma P.X. Hybrid polymer biomaterials for bone tissue regeneration. Front. Med. 2019;13(2):189–201.

100. Shen R., Xu W., Xue Y., Chen L., Ye H., Zhong E., Ye Z., Gao J., Yan Y. The use of chitosan/PLA nano-fibers by emulsion eletrospinning for periodontal tissue engineering. Artif. Cells Nanomed. Biotechnol. 2018;46(sup2):419–430.

101. Yun Y.P., Lee S.Y., Kim H.J., Song J.J., Kim S.E. Improvement of osteoblast functions by sustained release of bone morphogenetic protein-2 (BMP-2) from heparin-coated chitosan scaffold. Tissue Eng. Regen. Med. 2013;10:183–191.

102. Russo E., Gaglianone N., Baldassari S., Parodi B., Cafaggi S., Zibana C., Donalisio M., Cagno V., Lembo D., Caviglioli G. Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles. Colloids Surf. B: Biointerfaces. 2014;118:117–125.

103. Cao L., Werkmeister J.A., Wang J., Glattauer V., McLean K.M., Liu C. Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles. Biomaterials. 2014;35(9):2730–2742.

104. Cao L., Wang J., Hou J., Xing W., Liu C. Vascularization and bone regeneration in a critical sized defect using 2-N,6-O-sulfated chitosan nanoparticles incorporating BMP-2. Biomaterials. 2014;35(2):684–698.

105. Echave M.C., Saenz del Burgo L., Pedraz J.L., Orive G. Gelatin as Biomaterial for Tissue Engineering. Curr. Pharm. Des. 2017;23(24):3567–3584.

106. Poursamar S.A., Hatami J., Lehner A.N., da Silva C.L., Ferreira F.C., Antunes A.P. Gelatin porous scaffolds fabricated using a modified gas foaming technique: Characterisation and cytotoxicity assessment. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;48:63–70.

107. Peng Y.Y., Glattauer V., Ramshaw J.A. Stabilisation of Collagen Sponges by Glutaraldehyde Vapour Crosslinking. Int. J. Biomater. 2017;2017:8947823.

108. Yokota K., Matsuno T., Tabata Y., Mataga I. Evaluation of a Porous Hydroxyapatite Granule and Gelatin Hydrogel Microsphere Composite in Bone Regeneration. J. Hard Tissue Biol. 2017;26(2):203–214.

109. Elvin C.M., Brownlee A.G., Huson M.G., Tebb T.A., Kim M., Lyons R.E., Vuocolo T., Liyou N.E., Hughes T.C., Ramshaw J.A., Werkmeister J.A. The development of photochemically crosslinked native fibrinogen as a rapidly formed and mechanically strong surgical tissue sealant. Biomaterials. 2009;30(11):2059–2065

110. Monteiro N., Thrivikraman G., Athirasala A., Tahayeri A., França C.M., Ferracane J.L., Bertassoni L.E. Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental curing light for regenerative dentistry. Dent. Mater. 2018;34(3):389–399.

111. Lin C.H., Su J.J., Lee S.Y., Lin Y.M. Stiffness modification of photopolymerizable gelatin-methacrylate hydrogels influences endothelial differentiation of human mesenchymal stem cells. J. Tissue Eng. Regen. Med. 2018;12(10):2099–2111.

112. Kilic Bektas C., Hasirci V. Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated gelatin hydrogels. J. Tissue Eng. Regen. Med. 2018;12(4):e1899–e1910.

113. Gan Y., Li P., Wang L., Mo X., Song L., Xu Y., Zhao C., Ouyang B., Tu B., Luo L., Zhu L., Dong S., Li F., Zhou Q. An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration. Biomaterials. 2017;136:12–28.

114. Dong C., Lv Y. Application of Collagen Scaffold in Tissue Engineering: Recent Advances and New Perspectives. Polymers. 2016;8(2):42.

115. Zhang D., Wu X., Chen J., Lin K. The development of collagen based composite scaffolds for bone regeneration. Bioact. Mater. 2017;3(1):129–138.

116. Gu L., Shan T., Ma Y.X., Tay F.R., Niu L. Novel Biomedical Applications of Crosslinked Collagen. Trends Biotechnol. 2019;37(5):464–491.

117. Badieyan Z.S., Berezhanskyy T., Utzinger M., Aneja M.K., Emrich D., Erben R., Schüler C., Altpeter P., Ferizi M., Hasenpusch G., Rudolph C., Plank C. Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration. J. Control Release. 2016;239:137–148.

118. Hettiaratchi M.H., Krishnan L., Rouse T., Chou C., McDevitt T.C., Guldberg R.E. Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration. Sci. Adv. 2020;6(1):eaay1240.

119. Peckman S., Zanella J.M., McKay W.F. Infuse® Bone Graft. In: Drug-Device Combinatins for Chronic Diseases. New Jersey, USA: John Wiley & Sons; 2015;241–260.

120. Scalzone A., Flores-Mir C., Carozza D., d’Apuzzo F., Grassia V., Perillo L. Secondary alveolar bone grafting using autologous versus alloplastic material in the treatment of cleft lip and palate patients: systematic review and metaanalysis. Prog. Orthod. 2019;20(1):6.

121. Bowler D., Dym H. Bone Morphogenic Protein: Application in Implant Dentistry. Dent. Clin. North. Am. 2015;59(2):493–503.

122. Geiger M., Li R.H., Friess W. Collagen sponges for bone regeneration with rhBMP-2. Adv. Drug Deliv. Rev. 2003;55(12):1613-1629.

123. Oryan A., Kamali A., Moshiri A., Baharvand H., Daemi H. Chemical crosslinking of biopolymeric scaffolds: Current knowledge and future directions of crosslinked engineered bone scaffolds. Int. J. Biol. Macromol. 2018;107(Pt A):678–688.

124. Dai M., Liu X., Wang N., Sun J. Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in proinflammatory macrophages. Mater. Sci. Eng. C Mater. Biol. Appl. 2018;89:283–294.

125. Monaco G., Cholas R., Salvatore L., Madaghiele M., Sannino A. Sterilization of collagen scaffolds designed for peripheral nerve regeneration: Effect on microstructure, degradation and cellular colonization. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;71:335–344.

126. Delgado L.M., Fuller K., Zeugolis D.I. Influence of Cross-Linking Method and Disinfection/Sterilization Treatment on the Structural, Biophysical, Biochemical, and Biological Properties of Collagen-Based Devices. ACS Biomater. Sci. Eng. 2018;4(8):2739–2747.

127. Dai Z., Ronholm J.,TianY., Sethi B., Cao X. Sterilization techniques for biodegradable scaffolds in tissue engineering applications. J. Tissue Eng. 2016;7:2041731416648810.

128. Nune K.C., Misra R., Bai Y., Li S., Yang R. Interplay of topographical and biochemical cues in regulating osteoblast cellular activity in BMP-2 eluting three-dimensional cellular titanium alloy mesh structures. J. Biomed. Mater. Res. A. 2019;107(1):49–60.

129. Cha J.K., Song Y.W., Kim S., Thoma D.S., Jung U.W., Jung R.E. Core Ossification of Bone Morphogenetic Protein-2-Loaded Collagenated Bone Mineral in the Sinus. Tissue Eng. Part A. 2020;10.1089/ten.TEA.2020.0151.


Supplementary files

1. Fig. 1. Undifferentiated stem cells are seeded on a polymer scaffold together with differentiating agents and growth factors, followed by implanting in vivo.
Type Исследовательские инструменты
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2. This is to certify that the paper titled New-generation osteoplastic materials based on biological and synthetic matrices commissioned to us by Dmitry D. Lykoshin, Vladimir V. Zaitsev, Maria A. Kostromina, Roman S. Esipov has been edited for English language and spelling by Enago, an editing brand of Crimson Interactive Inc.
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  • Today, polymer and biocomposite matrices show great application promise, compared to the xenogenic matrix.
  • Particular attention is paid to the possibility of immobilizing osteogenic factors and target pharmaceutical substances on the scaffold material to control the dosage and delivery kinetics.
  • Polymeric and biocomposite materials can retard the release of pharmaceutical substances at the implantation site, reduce the toxicity, and prolong the therapeutic effect.
  • The use of composite scaffolds of different compositions in vivo results in high osteogenesis, promotes the initiation of biomineralization, and allows the tuning of the degradation rate of the material.


For citations:

Lykoshin D.D., Zaitsev V.V., Kostromina M.A., Esipov R.S. New-generation osteoplastic materials based on biological and synthetic matrices. Fine Chemical Technologies. 2021;16(1):36-54.

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