Review Article

An Introduction to Tissue Engineering and Orthopedic Applications


Nowadays, orthopedic-related pathologic conditions are considered as a growing concern. Also, the conventional treatments (grafting techniques) are not efficacious enough for the growing clinical needs. In the last decades, researches have been focused on finding more effective alternative treatments. Tissue engineering (TE) is a newly emerging field of science that has great potential to reduce these clinical issues. There are three main components in TE including cells, biomaterials, and signals. Choosing the best combination of these components is a vital decision in a TE process. In this review article, we are going to discuss TE and its components and also highlight some of the researches in the field of orthopedic TE by focusing on some tissues including bone, cartilage, skin, skeletal muscle, peripheral nervous system (PNS), tendon, and ligament. In the end, TE, as a new field of science, faces some major challenges that we will address some of them in this article.

1. Han F, Wang J, Ding L, Hu Y, Li W, Yuan Z, et al. Tissue engineering and regenerative medicine: achievements, future, and sustainability in Asia. Front Bioeng Biotechnol. 2020;8:83. doi: 10.3389/fbioe.2020.00083. [PubMed: 32266221]. [PubMed Central: PMC7105900].

2. Arjmand B, Goodarzi P, Mohamadi-Jahani F, Falahzadeh K, Larijani B. Personalized Regenerative Medicine. Acta Med Iran. 2017;55(3):144-9. [PubMed: 28282715].

3. Atala A. Tissue engineering and regenerative medicine: concepts for clinical application. Rejuvenation Res. 2004;7(1):15-31. doi: 10.1089/154916804323105053. [PubMed: 15256042].

4. Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A. 2015;112(47):14452-9. doi: 10.1073/pnas.1508520112. [PubMed: 26598661]. [PubMed Central: PMC4664309].

5. Wyles SP, Hayden RE, Meyer FB, Terzic A. Regenerative medicine curriculum for next-generation physicians. NPJ Regen Med. 2019;4:3. doi: 10.1038/s41536-019-0065-8. [PubMed: 30774984]. [PubMed Central: PMC6367326].

6. Eltom A, Zhong G, Muhammad A. Scaffold techniques and designs in tissue engineering functions and purposes: A review. Advances in Materials Science and Engineering. 2019;2019.

7. Nerem RM. Tissue engineering in the USA. Med Biol Eng Comput. 1992;30(4):CE8-12. doi: 10.1007/BF02446171. [PubMed: 1487936].

8. Howard D, Buttery LD, Shakesheff KM, Roberts SJ. Tissue engineering: strategies, stem cells and scaffolds. J Anat.


[PubMed: 18422523]. [PubMed Central: PMC2475566].

9. Murphy CM, O'Brien FJ, Little DG, Schindeler A. Cell-scaffold interactions in the bone tissue engineering triad. Eur Cell Mater. 2013;26:120-32. doi: 10.22203/ecm.v026a09. [PubMed: 24052425].

10. Sipe JD. Tissue engineering and reparative medicine. Ann N Y Acad Sci. 2002;961:1-9. doi: 10.1111/j.1749-6632.2002.tb03040.x. [PubMed: 12081856].

11. Pereira H, Cengiz F, Silva-Correia J, Oliveira M, Reis RL, Espregueira-Mendes J. Human Meniscus: From biology to tissue engineering strategies. In: Hutson M, Speed C, Editors. Sports injuries. Berlin, Germany: Springer; 2015. p. 1089-102.

12. Tatara AM, Mikos AG. Tissue engineering in orthopaedics. J BoneJointSurgAm.2016;98(13):1132-9.doi:10.2106/JBJS.16.00299. [PubMed: 27385687]. [PubMed Central: PMC4928040].

13. Dzobo K, Thomford NE, Senthebane DA, Shipanga H, Rowe A, Dandara C, et al. Advances in regenerative medicine and tissue engineering: innovation and transformation of medicine. Stem Cells Int. 2018;2018:2495848. doi: 10.1155/2018/2495848. [PubMed: 30154861]. [PubMed Central: PMC6091336].

14. Bean AC, Huard J. Tissue engineering applications in orthopedic surgery. In: Meyer U, Meyer T, Handschel J, Wiesmann HP, Editors. Fundamentals of tissue engineering and regenerative medicine. Berlin, Germany: Springer Science & Business Media; 2009. p. 913-9.

15. Laurencin CT, Ambrosio AM, Borden MD, Cooper JA Jr. Tissue engineering: orthopedic applications. Annu Rev Biomed Eng. 1999;1:19-46. doi: 10.1146/annurev.bioeng.1.1.19. [PubMed: 11701481].

16. Cengiz IF, Pereira H, de GL, Cucchiarini M, Espregueira-Mendes J, Reis RL, et al. Orthopaedic regenerative tissue engineering en route to the holy grail: disequilibrium between the demand and the supply in the operating room. J Exp Orthop. 2018;5(1):14. doi: 10.1186/s40634-018-0133-9. [PubMed: 29790042]. [PubMed Central: PMC5964057].

17. Alexander PG, Hofer HR, Clark KL. Mesenchymal stem cells in musculoskeletal tissue engineering. In: Lanza R, Langer R, Vacanti JP, Editors. Principles of tissue engineering. Cambridge, MA: Academic Press; 2014. p. 1171-99.

18. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng. 2012;40(5):363-408. doi: 10.1615/critrevbiomedeng.v40.i5.10. [PubMed: 23339648]. [PubMed Central: PMC3766369].

19. Shrivats AR, McDermott MC, Hollinger JO. Bone tissue engineering: state of the union. Drug Discov Today. 2014;19(6):781-6. doi: 10.1016/j.drudis.2014.04.010. [PubMed: 24768619].

20. Sheikh Z, Najeeb S, Khurshid Z, Verma V, Rashid H, Glogauer M. Biodegradable Materials for Bone Repair and Tissue Engineering Applications. Materials (Basel). 2015;8(9):5744-94. doi: 10.3390/ma8095273. [PubMed: 28793533]. [PubMed Central: PMC5512653].

21. Travnickova M, Bacakova L. Application of adult mesenchymal stem cells in bone and vascular tissue engineering. Physiol Res. 2018;67(6):831-50. doi: 10.33549/physiolres.933820. [PubMed: 30204468].

22. Mishra R, Bishop T, Valerio IL, Fisher JP, Dean D. The potential impact of bone tissue engineering in the clinic. Regen Med. 2016;11(6):571-87. doi: 10.2217/rme-2016-0042. [PubMed: 27549369]. [PubMed Central: PMC5007661].

23. Wubneh A, Tsekoura EK, Ayranci C, Uludag H. Current state of fabrication technologies and materials for bone tissue

engineering. Acta Biomater. 2018;80:1-30. doi:
10.1016/j.actbio.2018.09.031. [PubMed:

24. Hernigou P, Poignard A, Zilber S, Rouard H. Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop. 2009;43(1):40-5. doi: 10.4103/0019-5413.45322. [PubMed: 19753178]. [PubMed: PMC2739495].

25. Schmitt A, van Griensven M., Imhoff AB, Buchmann S. Application of stem cells in orthopedics. Stem Cells Int. 2012;2012:394962. doi: 10.1155/2012/394962. [PubMed: 22550505]. [PubMed Central: PMC3328166].

26. Goel A, Sangwan SS, Siwach RC, Ali AM. Percutaneous bone marrow grafting for the treatment of tibial non-union. Injury. 2005;36(1):203-6. doi: 10.1016/j.injury.2004.01.009. [PubMed: 15589942].

27. Russo S, Sadile F, Esposito R, Mosillo G, Aitanti E, Busco G, et al. Italian experience on use of E.S.W. therapy for avascular necrosis of femoral head. Int J Surg. 2015;24(Pt B):188-90. doi: 10.1016/j.ijsu.2015.11.038. [PubMed: 26644278].

28. Miller MA, Ivkovic A, Porter R, Harris MB, Estok DM, Smith RM, et al. Autologous bone grafting on steroids: preliminary clinical results. A novel treatment for nonunions and segmental bone defects. Int Orthop. 2011;35(4):599-605. doi: 10.1007/s00264-010-1013-9. [PubMed: 20414656]. [PubMed

Central: PMC3066321].

29. Tateiwa D, Yoshikawa H, Kaito T. Cartilage and Bone
Destruction in Arthritis: Pathogenesis and Treatment Strategy:
A Literature Review. Cells. 2019;8(8):818. doi:
10.3390/cells8080818. [PubMed: 31382539]. [PubMed Central:


30. Vinatier C, Guicheux J. Cartilage tissue engineering: From
biomaterials and stem cells to osteoarthritis treatments. Ann
Phys Rehabil Med. 2016;59(3):139-44. doi:

10.1016/ [PubMed: 27079583].

31. Medvedeva EV, Grebenik EA, Gornostaeva SN, Telpuhov VI, Lychagin AV, Timashev PS, et al. Repair of Damaged Articular Cartilage: Current Approaches and Future Directions. Int J Mol Sci. 2018;19(8):2366. doi: 10.3390/ijms19082366. [PubMed: 30103493]. [PubMed Central: PMC6122081].

32. Abdel-Sayed P, Pioletti DP. Strategies for improving the repair of focal cartilage defects. Nanomedicine (Lond). 2015;10(18):2893-905. doi: 10.2217/nnm.15.119. [PubMed: 26377158].

33. Brittberg M, Gomoll AH, Canseco JA, Far J, Lind M, Hui J. Cartilage repair in the degenerative ageing knee. Acta Orthop. 2016;87(sup363):26-38. doi: 10.1080/17453674.2016.1265877. [PubMed: 27910738]. [PubMed Central: PMC5389429].

34. Kwon H, Brown WE, Lee CA, Wang D, Paschos N, Hu JC, et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol. 2019;15(9):550-70. doi: 10.1038/s41584-019-0255-1. [PubMed: 31296933]. [PubMed Central: PMC7192556].

35. Richardson SM, Kalamegam G, Pushparaj PN, Matta C, Memic A, Khademhosseini A, et al. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods. 2016;99:69-80. doi: 10.1016/j.ymeth.2015.09.015. [PubMed: 26384579].

36. Iwasa J, Engebretsen L, Shima Y, Ochi M. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc. 2009;17(6):561-77. doi: 10.1007/s00167-008-0663-2. [PubMed: 19020862]. [PubMed Central: PMC2688024].

37. Filardo G, Perdisa F, Roffi A, Marcacci M, Kon E. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42. doi: 10.1186/s13018-016-0378-x. [PubMed: 27072345]. [PubMed Central: PMC4830073].

38. Chang YH, Liu HW, Wu KC, Ding DC. Mesenchymal Stem Cells and Their Clinical Applications in Osteoarthritis. Cell Transplant. 2016;25(5):937-50. doi: 10.3727/096368915X690288. [PubMed: 26688464].

39. Vega A, Martin-Ferrero MA, Del CF, Alberca M, Garcia V, Munar A, et al. Treatment of Knee Osteoarthritis with Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled

Trial. Transplantation. 2015;99(8):1681-90. doi: 10.1097/TP.0000000000000678. [PubMed: 25822648].

40. Kim HS, Sun X, Lee JH, Kim HW, Fu X, Leong KW. Advanced drug delivery systems and artificial skin grafts for skin wound healing. Adv Drug Deliv Rev. 2019;146:209-39. doi: 10.1016/j.addr.2018.12.014. [PubMed: 30605737].

41. Vig K, Chaudhari A, Tripathi S, Dixit S, Sahu R, Pillai S, et al. Advances in Skin Regeneration Using Tissue Engineering. Int J Mol Sci. 2017;18(4):789. doi: 10.3390/ijms18040789. [PubMed: 28387714]. [PubMed Central: PMC5412373].

42. Sheikholeslam M, Wright MEE, Jeschke MG, Amini-Nik S. Biomaterials for Skin Substitutes. Adv Healthc Mater. 2018;7(5). doi: 10.1002/adhm.201700897. [PubMed: 29271580].

43. Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration: Current status and advances. Biomaterials.


[PubMed: 31247480].

44. Kaur A, Midha S, Giri S, Mohanty S. Functional Skin Grafts: Where Biomaterials Meet Stem Cells. Stem Cells Int.
2019;2019:1286054. doi: 10.1155/2019/1286054. [PubMed:

31354835]. [PubMed Central: PMC6636521].

45. Goodarzi P, Falahzadeh K, Nematizadeh M, Farazandeh P, Payab M, Larijani B, et al. Tissue Engineered Skin Substitutes. Adv Exp Med Biol. 2018;1107:143-88. doi: 10.1007/5584_2018_226. [PubMed: 29855826].

46. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975;6(3):331-43. doi: 10.1016/s0092-8674(75)80001-8. [PubMed: 1052771].

47. Chang DK, Louis MR, Gimenez A, Reece EM. The Basics of Integra Dermal Regeneration Template and its Expanding Clinical Applications. Semin Plast Surg. 2019;33(3):185-9. doi:

10.1055/s-0039-1693401. [PubMed: 31384234]. [PubMed Central: PMC6680073].

48. Liu Y, Panayi AC, Bayer LR, Orgill DP. Current Available Cellular

and Tissue-Based Products for Treatment of Skin Defects. Adv

Skin Wound Care. 2019;32(1):19-25. doi:

10.1097/01.ASW.0000547412.54135.b7. [PubMed: 30570555].

49. Momeni M, Fallah N, Bajouri A, Bagheri T, Orouji Z, Pahlevanpour P, et al. A randomized, double-blind, phase I clinical trial of fetal cell-based skin substitutes on healing of donor sites in burn patients. Burns. 2019;45(4):914-22. doi: 10.1016/j.burns.2018.10.016. [PubMed: 30559055].

50. Vijayavenkataraman S. Nerve guide conduits for peripheral nerve injury repair: A review on design, materials and fabrication methods. Acta Biomater. 2020;106:54-69. doi: 10.1016/j.actbio.2020.02.003. [PubMed: 32044456].

51. Jahromi M, Razavi S, Bakhtiari A. The advances in nerve tissue engineering: From fabrication of nerve conduit to in vivo nerve regeneration assays. J Tissue Eng Regen Med. 2019;13(11):2077-100. doi: 10.1002/term.2945. [PubMed: 31350868].

52. Gu X, Ding F, Williams DF. Neural tissue engineering options for peripheral nerve regeneration. Biomaterials. 2014;35(24):6143-56. doi: 10.1016/j.biomaterials.2014.04.064. [PubMed: 24818883].

53. Belanger K, Dinis TM, Taourirt S, Vidal G, Kaplan DL, Egles C. Recent Strategies in Tissue Engineering for Guided Peripheral Nerve Regeneration. Macromol Biosci. 2016;16(4):472-81. doi: 10.1002/mabi.201500367. [PubMed: 26748820].

54. Hussain G, Wang J, Rasul A, Anwar H, Qasim M, Zafar S, et al. Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery. Int J Biol Sci. 2020;16(1):116-34. doi: 10.7150/ijbs.35653. [PubMed: 31892850]. [PubMed Central: PMC6930373].

55. Zhang BG, Quigley AF, Myers DE, Wallace GG, Kapsa RM, Choong PF. Recent advances in nerve tissue engineering. Int J Artif Organs. 2014;37(4):277-91. doi: 10.5301/ijao.5000317. [PubMed: 24811182].

56. Kuffler DP, Foy C. Restoration of Neurological Function Following Peripheral Nerve Trauma. Int J Mol Sci. 2020;21(5):1808. doi: 10.3390/ijms21051808. [PubMed: 32155716]. [PubMed Central: PMC7084579].

57. Kim JY, Jeon WJ, Kim DH, Rhyu IJ, Kim YH, Youn I, et al. An inside-out vein graft filled with platelet-rich plasma for repair of a short sciatic nerve defect in rats. Neural Regen Res. 2014;9(14):1351-7. doi: 10.4103/1673-5374.137587. [PubMed: 25221591]. [PubMed Central: PMC4160865].

58. Roque JS, Pomini KT, Buchaim RL, Buchaim DV, Andreo JC, Roque DD, et al. Inside-out and standard vein grafts associated with platelet-rich plasma (PRP) in sciatic nerve repair. A histomorphometric study. Acta Cir Bras. 2017;32(8):617-25. doi: 10.1590/s0102-865020170080000003. [PubMed: 28902937].

59. Sabongi RG, Fernandes M, Dos Santos JB. Peripheral nerve regeneration with conduits: use of vein tubes. Neural Regen Res. 2015;10(4):529-33. doi: 10.4103/1673-5374.155428. [PubMed: 26170802]. [PubMed Central: PMC4424734].

60. Boeckstyns ME, Sorensen AI, Vineta JF, Rosen B, Navarro X, Archibald SJ, et al. Collagen conduit versus microsurgical therapy. Acta Biomater. 2017;63:18-36. doi:

10.1016/j.actbio.2017.08.032. [PubMed: 28867648].

77. Qazi TH, Duda GN, Ort MJ, Perka C, Geissler S, Winkler T. Cell therapy to improve regeneration of skeletal muscle injuries. J Cachexia Sarcopenia Muscle. 2019;10(3):501-16. doi:

10.1002/jcsm.12416. [PubMed: 30843380]. [PubMed Central: PMC6596399].

78. Wang A, Breidahl W, Mackie KE, Lin Z, Qin A, Chen J, et al. Autologous tenocyte injection for the treatment of severe, chronic resistant lateral epicondylitis: A pilot study. Am J Sports Med. 2013;41(12):2925-32. doi: 10.1177/0363546513504285. [PubMed: 24068695].

79. Pearlin, Nayak S, Manivasagam G, Sen D. Progress of regenerative therapy in orthopedics. Curr Osteoporos Rep. 2018;16(2):169-81. doi: 10.1007/s11914-018-0428-x. [PubMed: 29488062].

80. Oreffo RO, Triffitt JT. Future potentials for using osteogenic stem cells and biomaterials in orthopedics. Bone 1999; 25(2 Suppl): 5S-9S. doi: 10.1016/s8756-3282(99)00124-6. [PubMed: 10458266].

81. Berebichez-Fridman R, Montero-Olvera PR. Sources and clinical applications of mesenchymal stem cells: State-of-the-art review. Sultan Qaboos Univ Med J. 2018;18(3):e264-e277. doi: 10.18295/squmj.2018.18.03.002. [PubMed: 30607265]. [PubMed Central: PMC6307657].

82. Tang D, Tare RS, Yang LY, Williams DF, Ou KL, Oreffo RO. Biofabrication of bone tissue: Approaches, challenges and translation for bone regeneration. Biomaterials. 2016;83:

363-82. doi: 10.1016/j.biomaterials.2016.01.024. [PubMed:


83. Zhang W, Zhu Y, Li J, Guo Q, Peng J, Liu S, et al. Cell-derived extracellular matrix: Basic characteristics and current applications in orthopedic tissue engineering. Tissue Eng Part B Rev. 2016;22(3):193-207. doi: 10.1089/ten.TEB.2015.0290. [PubMed: 26671674].

84. Phull AR, Eo SH, Abbas Q, Ahmed M, Kim SJ. Applications of Chondrocyte-Based Cartilage Engineering: An Overview. Biomed Res Int. 2016;2016:1879837. doi: 10.1155/2016/1879837. [PubMed: 27631002]. [PubMed Central: PMC5007317].

85. Rai V, Dilisio MF, Dietz NE, Agrawal DK. Recent strategies in cartilage repair: A systemic review of the scaffold development and tissue engineering. J Biomed Mater Res A. 2017;105(8):2343-54. doi: 10.1002/jbm.a.36087. [PubMed: 28387995].

86. Ho J, Walsh C, Yue D, Dardik A, Cheema U. Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review. Adv Wound Care (New Rochelle). 2017;6(6):191-209. doi: 10.1089/wound.2016.0723. [PubMed: 28616360]. [PubMed Central: PMC5467128].

87. Zhou H, You C, Wang X, Jin R, Wu P, Li Q, et al. The progress and challenges for dermal regeneration in tissue engineering. J Biomed Mater Res A. 2017;105(4):1208-18. doi: 10.1002/jbm.a.35996. [PubMed: 28063210].

88. Talikowska M, Fu X, Lisak G. Application of conducting polymers to wound care and skin tissue engineering: A review. Biosens Bioelectron. 2019;135:50-63. doi: 10.1016/j.bios.2019.04.001. [PubMed: 30999241].

89. Ng WL, Yeong WY, Naing MW. Cellular approaches to tissue-engineering of skin: A Review. J Tissue Sci Eng. 2015;6(2):1000150. doi: 10.4172/2157-7552.1000150.

90. Han YF, Tao R, Sun TJ, Chai JK, Xu G, Liu J. Advances and opportunities for stem cell research in skin tissue engineering. Eur Rev Med Pharmacol Sci. 2012;16(13):1873-7. [PubMed: 23208974].

91. Nourian Dehkordi A, Mirahmadi Babaheydari F, Chehelgerdi M, Raeisi Dehkordi S. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Ther. 2019;10(1):111. doi: 10.1186/s13287-019-1212-2. [PubMed: 30922387]. [PubMed Central: PMC6440165].
IssueVol 6, No 1 (2020) QRcode
SectionReview Article
Tissue Engineering; Orthopedic; Cell Engineering; Bioengineering; Tissue Therapy

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Baghaie Nia F, Khavari F, Firouzi M, Nabian MH. An Introduction to Tissue Engineering and Orthopedic Applications. J Orthop Spine Trauma. 2020;6(1):1-8.