Skip to main content

Advertisement

SpringerLink
Log in

Advancing Regenerative Medicine Through the Development of Scaffold, Cell Biology, Biomaterials and Strategies of Smart Material

  • Original Research
  • Published:
Regenerative Engineering and Translational Medicine Aims and scope Submit manuscript

Abstract

Cells are fundamental building block in the human body that can be refitted using various technologies and concepts in regenerative medicine to stimulate new functional tissue for disease treatment as well as aid in biomedical problems. By understanding the molecular genetics of cells and human system, strategic approaches are developed through application of stem cell, gene therapy, platelet-rich plasma (PRP) treatment as well as tissue engineering. In this review, we describe the fundamentals of regenerative medicine and their development in regeneration of cells and tissues as well as discuss the current use of biomaterials in tissue engineering application and its direction in future research. These strategies are advantageous as they are able to provide contemporary solutions by focusing on cures rather than treatment for complex diseases. Advancement in tissue engineering also led to the fabrication of various biomaterials and scaffolds with enhanced ability to mimic and control the internal cellular microenvironment of the original tissue, which are non-reproducible with synthetic materials. Indeed, new generation smart or intelligent biomaterials have symbiotic relationship with living tissues for improved outcomes. Smart biomaterials display excellent biocompatibility in vivo tissue repair, which substantially enhance tissue engineering and regenerative medicine efficacy.

Lay Summary

Cell and tissue regeneration are important aspects in regenerative medicine, which composes of specific cell and gene treatment to aid in tissue repair. Meanwhile, tissue engineering is the main subject of this review which focuses on developing substitutes to the damaged tissues by employing various potential biomaterials with diverse scaffold architecture. However, limitations in current biomaterials brought the development of smart biomaterials which is the way forward in regenerative medicine applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

AMD:

age-related macular degeneration

Ang-1:

angiotensin 1

Ang-2:

angiotensin 2

BMP-2:

bone morphogenetic protein 2

BMP-7:

bone morphogenetic protein 7

CNS:

central nervous system

DNA:

deoxyribonucleic acid

ECM:

extracellular matrix

EGF:

epidermal growth factor

EPO:

erythropoietin

FGF:

fibroblast growth factor 2

HGF:

hepatocyte growth factor

IGF-1:

insulin-like growth factor

iPSC:

induced pluripotent stem cells

IV:

intravenous

NGF:

nerve growth factor

ONFH:

osteonecrosis of the femoral hip

PCL:

polycaprolactone

PDMS:

polydimethylsiloxane

PDGF-AB (or -BB):

platelet-derived growth factor

PE:

polyethylene

PET:

polyethylene terephthalate

PHB:

polyhydroxybutyrate

pHEMA:

polyhydroxyethylmethacrylate

PLA:

polylactic acid

PLGA:

poly(lactic-co-glycolic) acid

PMMA:

polymethylmethacrylate

PRP:

platelet-rich plasma

PTFE:

polytetrafluoroethylene

RNA:

ribonucleic acid

RA:

rheumatoid arthritis

SLE:

systemic lupus erythematosus

TGF-β:

transforming growth factor beta

TGF-α:

transforming growth factor alpha

VEGF:

vascular endothelial growth factor

References

  1. Grizzi F, Chiriva-Internati M. The complexity of anatomical systems. Theor Biol Med Model. 2005;2:1–9.

    Article  CAS  Google Scholar 

  2. Zhao P, Gu H, Mi H, et al. Fabrication of scaffolds in tissue engineering: a review. Front Mech Eng. 2018;13:107–19.

    Article  Google Scholar 

  3. Rosenthal N, Badylak S. Regenerative medicine: today’s discoveries informing the future of medical practice. NPJ Regen Med. 2016;1:1–3.

    Article  Google Scholar 

  4. Mao AS, Mooney DJ. Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci U S A. 2015;112:14452–9.

    Article  CAS  Google Scholar 

  5. Zakrzewski W, Dobrzyński M, Szymonowicz M, et al. Stem cells: past, present, and future. Stem Cell Res Ther. 2019;10:1–22.

    Article  CAS  Google Scholar 

  6. Caddeo S, Boffito M, Sartori S. Tissue engineering approaches in the design of healthy and pathological in vitro tissue models. Front Bioeng Biotech. 2017;5:1–22.

    Article  Google Scholar 

  7. Yun MH. Changes in regenerative capacity through lifespan. Int J Mol Sci. 2015;16:25392–432.

    Article  CAS  Google Scholar 

  8. Iismaa SE, Kaidonis X, Nicks AM, Bogush M, Kikuchi K, Naqvi N, Harvey RP, Husain A, Graham RM. Comparative regenerative mechanisms across different mammalian tissues. NPJ Regen Med. 2018;3:1–20.

    Article  Google Scholar 

  9. Baddour JA, Sousounis K, Tsonis PA. Organ repair and regeneration: an overview. Birth Defects Res C Embryo Today. 2012;96:1–29.

    Article  CAS  Google Scholar 

  10. Mandrycky C, Phong K, Zheng Y. Tissue engineering toward organ-specific regeneration and disease modeling. MRS Commun. 2017;3:332–47.

    Article  CAS  Google Scholar 

  11. Pina S, Ribeiro VP, Marques CF, Maia FR, Silva TH, Reis RL, Oliveira JM. Scaffolding strategies for tissue engineering and regenerative medicine applications. Materials (Basel). 2019;12:1–42.

    Article  CAS  Google Scholar 

  12. Vigneswari S, Majid MIA, Amirul A-AA. Tailoring the surface architecture of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) scaffolds. J Appl Polym Sci. 2012;124:2777–2788.

  13. Sohn S, Buskirk VM, Buckenmeyer MJ, Londono R, Faulk D. Whole organ engineering: approaches, challenges, and future directions. Appl Sci. 2020;10(12):4277.

    Article  CAS  Google Scholar 

  14. Hashemi J, Pasalar P, Soleimani M, Khorramirouz R, Fendereski K, Enderami SE, Kajbafzadeh AM. Application of a novel bioreactor for in vivo engineering of pancreas tissue. J Cell Physiol. 2018;233:3805–16.

    Article  CAS  Google Scholar 

  15. Hwang NS, Varghese S, Elisseeff J. Controlled differentiation of stem cells. Adv Drug Deliv Rev. 2008;60:199–214.

    Article  CAS  Google Scholar 

  16. Fu RH, Wang YC, Liu SP, Huang CM, Kang YH, Tsai CH, Shyu WC, Lin SZ. Differentiation of stem cells: strategies for modifying surface biomaterials. Cell Transplant. 2011;20:37–47.

    Article  Google Scholar 

  17. Wert G, Mummery C. Human embryonic stem cells: research, ethics and policy. Hum Reprod. 2003;18:672–82.

    Article  Google Scholar 

  18. Caglayan S, Ahrens TD, Cieślar-Pobuda A, Staerk J. Chapter 3 - modern ways of obtaining stem cells. In: Los MJ, Hudecki A, Wiechec E, editors. Stem cells and biomaterials for regenerative medicine. U.S.A: Academic Press; 2019. p. 17–36.

    Chapter  Google Scholar 

  19. Goldthwaite CA. The promise of induced pluripotent stem cells (iPSCs). In: Stem cell information. National Institute of Health. 2006. https://stemcells.nih.gov/info/Regenerative_Medicine/2006Chapter10.htm. Accessed 15 Feb 2021.

  20. Clément F, Grockowiak E, Zylbersztejn F, Fossard G, Gobert S, Maguer-Satta V. Stem cell manipulation, gene therapy and the risk of cancer stem cell emergence. Stem cell investi. 2017;4:67.

    Article  CAS  Google Scholar 

  21. Hatzimichael E, Tuthill M. Hematopoietic stem cell transplantation. Stem Cells Cloning. 2010;3:105–17.

    Google Scholar 

  22. Aijaz A, Vaninov N, Allen A, Barcia RN, Parekkadan B. Convergence of cell pharmacology and drug delivery. Stem Cells Transl Med. 2019;8:874–9.

    Article  Google Scholar 

  23. Kitambi SS, Chandrasekar G. Stem cells: a model for screening, discovery and development of drugs. Stem Cells Cloning. 2011;4:51–9.

    CAS  Google Scholar 

  24. Feng H. Is stem cell therapy the future of orthopedics? Knee Surg Relat Res. 2018;30:177–8.

    Article  Google Scholar 

  25. Maniar HH, Tawari AA, Suk M, Horwitz DS. The current role of stem cells in orthopaedic surgery. Malays Orthop J. 2015;9:1–7.

    Article  CAS  Google Scholar 

  26. Wang MJ, Chen J, Chen F, Liu Q, Sun Y, Yan C, Yang T, Bao Y, Hu YP. Rejuvenating strategies of tissue-specific stem cells for healthy aging. Aging Dis. 2019;10:871–82.

    Article  Google Scholar 

  27. Honoki K. Preventing aging with stem cell rejuvenation: feasible or infeasible? World J Stem Cells. 2017;9:1–8.

    Article  Google Scholar 

  28. Brown KS, Rao MS, Brown HL. The future state of newborn stem cell banking. J Clin Med. 2019;8:1–10.

    Article  CAS  Google Scholar 

  29. Harris DT. Stem cell banking for regenerative and personalized medicine. Biomedicines. 2014;2:50–79.

    Article  Google Scholar 

  30. Volarevic V, Bojic S, Nurkovic J, Volarevic A, Ljujic B, Arsenijevic N, Lako M, Stojkovic M. Stem cells as new agents for the treatment of infertility: current and future perspectives and challenges. Biomed Res Int. 2014;2014:1–8.

    Article  Google Scholar 

  31. Radhakrishnan G. Stem cells—The new agents in infertility treatment: the light at the end of the tunnel? Fertility Science and Research. 2017;4:70–3.

    Article  Google Scholar 

  32. Carradori D, Eyer J, Saulnier P, Préat V, Rieux A. The therapeutic contribution of nanomedicine to treat neurodegenerative diseases via neural stem cell differentiation. Biomaterials. 2017;123:77–91.

    Article  CAS  Google Scholar 

  33. Dantuma E, Merchant S, Sugaya K. Stem cells for the treatment of neurodegenerative diseases. Stem Cell Res Ther. 2010;1:1–7.

    Article  Google Scholar 

  34. Zheng C, Chen J, Liu S, et al. Stem cell-based bone and dental regeneration: a view of microenvironmental modulation. Int J Oral Sci. 2019;11:1–15.

    Article  CAS  Google Scholar 

  35. Narang S, Sehgal N. Stem cells: a potential regenerative future in dentistry. Indian J Hum Genet. 2012;18:150–4.

    Article  CAS  Google Scholar 

  36. O'Neill HC, Limnios IJ, Barnett NL. Advancing a stem cell therapy for age-related macular degeneration. Curr Stem Cell Res Ther. 2020;15:89–97.

    Article  CAS  Google Scholar 

  37. Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015;385:509–16.

    Article  Google Scholar 

  38. Lee K, Gan S, Calne R. Stem cell therapy for diabetes. Indian Journal of Endocrinology and Metabolism. 2012;16:227–9.

    Article  CAS  Google Scholar 

  39. Solis MA, Moreno Velásquez I, Correa R, et al. Stem cells as a potential therapy for diabetes mellitus: a call-to-action in Latin America. Diabetol Metab Syndr. 2019;11:1–13.

    Article  Google Scholar 

  40. Ahmad A, Aslam HMU, Afzal MS, Bhutta Z. Organogenesis: need of the current world. Chin Med J. 2019;132:849–52.

    Article  Google Scholar 

  41. Lundstrom K. Viral vectors in gene therapy. Diseases. 2018;6:1–20.

    Article  CAS  Google Scholar 

  42. Kolios G, Moodley Y. Introduction to stem cells and regenerative medicine. Respiration. 2013;85:3–10.

    Article  Google Scholar 

  43. Lee HY, Hong IS. Double-edged sword of mesenchymal stem cells: cancer-promoting versus therapeutic potential. Cancer Sci. 2017;108(10):1939–46.

    Article  CAS  Google Scholar 

  44. Ma T, Sun J, Zhao Z, Lei W, Chen Y, Wang X, et al. A brief review: adipose-derived stem cells and their therapeutic potential in cardiovascular diseases. Stem Cell Res Ther. 2017;8:124.

    Article  CAS  Google Scholar 

  45. Gorabi AM, Kiaie N, Barreto GE, Read MI, Tafti HA, Sahebkar A. The therapeutic potential of mesenchymal stem cell–derived exosomes in treatment of neurodegenerative diseases. Mol Neurobiol. 2019;56:8157–67.

    Article  CAS  Google Scholar 

  46. Liau MT, Amini F, Ramasamy TS. The therapeutic potential of stem cells and progenitor cells for the treatment of Parkinson’s disease. Tissue Eng Regen Med. 2016;13:455–64.

    Article  CAS  Google Scholar 

  47. Connor DE, Paulus JA, Dabestani PJ, Thankam FK, Dilisio MF, Gross RM, Agrawal DK. Therapeutic potential of exosomes in rotator cuff tendon healing. J Bone Metab. 2019;37:759–67.

    Article  CAS  Google Scholar 

  48. Kucharzewski M, Rojczyk E, Wilemska-Kucharzewska K, Wilk R, Hudecki J. Los MJ Novel trends in application of stem cells in skin wound healing. Eur J Pharmacol. 2019;843:307–15.

    Article  CAS  Google Scholar 

  49. Kamal MM, Kassem DH. Therapeutic potential of wharton’s jelly mesenchymal stem cells for diabetes: achievements and challenges. Front Cell Dev Biol. 2020:8(16).

  50. Turubanova VD, Mishchenko TA, Balalaeva IV, et al. Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death. Sci Rep. 2021;11:7205.

    Article  CAS  Google Scholar 

  51. Salamanna F, Veronesi F, Maglio M, Della Bella E, Sartori M, Fini M. New and emerging strategies in platelet-rich plasma application in musculoskeletal regenerative procedures: general overview on still open questions and outlook. Biomed Res Int. 2015;2015:1–24.

    Article  CAS  Google Scholar 

  52. Taylor DW, Petrera M, Hendry M, Theodoropoulos JS. A systematic review of the use of platelet-rich plasma in sports medicine as a new treatment for tendon and ligament injuries. Clin J Sport Med. 2011;21:344–52.

    Article  Google Scholar 

  53. Kwon SG, Kwon YW, Lee TW, et al. Recent advances in stem cell therapeutics and tissue engineering strategies. Biomater Res. 2018;22:1–8.

    Article  CAS  Google Scholar 

  54. Zhou Y, Chyu J, Zumwalt M. Recent progress of fabrication of cell scaffold by electrospinning technique for articular cartilage tissue engineering. International Journal of Biomaterials. 2018;2018(1953636):1–11.

    Article  CAS  Google Scholar 

  55. O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14:88–95.

    Article  CAS  Google Scholar 

  56. Keane TJ, Badylak SF. Biomaterials for tissue engineering applications. Semin Pediatr Surg. 2014;23:112–8.

    Article  Google Scholar 

  57. Mantripragada VP, Lecka-Czernik B, Ebraheim NA, Jayasuriya AC. An overview of recent advances in designing orthopedic and craniofacial implants. J Biomed Mater Res A. 2013;101:3349–64.

    Google Scholar 

  58. Thavornyutikarn B, Chantarapanich N, Sitthiseripratip K, Thouas G, Chen Q. Bone tissue engineering scaffolding: computer-aided scaffolding techniques. Progress in Biomaterials. 2014;3:61–102.

    Article  Google Scholar 

  59. Hong J, Yeo M, Yang GH, Kim G. Cell-electrospinning and its application for tissue engineering. Int J Mol Sci. 2019;20:1–14.

    Article  Google Scholar 

  60. Zhou H, Bhaduri SB. Chapter 12- 3D printing in the research and development of medical devices. In: Yang L, Webster TJ, Bhaduri SB, editors. Biomaterials in translational medicine. London: Academic Press; 2019. p. 269–89.

    Chapter  Google Scholar 

  61. Majidi HJ, Babaei A, Kazemi-Pasarvi S, Arab-Bafrani Z, Amiri M. Tuning polylactic acid scaffolds for tissue engineering purposes by incorporating graphene oxide-chitosan nano-hybrids. Polym Adv Technol. 2020;32(4):1654–66.

    Article  CAS  Google Scholar 

  62. Vigneswari S, Gurusamy TP, Abdul Khalil HPS, Ramakrishna S, Amirul AA. Elucidation of antimicrobial silver sulfadiazine (SSD) blend/poly(3-hydroxybutyrate-co-4-hydroxybutyrate) immobilised with collagen peptide as potential biomaterial. Polymer (MDPI). 2020;12(12):2979.

    Article  CAS  Google Scholar 

  63. Ismail AK, Abdullah MZ, Zubair M, Jamaludin AR, Ahmad ZA. Effect of ceramic coating in combustion and cogeneration performance of Al2O3 porous medium. J Energy Inst. 2016;89:81–93.

    Article  CAS  Google Scholar 

  64. Azuraini MJ, Huong KH, Khalil HPSA, Amirul AA. Fabrication and characterization of P(3HB-co-4HB)/gelatine biomimetic nanofibrous scaffold for tissue engineering application. J Polym Res. 2019:26(257).

  65. Vigneswari S, Chai JM, Shantini K, Bhubalan K, Amirul AA. Designing novel interfaces via surface functionalization of short-chain-length polyhydroxyalkanoates. Adv Polym Technol. 2019;3831251.

  66. Vigneswari S, Chai JM, Kamarudin KH, Amirul AA, Focarate ML, Ramakrishna S. Elucidating the surface functionality of biomimetic RGD peptides immobilized on nano-P(3HB-co-4HB) for H9c2 myoblast cell proliferation. Front Bioeng Biotechnol. 2020;8:567693.

    Article  Google Scholar 

  67. Agrawal CM, Ong JL, Appleford MR, Mani G. Introduction to biomaterials: basic theory with engineering applications. 1st ed. Cambridge: Cambridge University Press; 2014.

    Google Scholar 

  68. Rastin H, Zhang B, Bi J, Hassan K, Tung TT, Losic D. 3D printing of cell-laden electroconductive bioinks for tissue engineering applications. J Mater Chem B. 2020;8:5862–76.

    Article  CAS  Google Scholar 

  69. Ghilan A, Chiriac AP, Nita LE, et al. Trends in 3D printing processes for biomedical field: opportunities and challenges. J Polym Environ. 2020;28:1345–67.

    Article  CAS  Google Scholar 

  70. Tang X, Thankappan SK, Lee P, Fard SE, Harmon MD, Tran K, Yu X. Chapter 21- Polymeric biomaterials in tissue engineering and regenerative medicine. In: Kumbar S.G, Laurencin C.T, Deng M, editors. Natural and synthetic biomedical polymers. Elsevier Inc; 2014. p. 351–371.

  71. Daraei J. Production and characterization of PCL (Polycaprolactone) coated TCP/nanoBG composite scaffolds by sponge foam method for orthopedic applications. J Composites Compounds. 2020;2(2):44–9.

    Google Scholar 

  72. Ismadi MZ, Gupta P, Fouras A, Verma P, Jadhav S, Bellare J, et al. Flow characterization of a spinner flask for induced pluripotent stem cell culture application. PLoS One. 2014;9:1–11.

    Article  CAS  Google Scholar 

  73. Aydogdu MO, Mutlu B, Kurt M, Inan AT, Kuruca SE, Erdemir G, et al. Developments of 3D polycaprolactone/beta-tricalcium phosphate/collagen scaffolds for hard tissue engineering. J Aust Ceram Soc. 2019;55:849–55.

    Article  CAS  Google Scholar 

  74. Singh G, Singh S, Prakash C, Kumar R, Kumar R, Seeram R. Characterization of three-dimensional printed thermal stimulus polylactic acid-hydroxyapatite-based shape memory scaffolds. Polym Compos. 2020;41(9):3871–91.

    Article  CAS  Google Scholar 

  75. Faezah AN, Rahayu A, Vigneswari S, Majid MIA, Amirul AA. Regulating the molar fraction of 4-hydroxybutyrate in poly(3-hydroxybutyrate-co-4-hydroxybutyrate) by biological fermentation and enzymatic degradation. World J Microbiol Biotechnol. 2011;27:2455–9.

    Article  CAS  Google Scholar 

  76. Vyas C, Mishbak H. Cooper. G et al Biological perspectives and current biofabrication strategies in osteochondral tissue engineering Biomanuf Rev. 2020;5:2.

    Google Scholar 

  77. Vigneswari S, Murugaiyah V, Kaur G, Abdul Khalil HPS, Amirul AA. Biomacromolecule immobilization: grafting of fish-scale collagen peptides onto aminolyzed P(3HB-co-4HB) scaffolds as a potential wound dressing. Biomed Mater. 2016;11:1–14.

    Article  CAS  Google Scholar 

  78. Radhakrishnan S, Nagarajan S, Bechelany M, Kalkura SN. Collagen based biomaterials for tissue engineering applications: a review. In: Frank-Kamenetskaya O, Vlasov D, Panova E, Lessovaia S, editors. Processes and phenomena on the boundary between biogenic and abiogenic nature. Cham: Lecture Notes in Earth System Sciences. Springer; 2020.

    Google Scholar 

  79. Dai L, Si C. Recent advances on cellulose-based nano-drug delivery systems: design of prodrugs and nanoparticles. Curr Med Chem. 2019;26:2410–29.

    Article  CAS  Google Scholar 

  80. Sharif F, Muhammad N, Zafar T. Cellulose based biomaterials: benefits and challenges. In: Khan A, Mavinkere RS, Siengchin S, Asiri A, editors. Biofibers and biopolymers for biocomposites. Cham: Springer; 2020. https://doi.org/10.1007/978-3-030-40301-0_11.

    Chapter  Google Scholar 

  81. Amadori S, Torricelli P, Panzavolta S, Parrilli A, Fini M, Bigi A. Highly porous gelatin reinforced 3D scaffolds for articular cartilage regeneration. Macromol Biosci. 2015;15:941–52.

    Article  CAS  Google Scholar 

  82. Dainiak MB, Allan IA, Savina IN, Cornelio L, James ES, James SL, Mikhalovsky SV, Jungvid H, Galaev IY. Gelatin–fibrinogen cryogel dermal matrices for wound repair: preparation, optimisation and in vitro study. Biomaterials. 2010;31:67–76.

    Article  CAS  Google Scholar 

  83. Bessa PC, Machado R, Nürnberger S, Dopler D, Banerjee A, Cunha AM, Rodríguez-Cabello JC, Redl H, van Griensven M, Reis RL, Casal M. Thermoresponsive self-assembled elastin-based nanoparticles for delivery of BMPs. J Control Release. 2010;142:312–8.

    Article  CAS  Google Scholar 

  84. Sahoo DR, Biswal T. Alginate and its application to tissue engineering. SN Appl Sci. 2021;3:30.

    Article  CAS  Google Scholar 

  85. Lampe KJ, Antaris AL, Heilshorn SC. Design of three-dimensional engineered protein hydrogels for tailored control of neurite growth. Acta Biomater. 2013;9:5590–9.

    Article  CAS  Google Scholar 

  86. Aguilar A, Zein N, Harmouch E, Hafdi B, Bornert F, Offner D, Clauss F, Fioretti F, Huck O, Benkirane-Jessel N, Hua G. Application of chitosan in bone and dental engineering. Molecules. 2019;24:1–17.

    Article  Google Scholar 

  87. Apel PJ, Garrett JP, Sierpinski P, Ma J, Atala A, Smith TL, Koman LA, Van Dyke ME. Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model. J Hand Surg [Am]. 2008;33:1541–7.

    Article  Google Scholar 

  88. Cheng G, Davoudi Z, Xing X, Yu X, Cheng X, Li Z, Deng H, Wang Q. Advanced silk fibroin biomaterials for cartilage regeneration. ACS Biomater Sci Eng. 2018;4:2704–15.

    Article  CAS  Google Scholar 

  89. Misra S, Hascall VC, Atanelishvili I, Moreno Rodriguez R, Markwald RR, Ghatak S. Utilization of glycosaminoglycans/proteoglycans as carriers for targeted therapy delivery. Int J Cell Biol. 2015;2105; Article ID 537560:1–26.

    Article  CAS  Google Scholar 

  90. Li L, Ni R, Shao Y, Mao S. Carrageenan and its applications in drug delivery. Carbohydr Polym. 2014;103:1–11.

    Article  CAS  Google Scholar 

  91. Mihaila SM, Popa EG, Reis RL, Marques AP, Gomes ME. Fabrication of endothelial cell-laden carrageenan microfibers for microvascularized bone tissue engineering applications. Biomacromolecules. 2014;15:2849–60.

    Article  CAS  Google Scholar 

  92. Claro FA, Lima JR, Salgado MA, Gomes MF. Porous polyethylene for tissue engineering applications in diabetic rats treated with calcitonin: histomorphometric analysis. Int J Oral Maxillofac Implants. 2005;20:211–9.

    Google Scholar 

  93. Yegappan R, Selvaprithiviraj V, Amirthalingam S, Jayakumar R. Carrageenan based hydrogels for drug delivery, tissue engineering and wound healing. Carbohydr Polym. 2018;198:385–400.

    Article  CAS  Google Scholar 

  94. Popa EG, Caridade SG, Mano JF, et al. Chondrogenic potential of injectable kappa-carrageenan hydrogel with encapsulated adipose stem cells for cartilage tissue engineering applications. J Tissue Rodríguez JM, Renou SJ, Guglielmotti MB, Olmedo DG. Tissue response to porous high-density polyethylene as a three-dimensional scaffold for bone tissue engineering: an experimental study. J Biomater Sci Polym Ed. 2019;30:486–99.

    CAS  Google Scholar 

  95. Hu CY, Yoon TR. Recent updates for biomaterials used in total hip arthroplasty. Biomater Res. 2018;22:1–12.

    Article  CAS  Google Scholar 

  96. Tithito T, Suntornsaratoon P, Charoenphandhu N, Thongbunchoo J, Krishnamra N, Tang IM, Pon-On W. Fabrication of biocomposite scaffolds made with modified hydroxyapatite inclusion of chitosan-grafted-poly(methyl methacrylate) for bone tissue engineering. Biomed Mater. 2019;14:025013.

    Article  CAS  Google Scholar 

  97. Lam MT, Wu JC. Biomaterial applications in cardiovascular tissue repair and regeneration. Expert Rev Cardiovasc Ther. 2012;10:1039–49.

    Article  CAS  Google Scholar 

  98. Subramaniam A, Sethuraman S. Chapter 18 - Biomedical applications of nondegradable polymers. In: Kumbar S.G, Laurencin C.T, Deng M, editors. Natural and synthetic biomedical polymers. Elsevier Inc; 2014. pp. 301-308

  99. Lantada AD, Iniesta HA, Sánchez BP, García-Ruíz JP. Free-form rapid prototyped porous PDMS scaffolds incorporating growth factors promote chondrogenesis. Adv Mater Sci Eng. 2014;2014; Article ID 612976:1–11.

    Article  CAS  Google Scholar 

  100. Lee D, Cho S, Park HS, Kwon I. Ocular drug delivery through pHEMA-hydrogel contact lenses co-loaded with lipophilic vitamins. Sci Rep. 2016;6:1–8.

    CAS  Google Scholar 

  101. Musgrave CSA, Fang F. Contact lens materials: a materials science perspective. Materials. 2019;12:1–35.

    Article  CAS  Google Scholar 

  102. Lopes MS, Jardini AL, Filho RM. Poly (lactic acid) production for tissue engineering applications. Procedia Engineering. 2012;42:1402–13.

    Article  CAS  Google Scholar 

  103. Narayanan G, Vernekar VN, Kuyinu EL, Laurencin CT. (2016). Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering. Adv Drug Deliv Rev. 2016;107:247–76.

    Article  CAS  Google Scholar 

  104. Qi F, Wu J, Li H, Ma G. Recent research and development of PLGA/PLA microspheres/nanoparticles: a review in scientific and industrial aspects. Front Chem Sci Eng. 2018;13:14–27.

    Article  CAS  Google Scholar 

  105. Mondal D, Griffith M, Venkatraman SS. Polycaprolactone-based biomaterials for tissue engineering and drug delivery: current scenario and challenges. Int J Polym Mater Polym Biomater. 2016;65:255–65.

    Article  CAS  Google Scholar 

  106. Dwivedi R, Kumar S, Pandey R, Mahajan A, Nandana D, Katti DS, Mehrotra D. Polycaprolactone as biomaterial for bone scaffolds: review of literature. J Oral Biol Craniofac Res. 2019;10:381–8.

    Article  Google Scholar 

  107. Bonartsev AP, Bonartseva GA, Reshetov IV, Kirpichnikov MP, Shaitan KV. Application of polyhydroxyalkanoates in medicine and the biological activity of natural poly(3-hydroxybutyrate). Acta Nat. 2019;11:4–16.

    Article  CAS  Google Scholar 

  108. Piconi C, Condo SG, Kosmač T. Chapter 11 - alumina- and zirconia-based ceramics for load bearing applications. In: Shen JZ, Kosmac T, editors. Advanced ceramics for dentistry. Oxford: Butterworth-Heinemann; 2014. p. 1–67.

    Google Scholar 

  109. Piconi C, Maccauro G, Muratori F, Prever EBD. Alumina and zirconia ceramics in joint replacements. Journal of Applied Biomaterials and Biomechanics. 2003;1:19–32.

    CAS  Google Scholar 

  110. Jeong J, Kim JH, Shim JH, et al. Bioactive calcium phosphate materials and applications in bone regeneration. Biomater Res. 2019;23:1–11.

    Article  CAS  Google Scholar 

  111. Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behaviour. Acta Biomater. 2013;9:8037–45.

    Article  CAS  Google Scholar 

  112. Hermawan H, Ramdan D, Djuansjah JRP. Metals for biomedical applications. In: Rezai R.F, editor. Biomedical engineering – from theory to applications. Intech Open. 2011:411–30.

  113. Bekmurzayeva A, Duncanson WJ, Azevedo HS, Kanayeva D. Surface modification of stainless steel for biomedical applications: revisiting a century-old material. Mater Sci Eng C. 2018;93:1073–89.

    Article  CAS  Google Scholar 

  114. Mavrogenis AF, Papagelopoulos PJ, Babis GC. Osseointegration of cobalt-chrome alloy implants. J Long-Term Eff Med Implants. 2011;21:349–58.

    Article  CAS  Google Scholar 

  115. Yao C, Lu J, Webster TJ. Chapter 2-Titanium and cobalt–chromium alloys for hips and knees. In: Lysaght M, Webster T.J, editors. Biomaterials for artificial organs. Woodhead Pubslishing; 2011. pp. 34-55.

  116. Deepak K. Nitinol for medical applications: a brief introduction to the properties and processing of nickel titanium shape memory alloys and their use in stents. Johnson Matthey Technology Review. 2017;61:66–76.

    Article  Google Scholar 

  117. Duerig T, Pelton A, Stöckel D. An overview of nitinol medical applications. Mater Sci Eng A. 1999;273–275:149–60.

    Article  Google Scholar 

  118. Sucosky P, Osorio DF, Brown JB, Neitzel GP. Fluid mechanics of a spinner-flask bioreactor. Biotechnol Bioeng. 2004;85:34–46.

    Article  CAS  Google Scholar 

  119. Radtke AL, Herbst-Kralovetz MM. Culturing and applications of rotating wall vessel bioreactor derived 3D epithelial cell models. J Vis Exp. 2012;62:1–10.

    Google Scholar 

  120. Granet C, Laroche N, Vico L, et al. Rotating-wall vessels, promising bioreactors for osteoblastic cell culture: comparison with other 3D conditions. Med Biol Eng Comput. 1998;36:513–9.

    Article  CAS  Google Scholar 

  121. Storm MP, Sorrell I, Shipley R, Regan S, Luetchford KA, Sathish J, Webb S, Ellis MJ. Hollow fiber bioreactors for in vivo-like mammalian tissue culture. J Vis Exp 2016; 111:1-12.

  122. Eghbali H, Nava MM, Mohebbi-Kalhori D, Raimondi MT. Hollow fiber bioreactor technology for tissue engineering applications. The International Journal of Artificial Organs. 2016;39:1–15.

    Article  CAS  Google Scholar 

  123. Dahlin RL, Meretoja VV, Ni M, Kasper FK, Mikos AG. Design of a high-throughput flow perfusion bioreactor system for tissue engineering. Tissue Eng Part C Methods. 2012;18:817–20.

    Article  CAS  Google Scholar 

  124. Shahin K, Doran PM. Shear and compression bioreactor for cartilage synthesis. Methods Mol Biol. 2015;1340:221–33.

    Article  CAS  Google Scholar 

  125. Seo J, Shin JY, Leijten J, Jeon O, Bal Öztürk A, Rouwkema J, Li Y, Shin SR, Hajiali H, Alsberg E, Khademhosseini A. Interconnectable dynamic compression bioreactors for combinatorial screening of cell mechanobiology in three dimensions. ACS Appl Mater Interfaces. 2018;10:13293–303.

    Article  CAS  Google Scholar 

  126. Lendlein A, Gould OEC. Reprogrammable recovery and actuation behaviour of shape-memory polymers. Nat Rev Mater. 2019;4:116–33.

    Article  Google Scholar 

  127. Sutradhar KB, Sumi CD. Implantable microchip: the futuristic controlled drug delivery system. Drug Deliv. 2016;23:1–11.

    Article  CAS  Google Scholar 

  128. Lee S, Trinh TH, Yoo M, Shin J, Lee H, Kim J, et al. Self-assembling peptides and their application in the treatment of diseases. Int J Mol Sci. 2019;20:1–22.

    Article  Google Scholar 

  129. Khan F, Tanaka M. Designing smart biomaterial for tissue engineering. Int J Mol Sci. 2018;19:1–14.

    CAS  Google Scholar 

  130. Mittal A, Negi P, Garkhal K, Verma S, Kumar N. Integration of porosity and bio-functionalization to form a 3D scaffold: cell culture studies and in vitro degradation. Biomed Mater. 2010;5:045001.

    Article  CAS  Google Scholar 

  131. Truong VX, Ablett MP, Richardson SM, Hoyland JA, Dove AP. Simultaneous orthogonal dual-click approach to tough, in-situ-forming hydrogels for cell encapsulation. J Am Chem Soc. 2015;137:1618–22.

    Article  CAS  Google Scholar 

  132. Guo B, Ma PX. Conducting polymers for tissue engineering. Biomacromolecules. 2018;19(6):1764–82.

    Article  CAS  Google Scholar 

  133. Chen J, Zou X. Self-assemble peptide biomaterials and their biomedical applications. Bioactive Materials. 2019;4:120–31.

    Article  Google Scholar 

  134. Lombardi L, Falanga A, Del Genio V, Galdiero S. A new hope: self-assembling peptides with antimicrobial activity. Pharmaceutics. 2019;11(4):166.

    Article  CAS  Google Scholar 

  135. Castillo-Díaz LA, Ruiz-Pacheco JA, Elsawy MA, Reyes-Martínez JE, Enríquez-Rodríguez AI. Self- assembling peptides as an emerging platform for the treatment of metabolic syndrome. Int J Nanomedicine. 2020;15:10349–70.

    Article  Google Scholar 

  136. Chen Z, Bachhuka A, Han S, Wei F, Lu S, Visalakshan RM, Vasilev K, Xiao Y. Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications. ACS Nano. 2017;11:4494–506.

    Article  CAS  Google Scholar 

  137. Hu Z, Ma C, Rong X, Zou S, Liu X. Immunomodulatory ECM-like microspheres for accelerated bone regeneration in diabetes mellitus. ACS Appl Mater Interfaces. 2018;10:2377–90.

    Article  CAS  Google Scholar 

  138. Liu X, Zhao K, Gong T, Song J, Bao C, Luo E, Weng J, Zhou S. Delivery of growth factors using a smart porous nanocomposite magnetic to repair a mandibular bone defect. IEEE Trans Biomed Eng. 2014;53:2075–83.

    Google Scholar 

  139. Hendrikson WJ, Rouwkema J, Clementi F, van Blitterswijk CA, Farè S, Moroni L. Towards 4D printed scaffolds for tissue engineering: exploiting 3D shape memory polymers to deliver time-controlled stimulus on cultured cells. Biofabrication. 2017;9:031001.

    Article  CAS  Google Scholar 

  140. Politakos N, Diamanti E, Moya SE. Smart, biocompatible, responsive surfaces on pH, temperature and ionic strength of titanium oxide and niobium oxide with polymer brushes of poly(acrylic acid), poly(N-isopropylacrylamide) and poly([2-(methacryloyloxy)ethyl] trimethylammonium chloride). Eur Polym J. 2019;112:306–19.

    Article  CAS  Google Scholar 

  141. Kearney CJ, Skaat H, Kennedy SM, Hu J, Darnell M, Raimondo TM, Mooney DJ. Switchable release of entrapped nanoparticles from alginate hydrogels. Advance Healthcare Materials. 2015;4(11):1634–9.

    Article  CAS  Google Scholar 

  142. Damaraju SM, Shen Y, Elele E, Khusid B, Eshghinejad A, Li J, Jaffe M, Arinzeh TL. Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation. Biomaterials. 2017;149:51–62.

    Article  CAS  Google Scholar 

  143. Ribeiro C, Moreira S, Correia V, Sencadas V, Rocha JG, Gma FM, Gómez-Ribelles JL, Lanceros-Méndez S. Enhanced proliferation of pre-osteoblastic cells by dynamic piezoelectric stimulation. RSC Adv. 2012;2:11504–9.

    Article  CAS  Google Scholar 

  144. Qu H, Fu H, Hana Z, Sun Y. Biomaterials for bone tissue engineering scaffolds: a review. Royal Society of Chemistry. 2019;9:26252–62.

    CAS  Google Scholar 

  145. Lee SJ, Yoo JJ, Atala A. Biomaterials and tissue engineering. In: Denstedt J, Atala A, editors. Clinical regenerative medicine in urology. Singapore: Springer; 2018. p. 17–51.

    Chapter  Google Scholar 

  146. Sohail M, Mudassir, Minhas MU, Khan S, Hussain Z, de Matas M, Shah SA, Khan S, Kousar M, Ullah K. Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects. Drug Delivery and Translational Research. 2018;9:595–614.

    Article  CAS  Google Scholar 

  147. Ruskowitz ER, DeForest CA. Photoresponsive biomaterial for targeted drug delivery and 4D cell culture. Nature Review Materials. 2018;3:17087.

    Article  CAS  Google Scholar 

  148. Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J R Soc Interface. 2011;8:153–70.

    Article  CAS  Google Scholar 

  149. Murphy WL, McDevitt TC, Engler AJ. Materials as stem cell regulators. Nat Mater. 2014;13:547–57.

    Article  CAS  Google Scholar 

  150. Franz S, Rammelt S, Scharnweber D, Simon JC. Immune responses to implants. A review of the implications for the design of immunomodulatory biomaterials. Biomaterials. 2011;32:6692–709.

    Article  CAS  Google Scholar 

  151. Wu T, Yu S, Chen D, Wang Y. Bionic design, materials and performance of bone tissue scaffolds. Materials. 2017;10:1187.

    Article  CAS  Google Scholar 

  152. Mullen LM, Best SM, Rushton N, Cameron RE. Bioactive IGF-1 release from collagen – GAG scaffold to enhance cartilage repair in vitro. J Mater Sci Mater Med. 2015;26:5325.

    Article  CAS  Google Scholar 

  153. Wei P, Xu Y, Gu Y, Yao Q, Li J, Wang L. IGF-1-releasing PLGA nanoparticles modified 3D printed PCL scaffolds for cartilage tissue engineering. Drug Delivery. 2020;27:1106–14.

    Article  CAS  Google Scholar 

  154. Rosellini E, Barbani N, Frati C, Madeddu D, Massai D, Morbiducci U, et al. IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium. Biomaterials for Tissue Engineering. 2021;35:762–75.

    CAS  Google Scholar 

  155. Sun Y, Han X, Wang X, Zhu B, Li B, Chen Z, et al. Sustained release of IGF-1 by 3D mesoporous scaffolds promoting cardiac stem cell migration and proliferation. Cell Physiol Biochem. 2018;49:2358–70.

    Article  CAS  Google Scholar 

  156. Zhang Z, Li L, Yang W, Cao Y, Shi Y, Li X, Zhang Q. The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits. Osteoarthr Cartil. 2017;25:309–20.

    Article  CAS  Google Scholar 

  157. Sridhar BV, Doyle NR, Randolph MA, Anseth KS. Covalently ethered TGF-β1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production. J Biomed Mater Res A. 2015;102:4464–72.

    Article  CAS  Google Scholar 

  158. Luca A, Klein-gunnewiek DM, Vancso JG, Blitterswijk CA, Van BEM, Moroni L. Covalent binding of bone morphogenetic protein-2 and transforming growth factor-β3 to 3D plotted scaffolds for osteochondral tissue regeneration. Biotechnol J. 2017;12:1700072.

    Article  CAS  Google Scholar 

  159. Coluccino L, Stagnaro P, Vassalli M, Scaglione S. Bioactive TGF-β1/HA alginate-based scaffolds for osteochondral tissue repair: design, realization and multilevel characterization. J Appl Biomater Funct Mater. 2016;14:42–52.

    Google Scholar 

  160. Gilbert J, Davis FC. Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters. Behav Brain Res. 2009;198:440–8.

    Article  CAS  Google Scholar 

  161. Li Y, Fan J, Chen M, Li W, Woodley DT. Transforming growth factor-alpha: a major human serum factor that promotes human keratinocyte migration. J Investig Dermatol. 2006;126:2096–105.

    Article  CAS  Google Scholar 

  162. Li C, Vepari C, Jin H, Joo H, Kaplan DL. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials. 2006;27:3115–24.

    Article  CAS  Google Scholar 

  163. Lin H, Tang Y, Lozito TP, Oyster N, Wang B, Tuan RS. Efficient in vivo bone formation by BMP-2 engineered human mesenchymal stem cells encapsulated in a projection stereolithographically fabricated hydrogel scaffold. Stem Cell Res Ther. 2019;10:1–13.

    Article  CAS  Google Scholar 

  164. Dashtimoghadam E, Fahimipour F, Tongas N, Tayebi L. Microfluidic fabrication of microcarriers with sequential delivery of VEGF and BMP-2 for bone regeneration. Sci Rep. 2020;10:11764.

    Article  CAS  Google Scholar 

  165. Chen R, Yu J, Gong HL, Jiang Y, Xue M, Xu N, et al. An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells. J Tissue Eng Regen Med. 2020;14:964–72.

    Article  CAS  Google Scholar 

  166. Qu F, Liu Y, Zhu D. Construction of tissue-engineered cartilage with BMP7 gene-transfected chondrocytes. The Journal of International Medical Research. 2008;36:837–47.

    Article  CAS  Google Scholar 

  167. Manson SR, Austin PF, Guo Q, Moore KH. Chapter 3-BMP-7 signaling and its critical roles in kidney development, the responses to renal injury, and chronic kidney disease. In: Litwack G, editor. Bone morphogenic protein (1st ed.). Elsevier Inc; 2015. pp. 91-144.

  168. Li RX, Yiu WH, Tang SCW. Role of bone morphogenetic protein-7 in renal fibrosis. Front Physiol. 2015;6:1–9.

    Article  Google Scholar 

  169. Matthews JA, Speer AL, Warburton D. VEGF optimizes the formation of tissue-engineered small intestine R esearch A rticle. Regen Med. 2011;6:559–67.

    Article  CAS  Google Scholar 

  170. Rosa AR, Steffens D, Santi B, Quintiliano K, Steffen N, Pilger DA, Pranke P. Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering. Braz J Med Biol Res. 2017;50:1–12.

    Article  CAS  Google Scholar 

  171. Kim J, Kim T, Kang MS, Kim H. Angiogenic effects of collagen/ mesoporous nanoparticle composite scaffold delivering VEGF165. Biomed Res Int. 2016;2016;Article ID 9676934:1–9.

    Google Scholar 

  172. Liu C, Wang C, Zhao Q, Li X, Xu F, Yao X, Wang M. Incorporation and release of dual growth factors for nerve tissue engineering using nanofibrous bicomponent scaffolds. Biomed Mater. 2018;13:1–18.

    Article  Google Scholar 

  173. Büyüköz M, Erdal E, Altinkaya SA. Nanofibrous gelatine scaffolds integrated with nerve growth factor-loaded alginate microspheres for brain tissue engineering. Tissue Engineering and Regenerative Medicine. 2016;12:707–19.

    Google Scholar 

  174. Kapur TA, Shoichet MS. Chemically-bound nerve growth factor for neural tissue engineering applications. J Biomater Sci Polym Ed. 2003;14:383–94.

    Article  CAS  Google Scholar 

  175. Liu Y, Yu S, Gu X, Cao R. Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages. J Neural Eng. 2019;16:1–17.

    Article  Google Scholar 

  176. Zhang PX, Han N, Kou YH, Zhu QT, Liu XL, Quan DP, et al. Tissue engineering for the repair of peripheral nerve injury. Neural Regen Res. 2019;14:51–8.

    Article  Google Scholar 

  177. Norouzi M, Shabani I, Atyabi F, Soleimani M. EGF-loaded nanofibrous scaffold for skin tissue engineering applications. Fibers and Polymers. 2015;16:782–7.

    Article  CAS  Google Scholar 

  178. Pulavendran S, Thiyagarajan G. Three-dimensional scaffold containing EGF incorporated biodegradable polymeric nanoparticles for stem cell based tissue Engineering Applications. Biotechnol Bioprocess Eng. 2015;16:393–9.

    Article  CAS  Google Scholar 

  179. Wang W, Yu Y, Jiang Y, Qu J, Niu L, Yang J, Li M. Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration. Tissue Engineering and Regenerative Medicine. 2019;13:715–28.

    Article  CAS  Google Scholar 

  180. Lee J, Parthiban P, Jin G. Materials roles for promoting angiogenesis in tissue regeneration. Prog Mater Sci. 2020;100732.

  181. Huang S, Yang Y, Yang Q, Zhao Q, Ye X. Engineered circulatory scaffolds for building cardiac tissue. Journal of Thoracic Disease. 2018;10:2312–28.

    Article  Google Scholar 

  182. Ludwig M, Steinhoff G, Li J. The regenerative potential of angiotensin AT2 receptor in cardiac repair. Can J Physiol Pharmacol. 2012;90:287–93.

    Article  CAS  Google Scholar 

  183. Sun YAO, Zhang J, Lu LI, Bedigian MP, Robinson AD, Weber KT. Tissue angiotensin II in the regulation of inflammatory and fibrogenic components of repair in the rat heart. J Lab Clin Med. 2004;143:41–51.

    Article  CAS  Google Scholar 

  184. Nair A, Tsai YT, Shah K, Shen J, Weng H, Zhou J, et al. The effect of erythropoietin on autologous stem cell-mediated bone regeneration. Biomaterials. 2013;34:7364–71.

    Article  CAS  Google Scholar 

  185. Kharkova NV, Reshetov IV, Zelianin AS, Philippov VV, Sergeeva NS, Sviridova IK, et al. Three-dimensional TCP scaffolds enriched with Erythropoietin for stimulation of vascularization and bone formation. Electronic Journal of General Medicine. 2019;16:1–10.

    Google Scholar 

  186. Salehi M, Bastami F, Rad MR, Nokhbatolfoghahaei, Hanieh Paknejad Z, Nazeman P, Hassani A, Khojasteh. A Investigation of cell-free poly lactic acid/nanoclay scaffolds prepared via thermally induced phase separation technique containing hydroxyapatite nanocarriers of erythropoietin for bone tissue engineering applications. Polymers for Advanced Technologies. 2020;32:670–80.

    Article  CAS  Google Scholar 

  187. Hendrik J, Rölfing D. The effect of erythropoietin on bone. Acta Orthop. 2014;85:353.

    Google Scholar 

  188. Kamp J, De V, Jahnen-dechent W, Rath B, Knuechel R, Neuss S. Hepatocyte growth factor-loaded biomaterials for mesenchymal stem cell recruitment. Stem Cells Int. 2013;892065:1–9.

    Article  CAS  Google Scholar 

  189. Li J, Duan H, Wu C, Zhang D, Deng Y, Yin H, et al. HGF accelerates wound healing by promoting the dedifferentiation of epidermal cells through β1-integrin/ILK pathway. Biomed Res Int. 2013;470418:1–10.

    Google Scholar 

  190. Witt R, Weigand A, Boos AM, Cai A, Dippold D, Boccaccini AR, et al. Mesenchymal stem cells and myoblast differentiation under HGF and IGF-1 stimulation for 3D skeletal muscle tissue engineering. BMC Cell Biol. 2017;18:1–16.

    Article  CAS  Google Scholar 

  191. Miller KJ, Thaloor D, Matteson S, Pavlath GK, Kristy J, Thaloor D, et al. Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle. Am J Physiol Cell Physiol. 2000;278:174–81.

    Article  Google Scholar 

  192. Yamane K, Mazaki T, Shiozaki Y, Yoshida A. Collagen-binding hepatocyte growth factor ( HGF ) alone or with a gelatin-furfurylamine hydrogel enhances functional recovery in mice after spinal cord injury. Sci Rep. 2018;8:1–12.

    Article  CAS  Google Scholar 

  193. Wirz S, Dietrich M, Flanagan TC, Bokermann G, Wagner W, Schmitz-Rode T, Jockenhoevel S. Influence of platelet-derived growth factor-AB on tissue development in autologous platelet-rich plasma gels. Tissue Eng A. 2011;17:1891–9.

    Article  CAS  Google Scholar 

  194. Jin Q, Ma PX, Giannobile WV. Platelet-derived growth factor delivery via nanofibrous scaffolds for soft-tissue repair. Advanced Skin Wond Care. 2010;1:375–38.

    Google Scholar 

  195. Zhang M, Yu W, Niibe K, Zhang W, Egusa H, Tang T, Jiang X. The effects of platelet-derived growth factor-BB on bone marrow stromal cell-mediated vascularized bone regeneration. Stem Cells Int. 2018;2018; Article ID 3272098:1–16.

    Google Scholar 

  196. Marra KG, DeFail AJ, Clavijo-Alvarez JA, Badylak SF, Taieb A, Schipper B, et al. P. FGF-2 enhances vascularization for adipose tissue engineering. Plast Reconstr Surg. 2008;121:1153–64.

    Article  CAS  Google Scholar 

  197. Yun YR, Lee S, Jeon E, Kang W, Kim KH, Kim HW, Jang JH. Fibroblast growth factor 2 functionalized collagen matrices for skeletal muscle tissue engineering. Biotechnol Lett. 2012;34:772–8.

    Article  CAS  Google Scholar 

  198. Zhang F, Peng W, Wang L, Zhang J, Dong W, Wu J, et al. Role of FGF-2 transfected bone marrow mesenchymal stem cells in engineered bone tissue for repair of avascular necrosis of femoral head in rabbits. Cell Physiol Biochem. 2018;48:773–84.

    Article  CAS  Google Scholar 

  199. Charoenlarp P, Rajendran AK, Iseki S. Role of fibroblast growth factors in bone regeneration. Inflammation and Regeneration. 2017:37.1–7.

  200. Jacob J, More M, Kalia K, Kapusetti G. Piezoelectric smart biomaterials for bone and cartilage tissue engineering. Inflammation and Regeneration. 2018;38:1–11.

    Article  CAS  Google Scholar 

  201. Mason WP. Piezoelectricity, its history and applications. The Journal of the Acoustical Society of America. 1981;70:1561–6.

    Article  CAS  Google Scholar 

  202. Markx GH. (2008). The use of electric fields in tissue engineering. Organogenesis. 2008;4:11–7.

    Article  Google Scholar 

  203. Singh J, Rani S, Rohini, Parida A. Generation of piezoelectricity from the human body. Annual International Conference on Emerging Research Areas: Magnetics, Machines and Drives (AICERA/iCMMD). 2014:1-5

  204. Rajabi AH, Jaffe M, Arinzeh TL. Piezoelectric materials for tissue regeneration: a review. Acta Biomater. 2015;24:12–23.

    Article  CAS  Google Scholar 

  205. More N, Kapusetti, G. Piezoelectric material—a promising approach for bone and cartilage regeneration. Med Hypotheses 2017;108:10–16.

  206. Minary-Jolandan M, Yu MF. Nanoscale characterization of isolated individual type I collagen fibrils: polarization and piezoelectricity. Nanotechnology. 2009;20:085706.

    Article  CAS  Google Scholar 

  207. Ross G, Watts J, Hill M, Morrissey P. Surface modification of poly (vinylidene fluoride) by alkaline treatment1. The degradation mechanism. Polymer. 2000;41:1685–96.

    Article  CAS  Google Scholar 

  208. Martins P, Ribeiro S, Ribeiro C, Sencadas V, Gomes A, Gama F, Lanceros-Méndez S. Effect of poling state and morphology of piezoelectric poly(vinylidene fluoride) membranes for skeletal muscle tissue engineering. RSC Adv. 2013;3:17938–44.

    Article  CAS  Google Scholar 

  209. Weber N, Leem YS, Shanmugasundaram S, Jaffe M, Arinzeh TL. Characterization and in vitro cytocompatibility of piezoelectric electrospun scaffolds. Acta Biomater. 2010;6:3550–6.

    Article  CAS  Google Scholar 

  210. Valentini RF. Negatively charged polymeric electret implant. 1998:U.S. Patent No 5759205A

  211. Arinzeh T, Collins G, Lee YS. System and method for a piezoelectric scaffold for nerve growth and repair. 2016:U.S. Patent No. 2013/0052254A1.

  212. Pereira JD, Camargo RC, José Filho C, Alves N, Rodriguez-Perez MA, Constantino CJ. Biomaterials from blends of fluoropolymers and corn starch—implant and structural aspects. Mater Sci Eng. 2014;36:226–36.

    Article  CAS  Google Scholar 

  213. Esmaeili M, Baei MS. Fabrication of biodegradable polymer nanocomposite from copolymer synthesized by C. necator for bone tissue engineering. World Appl Sci J. 2011;14:106–11.

    Google Scholar 

  214. Ke S, Huang H, Ren L, Wang Y. Nearly constant dielectric loss behavior in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) biodegradable polyester. J Appl Phys. 2009;105:1–3.

    Article  Google Scholar 

  215. Fukada E. History and recent progress in piezoelectric polymers. IEEE Trans Ultrasonics Ferroelectric Frequency Control. 2000;47:1277–90.

    Article  CAS  Google Scholar 

  216. Köse GT, Korkusuz F, Özkul A, Soysal Y, Özdemir T, Yildiz C, Hasirci V. Tissue engineered cartilage on collagen and PHBV matrices. Biomaterials. 2005;26:5187–97.

    Article  CAS  Google Scholar 

  217. Barroca, N., Daniel-da-Silva, A., Gomes, P., Fernandes, M., Lanceros-Méndez, S., Sharma, P., . . . M.Vilarinho, P. Suitability of PLLA as piezoelectric substrates for tissue engineering evidenced by microscopy techniques. Microsc Microanal 2012; 18(S5), 63-64.

  218. Puppi D, Chiellini F, Piras A, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Polym Sci. 2010;35:403–40.

    Article  CAS  Google Scholar 

  219. Zaborowska M, Bodin A, Bäckdahl H, Popp J, Goldstein A, Gatenholm P. Microporous bacterial cellulose as a potential scaffold for bone regeneration. Acta Biomater. 2010;6:2540–7.

    Article  CAS  Google Scholar 

  220. Silva C, Thomazini D, Pinheiro A, Aranha N, Figueiro S, Goes J, Sombra A. Collagen–hydroxyapatite films: piezoelectric properties. Mater Sci Eng. 2001;86:210–8.

    Article  Google Scholar 

  221. Ciofani G, Danti S, Genchi GG, Mazzolai B, Mattoli V. Boron nitride nanotubes: biocompatibility and potential spill-over in nanomedicine. Small. 2013;9:1672–85.

    Article  CAS  Google Scholar 

  222. Ciofani G, Ricotti L, Mattoli V. Preparation, characterization and in vitro testing of poly(lactic-co-glycolic) acid/barium titanate nanoparticle composites for enhanced cellular proliferation. Biomed Microdevices. 2011;13:255–66.

    Article  CAS  Google Scholar 

  223. Baxter FR, Bowen CR, Turner IG, Dent AC. Electrically active bioceramics: a review of interfacial responses. Ann Biomed Eng. 2010;38:2079–92.

    Article  CAS  Google Scholar 

  224. Fan Z, Lu JG. Zinc oxide nanostructures: synthesis and properties. J Nanosci Nanotechnol. 2005;5:1561–73.

    Article  CAS  Google Scholar 

  225. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;199868:447–63.

    Article  Google Scholar 

  226. Ciofani G, Raffa V, Menciassi A, Dario P. Preparation of boron nitride nanotubes aqueous dispersions for biological applications. J Nanosci Nanotechnol. 2008;8:6223–31.

    Article  CAS  Google Scholar 

  227. Ciofani G, Ricotti L, Canale C, D’Alessandro D, Berrettini S, Mazzolai B, Mattoli V. Effects of barium titanate nanoparticles on proliferation and differentiation of rat mesenchymal stem cells. Colloids Surf B. 2013;102:312–20.

    Article  CAS  Google Scholar 

  228. Carville NC, Collins L, Manzo M, Gallo K, Lukasz BI, McKayed KK, Simpson JC, Rodriguez BJ. Biocompatibility of ferroelectric lithium niobate and the influence of polarization charge on osteoblast proliferation and function. J Biomed Mater Res. 2015;103:2540–8.

    Article  CAS  Google Scholar 

  229. Atanasoska L, Radhakrishnan R, Schewe S. Medical devices employing piezoelectric materials for delivery of therapeutic agents. 2014:U.S. Patent No. 20110196347A1

  230. Buckley PR, McKinley GH, Wison TS, Small W, Benet WJ, Bearinger JP, McElfresh MW. Maitland DJ Inductively heated shape memory polymer for the magnetic actuation of medical devices. IEEE Transactions of Biomedical Engineering. 2006;53:2075–83.

    Article  Google Scholar 

  231. Mohr R, Kratz K, Weigel T, Lucka-Gabor M, Moneka M, Lendlein A. Initiation of shape-memory effect by inductive heating of magnetic nanoparticles in thermoplastic polymers. Proceedings of National Academy of Sciences USA. 2006;103:3540–5.

    Article  CAS  Google Scholar 

  232. Langer R. Tirrell DA Designing materials for biology and medicine. Nature. 2004;428:487–92.

    Article  CAS  Google Scholar 

  233. Montgomery M, Ahadian S, Huyer LD, Rito ML, Civitarese RA, Vanderlaa RD, Wu J, Reis LA, Momen A, Akbari S, Pahnke A, Li R, Caldarone CA, Radisic M. Flexible shape-memory scaffold for minimally invasive delivery of functional tissues. Nat Mater. 2017;16:1038–46.

    Article  CAS  Google Scholar 

  234. An J, Teoh JEM, Suntornnond R, Chee KC. Design and 3D printing of scaffolds and tissues. Engineering. 2015;1:261–8.

    Article  Google Scholar 

  235. Diba M, Spaans S, Ning K, Ippel BD, Yang F, Loomans B, Dankers PYW, Leeuwenburgh SCG. Self-healing biomaterials: from molecular concepts to clinical applications. Adv Mater Interfaces. 2018;5:1800118.

    Article  CAS  Google Scholar 

  236. Chung L, Maestas DR, Housseau F, Elisseeff JH. Key players in the immune response to biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev. 2017;114:184–92.

    Article  CAS  Google Scholar 

  237. Lizarraga-Valderrama LR, Panchal B, Thomas C, Boccaccini AR, Roy I. Biomedical applications of polyhydroxyalkanoates. Biomaterials from Natural for Advanced Devices and Therapies. 2016;3:337–83.

    Article  CAS  Google Scholar 

  238. Fu N, Meng Z, Jiao T, Luo X, Tang Z, Zhu B, et al. P34HB electrospun fibres promote bone regeneration in vivo. Cell Prolif. 2019;52:1–10.

    Article  CAS  Google Scholar 

  239. Koller M. Biodegradable and biocompatible polyhydroxy-alkanoates (PHA): auspicious microbial macromolecules for pharmaceutical and therapeutic applications. Molecules. 2018;23:1–20.

    Article  CAS  Google Scholar 

  240. Rebouças JDS, Santos-Magalhães NS, Formiga FR. Cardiac regeneration using growth factors, advances and challenges. Arq Bras Cardiol. 2016;107:271–5.

    Google Scholar 

  241. Shafei AES, Ali MA, Ghanem HG, Shehata AI, Abdelgawad AA, Handal HR, Talaat KA, Ashaal AE, El-Shal AS. Mesenchymal stem cell therapy. A promising cell-based therapy for treatment of myocardial infarction. J Gene Med. 2017;19:1–10.

    Article  CAS  Google Scholar 

  242. Katarzyna R. Adult stem cell therapy for cardiac repair in patients after acute myocardial infarction leading to ischemic heart failure, an overview of evidence from the recent clinical trials. Curr Cardiol Rev. 2017;13:223–31.

    Article  Google Scholar 

  243. Ishak SA, Djuanshah JRP, Kadir MR, Sukmana I. Angiogenesis in tissue engineering: from concept to the vascularization of scaffold construct. Mater Sci Eng C. 2014;58:1–6.

    Google Scholar 

  244. Raggi C, Berardi AC. Mesenchymal stem cells, aging and regenerative medicine. Muscles Ligaments Tendons J. 2012;2:239–42.

    Google Scholar 

  245. Yang YK. Aging of mesenchymal stem cells: implication in regenerative medicine. Regenerative Therapy. 2018;9:120–2.

    Article  Google Scholar 

  246. Sousounis K, Baddour JA, Tsonis PA. Aging and regeneration in vertebrates. Curr Top Dev Biol. 2014;108:217–46.

    Article  CAS  Google Scholar 

  247. Miller VM, Rocca WA, Faubion SS. Sex differences research, precision medicine, and the future of women's health. J Women's Health (Larchmt). 2015;24(12):969–71.

    Article  Google Scholar 

  248. Liu KA, Mager NA. Women's involvement in clinical trials: historical perspective and future implications. Pharm Pract (Granada). 2016;14:1–9.

    Article  CAS  Google Scholar 

  249. Schenke-Layland K, Brucker SY. Prospects for regenerative medicine approaches in women’s health. J Anat. 2015;227:781–5.

    Article  Google Scholar 

  250. Saber N, Bruin JE, O'Dwyer S, Schuster H, Rezania A, Kieffer TJ. Sex differences in maturation of human embryonic stem cell-derived β cells in mice. Endocrinology. 2018;159:1827–41.

    Article  CAS  Google Scholar 

  251. Deasy BM, Lu A, Tebbets JC, Feduska JM, Schugar RC, Pollett JB, Sun B, Urish KL, Gharaibeh BM, Cao B, Rubin RT, Huard J. A role for cell sex in stem cell–mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency. J Cell Biol. 2007;177:73–86.

    Article  CAS  Google Scholar 

  252. Lau A, West L, Tullius SG. The impact of sex on alloimmunity. Trends Immunol. 2018;39:407–18.

    Article  CAS  Google Scholar 

Download references

Glossary

Chromosome

A threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.

Centrifuged

Separate fluids of different densities with a machine that rapidly rotates and applies centrifugal force to its contents

Huntington disease

Brain disorder that causes uncontrolled movements, emotional problems and loss of thinking ability

Intravenously

Delivers fluids directly into a vein

Myelodysplastic syndrome

Type of cancers where blood cells in the bone marrow do not mature to form healthy blood cells

Myeloproliferative disorder

Type of blood cancers which causes the bone marrow to produce excess abnormal red blood cells, white blood cells, or platelets and accumulate in the blood

Platelet

Small colourless disc-shaped cell fragment without a nucleus, found in large numbers in blood and involved in clotting.

Progenitor cell

Stem cell that can differentiate into a specific type of target cell

Vector

Tools commonly used by molecular biologists to deliver genetic material into cells

Availability of Data and Material

Not applicable.

Code Availability

Not applicable

Author information

Authors and Affiliations

  1. School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Abd Rahim Aiman & Al-Ashraf Amirul

  2. Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia

    Sevakumaran Vigneswari & Nur Athirah Amran

  3. Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Vikneswaran Murugaiyah

  4. Centre for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas, Penang, Malaysia

    Al-Ashraf Amirul

  5. Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, Singapore, 117581, Singapore

    Seeram Ramakrishna

Authors
  1. Abd Rahim Aiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sevakumaran Vigneswari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nur Athirah Amran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vikneswaran Murugaiyah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Al-Ashraf Amirul
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seeram Ramakrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, S.V. and S.R.; validation S.V., V.M and S.R.; writing—original draft preparation, A.R.A., N.A.A., S.V. and S.R.; writing—review and editing, A.R.A., N.A.A., S.V., V.M, S.R.; visualization, N.A.A., S.V., V.M, S.R., A.A.A. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Seeram Ramakrishna.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aiman, A.R., Vigneswari, S., Amran, N.A. et al. Advancing Regenerative Medicine Through the Development of Scaffold, Cell Biology, Biomaterials and Strategies of Smart Material. Regen. Eng. Transl. Med. 8, 298–320 (2022). https://doi.org/10.1007/s40883-021-00227-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40883-021-00227-w

Keywords

Search

Navigation