Crimson Publishers Publish With Us Reprints e-Books Video articles

Full Text

Innovation in Tissue Engineering & Regenerative Medicine

Regenerative Medicine: A Multidisciplinary Approach to a Complex Problem

Carlotta Pucci1*, Chiara Martinelli1 and Gianni Ciofani2

1Smart Bio-Interfaces, Italy

2Department of Mechanical and Aerospace Engineering, Italy

*Corresponding author:Carlotta Pucci, Smart Bio-Interfaces, Italy

Submission: June 10, 2019;Published: September 13, 2019

Volume1 Issue4
September, 2019

Introduction

Despite the successful progresses in organ transplant, the organs shortage and the long waiting lists make it of the most challenging issues of our times. In fact, just a small percentage of patients receive transplants [1,2]. while every day around 18 people die waiting for them [3]. The possibility to create de novo tissues and organs and/or to promote their regeneration is of prominent interest in the research community. In the last years, many innovative approaches have been introduced and new technological advancements are undergoing. Currently, the most diffused methodologies rely on regenerative medicine, that combines the use of stem cells, stimulated with specific factors, and scaffolds, where cells can grow to substitute damaged tissues, inducing their repair and improving their functions [4]. Scaffolds possess a defined structure, with precise pore size and distribution [5,6], and determined mechanical properties which can tackle stress ensuring biological interconnections [7]. Regenerative medicine combines different disciplines, such as chemistry, physics, biology and tissue engineering to obtain functional materials. In this minireview, we will focus on the materials and fabrication methods that are used to prepare the scaffolds, the type of cells that are commonly used for regeneration, and finally the current advances in clinical approval.

The Scaffold: Materials and Fabrication Procedures

Three-dimensional Nano scaffolds are usually composed biodegradable, biocompatible and non-immunogenic polymers. Natural polymers extracted from Extracellular Matrix Components (ECM), such as collagen, fibrin and hyaluronic acid [8-10], alginate [11] and agarose [12], present the advantage of being easily biodegraded through enzymatic degradation or other natural chemical processes, and they often contain already the necessary components for cellular adhesion [13]. Synthetic polymers, on the other hand, can be easily engineered to obtain the desired mechanical properties and they can also be functionalized with proteins or peptides to improve cell adhesion and growth [13]. Among the most used synthetic polymers we can find Polyethylene glycol (PEG), Poly (2-Hydroxy Ethyl Methacrylate) (PHEMA) [14], Polyacrylamide [15], Poly(N-isopropyl Acrylamide) (PNIPAAm) [16], Poly(Lactic-co-Glycolic Acid) (PLGA), Poly(L-Lactic Acid) (PLLA), poly(Caprolactone) (PCL), poly(ethylene oxide) (PEO), poly(vinyl alcohol) (PVA) [17].

The morphology, the structure, the porosity and the mechanical properties of the scaffolds must be controlled during the fabrication procedure to obtain the desired performances. Usually, there are composed of hydrogels or nanofibers. Hydrogels can be prepared via natural gelation processes induced by temperature, pH, ionic strength or enzymatic crosslinking [13]. Other fabrication techniques include solvent casting or particles leaching, freeze drying, gas foaming, 3D bioprinting, photolithography. 3D bioprinting is one of the most innovative fabrication techniques, allowing to prepare biocompatible scaffolds suitable for cell growth [18,19] that are able to reproduce extracellular matrix, vascular and nervous systems properties [20-22].

Regarding the preparation of nanofibers, the most common techniques are electrospinning, self-assembly, and phase separation. Electrospinning uses an electric field to draw charged polymer solutions into fibers with diameter in the order of few nanometer [23]; however the production is limited to thin two-dimensional (2D) sheets. Selfassembly, on the other hand, exploits noncovalent bonds to fabricate 3D scaffolds [24]. Thermally Induced Phase Separation (TIPS) is a new technique based on the polymer dissolution in a good solvent, with subsequent phase separation and gelation, solvent removal and freeze-drying. The advantage of this technique is that it can be used in combination with the other techniques mentioned before to increase the complexity and functionality of the final structure [23,24].

The Cells

Cells seeded on the scaffolds can be derived from the patient itself (autologous), a different individual (allogeneic) or can be originated from animals (xenogeneic). Commonly, stem cells, chondrocytes and fibroblasts have been exploited in regenerative medicine [25-28]. In parallel, administration of factors stimulating body’s healing process has been also successfully used. While some human tissues, such as liver and lungs show high regeneration capacities, others are very limited, as cornea and cartilages [29]. Materials mimicking the extracellular matrix have been applied both as substrates and as means for providing factors and molecules necessary for promoting cellular differentiation and regeneration [30-32]we test the hypothesis that tissue-specific ECM influences the differentiation of murine ESCs. We induced murine ESCs to differentiate by embryoid body formation, followed by dissociation and culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1.

Advances in Clinical Translation

Currently, four clinical trials are ongoing exploiting specifically scaffolds for treating different kinds of disease conditions and three have been already completed [33]. Several of these technologies and some developed medical devices are being evaluated in clinical trials or have been approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA). It has to be noted that the vast majority of them are based on cell-free instruments, due to a series of limitations related to high costs of production and time-consuming procedures required before approval on the market [34,35].

References

  1. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, et al. (2017) These promise of organ and tissue preservation to transform medicine. Nat Biotechnol 35(6): 530-542.
  2. (2012) Keeping kidneys. Bull World Health Organ 90(10): 718-719.
  3. https://www.organdonor.gov. https://www.organdonor.gov
  4. Guan X, Adali AM, Alarçin E, Cheng H, Kashaf SS, et al. (2017) Development of hydrogels for regenerative engineering. Biotechnol J 12(5).
  5. Scaffaro R, Lopresti F, Botta L, Rigogliuso S, Ghersi G (2016) Preparation of three-layered porous PLA/PEG scaffold: Relationship between morphology, mechanical behavior and cell permeability. J Mech Behav Biomed Mater 54: 8-24.
  6. Hollister SJ, Maddox RD, Taboas JM (2002) Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials 23(20): 4095-4103.
  7. Chan BP, Leong KW (2008) Scaffolding in tissue engineering: General approaches and tissue-specific considerations. In: European Spine Journal 4: 469-479.
  8. Naito H, Yoshimura M, Mizuno T, Takasawa S, Tojo T, et al. (2013) The advantages of three-dimensional culture in a collagen hydrogel for stem cell differentiation. J Biomed Mater Res A 101(10): 2838-2845.
  9. McCall AD, Nelson JW, Leigh NJ, Duffey ME, Lei P, et al. (2013) Growth factors polymerized within fibrin hydrogel promote amylase production in parotid cells. Tissue Eng Part A 19(19-20): 2215-2225.
  10. Burdick JA, Chung C, Jia X, Randolph MA, Langer R (2005) Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules 6(1): 386-391.
  11. Pataky K, Braschler T, Negro A, Renaud P, Lutolf MP, et al. (2012) Microdrop printing of hydrogel bioinks into 3D tissue-like geometries. Adv Mater 24(3): 391-396.
  12. Aizawa Y, Wylie R, Shoichet M (2010) Endothelial cell guidance in 3D patterned scaffolds. Adv Mater 22(43): 4831-4835.
  13. Bajaj P, Schweller RM, Khademhosseini A, West JL, Bashir R (2014) 3D Biofabrication strategies for tissue engineering and regenerative medicine. Annu Rev Biomed Eng 16: 247-276.
  14. Hanson Shepherd JN, Parker ST, Shepherd RF, Martha UG, Jennifer AL, et al. (2011) 3D microperiodic hydrogel scaffolds for robust neuronal cultures. Adv Funct Mater 21(1): 47-54.
  15. Barry RA, Shepherd RF, Hanson JN, Ralph GN, Pierre W, et al. (2009) Direct-write assembly of 3D hydrogel scaffolds for guided cell growth. Adv Mater 21(23): 2407-2410.
  16. Tekin H, Sanchez JG, Landeros C, Dubbin K, Langer R, et al. (2012) Controlling spatial organization of multiple cell types in defined 3D geometries. Adv Mater 24(41): 5543-5547.
  17. Dzobo K, Thomford NE, Senthebane DA, Shipanga H, Rowe A, et al. (2018) Advances in regenerative medicine and tissue engineering: Innovation and transformation of medicine. Stem Cells Int.
  18. Nakamura M, Iwanaga S, Henmi C, Arai K, Nishiyama Y (2010) Biomatrices and biomaterials for future developments of bioprinting and biofabrication. Biofabrication 2(1).
  19. Gao G, Cui X (2016) Three-dimensional bioprinting in tissue engineering and regenerative medicine. Biotechnol Lett 38(2): 203-211.
  20. Ozbolat IT (2015) Bioprinting scale-up tissue and organ constructs for transplantation. Trends Biotechnol 33(7): 395-400.
  21. Kuo KC, Lin RZ, Tien HW, Wu PY, Li YC, et al. (2015) Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix. Acta Biomater 27: 151-166.
  22. Loo Y, Hauser CAE (2015) Bioprinting synthetic self-assembling peptide hydrogels for biomedical applications. Biomed Mater 11(1).
  23. Smith IO, Liu XH, Smith LA, Ma PX (2009) Nanostructured polymer scaffolds for tissue engineering and regenerative medicine. Wiley Interdiscip Rev Nanomedicine Nanobiotechnology 1(2): 226-236.
  24. Chen VJ, Smith LA, Ma PX (2006) Bone regeneration on computer-designed nano-fibrous scaffolds. Biomaterials 27(21): 3973-3979.
  25. Mistry H, Connock M, Pink J, Shyangdan D, Clar C, et al. (2017) Autologous chondrocyte implantation in the knee: Systematic review and economic evaluation. Health Technol Assess 21(6): 1-294.
  26. Drowley L, Koonce C, Peel S, Jonebring A, Plowright AT, et al. (2016) Human induced pluripotent stem cell-derived cardiac progenitor cells in phenotypic screening: A transforming growth factor-β type 1 receptor kinase inhibitor induces efficient cardiac differentiation. Stem Cells Transl Med 5(2): 164-174.
  27. Dzobo K, Turnley T, Wishart A, Rowe A, Kallmeyer K, et al. (2016) Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro. Int J Mol Sci 17(8).
  28. Saris DBF, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, et al. (2009) Treatment of symptomatic cartilage defects of the knee: Characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(1): 10S-19S.
  29. Kotton DN, Morrisey EE (2014) Lung regeneration: Mechanisms, applications and emerging stem cell populations. Nat Med 20(8): 822-832.
  30. Evans ND, Gentleman E, Chen X, Roberts CJ, Polak JM, et al. (2010) Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells. Biomaterials 31(12): 3244-3252.
  31. Jiang B, Zhang G, Brey EM (2013) Dual delivery of chlorhexidine and platelet-derived growth factor-BB for enhanced wound healing and infection control. Acta Biomater 9(2): 4976-4984.
  32. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A (1991) Role of platelet‐derived growth factor in wound healing. J Cell Biochem 45(4): 319-326.
  33. gov. www.clinicaltrials.gov
  34. Witten CM, McFarland RD, Simek SL (2015) Concise review: The US food and drug administration and regenerative medicine. Stem Cells Transl Med 4(12): 1495-1499.
  35. Knoepfler PS (2015) From bench to FDA to bedside: US regulatory trends for new stem cell therapies. Adv Drug Deliv Rev 82-83: 192-196.

© 2019 Carlotta Pucci. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.



About Crimson

We at Crimson Publishing are a group of people with a combined passion for science and research, who wants to bring to the world a unified platform where all scientific know-how is available read more...

Leave a comment

Contact Info

  • Crimson Publishers, LLC
  • 555 Madison Avenue, 5th floor
  •     New York, NY 10022, USA
  • +1 (929) 600-8049
  • +1 (929) 447-1137
  • info@crimsonpublishers.com
  • www.crimsonpublishers.com