Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:

Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_980_Библиотеки_им_академика_М_И_Перельмана

.pdf
Скачиваний:
0
Добавлен:
31.08.2026
Размер:
28 Мб
Скачать
350
https://t.me/medicina_free
S. Mohaghegh and H. Nokhbatolfoghahaei
3.1.3 Irradiation
Three types of irradiations can be used to trigger free radical production [54]. First is single photoemission, in which a single high-energy photon is used. Second is the two or multiple emission approaches, in which several low-energy photons are responsible for creating the free radicals [55, 56]. Third is infrared, which is the common source in the last two methods, although both UV and visible light can be used in the rst method [54].
Photons can be irradiated to the initiators through two main techniques: digital light processing (DLP) and direct laser bioprinting [57]. In DLP, a digital micromir­ror device (DMD) consisting of a group of mirrors reects the photons in a pre­specied manner [58]. The irradiation pattern denes the orientation of the mirrors. This approach is used in almost all SLA bioprinting systems [44]. Both visible light and UV are used in this system.
Two-photon emission approach is used in conjunction with the direct laser writing bioprinting system. On the contrary to the single-photon method, the material is cross­linked in the bulk volume rather than in a layer-by-layer manner. A laser beam is used for the excitation of the photoinitiators. The intensity of the irradiation is adjusted by altering the width modulation. Thus, it is feasible to use infrared wavelengths for crosslinking hydrogels absorbing UV light [59]. This approach does not have a sig­nicant impact on cell viability. Indeed, cells are more sensitive to chemical reactions, not the laser beam [60]. Although the two-photon emission approach increases the pace of crosslinking procedure, it requires more expensive apparatus than DLP [44].
4 Inkjet Bioprinting
4.1 Thermal Inkjet Bioprinting
Inkjet printing is categorized into continuous and drop-on-demand methods. Thermal inkjet printing which is one of the methods related to the second category has been widely used for bioprinting [61]. The short-lasting applied heat can only increase the temperature by 4–10°C for a few microseconds [62]. Besides, extru­sion stress can also impact cell viability, as seen in extrusion-based bioprinting [63]. The stress increases, especially in the case of using narrow nozzles.
4.2 Piezoelectric Inkjet Bioprinting
Piezoelectric inkjet printing is not recommended to be used for bio-fabrication since the applied sonication may harm cell membrane and lead to cell lysis [62]. However, the successful application of piezoelectric inkjet printing has been reported [64, 65]. It has been tried to decrease the stress applied to the cells by altering the amplitude and increasing the printing time [66]. However, no correlation between survival rate and the factors mentioned above has been reported. Meanwhile, cell agglomeration and sedimentation signicantly impact cell survival [67]. In addition to the
Application ofBioprinting Technology inOral andMaxillofacial Surgery
https://t.me/medicina_free
351
mentioned factors, low droplet directionality, nonuniform droplets, and frequent nozzle clogging are the other drawbacks of piezoelectric inkjet bioprinting [68, 69].
To overcome the issues of piezoelectric method, acoustic inkjet printers can be used in which the application of heat and pressure is eliminated and more uniform droplets are formed [68, 70]. Besides, an open-pooled nozzle scan used in acoustic systems decreases the shear stress applied to the cells during extrusion [1].
4.3 Advantages andDisadvantages
Considering that the number of cells in each droplet can be specied in this method, it is pragmatic to consider inkjet bioprinting for quantitative cell seeding proce­dures. Compared to the piezoelectric approach, more technical modications can be applied in thermal inkjet printing. Low cost, availability, and high printing speed are the other advantages of thermal inkjet printing [68].
Droplet drying is one of the drawbacks of inkjet printing. Considering that there is a possibility of blotting, mixing, and diffusion of the bio-ink in this procedure, materials with gelation ability such as sodium alginate have been used in the elec­trostatic inkjet printing to avoid the mentioned incidents [68]. Although using hydrogels may complicate the scaffold manipulation, direct printing of the product on the defect can solve this problem [71]. This method has been used for cartilage and skin regeneration [1].
Low cell concentrations are usually used in inkjet bioprinting to avoid nozzle clogging, facilitate droplet formation, and decrease shear stress. On the other hand, high cell concentration can impact the crosslinking procedure [71].
5 Comparison ofBioprinting Methods
Based on a study performed by Murphy etal. [1], the following points can be men­tioned to compare bioprinting technologies (Fig.3): Bio-ink prepared for the laser­based bioprinting must have a higher viscosity compared to the other methods.
Viscosity
SLA>EB>IJ IJ>SLA>EB SLA>EB>IJ SLA>IJ>EB
Fig. 3 Comparison of the bioprinting technologies
Printing
Speed
Bioprinting
technologies
Printing
Resolution
Cell viability Crosslinking
EB: Thermal,
Chemical,
Photo
Chemical and
IJ and SLA:
Photo
352
https://t.me/medicina_free
S. Mohaghegh and H. Nokhbatolfoghahaei
Besides, chemical, thermal, and photocrosslinking can be used in the extrusion­based method. However, thermal crosslinking has not been applied in laser-based and inkjet bioprinting. Inkjet printing has the highest printing speed, and extrusion­based has the lowest. Laser-based is the optimal choice regarding the printing reso­lution, while inkjet printing has the lowest resolution. The rate of cell death is the highest in extrusion-based and lowest in laser-based. Concerning the crosslinking method, chemical, thermal, and photocrosslinking can be used in extrusion-based, while thermal crosslinking is not used in laser-based and inkjet bioprinting.
References
1. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773–85.
2. Truby RL, Lewis JA.Printing soft matter in three dimensions. Nature. 2016;540(7633):371–8.
3. Grifth LG, Swartz MA.Capturing complex 3D tissue physiology invitro. Nat Rev Mol Cell Biol. 2006;7(3):211–24.
4. Achilli TM, Meyer J, Morgan JR.Advances in the formation, use and understanding of multi­cellular spheroids. Expert Opin Biol Ther. 2012;12(10):1347–60.
5. Abbott A.Cell culture: biology’s new dimension. Nature. 2003;424(6951):870–2.
6. Kim W, Kim G.Collagen/bioceramic-based composite bioink to fabricate a porous 3D hASCs­laden structure for bone tissue regeneration. Biofabrication. 2019;12(1):015007.
7. Hazrati P, et al. Current trends, advances, and challenges of tissue engineering-based approaches of tooth regeneration: a review of the literature. Curr Stem Cell Res Ther. 2022.
8. Raja N, Yun H-S.A simultaneous 3D printing process for the fabrication of bioceramic and cell-laden hydrogel core/shell scaffolds with potential application in bone tissue regeneration. J Mater Chem B. 2016;4(27):4707–16.
9. Wang XF, etal. Osteogenic differentiation of three-dimensional bioprinted constructs consist­ing of human adipose-derived stem cells invitro and invivo. PLoS One. 2016;11(6):e0157214.
10. Somasekharan LT, etal. Formulation and characterization of alginate dialdehyde, gelatin, and platelet-rich plasma-based bioink for bioprinting applications. Bioengineering. 2020;7(3):108.
11. Haeri Boroojeni HS, Mohaghegh S, Khojasteh A.Application of CAD-CAM technologies for maxillofacial bone regeneration: a narrative review of the clinical studies. Curr Stem Cell Res Ther; 2022.
12. Chen DX.Extrusion bioprinting of scaffolds. In: Extrusion bioprinting of scaffolds for tissue engineering applications. Cham: Springer; 2019. p.117–45.
13. Xie Z, etal. 3D bioprinting in tissue engineering for medical applications: the classic and the hybrid. Polymers. 2020;12(8):1717.
14. Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. Tissue Eng Part A. 2010;16(8):2675–85.
15. Dababneh AB, Ozbolat IT.Bioprinting technology: a current state-of-the-art review. J Manuf Sci Eng. 2014;136(6):0610161–611.
16. Soltan N, etal. Printability and cell viability in bioprinting alginate dialdehyde-gelatin scaf­folds. ACS Biomater Sci Eng. 2019;5(6):2976–87.
17. Willson K, etal. Extrusion-based bioprinting: current standards and relevancy for human-sized tissue fabrication. In: 3D bioprinting. Cham: Springer; 2020. p.65–92.
18. Liu B, et al. 3D-bioprinted functional and biomimetic hydrogel scaffolds incorporated with nanosilicates to promote bone healing in rat calvarial defect model. Mater Sci Eng C. 2020;112:110905.
19. Sadat-Shojai M, Khorasani M-T, Jamshidi A. 3-Dimensional cell-laden nano-hydroxyapatite/ protein hydrogels for bone regeneration applications. Mater Sci Eng C. 2015;49:835–43.
20. Kosik-Kozioł A, etal. 3D bioprinted hydrogel model incorporating β-tricalcium phosphate for calcied cartilage tissue engineering. Biofabrication. 2019;11(3):035016.
Application ofBioprinting Technology inOral andMaxillofacial Surgery
https://t.me/medicina_free
21. Rottensteiner U, et al. In vitro and in vivo biocompatibility of alginate dialdehyde/gelatin hydrogels with and without nanoscaled bioactive glass for bone tissue engineering applica­tions. Materials. 2014;7(3):1957–74.
22. Gao G, et al. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three­dimensional scaffold and human mesenchymal stem cells. Biotechnol J. 2014;9(10):1304–11.
23. Ye Q, etal. Three dimensional printed bioglass/gelatin/alginate composite scaffolds with pro­moted mechanical strength, biomineralization, cell responses and osteogenesis. J Mater Sci Mater Med. 2020;31(9):77.
24. Wu Z, etal. In vitro and invivo biocompatibility evaluation of a 3D bioprinted gelatin-sodium alginate/rat Schwann-cell scaffold. Mater Sci Eng C Mater Biol Appl. 2020;109:110530.
25. Zhang J, etal. Optimization of mechanical stiffness and cell density of 3D bioprinted cell­laden scaffolds improves extracellular matrix mineralization and cellular organization for bone tissue engineering. Acta Biomater. 2020;114:307–22.
26. Chaudhuri O, etal. Hydrogels with tunable stress relaxation regulate stem cell fate and activ­ity. Nat Mater. 2016;15(3):326–34.
27. Tabriz AG, etal. Three-dimensional bioprinting of complex cell laden alginate hydrogel struc­tures. Biofabrication. 2015;7(4):045012.
28. Mancha Sánchez E, etal. Hydrogels for bioprinting: a systematic review of hydrogels syn­thesis, bioprinting parameters, and bioprinted structures behavior. Front Bioeng Biotechnol. 2020;8:776.
29. Leite ÁJ, etal. Bioplotting of a bioactive alginate dialdehyde-gelatin composite hydrogel con­taining bioactive glass nanoparticles. Biofabrication. 2016;8(3):035005.
30. Zehnder T, Boccaccini AR, Detsch R.Biofabrication of a co-culture system in an osteoid-like hydrogel matrix. Biofabrication. 2017;9(2):025016.
31. Grigore A, etal. Behavior of encapsulated MG-63 cells in RGD and gelatine-modied alginate hydrogels. Tissue Eng Part A. 2014;20(15-16):2140–50.
32. Dranseikiene D, etal. Cell-laden alginate dialdehyde–gelatin hydrogels formed in 3D printed sacricial gel. J Mater Sci Mater Med. 2020;31(3):31.
33. Erickson CB, etal. In vivo degradation rate of alginate-chitosan hydrogels inuences tissue repair following physeal injury. J Biomed Mater Res B Appl Biomater. 2020;108(6):2484–94.
34. Chen DX.Preparation of Scaffold solutions and characterization of their ow behavior. In: Extrusion bioprinting of scaffolds for tissue engineering applications. Cham: Springer; 2019. p.91–115.
35. Tirella A, Ahluwalia A.The impact of fabrication parameters and substrate stiffness in direct writing of living constructs. Biotechnol Prog. 2012;28(5):1315–20.
36. Reid JA, etal. Accessible bioprinting: adaptation of a low-cost 3D-printer for precise cell placement and stem cell differentiation. Biofabrication. 2016;8(2):025017.
37. Faulkner-Jones A, etal. Bioprinting of human pluripotent stem cells and their directed dif­ferentiation into hepatocyte-like cells for the generation of mini-livers in 3D.Biofabrication. 2015;7(4):044102.
38. Billiet T, etal. The 3D printing of gelatin methacrylamide cell-laden tissue-engineered con­structs with high cell viability. Biomaterials. 2014;35(1):49–62.
39. Hendriks J, et al. Optimizing cell viability in droplet-based cell deposition. Sci Rep. 2015;5(1):11304.
40. Chen DX.Extrusion bioprinting of scaffolds: an introduction. In: Extrusion bioprinting of scaffolds for tissue engineering applications. Cham: Springer; 2019. p.1–13.
41. Hong S, etal. Coaxial bioprinting of cell-laden vascular constructs using a gelatin–tyramine bioink. Biomater Sci. 2019;7(11):4578–87.
42. Yu Y, etal. Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. J Biomech Eng. 2013;135(9):91011.
43. Hölzl K, et al. Bioink properties before, during and after 3D bioprinting. Biofabrication. 2016;8(3):032002.
44. Kumar H, Kim K.Stereolithography 3D bioprinting. Methods Mol Biol. 2020;2140:93–108.
353
354
https://t.me/medicina_free
45. Göckler T, etal. Tuning superfast curing thiol-norbornene-functionalized gelatin hydrogels for 3D bioprinting. Adv Healthc Mater. 2021;10(14):2100206.
46. Tibbitt MW, etal. Mechanical properties and degradation of chain and step-polymerized pho­todegradable hydrogels. Macromolecules. 2013;46(7):2785–92.
47. Wang Z, etal. Visible light photoinitiation of cell-adhesive gelatin methacryloyl hydrogels for stereolithography 3D bioprinting. ACS Appl Mater Interfaces. 2018;10(32):26859–69.
48. McCall JD, Anseth KS.Thiol-ene photopolymerizations provide a facile method to encapsu­late proteins and maintain their bioactivity. Biomacromolecules. 2012;13(8):2410–7.
49. Cramer NB, Bowman CN.Kinetics of thiol–ene and thiol–acrylate photopolymerizations with real-time fourier transform infrared. J Polym Sci A Polym Chem. 2001;39(19):3311–9.
50. Jing D, etal. Effect of low-level mechanical vibration on osteogenesis and osseointegration of porous titanium implants in the repair of long bone defects. Sci Rep. 2015;5(1):1–13.
51. Tytgat L, etal. Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tis­sue engineering. Acta Biomater. 2019;94:340–50.
52. Klotz BJ, etal. Gelatin-methacryloyl hydrogels: towards biofabrication-based tissue repair. Trends Biotechnol. 2016;34(5):394–407.
53. Fairbanks BD, et al. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl- 2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials. 2009;30(35):6702–7.
54. Kumar H, Kim K.Stereolithography 3D bioprinting. In: 3D Bioprinting. Cham: Springer;
2020. p.93–108.
55. Li L, Fourkas JT.Multiphoton polymerization. Mater Today. 2007;10(6):30–7.
56. Erben A, etal. Precision 3D-printed cell scaffolds mimicking native tissue composition and mechanics. Adv Healthc Mater. 2020;9(24):2000918.
57. Mao Q, et al. Fabrication of liver microtissue with liver decellularized extracellu­lar matrix (dECM) bioink by digital light processing (DLP) bioprinting. Mater Sci Eng C. 2020;109:110625.
58. Goodarzi Hosseinabadi H, etal. Digital light processing bioprinting advances for microtissue models. ACS Biomater Sci Eng. 2022;8(4):1381–95.
59. Lee K-S, etal. Advances in 3D nano/microfabrication using two-photon initiated polymeriza­tion. Prog Polym Sci. 2008;33:631–81.
60. Ovsianikov A, etal. Laser photofabrication of cell-containing hydrogel constructs. Langmuir. 2014;30(13):3787–94.
61. Solis LH, etal. Thermal inkjet bioprinting triggers the activation of the VEGF pathway in human microvascular endothelial cells invitro. Biofabrication. 2019;11(4):045005.
62. Cui X, etal. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul. 2012;6(2):149–55.
63. Li X, etal. Inkjet bioprinting of biomaterials. Chem Rev. 2020;120(19):10793–833.
64. Hewes S, Wong AD, Searson PC.Bioprinting microvessels using an inkjet printer. Bioprinting. 2017;7:14–8.
65. Takagi D, etal. High-precision three-dimensional inkjet technology for live cell bioprinting. Int J Bioprinting. 2019;5(2):208.
66. Saunders RE, Gough JE, Derby B.Delivery of human broblast cells by piezoelectric drop­on- demand inkjet printing. Biomaterials. 2008;29(2):193–203.
67. Mau R, etal. Inkjet printing of viable human dental follicle stem cells. Curr Dir Biomed Eng. 2015;1(1):112–5.
68. Zohora FT, Azim AYMA.Inkjet printing: an emerging technology for 3d tissue or organ print­ing. Eur Sci J. 2014;10(30):339–52.
69. Saunders RE, Derby B.Inkjet printing biomaterials for tissue engineering: bioprinting. Int Mater Rev. 2014;59(8):430–48.
70. Tasoglu S, Demirci U.Bioprinting for stem cell research. Trends Biotechnol. 2013;31(1):10–9.
71. Campbell PG, Weiss LE.Tissue engineering with the aid of inkjet printers. Expert Opin Biol Ther. 2007;7(8):1123–7.
S. Mohaghegh and H. Nokhbatolfoghahaei
Application ofBioreactors inOral
https://t.me/medicina_free
andMaxillofacial Surgery
HeliaSadatHaeriBoroojeni andHaniehNokhbatolfoghahaei
1 Introduction
Bone tissue engineering (BTE) strategies include numerous manipulative measures for the reconstruction of bone defects, using cell-laden, hierarchically organized, and anatomical and functional tissue fragments, highly resembling the natural inherent characteristics of bone tissue [1, 2]. However, the current methodology has not always resulted in optimal generation of a 100% physiologic environment with competent immune, nervous, and hormonal systems, necessary for development of functional tissues and organs [35]. A major shortcoming is associated with rela­tively time-consuming and compromised vascularization capacities. This results in prolonged vascularization periods and, so, compromised regenerative outcomes. Given that oxygen diffusion takes place at approximately 200μm, cells located at the core of implanted constructs can go through hypoxic conditions during these periods. These conditions can contribute to representation of an altered metabolism and eventually cell death in some cases. Scientic consensus and methodical evi­dence have indicated that dynamicity can promote biological systems and func­tional tissue engineering [68]. Therefore, dynamic systems have been designed with the aim of mimicking the specics of micro- and macro-tissue environments and reproduction of their mechanical and physiological features [810]. The same tactic has been implied for bone tissue engineering. Bone tissues are under sporadic pressure. The skeletal function encompasses bearing body loads in accordance with the body weight and physical activities that are performed throughout the daily life.
H. S. H. Boroojeni Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
H. Nokhbatolfoghahaei (*) Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 A. Khojasteh et al. (eds.), Emerging Technologies in Oral and Maxillofacial Surgery, https://doi.org/10.1007/978-981-19-8602-4_18
355
356
https://t.me/medicina_free
H. S. H. Boroojeni and H. Nokhbatolfoghahaei
These functions are translated as a natural dynamicity that involves the skeletal architecture of the body and cause consecutive deformation of extracellular matrix (ECM) and lacuna-canalicular uid ow [7, 8, 11, 12]. Bony cells being highly mechanosensitive can sense the hydrostatic pressure directly [7]. The application of ow-induced interstitial shear stress has revealed the occurrence of a sequential sensing procedure consisted of active direction of cellular differentiation and activa­tion of bone remodeling series of extracellular signaling pathways (i.e., ERK1/2, Wnt, bone morphogenetic protein (BMP)) [13]. These observations bring further notice to the stimulating impact of mechanical encounter upon invivo bone regen­eration processes [1421].
Although static cultural settings are deprived of the pivotal impact of mechanical stimulation, majority of invitro investigations have been designed and conducted in a static manner [7, 8]. Static culture conditions impose hurdles upon tissue develop­ment, consequent to their compromised delivery of adequate substances and waste removal. According to the literature, maximum diffusion distance for biotic sub­stances is below the range of 100–200μm [7, 8]. Therefore, cells, placed at the scaffold core, bear lower chances of survival, especially when cultured statically. Moreover, static culturing conditions contribute to the cellular tendency for surface attachment instead of even cellular diffusion throughout the structure [8].
Two types of mechanical stimuli have been revealed to induce cellular osteo­genic differentiation: (a) uid shear stress following the movement of interstitial uid through the lacunae during load bearing and (b) strain resulted from deforma­tion, after occurrence of bending and compression with physical activity [8, 11, 22].
Mechanical stimuli allow culture medium streaming within scaffolds, further contributing to the role of dynamicity in tissue engineering. Hence, restricted expression of osteogenic markers, inhibited stem cell differentiation, and limited nutrient diffusion to the scaffold core are among the drawbacks of static cultural settings that inherently tend to disregard the role of dynamicity in tissue generation and growth. Constraints of static culturing have led to an ongoing endeavors for incorporating mechanical stimuli [6, 23], using bioreactors. Bioreactors are housing devices that provide controlled conditions that allow enactment of physiologic, bio­logic, and biochemical phenomena within articial tissue constructs. Initial objec­tive of bioreactors was to test biomaterials, but afterward, various modalities were developed aiming for extracorporeal tissue growth. Incorporation of bioreactors in terms of tissue engineering has led to the recent emergence of the term “Tissue Engineering Quadriad” as for the combination of cells, carrier constructs, signaling factors, and bioreactor systems, which formerly only consisted of rst three compo­nents, the so-called tissue engineering triad [6]. Bioreactors have helped with addressing the static culturing-associated limitations and culminated in a paradigm shift regarding extracorporeal fabrication of viable tissue fragments. Osteogenic­based bioreactors are designed to promote osteogenic capabilities of bio-scaffolds and “in vitro bone tissue morphogenesis,” namely, the generation of bone-like struc­tures and ECM [24]. Bioreactors are used for facilitation, monitoring, and control­ling the inherent biological or biochemical phenomena that occur within natural tissue. Complex bioreactors allow tuning of certain physiologic parameters,
Application ofBioreactors inOral andMaxillofacial Surgery
https://t.me/medicina_free
357
Spinner Flask
Bioreactors
for
Bone Tissue
Engineering
In Vitro Bioreactors
In Vivo Bioreactors
Hydrodynamic-Based
Shear-Loading
Compression (Direct
Mechanical Stress)
EMF-Based
Combined
Flap Techniques
Vascular Techniques
Rotating
Perfusion-Based
Subcutaneous Pocket
Muscular Flap
Periosteal Flap
Axial Vascular Bundle (AVB)
Arteriovenous Loop (AV-Loop)
Fig. 1 Bioreactors for bone tissue engineering
including the temperature, pH, different substance concentrations, and diverse set of stimuli, when growth modulation is yearned for [25]. Incorporated devices in a bioreactor system are made of biologically and chemically inert materials so that undesired reactions are primarily prohibited in the internal humidied milieu [26].
Bioreactors are known to possess the following criteria: (1) distribute cells evenly; (2) sustain cellular requisites; (3) mix the culture mediums to emend substance dif­fusion and convection; (4) provide physical stimuli; and (5) provide requisites for reproducibility, control, monitoring, and automation [27]. In vitro bioreactors helped dened recapitulation of in vivo microenvironments within an ex vivo setting. However, invitro developed tissues have showed lack of inherent vascular and neural networks. This has made tissue fragments chiey reliant upon the ingrowth of neo­vascular sprouts of the recipient beds of host. Therefore, the principle of invivo bioreactor (IVB) has developed to address such shortcomings (Fig.1).
2 Bioreactors forBone Tissue Engineering
Various bioreactor modalities have been designed to give a desired combination of stimulation specics. Theoretical concepts can help the designing and fabrication of bioreactors. For instance, mathematical modelling allows calculation of scaffold
358
https://t.me/medicina_free
uid ow rates, diffusion of oxygen, implied forces, and other variables [28], through providing insights for culturing bulk materials.
Based upon their design, bioreactors are categorized in three groups: (a) those that are designed based on implication of hydrodynamic shear stresses, (b) those that are designed based on implication of direct mechanical stresses, and (c) those that are designed based on implication of electromagnetic elds (EMF) [8, 29].
H. S. H. Boroojeni and H. Nokhbatolfoghahaei
2.1 Hydrodynamic-Based Shear-Loading Bioreactors
One of simplest and most pervasive bioreactor designs is attained with hydrody­namic shear stress. The hydrodynamic shear stress is applied through medium uid circulation. Shear-loading devices include spinner ask, rotating, and perfusion­based bioreactors [29].
2.1.1 Spinner Flask Bioreactors
The spinner ask bioreactors create a turbulent ow leading to a promoted diffusion of biotic substances [29]. These bioreactors are relatively simple and inexpensive systems. Spinner asks consisted of a glass reservoir, side arms, and porous ltering covers. The reservoir holds the media, and the side arms are unlocked to reach the reservoir’s internal space. While scaffolds are attached to the lid of unit ask with needles, an assembled mixer starts convective forces and medium ow at the ask center unit. Mixer’s stirring speed is set based on the aimed for shear stress that is to be applied on scaffolds. The porous ltering covers allow the gas by-products to exchange within the system. Once prepared, the whole ask is retained in incuba­tors with pre-controlled temperature and oxygen-delivery content [6, 23, 30].
Spinner ask bioreactors were primarily designed to be used in BTE [31]. Spinner ask systems have been known as facile and low-cost setups, capable of promoting proliferation and differentiation of cultured cells [6, 29, 31, 32]. They are capable of more efciently enhancing nutrient mass transport when compared to rotating wall vessels [6, 29]. Moreover, spinner asks can impart higher stress val­ues upon cells. Spinner ask bioreactors can house multiple small scaffolds and culture clinically relevant engineered tissue fragments concomitantly. This can put spinner ask bioreactor at use when reconstruction of segmental skeletal defects is planned [6]. With regard to development of thin bone substitutes that are used as bone patches in restorative interventions or at bone reconstructions, spinner asks and rotating wall vessels are both rational choices [6]. In addition to their differen­tial and proliferative impacts, spinner ask systems have the advantage of low acquisition costs [29].
Being hydrodynamically capable of implying shear stress, spinner ask bioreac­tors have improved nutrient transfer into scaffolds. However, many constraints are still present with them. For instance, stirring action of mixers can cause a turbulent environment within the media. This bears the probability to dissociate the attached cells. Spinner asks’ abilities are limited in terms of mass transport and application of desired levels of stress upon cells. An impaired systemic seal is associated with
Application ofBioreactors inOral andMaxillofacial Surgery
https://t.me/medicina_free
359
them that averts sufcient control over the O2/CO2 content of asks. There has also remained a need for constant obligatory replacement of cultural media. Of note, when cultivating combined cell-scaffold structures, it is likely to witness a dense supercial cell layer. This layer can impede the biotic supply of core-retained cells in such bioreactors. Moreover, the gradient set of convective forces in ask result in heterogeneous application of shear stress. Concerns are present with their potential in supporting of functional bone maturation [29, 31, 33] (Fig.2).
2.1.2 Rotating Bioreactors (Rotating Wall Vessel (RWV))
The rationale behind the design of rotating bioreactors is to use microgravity to form three-dimensional cell clusters [23]. Rotating bioreactors imply low shear stresses and thus promote nutrient transfer [29]. The rotating vessels of system pro­duce shear stresses by initiating laminar ow in a horizontal axis [29]. The produced shear stresses, despite being low in degree, contribute to the diffusion of nutrients and waste products [29]. In preliminary models of rotating bioreactor, scaffolds were left to oat within the media [29], resulting in collision of constructs with
Fig. 2 Spinner ask bioreactor