Добавил:
Sekretar
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_998_Библиотеки_им_академика_М_И_Перельмана
.pdf
14
https://t.me/medicina_free
M. M. Aitzetmüller et al.
epsilon-(carboxymethyl)lysine and N epsilon(carboxymethyl)hydroxylysine in human skin collagen. Biochemistry. 1991;30(5):1205–10.
28. Rhie G, Shin MH, Seo JY, Choi WW, Cho KH,
Kim KH, Park KC, Eun HC, Chung JH. Agingand photoaging- dependent changes of enzymic
and nonenzymic antioxidants in the epidermis and
dermis of human skin in vivo. J Invest Dermatol.
2001;117(5):1212–7.
29. Kohen R.Skin antioxidants: their role in aging and in
oxidative stress—new approaches for their evaluation.
Biomed Pharmacother. 1999;53(4):181–92.
30. Harman D. Aging: a theory based on free
radical and radiation chemistry. J Gerontol.
1956;11(3):298–300.
31. Harman D.The free radical theory of aging. Antioxid
Redox Signal. 2003;5(5):557–61.
32. Surjushe A, Vasani R, Saple D. Aloe vera: a short
review. Indian J Dermatol. 2008;53(4):163.
33. Hodges YK, Reese SM, Pahl PM, Horwitz
LD. Paradoxical effects of iron chelation on growth
of vascular endothelial cells. J Cardiovasc Pharmacol.
2005;45(6):539–44.
34. Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti
L, Malaventura C, Putti MC, Lippi A, Romeo MA,
Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo
L, Missere M, Midiri M, Rossi G, Positano V,
Lombardi M, Maggio A. Deferasirox, deferiprone
and desferrioxamine treatment in thalassemia major
patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging.
Haematologica. 2011;96(1):41–7.
35. Kuo KH, Mrkobrada M. A systematic review
and meta-analysis of deferiprone monotherapy
and in combination with deferoxamine for reduction of iron overload in chronically transfused
patients with beta2014;38(6):409–21.
36. Moayedi Esfahani BA, Reisi N, Mirmoghtadaei
M. Evaluating the safety and efcacy of silymarin
in beta-thalassemia patients: a review. Hemoglobin.
2015;39(2):75–80.
37. Ram M, Singh V, Kumawat S, Kumar D, Lingaraju
MC, Uttam Singh T, Rahal A, Tandan SK, Kumar
D. Deferoxamine modulates cytokines and growth
factors to accelerate cutaneous wound healing in diabetic rats. Eur J Pharmacol. 2015;764:9–21.
38. Temiz G, Sirinoglu H, Yesiloglu N, Filinte D, Kacmaz
C. Effects of Deferoxamine on fat graft survival.
Facial Plast Surg. 2016;32(4):438–43.
39. Lu H, Dalgard CL, Mohyeldin A, McFate T, Tait AS,
Verma A. Reversible inactivation of HIF-1 prolyl
hydroxylases allows cell metabolism to control basal
HIF-1. J Biol Chem. 2005;280(51):41928–39.
40. Duscher D, Neofytou E, Wong VW, Maan ZN,
Rennert RC, Inayathullah M, Januszyk M, Rodrigues
M, Malkovskiy AV, Whitmore AJ, Walmsley GG,
Galvez MG, Whittam AJ, Brownlee M, Rajadas J,
Gurtner GC. Transdermal deferoxamine prevents
pressure-induced diabetic ulcers. Proc Natl Acad Sci
U S A. 2015;112(1):94–9.
thalassemia. Hemoglobin.
41. Miller JR, Moon RT. Signal transduction through
beta-catenin and specication of cell fate during
embryogenesis. Genes Dev. 1996;10(20):2527–39.
42. Brennan KR, Brown AM.Wnt proteins in mammary
development and cancer. J Mammary Gland Biol
Neoplasia. 2004;9(2):119–31.
43. Barham W, Frump AL, Sherrill TP, Garcia CB, SaitoDiaz K, VanSaun MN, Fingleton B, Gleaves L, Orton
D, Capecchi MR, Blackwell TS, Lee E, Yull F, Eid
JE. Targeting the Wnt pathway in synovial sarcoma
models. Cancer Discov. 2013;3(11):1286–301.
44. Leavitt T, Hu MS, Marshall CD, Barnes LA, Lorenz
HP, Longaker MT. Scarless wound healing: nding the right cells and signals. Cell Tissue Res.
2016;365(3):483–93.
45. Saraswati S, Alfaro MP, Thorne CA, Atkinson J, Lee
E, Young PP.Pyrvinium, a potent small molecule Wnt
inhibitor, promotes wound repair and post-MI cardiac
remodeling. PLoS One. 2010;5(11):e15521.
46. Thorne CA, Hanson AJ, Schneider J, Tahinci E, Orton
D, Cselenyi CS, Jernigan KK, Meyers KC, Hang
BI, Waterson AG, Kim K, Melancon B, Ghidu VP,
Sulikowski GA, LaFleur B, Salic A, Lee LA, Miller
DM 3rd, Lee E.Small-molecule inhibition of Wnt signaling through activation of casein kinase 1alpha. Nat
Chem Biol. 2010;6(11):829–36.
47. Saraswati S, Deskins DL, Holt GE, Young
PP.Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs). Wound
Repair Regen. 2012;20(2):185–93.
48. Plikus MV, Guerrero-Juarez CF, Ito M, Li YR,
Dedhia PH, Zheng Y, Shao M, Gay DL, Ramos R,
Hsi TC, Oh JW, Wang X, Ramirez A, Konopelski
SE, Elzein A, Wang A, Supapannachart RJ, Lee HL,
Lim CH, Nace A, et al. Regeneration of fat cells
from myobroblasts during wound healing. Science.
2017;355(6326):748–52.
49. Plikus MV, Mayer JA, de la Cruz D, Baker RE, Maini
PK, Maxson R, Chuong CM. Cyclic dermal BMP
signalling regulates stem cell activation during hair
regeneration. Nature. 2008;451(7176):340–4.
50. Chan CK, Longaker MT. Fibroblasts become fat to
reduce scarring. Science. 2017;355(6326):693–4.
51. Banerjee J, Chan YC, Sen CK. MicroRNAs in
skin and wound healing. Physiol Genomics.
2011;43(10):543–56.
52. Lai WF, Siu PM.MicroRNAs as regulators of cutaneous wound healing. J Biosci. 2014;39(3):519–24.
53. Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M,
Fatima A, Lavker RM. MicroRNA-184 antagonizes
microRNA-205 to maintain SHIP2 levels in epithelia.
Proc Natl Acad Sci USA. 2008;105(49):19300–5.
54. Wang XH, Qian RZ, Zhang W, Chen SF, Jin HM, Hu
RM.MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with
insulin-like growth factor-1 in type 2 diabetic rats.
Clin Exp Pharmacol Physiol. 2009;36(2):181–8.
55. Dykxhoorn DM, Palliser D, Lieberman J.The silent
treatment: siRNAs as small molecule drugs. Gene
Ther. 2006;13(6):541–52.
3 Basic Principles andCurrent Approach forSoft Tissue Regeneration
https://t.me/medicina_free
15
56. Shaw TJ, Martin P. Wound repair at a glance. J Cell
Sci. 2009;122(Pt 18):3209–13.
57. Liu X, Ma L, Liang J, Zhang B, Teng J, Gao C.RNAi
functionalized collagen-chitosan/silicone membrane
bilayer dermal equivalent for full-thickness skin
regeneration with inhibited scarring. Biomaterials.
2013;34(8):2038–48.
58. Brummelkamp TR, Bernards R, Agami R.Stable suppression of tumorigenicity by virus-mediated RNA
interference. Cancer Cell. 2002;2(3):243–7.
59. Ding H, Schwarz DS, Keene A, Affar e B, Fenton L,
Xia X, Shi Y, Zamore PD, Xu Z. Selective silencing
by RNAi of a dominant allele that causes amyotrophic
lateral sclerosis. Aging Cell. 2003;2(4):209–17.
60. Toloue MM, Ford LP.Antibody targeted siRNA delivery. Methods Mol Biol. 2011;764:123–39.
61. Gary DJ, Puri N, Won YY. Polymer-based siRNA
delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA
delivery. J Control Release. 2007;121(1–2):64–73.
62. Walmsley GG, Maan ZN, Wong VW, Duscher D, Hu
MS, Zielins ER, Wearda T, Muhonen E, McArdle A,
Tevlin R, Atashroo DA, Senarath-Yapa K, Lorenz
HP, Gurtner GC, Longaker MT. Scarless wound
healing: chasing the holy grail. Plast Reconstr Surg.
2015;135(3):907–17.
63. Scarabel L, Perrone F, Garziera M, Farra R, Grassi
M, Musiani F, Russo Spena C, Salis B, De Stefano
L, Toffoli G, Rizzolio F, Tonon F, Abrami M,
Chiarappa G, Pozzato G, Forte G, Grassi G, Dapas
B. Strategies to optimize siRNA delivery to hepatocellular carcinoma cells. Expert Opin Drug Deliv.
2017;14(6):797–810.
64. Rennert RC, Sorkin M, Januszyk M, Duscher D,
Kosaraju R, Chung MT, Lennon J, Radiya-Dixit
A, Raghvendra S, Maan ZN, Hu MS, Rajadas J,
Rodrigues M, Gurtner GC. Diabetes impairs the
angiogenic potential of adipose-derived stem cells by
selectively depleting cellular subpopulations. Stem
Cell Res Ther. 2014;5(3):79.
65. Duscher D, Rennert RC, Januszyk M, Anghel E,
Maan ZN, Whittam AJ, Perez MG, Kosaraju R, Hu
MS, Walmsley GG, Atashroo D, Khong S, Butte
AJ, Gurtner GC. Aging disrupts cell subpopulation
dynamics and diminishes the function of mesenchymal stem cells. Sci Rep. 2014;4:7144.
66. Hadjipanayi E, Schilling AF. Regeneration through
autologous hypoxia preconditioned plasma.
Organogenesis. 2014;10(2):164–9.
67. Hadjipanayi E, Bauer AT, Moog P, Salgin B, Kuekrek
H, Fersch B, Hopfner U, Meissner T, Schlüter A,
Ninkovic M, Machens HG, Schilling AF. Cell-free
carrier system for localized delivery of peripheral blood cell-derived engineered factor signaling: towards development of a one-step device for
autologous angiogenic therapy. J Control Release.
2013;169(1–2):91–102.
68. Yildirimer L, Thanh NT, Seifalian AM.Skin regeneration scaffolds: a multimodal bottom-up approach.
Trends Biotechnol. 2012;30(12):638–48.
69. Wong VW, Rustad KC, Galvez MG, Neofytou E,
Glotzbach JP, Januszyk M, Major MR, Sorkin M,
Longaker MT, Rajadas J, Gurtner GC. Engineered
pullulan-collagen composite dermal hydrogels
improve early cutaneous wound healing. Tissue Eng
Part A. 2011;17(5–6):631–44.
70. Rennert RC, Rodrigues M, Wong VW, Duscher D,
Hu M, Maan Z, Sorkin M, Gurtner GC, Longaker
MT.Biological therapies for the treatment of cutaneous wounds: phase III and launched therapies. Expert
Opin Biol Ther. 2013;13(11):1523–41.
71. Wong VW, Rustad KC, Glotzbach JP, Sorkin M,
Inayathullah M, Major MR, Longaker MT, Rajadas
J, Gurtner GC. Pullulan hydrogels improve mesenchymal stem cell delivery into high-oxidative-stress
wounds. Macromol Biosci. 2011;11(11):1458–66.
72. Rustad KC, Wong VW, Sorkin M, Glotzbach JP,
Major MR, Rajadas J, Longaker MT, Gurtner
GC.Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials. 2012;33(1):80–90.
73. Garg RK, Rennert RC, Duscher D, Sorkin M, Kosaraju
R, Auerbach LJ, Lennon J, Chung MT, Paik K, Nimpf
J, Rajadas J, Longaker MT, Gurtner GC. Capillary
force seeding of hydrogels for adipose-derived stem
cell delivery in wounds. Stem Cells Transl Med.
2014;3:1079–89.
74. Lam MT, Nauta A, Meyer NP, Wu JC, Longaker
MT.Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival
and proliferation and reduced scarring in skin wound
healing. Tissue Eng Part A. 2013;19(5–6):738–47.
Sophisticated Biocomposite
https://t.me/medicina_free
Scaolds fromRenewable
Biomaterials forBone Tissue
Engineering
YavuzEmreArslan, ErenOzudogru,
TugbaSezgin Arslan, BurakDerkus,
EmelEmregul, andKaanC.Emregul
4
4.1 Introduction
Loss or the dysfunction of bone tissue may occur
due to trauma, injury, disease, or aging [1].
Currently there are excessive amount of materials
to be applied to bone regeneration [2]. In turn, the
autograft-, allograft-, or xenograft-based bone
regeneration techniques have their disadvantages
such as the need for extra surgical procedures,
infection, chronic pain, or tissue rejection, which
in turn has increased the importance of tissue
engineering and regenerative medicine [3]. The
main goal of tissue engineering is to assemble
isolated functional cells and biodegradable tissue
scaffolds made from bioengineered materials
with the aim of regenerating diseased or damaged
tissue. Many scientists from this multidisciplinary eld have focused on designing and generating appropriate scaffolds for various tissues,
by primarily overcoming cell-dependent prob-
Y. E. Arslan (*) · E. Ozudogru · T. Sezgin Arslan
Regenerative Biomaterials Laboratory, Department of
Bioengineering, Engineering Faculty, Canakkale
Onsekiz Mart University, Canakkale, Turkey
B. Derkus
Department of Biomedical Engineering, Engineering
Faculty, Eskisehir Osmangazi University,
Eskisehir, Turkey
E. Emregul · K. C. Emregul
Bioelectrochemistry Laboratory, Department of
Chemistry, Ankara University, Tandogan,
Ankara, Turkey
lems in addition to scrutinizing tissue engineering structures invitro and invivo [4].
This chapter aims at describing the importance of renewable materials which have great
potential for use in bone tissue engineering. In
this context, the chapter offers new approaches
in the improvement of polymeric composite
matrices with the aim of obtaining 3D
tissue- engineered scaffolds from renewable
biomaterials.
4.2 Biology ofBone Tissue:
Structure andFunction
Bone tissues are responsible for many crucial
assignments, the most notable ones being structural support and protection against external
forces in the vertebrates. Its ability to self-repair
and rebuild by promoting mechanical requirements makes this tissue very unique in a structural sense. However, healthy bone functions can
be inuenced by many different pathological situations or diseases. On the other hand, the bone
tissue has been established to have limited regenerative capacities depending on patient age, anatomical site, and fracture size since it is hard for
the body to repair huge gaps by itself [5, 6].
Critical-sized fractures (~5mm) do not have the
ability to heal on their own and need surgical procedures to ensure the appropriate restoration.
Typical fractures seldom give rise to the formation of a hole of critical size, whereas some trau-
© Springer Nature Switzerland AG 2019
D. Duscher, M. A. Shiffman (eds.), Regenerative Medicine and Plastic Surgery,
https://doi.org/10.1007/978-3-030-19958-6_4
17
18
Central
20-200 nm
https://t.me/medicina_free
Y. E. Arslan et al.
matic defects, cancer, infections of the bone, or
age-related degenerations result in areas where
the bone cannot renew by itself. Thus, bone tissue
transplantation is the second most performed
procedure after blood, with over 100 million
operations a year, where patients only in the USA
pay approximately $800billion for treating bone
diseases annually [6].
Bone, an enduring and extremely vascularized tissue, can keep reconstructing itself
throughout a life span. Within its dynamics are
different mechanical, biological, and chemical
functions which act in controlled harmony.
These include structural support, protection and
regulation and storage of restorative cells and
minerals, in addition to protection and regulation
of Ca and P ions by arrangement of crucial electrolyte concentrations in the blood [7]. It actively
contributes to the generation of various types of
blood cells (known as hematopoiesis) by regulating homeostasis [8]. The bone structure has a
complementary role in mobility, through the
skeletal structure which has sufcient load-bear-
ing capability and behaves as a protective cover
for the sensitive interior organs of the body [9].
For a better understanding of the mechanical
features of a compact bone tissue, it is signicant
in understanding the hierarchical constructional
behavior they possess: (1) cancellous and cortical bone; (2) the microstructure (from 10 to
500μm); Haversian systems, osteons, single trabeculae; (3) the sub- microstructure (1–10 μm);
lamellae; (4) the nanostructure (from a few hundred nanometers to 1 micron): molecular structure of constituent elements like brillar collagen
and embedded mineral; and (5) the sub-nanostructure (less than a few nanometers): molecular structure of component elements such as
minerals, collagen, and non-collagenous organic
proteins (Fig. 4.1). Thus, the components of
bone material are both heterogeneous and anisotropic in nature [10].
The bone ultrastructure is composed of collagen and minerals such as tricalcium phosphate,
and hydroxyapatite (HA), Ca
(PO4)6(OH)2.
10
Synthetic HA is one of the most preferred bioc-
Osteon
Spongy Bone
Compact Bone
Bone Marrow
Periosteum
Osteoblast
Osteoclast
c=0.6881 nm
P
Ca
O
H
Osteocyte
a=0.9432 nm
Ca10(PO4)6(OH)
2
Medullary
trabecular
bone
OH dipole
Osteogenic
cell
Hydroxyapatite
Nanocrystals
~10 nm
Concentric
lamellae
Tropocollagen
triple helix
~300 nm
~1.4 nm
Overlap
Hole
Fig. 4.1 Anatomy of bone tissue: The ultrastructure of compact bone [16]
Collagen fibers
run in different
directions
Nerve fiber
Pores
HAp
NCPs
Zone
Zone
Nonenzymatic cross-links
(intra/interfibrillar)
Mature enzymatic cross-links
(interfibrillar)
27nm 40nm
Vein
Collagen
Fibril
Lymphatic
vessel
67 nm
Artery
Collagen
Fiber
canal
4 Sophisticated Biocomposite Scaolds fromRenewable Biomaterials forBone Tissue Engineering
https://t.me/medicina_free
19
eramic structures used in the construction of bone
substitutes. When examined in detail, bone macromolecules are formed from collagen type I
(90%) and over 200 different types of noncollagenous matrix proteins (i.e., osteocalcin,
osteonectin, glycoproteins, proteoglycans, and
sialoprotein) [11, 12]. These non-collagenous
matrix proteins induce intermediate extracellular
signals which tend to regulate the homeostasis of
various cell types such as osteoblast, osteocyte,
and osteoclast. The other crucial section of bone
is the mineralized inorganic components (composed of 4-nm-thick plate-like carbonated apatite
mineralities). Moreover, the compact structure
composed of collagen and HA gives this tissue a
unique compressive strength and high fracture
toughness [12].
HA is a bioactive, biocompatible, osteoconductive, nontoxic, noninammatory, and nonimmunogenic ceramic for bone tissue engineering
and one of the most widely used biomaterials due
to its resemblance to the inorganic constituent of
the vertebrae, bone and its ability to encourage
cell-scaffold adaptation [13]. Hydroxyapatite
nanoparticles (HAp) in collagen bers reach for
supporting assistants by activating the production
of alkaline phosphatase in bone, resulting in its
overwhelming endurance [14]. Nanoscale HAp
(50×25×3nm
3
) is crucial for appropriate generation of osteocytes in the bone matrix. Naturally
produced HAp has a Ca:P ratio of 1.67 which
needs to be imitated in the production of HAp to
acquire the necessary biological response, solubility, and mechanical sensitivity [15].
Autogenous bone implants are widely selected
in bone replacement. Nevertheless, this treatment
technique is limited due to insufciency of
donors, infection, veto of implant, etc., especially
in wide fractures [17]. Various studies have been
conducted since the discovery of the differentiation potential of human adipose-derived mesenchymal stem cells (hAMSCs) into osteogenic
lineage, and hence these cells have been considered as an excellent source for bone tissue engineering applications. Even though rst practices
included the direct implementation of stem cells
into fracture locations, nowadays scaffolds combined with stem cells, particularly MScs, are
applied, so that they promote cell colonization,
immigration, growth, and differentiation [18].
An optimal scaffold for bone tissue engineering practices should permit or enhance cell viability, attachment, proliferation, homing,
osteogenic differentiation, vascularization, host
integration, and high load-bearing capacity
(Fig. 4.2). In addition, it should be simple to
apply and susceptible to minimally invasive
implant treatment. It should be reproducible on
an industrial scale and at the same time be sterile.
Eventually, all its features should be practical and
meet the demands [19].
4.3 An Overview ofBiomaterials
inTissue Engineering
The eld of tissue engineering involves chemistry, biology, medicine, and engineering
approaches, with the aim of repairing and/or
replacing injured tissues and organs with the aid
of bioarticial substitutes using biopolymers,
cells, and biologically active agents such as
growth factors and cytokines (Fig.4.3). This is a
thriving interdisciplinary eld presenting new
opportunities to scientists [7, 20]. The extracellular matrix comprises a complex combination
of structural and functional proteins, glycoproteins and proteoglycans that are organized in a
unique tissue-specic three-dimensional structure. They play a vital role in morphogenesis,
composition, and function of tissues as well as
organs [21].
Providing a suitable microenvironment, that is
to say, fabricating scaffolds or decellularized
extracellular matrices for cell growth, migration,
and proliferation is crucial in tissue engineering
(Fig. 4.4). This is due to the fact that scaffolds
which include growth factors or other signaling
molecules serve as a so-called niche for cells [7,
23, 24]. In essence, big progress in the fabrication
of novel three-dimensional (3D) tissueengineered scaffolds, using biodegradable polymers for the purpose of therapy, has been
achieved. An extensive number of attempts at
developing new scaffold technologies using both
polymers and cells, including stem and/or
20
https://t.me/medicina_free
Y. E. Arslan et al.
Non-toxic
Biocompatible
Bioresorbable
Biodegradable
Non-immunogenic
Bioactive
Smart
Biomaterials
-Ceramics
- Polymerics
-Composites
Biological
requirements
Composition
SCAFFOLD
FOR BONE
REGENERATION
AIMS
Structural
features
Manufacturing
technologies
Biomimetic
Bioinspired
Ta ilored architecture
Customized shape
High porosity
Pore interconnection
Mechanical Properties
Surface Topography
Conventional
-Gas foaming
-Solvent casting
-Freeze Drying
Advanced
-EIectrospinning
-Rapid Prototyping
CELL AT TACHMENT CELL VIABILITY
OSTEOGENIC DIFFERENTIATION
Fig. 4.2 General overview of scaffold construction for bone regeneration [19]
somatic cells, isolated from various tissues have
been made. Polymers used in the fabrication of
scaffolds in regenerative medicine can usually be
categorized as synthetic or natural, where the
commonly used polysaccharides (starch, alginate,
chitosan, hyaluronic acid derivatives, etc.) and
proteins (collagen, brin gels, silk, keratin, etc.)
are examples for natural polymers (Table 4.1).
On the other hand, synthetic polymers such as
polylactic acid (PLA), poly(-lactic acid)
(PLLA), poly(,-lactic-co-glycolic acid)
(PLGA), polyglycolic acid (PGA), and polycaprolactone (PCL), approved by U.S.Food & Drug
Administration (FDA), can be easily processed
and handled in contrast to natural polymers
which is their superiority (Table4.2) [25]. Major
CELL HOMING
advances seen in biomaterials technology in
recent years have led to the development of
sophisticated materials [26]. Ideally, functionalized biomaterials like ceramics and natural/synthetic biodegradable polymers can be utilized for
the production of 3D scaffolds which tend to supply not only mechanical support but also
microscale architecture for neo-tissue construction allowing in vitro and in vivo cell growth,
attachment, migration, and proliferation [24, 27,
28]. These biomaterials are seen to have a wide
range of applications, including replacement of
biological tissues and development of instruments for injury and surgical applications, and
medical diagnosis has led to a revolution in biomaterial science [26].
CELL PROLIFERATION
VASCULAR INGROWTHHOST INTEGRATION LOAD BEARING
4 Sophisticated Biocomposite Scaolds fromRenewable Biomaterials forBone Tissue Engineering
https://t.me/medicina_free
PeriosteumMarrow Cortical bone
21
(ii)
(A) Normal
(i)
Day 0-3 Day 3-5 Day 5-10 Day 10-16 Day 16-21 Day 21-35
time course of
bone healing
(B) Delays in
bone healine
Haematoma
Monocyte
T cell
Macrophage
Prolonged
hematoma or
inflammation
vascularisation
Lack of
Haematoma
Insufficient
recruitment of
cells
PMN
B cell Stem cell
Soft callus/
unmineralized
cartilage
Chondrocyte
Osteoblast
Delayed
formation of
fibrocartilage
Fibrous
tissue
Hypertrophic
chondrocyte
Osteoclast
Insufficient
mineralisation
and formation of
woven bone
Hard callus/
secondary bone
Myelopoietic
Haematopoietic
cell
Dysregulation of
cell
remodelling
Fig. 4.3 The repairing mechanism of femur fractures and common complications that may occur [9]
4.4 The Importance ofPopular
Renewable Materials
forRegenerative Medicine
devoted themselves to the development of durable hybrid biomaterials of hydroxyapatite with
proteins and alternative synthetic polymers [31–
35]. For many years, HA ceramics that can
The applicability of native materials containing
polysaccharides and proteins in the structure of
hydrogels has been well studied. These materials,
including ECM proteins such as collagen, elastin,
brin, keratin, hydroxyapatite, and hyaluronic
acid, show signicant bioactivity in biomedical
applications [30].
Bone is a complicated material consisting of
mostly collagen, proteins, with hydroxyapatite
in organic component. Although HA is the
essential inorganic constituent of bone, it does
not have the ability to be applied as bone healing material alone because of its delicate and
brittle nature. At present, many researchers have
improve bone mass and formation of the implant
and the bone interface have become quite important as bone grafting material, due to their great
mechanical properties, corrosion resistance,
biocompatibility, bioactive properties, and perfect osteoconductive features [17, 36, 37]. Using
an enhanced hygienic, nontoxic and in addition
to an environmentally friendly approach, HA
powders have been obtained utilizing bioproducts such as corals, cuttlesh shells, natural
gypsum, natural calcite, bovine bone, sea
urchin, starsh, and eggshell [38–41]. Chemical
studies have demonstrated that these bio-wastes,
contrary to popular opinion, are rich in calcium
(iii)
Hard callus/
remodelled
bone
Osteocyte
Poor Quality
Bone formation
22
1. Pre-made porous scaffolds
f
technologies
2. Decellularized extracellular
3. Cell sheets with secreted
4. Cell encapsulated in self-
https://t.me/medicina_free
Y. E. Arslan et al.
matrix (ECM)
abrication
cell seeding cell seeding
Fig. 4.4 Different scaffold fabrication techniques in tissue engineering and regenerative medicine [22]
raw materials
decellularization
porous scaffolds
cell-seeding scaffolds cell-seeding scaffolds multiple cell sheets
Implantation Implantation
native tissues
ECM secretion
porous scaffolds
Defective tissues
extracellular matrix
Iamination
assembled hydrogel
confluent cells monomer solution
initiation of
self-assembly
cell sheet
Implantation
cell encapsulated in hydrogel
cell
mixing
Injection
in the form of carbonates and oxides. Eggshells
are one of the best examples for bio-waste.
Millions of tons of eggshells are produced by
people as bio-waste on daily basis throughout
the world. The eggshell constitutes ~11% of the
whole weight of an egg and consisted of calcium carbonate (~94%), calcium phosphate
(~1%), and organic matter (~4%) [42]. In addition, eggshells are inexpensive, abundant in
nature, biocompatible, yet not osteoconductive.
Therefore, transforming these powders in HA
before implantation is favorable [43].
Keratins are structural proteins that display
high mechanical resistance owing to numerous
intra- and intermolecular disulde bonds containing a fair amount of cysteine [44]. Keratin is
mostly consisting of ß-sheets, a small number of
α-helices, and loops [45, 46]. Waste keratins are
generally obtained from human hair (Fig. 4.5),
animal nails, horns, hoofs, wool, and feathers
[47]. Additionally, about 300,000 tons of hair is
wasted in hair salons, hospitals, and similar
places each year [48]. Keratin obtained from
renewable sources is highly biocompatible, possesses cellular interaction sites, and exhibits
enhanced biodegradability. In contrast to alternative natural materials, human hair keratins have
different benets like being abundant, bioactive,
having a powerful capacity to self-assemble
inside hydrogels, and being an exact source of
autologous proteins [49, 50]. Likewise, in addition to enhancing mechanical properties, this
autologous protein has some signaling patterns
like Leucine-Aspartic Acid-Valine (LDV) and
Glutamic Acid-Aspartic Acid-Serine (EDS) peptide regions which increase the adhesion characteristics of cells [47, 51]. Nonetheless, new
improvements have been made to obtain keratin
easily from human hair which has resulted in
good tissue engineering applications [52].
Collagen is the most widespread protein in
the body and provides endurance and constructional stability to tissues containing skin, blood
vessels, tendons, cartilage, and bone [27]. The
characterizing property of the collagen is its
molecular form that is dened by a unique
4 Sophisticated Biocomposite Scaolds fromRenewable Biomaterials forBone Tissue Engineering
https://t.me/medicina_free
vessels, muscle
tympanic membrane, vessels,
ligaments, vessels, nerves, bladder,
liver
Skin, cartilage, nerves ligaments,
vessels, liver
Skin, cartilage, bone, nerves, muscle,
pancreas
Skin, cartilage, bone, nerves, muscle,
pancreas
ligaments
vessels ligaments
ligaments, heart;
tendons
23
Bulk, controllable Skin, cartilage, bone, tendons,
Proteolytic removal of small non-
Bulk, 1h to
1month
helical telopeptides
Highly viscous solution, many
purication steps after chemical
modication
Uncontrollable dissolution of hydrogel Bulk, 1day to
3months
Bulk, 3days to
6months
Uncontrollable deacetylation and
molecular weight
Weak mechanical property Bulk, controllable Skin, bone, cartilage, breast
Weak mechanical property Bulk, controllable Skin, bone, cartilage, liver, tendons,
Inammation of sericin Bulk, controllable Skin, ligaments, bone, cartilage,
Pyrogen removed Bulk, controllable Skin, bone, tendons, nerves cartilage,
Polymer Biocompatibility Disadvantage Biodegradability Application
Collagen Minimal cytotoxicity, mild foreign body
Table 4.1 Well-known naturally derived polymers used in tissue engineering and regenerative medicine [29]
reaction, minimal inammation
inammation
Hyaluronic acid Minimal foreign body reaction, no
inammation
inammation
Alginic acid Minimal foreign body reaction, no
Chitosan Minimal foreign body reaction, no
Gelatin Minimal cytotoxicity, mild foreign body
reaction, minimal inammation
reaction, minimal inammation
Fibrin Minimal cytotoxicity, mild foreign body
Poly(hydroxyalkanoate) Minimal cytotoxicity, mild foreign body
reaction, minimal inammation
reaction, minimal inammation
Silk Minimal cytotoxicity, mild foreign body
24
Y. E. Arslan et al.
https://t.me/medicina_free
Table 4.2 Well-known synthetic polymers used in tissue engineering and regenerative medicine [29]
Polymer
Biocompatibility Disadvantage Biodegradability Application
Poly(lactic acid) Minimal cytotoxicity,
Poly(glycolic acid) Minimal cytotoxicity,
Poly(lactic-coglycolic acid)
Poly(caprolactone) Minimal cytotoxicity,
Poly(ethylene
oxide)
Polyanhydrides Minimal foreign body
Poly(propylene
fumarate)
Poly(orthoester)s Mild inammation,
Polyphosphazene Minimal foreign body
mild foreign body
reaction, minimal
inammation
mild foreign body
reaction, minimal
inammation
Minimal cytotoxicity,
mild foreign body
reaction, minimal
inammation
mild foreign body
reaction, minimal
inammation
Mild foreign body
reaction, no
inammation
reaction, minimal
inammation, minimal
cytotoxicity
Mild foreign body
reaction, minimal
inammation
mild foreign body
reaction
reaction, minimal
inammation
Local inammation,
random chain
hydrolysis
Local inammation,
random chain
hydrolysis
Local inammation,
random chain
hydrolysis
Hydrophobic Bulk, 3years Skin, cartilage,
Complex
biodegradability
Limited mechanical
property
Weak mechanical
property
Weak mechanical
property
Wide molecular
weight distribution
Bulk, 24months Skin, cartilage,
Bulk, 6–12months Skin, cartilage,
Bulk, 1–6months Skin, cartilage,
Bulk,
1month-5years
Surface erosion,
controllable
Surface erosion,
1week–16months
Bulk∼several
months
Surface erosion,
1week–3years
bone ligaments,
tendons, vessels,
nerves, bladder,
liver
bone ligaments,
tendons, vessels
nerves, bladder,
liver
bone ligaments,
tendons, vessels,
nerves, bladder,
liver
bone ligaments,
tendons, vessels,
nerves
Skin, cartilage,
bone, muscles
Bone
Bone
Ear, bone, cartilage
Skin, cartilage,
bone, nerves,
ligaments
conformation which is a three α-polypeptide
chain of one or more spaces formed in a triplehelical structure of [Gly–X–Y]n arrangement in
one of the main sorts of constructional ECM
proteins [30, 53]. This design comprises a
supercoiled triple helix that consists of three
left-handed polyproline-like chains twisted
together into a right-handed triple- helix.
Hydroxyapatite and collagen, the most important structural protein present in bone, are two
main constituents of bone. They compose 89%
of the organic matrix and 32% of the volumetric constituent of bone. Therefore, it is a special
protein that promises to produce bone from cultured cells [54]. Collagen is one of the most
frequently used materials due to its superior
biocompatibility, biodegradability, weak immunogenicity, and cell-adhesive properties in tissue engineering [55, 56]. Although collagen
can be produced from different organisms, generally, bovine skin, tendon, and porcine skinderived collagens for tissue engineering
practices are preferred. Yet, collagen obtained
from bovine sources includes the risk of infection with illnesses such as bovine sponge-like
encephalopathy. Additionally, particularly porcine-derived mammalian collagens are refused
for religious reasons [57]. Marine living
creatures are also a native origin of collagen
and, probably, are more secure source than
Соседние файлы в папке Библиотека им академика М.И. Перельмана