Welcome to Scribd. Sign in or start your free trial to enjoy unlimited e-books, audiobooks & documents.Find out more
Download
Standard view
Full view
of .
Look up keyword
Like this
12Activity
0 of .
Results for:
No results containing your search query
P. 1
Biomaterials 21 (2000) 2529}2543

Biomaterials 21 (2000) 2529}2543

Ratings: (0)|Views: 203|Likes:
Published by gopikrrishna.j

More info:

Published by: gopikrrishna.j on Oct 22, 2009
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

09/16/2014

pdf

text

original

 
Biomaterials 21 (2000) 2529
}
2543
Sca
olds in tissue engineering bone and cartilage
Dietmar W. Hutmacher
 Laboratory for Biomedical Engineering, Institute of Engineering Science, Department of Orthopedic Surgery, National Uni
v
ersity of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore
Abstract
Musculoskeletal tissue, bone and cartilage are under extensive investigation in tissue engineering research. A number of biodegradable and bioresorbable materials, as well as sca
old designs, have been experimentally and/or clinically studied. Ideally,a sca
old should have the following characteristics: (i) three-dimensional and highly porous with an interconnected pore network forcell growth and
#
ow transport of nutrients and metabolic waste; (ii) biocompatibleand bioresorbablewith a controllable degradationand resorptionrate to match cell/tissuegrowth in vitro and/orin vivo; (iii) suitablesurfacechemistry for cell attachment,proliferation,and di
erentation and (iv) mechanical properties to match those of the tissues at the site of implantation. This paper reviews researchon the tissue engineering of bone and cartilage from the polymeric sca
old point of view.
2000 Elsevier Science Ltd. All rightsreserved.
 Keywords:
Tissue engineering of bone and cartilage; Design and fabrication of 3-D sca
old; Biodegradable and bioresorbable polymers
1. Introduction
Bone and cartilage generation by autogenous cell/tis-sue transplantation is one of the most promising tech-niques in orthopedic surgery and biomedical engineering[1]. Treatment concepts based on those techniqueswould eliminate problems of donor site scarcity, immunerejection and pathogen transfer [2]. Osteoblasts, chon-drocytes and mesenchymal stem cells obtained from thepatient
'
s hard and soft tissues can be expanded in cultureand seeded onto a sca
old that will slowly degrade andresorb as the tissue structures grow in vitro and/orin vivo [3]. The sca
old or three-dimensional (3-D) con-struct provides the necessary support for cells to prolifer-ate and maintain their di
erentiated function, and itsarchitecture de
"
nes the ultimate shape of the new boneand cartilage. Several sca
old materials have been inves-tigated for tissue engineering bone and cartilage includ-ing hydroxyapatite (HA), poly(
-hydroxyesters), andnatural polymers such as collagen and chitin. Severalreviews have been published on the general propertiesand design features of biodegradable and bioresorbablepolymersand sca
olds [4
}
12]. The aim of this paper is tocomplete the information collected so far, with specialemphasis on the evaluation of the material and designcharacteristics which are of speci
"
c interest in tissueengineering the mesenchymal tissues bone and cartilage.The currently applied sca
old fabrication technologies,with special emphasis on the so-called solid-free formfabrication technologies, will also be bench marked. Fi-nally, the paper discusses the author
'
s research on thedesign and fabrication of 3-D sca
olds for tissue engi-neering an osteochondral transplant.
2. Polymer-based sca
old materials
The meaning and de
"
nition of the words biodegrad-able, bioerodable, bioresorbable and bioabsorbable(Table 1)
*
which are often used misleadingly in the tissueengineering literature
*
are of importance to discuss therationale, function as well as chemical and physical proper-ties of polymer-based sca
olds. In this paper, the polymerproperties are based on the de
"
nitions given by Vert [13].The tissue engineering program for bone and cartilagein the author
'
s multidisciplinary research curriculum hasbeen classi
"
ed into six phases (Table 2). Each tissueengineering phase must be understood in an integratedmanner across the research program
*
from the polymermaterial properties, to the sca
old micro- and macro-architecture, to the cell, to the tissue-engineered trans-plant, to the host tissue. Hence, the research objectives ineachphaseare cross-disciplinaryandthe sub-projectsarelinked horizontally as well as vertically.
0142-9612/00/$-see front matter
2000 Elsevier Science Ltd. All rights reserved.PII: S0 1 42 -9 6 1 2 (0 0 ) 0 0 1 21 - 6
 
Table 1De
"
nitions given by VertBiodegradable are solid polymeric materials and devices which breakdown due to macromolecular degradation with dispersion in vivo butno proof for the elimination from the body (this de
"
nition excludesenvironmental, fungi or bacterial degradation). Biodegradable poly-meric systems or devices can be attacked by biological elements so thatthe integrity of the system, and in some cases but not necessarily, of themacromolecules themselves, is a
ected and gives fragments or otherdegradation by-products. Such fragments can move away from theirsite of action but not necessarily from the body.Bioresorbable are solid polymeric materials and devices which showbulk degradation and further resorb in vivo; i.e. polymers which areeliminated through natural pathways either because of simple
"
ltrationof degradation by-products or after their metabolization.Bioresorptionis thus a concept which re
#
ects total elimination of the initial foreignmaterial and of bulk degradation by-products (low molecular weightcompounds) with no residual side e
ects. The use of the word
&
bio-resorbable
'
assumes that elimination is shown conclusively.Bioerodible are solid polymeric materials or devices, which show sur-face degradation and further, resorb in vivo. Bioerosion is thus a con-cept, too, which re
#
ects total elimination of the initial foreign materialand of surface degradation by-products (low molecular weight com-pounds) with no residual side e
ects.Bioabsorbable are solid polymeric materials or devices, which candissolve in body
#
uids without any polymer chain cleavage or molecu-lar mass decrease. For example, it is the case of slow dissolution of water-soluble implants in body
#
uids. A bioabsorbable polymer can bebioresorbable if the dispersed macromolecules are excreted.Table 2The research program for tissue engineering bone and cartilage classi-
"
ed into six phasesI
*
Fabrication of bioresorbable sca
oldII
*
Seeding of the osteoblasts/chondrocytes populations into thepolymeric sca
old in a static culture (petri dish)III
*
Growth of premature tissue in a dynamic environment(spinner
#
ask)IV
*
Growthof mature tissue in a physiologicenvironment (bioreactor)V
*
Surgical transplantationVI
*
Tissue-engineered transplant assimilation/remodeling
The
"
rst stage of tissue engineering bone or cartilagebegins with the design and fabrication of a porous 3-Dsca
old, the main topic of this review paper. In general,the sca
old should be fabricated from a highly biocom-patible material which does not have the potential toelicit an immunological or clinically detectable primaryor secondary foreign body reaction [9]. Furthermore,a polymer sca
old material has to be chosen that willdegrade and resorb at a controlled rate at the same timeas the speci
"
c tissue cells seeded into the 3-D constructattach, spread and increase in quantity (number of cells/pervoid volume) as well as in quality. Currently, thedesign and fabrication of sca
olds in tissue engineeringresearch is driven by three material categories: I. Regula-tory approved biodegradable and bioresorbable poly-mers (Table 3), such as collagen, polyglycolide (PGA),polylactides (PLLA, PDLA), polycaprolactone (PCL),etc. II. A number of non-approved polymers, such aspolyorthoester (POE), polyanhydrides, etc. which arealso under investigation. III. The synthesis of entrepre-neurial polymeric biomaterials, such as poly (lactic acid-co-lysine),etc.,which can selectivelyshepherd speci
"
ccellphenotypes and guide the di
erentiation and prolifer-ation into the targeted functional premature and/or ma-ture tissue.In general, polymers of the poly(
-hydroxy acids)group undergo bulk degradation. The molecular weightof the polymer commences to decrease on day one (PGA,PDLA) or after a few weeks (PLLA) upon placement inan aqueous media [12]. However, the mass loss does notstart until the molecular chains are reduced to a sizewhich allows them to freely di
use out of the polymermatrix[14]. Thisphenomenondescribed andanalyzed indetail by a number of research groups [15
}
18], results inaccelerated degradation and resorption kinetics until thephysicalintegrity of polymermatrixis compromised.Themass loss is accompanied by a release gradient of acidicby-products.In vivo, massive release of acidic degradation andresorption by-products results in in
#
ammatory reac-tions, as reported in the bioresorbable device literature[19
}
22]. If the capacity of the surrounding tissue toeliminate the by-products is low, due to the poor vas-cularization or low metabolic activity, the chemical com-position of the by-products may lead to local temporarydisturbances.One exampleof this is the increaseof osmo-tic pressure or pH manifested through local
#
uidaccumulation or transient sinus formation from
"
berreinforced polyglycolide pins applied in orthopedic sur-gery [21]. Potential problems of biocompatibility intissue engineering bone and cartilage, by applying degra-dable, erodable, and resorbable polymer sca
olds, mayalso be related to biodegradability and bioresorbability.Therefore, it is important that the 3-D sca
old/cell con-struct is exposed at all times to su
$
cient quantities of neutral culture media, especially during the period wherethe mass loss of the polymer matrix occurs.The incorporation of a tricalciumphosphate (TCP)[23], hydroxyapatite (HA) [24] and basic salts [15] intoa polymer matrix produces a hybrid/composite material.These inorganic
"
llers allow to tailor the desired degra-dation and resorption kinetics of the polymer matrix.A compositematerial would also improve biocompatibil-ity and hard tissue integration in a way that ceramicparticles, which are embedded into the polymer matrix,allow for increased initial
#
ash spread of serum proteinscompared to the more hydrophobic polymer surface [9].In addition, the basic resorption products of HA or TCPwould bu
er the acidic resorption by-products of thealiphatic polyester and may thereby help to avoid theformation of an unfavorable environment for the cellsdue to a decreased pH [15,23,24].
2530
D.W. Hutmacher 
/
Biomaterials 21 (2000) 2529
}
2543
 
    T   a    b    l   e    3    P   r   o   p   e   r    t    i   e   s   o    f    b    i   o   r   e   s   o   r    b   a    b    l   e   a   n    d    b    i   o   e   r   o    d   a    b    l   e   p   o    l   y   m   e   r   s    P   o    l   y   m   e   r    C   o   m   p   a   r    i   s   o   n   o    f   m   e   c    h   a   n    i   c   a    l   p   r   o   p   e   r    t    i   e   s   o    f    b    i   o   e   r   o    d   a    b    l   e   a   n    d    b    i   o   r   e   s   o   r    b   a    b    l   e   p   o    l   y   m   e   r   s    D   e   g   r   a    d   a    t    i   o   n   a   n    d   r   e   s   o   r   p    t    i   o   n   p   r   o   c   e   s   s   v    i   a    h   y    d   r   o    l   y   s    i   s    M   o    l   e   c   u    l   a   r   w   e    i   g    h    t    l   o   s   s    /    l   o   s   s   o    f   m   e   c    h   a   n    i   c   a    l   p   r   o   p   e   r    t    i   e   s    (    i   n   m   o   n    t    h    )
             
    M   a   s   s    l   o   s   s    (    i   n   m   o   n    t    h    )
             
    R   e    f   e   r   e   n   c   e   s    (   s   c   a
     !
   o    l    d   s    )    R   e    f   e   r   e   n   c   e   s    (   m   e    d    i   c   a    l    d   e   v    i   c   e    )    A   r   e   a   o    f   a   p   p    l    i   c   a    t    i   o   n    P   r   o    d   u   c    t   s   w    i    t    h   r   e   g   u    l   a    t   o   r   y   a   p   p   r   o   v   a    l    P   o    l   y    (
    L
  -    l   a   c    t    i    d   e    )
     #     #     #
    B   u    l    k   e   r   o   s    i   o   n    9
  }
    1    5    3    6
  }
    4    8    4    6 ,    4    8 ,    4    9 ,    6    0
  }
    6    4 ,    7    0
  }
    7    2    1    9 ,    2    0 ,    2    4    O   r    t    h   o   p   e    d    i   c    S   u   r   g   e   r   y ,    O   r   a    l   a   n    d    M   a   x    i    l    l   o    f   a   c    i   a    l    S   u   r   g   e   r   y    F    i   x    S   o   r    b    S   y   s    t   e   m    (   s   c   r   e   w   s ,   n   a    i    l   s ,   p    i   n   s    )    N   e   o
     "
   x    (   s   c   r   e   w   s ,   n   a    i    l   s ,   p    i   n   s    )    P   o    l   y    (
    L
  -    l   a   c    t    i    d   e  -   c   o  -
    D
 ,
    L
  -    l   a   c    t    i    d   e    )    7    0    /    3    0
     #     #
    B   u    l    k   e   r   o   s    i   o   n    5
  }
    6    1    2
  }
    1    8    2    2 ,    2    3    O   r   a    l   a   n    d    M   a   x    i    l    l   o    f   a   c    i   a    l    S   u   r   g   e   r   y ,    O   r    t    h   o   p   e    d    i   c    S   u   r   g   e   r   y    R   e   s   o   r    P    i   n ,    L   e   a    d
     "
   x    M   a   c   r   o    S   o   r    b    S   y   s    t   e   m    (   s   c   r   e   w   s   a   n    d   p    l   a    t   e   s ,   m   e   s    h ,   n   a    i    l   s ,   p    i   n   s    )    P   o    l   y    P    i   n    P   o    l   y    (
    L
  -    l   a   c    t    i    d   e  -   c   o  -   g    l   y   c   o    l    i    d   e    )    1    0    /    9    0
     #     #
    B   u    l    k   e   r   o   s    i   o   n    1
  }
    2    3
  }
    4    2    8 ,    6    3    S   u    t   u   r   e    P   e   r    i   o    d   o   n    t   a    l    S   u   r   g   e   r   y ,    S   u   r   g   e   r   y ,    V    i   c   r   y    l    S   u    t   u   r   e ,    V    i   c   r   y    l    M   e   s    h    P   o    l   y   g    l   y   c   o    l    i    d   e
     #     #     #
    B   u    l    k   e   r   o   s    i   o   n    0 .    5
  }
    1    3
  }
    4    6 ,    3    0
  }
    3    5 ,    4    1 ,    6    5    O   r    t    h   o   p   e    d    i   c    S   u   r   g   e   r   y    B    i   o
     "
   x    P   o    l   y    (
    D
 ,
    L
  -    l   a   c    t    i    d   e    )
     #
    B   u    l    k   e   r   o   s    i   o   n    1
  }
    2    5
  }
    6    6 ,    3    1 ,    3    4 ,    4    9 ,    6    0    P   o    l   y    (
    D
 ,
    L
  -    l   a   c    t    i    d   e  -   c   o  -   g    l   y   c   o    l    i    d   e    )    8    5    /    1    5
     #
    B   u    l    k   e   r   o   s    i   o   n    1
  }
    2    4
  }
    5    5    3
  }
    5    6 ,    6    0 ,    7    0    P   o    l   y    (
    D
 ,
    L
  -    l   a   c    t    i    d   e  -   c   o  -   g    l   y   c   o    l    i    d   e    )    7    5    /    2    5
     #
    B   u    l    k   e   r   o   s    i   o   n    1
  }
    2    4
  }
    5    4    9 ,    6    1    P   o    l   y    (
    D
 ,
    L
  -    l   a   c    t    i    d   e  -   c   o  -   g    l   y   c   o    l    i    d   e    )    5    0    /    5    0
     #     #
    B   u    l    k   e   r   o   s    i   o   n    1
  }
    2    3
  }
    4    2    8    P   o    l   y   c   a   p   r   o    l   a   c    t   o   n   e
     #
    B   u    l    k   a   n    d   s   u   r    f   a   c   e   e   r   o   s    i   o   n    9
  }
    1    2    2    4
  }
    3    6    2    9    D   r   u   g    d   e    l    i   v   e   r   y    C   a   p   r   a   n   o   r    P   o    l   y   o   r    t    h   o   e   s    t   e   r
     #     #
    S   u   r    f   a   c   e   e   r   o   s    i   o   n    4
  }
    6    1    2
  }
    1    8    P   o    l   y   a   n    h   y    d   r    i    d   e   s
     #     #
    S   u   r    f   a   c   e   e   r   o   s    i   o   n    4
  }
    6    1    2
  }
    1    8    5    9    A   n    i   m   a    l   e   x   p   e   r    i   m   e   n    t   s
             
    M   o    l   e   c   u    l   a   r   w   e    i   g    h    t   a   n    d   m   a   s   s    l   o   s   s   v   a   r   y    d   e   p   e   n    d    i   n   g   o   n    f   a   c    t   o   r   s   s   u   c    h   a   s   c    h   e   m    i   c   a    l   s    t   r   u   c    t   u   r   e   a   n    d   c   o   m   p   o   s    i    t    i   o   n   ;   p   r   e   s   e   n   c   e   o    f    i   o   n    i   c   g   r   o   u   p   s   a   n    d   o    f   s    i    d   e   g   r   o   u   p    d   e    f   e   c    t   s   ;   c   o   n
     "
   g   u   r   a    t    i   o   n   o    f    t    h   e   s    t   r   u   c    t   u   r   e   m   o    l   e   c   u    l   a   r   w   e    i   g    h    t   a   n    d   m   o    l   e   c   u    l   a   r   w   e    i   g    h    t    d    i   s    t   r    i    b   u    t    i   o   n    (   p   o    l   y    d    i   s   p   e   r   s    i    t   y    )   ;   p   r   e   s   e   n   c   e   o    f    l   o   w   m   o    l   e   c   u    l   a   r   w   e    i   g    h    t   c   o   m   p   o   n   e   n    t   s    (   m   o   n   o   m   e   r   s ,   o    l    i   g   o   m   e   r   s ,   s   o    l   v   e   n    t   s ,   s   o    f    t   e   n   e   r   s ,    d   r   u   g   s ,   g   r   o   w    t    h    f   a   c    t   o   r   s ,   e    t   c .    )   ;   p   r   o    d   u   c    t    i   o   n   a   n    d   m   a   n   u    f   a   c    t   u   r    i   n   g   p   r   o   c   e    d   u   r   e   s   a   n    d    t    h   e    i   r   p   r   o   c   e   s   s   p   a   r   a   m   e    t   e   r   s ,    i   m   p    l   a   n    t    d   e   s    i   g   n ,   s    t   e   r    i    l    i   z   a    t    i   o   n   m   e    t    h   o    d ,   m   o   r   p    h   o    l   o   g   y    (   a   m   o   r   p    h   o   u   s   v   e   r   s   u   s   s   e   m    i  -   c   r   y   s    t   a    l    l    i   n   e ,   p   r   e   s   e   n   c   e   o    f   m    i   c   r   o   s    t   r   u   c    t   u   r   e   s   a   n    d   s    t   r   e   s   s   w    i    t    h    i   n    t    h   e   c   o   m   p   o   n   e   n    t   s    ) ,    t   e   m   p   e   r    i   n   g ,   s    t   o   r   a   g   e ,    i   m   p    l   a   n    t   s    i    t   e .
     #     #     #
 ,   g   o   o    d   ;
     #     #
 ,   a   v   e   r   a   g   e   ;
     #
 ,   p   o   o   r .
 D.W. Hutmacher 
/
Biomaterials 21 (2000) 2529
}
2543
2531

Activity (12)

You've already reviewed this. Edit your review.
1 thousand reads
1 hundred reads
nileshsaw liked this
Kalyan Ray Gupta liked this
Kalyan Ray Gupta liked this
harisadu liked this
josephting liked this
shine2rica liked this

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->