Bone Scaffolds with homogeneousand discrete gradient mechanicalproperties
C. Jelen, G. Mattei, F. Montemurro, C. De Maria, M. Mattioli Belmonte, G.
Vozzi
PII: S0928-4931(12)00364-5
DOI: doi: 10.1016/j.msec.2012.07.046
Reference: MSC 3536
To appear in: Materials Science & Engineering C
Received date: 19 November 2011
Revised date: 29 June 2012
Accepted date: 30 July 2012
Please cite this article as: C. Jelen, G. Mattei, F. Montemurro, C. De Maria, M. Mattioli
Belmonte, G. Vozzi, Bone Scaffolds with homogeneous and discrete gradient mechanical
properties, Materials Science & Engineering C (2012), doi: 10.1016/j.msec.2012.07.046
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
1
Bone Scaffolds with homogeneous and discrete gradient mechanical
properties
Author:
Jelen C
1
, Mattei G
1,2
, Montemurro F
1,2,3,4
, De Maria C
1,2,3,4,*
, Mattioli Belmonte M
5
, Vozzi G
1,2
Affiliation:
1 - Interdepartmental Research Center E.Piaggio, Faculty of Engineering, University of Pisa, Pisa,
Italy
2 - Department of Chemical Engineering Industrial Chemistry and Materials Science (DICCISM),
Faculty of Engineering, University of Pisa, Pisa, Italy
3 - Let People Move Research Institute, Bioengineering Division, Arezzo, Italy
4 - Nicola’s Foundation Onlus, Arezzo, Italy
5 - Department of Molecular Pathology and Innovative Therapies, Marche Polytechnic University,
Ancona, Italy
* - Corresponding author: carmelo.demaria@centropiaggio.unipi.it
Abstract
Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a
carrier or template for implanted bone cells or other agents. We prepared different bone tissue
constructs based on collagen, gelatin and hydroxyapatite using genipin as cross-linking agent. The
fabricated construct did not present a release neither of collagen neither of genipin over its toxic
level in the surrounding aqueous environment. Each scaffold has been mechanically characterized
with compression, swelling and creep tests, and their respective viscoelastic mechanical models
were derived. Mechanical characterisation showed a practically elastic behaviour of all samples
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
2
and that compressive elastic modulus basically increases as content of HA increases, and it is
strongly dependent on porosity and water content.
Moreover, by considering that gradients in cellular and extracellular architecture as well as in
mechanical properties are readily apparent in native tissues, we developed discrete Functionally
Graded Scaffolds (discrete FGSs) in order to mimic the graded structure of bone tissue.
These new structures were mechanically characterized showing a marked anisotropy as the native
bone tissue. Results obtained have shown FGSs could represent valid bone substitutes.
Keywords:
bone scaffold, hydroxyapatite, genipin, mechanical properties, gradient
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
3
Introduction
Many surgical cases require reconstruction of bone defects, that may be congenital or induced by
a disease or a trauma. The traditional methods of bone-defect reconstruction include autografting
and allografting cancellous bone, applying vascularized grafts of different bone site, such as fibula
and iliac crest. Bone grafting can induce functional bone remodeling, and morbidity of the
harvesting site [1-5]. Moreover there is a limit on amount of usable material and possible
mismatches between graft and defect shape. Furthermore, since bone grafts are avascular and
dependent on diffusion, the size of defect and viability of host bed can limit their application. New
bone volume maintenance can be problematic due to unpredictable bone resorption (in large
defects, grafts can be resorbed by external environment before osteogenesis is completed [6-7]).
Allografting introduces the risk of disease and/or infection, vascularized grafts requires
sophisticated surgical methods and distraction osteogenesis techniques are reserved only for most
motivated patients [8-9].
On the other side, synthetic material reconstruction has no limit on usable material, and shapes
can be specifically manufactured for a given reconstruction. However, synthetic materials do not
integrate perfectly with biological tissue, inducing an inflammatory response due to stress-
shielding effect [10].
Although previous reconstruction methods have been successfully applied in many applications,
their shortcomings have motivated a novel approach, called bone tissue engineering (bone TE).
Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a
carrier or template for implanted bone cells or other agents. The scaffold provides an initial
support structure that slowly degrades as healing bone tissue gradually regenerates. Scaffolds
must be biocompatible, non-immunogenic, non-toxic and absorbable, with an absorption rate
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
4
similar to that of new bone formation. Materials used as bone tissue-engineered scaffolds may be
injectable or rigid. Injectable materials (small particles or semi-liquid polymers that can be cross-
linked in situ) are preferable for irregular defects reconstruction, while solid materials are more
appropriate for large bone defects [11]. Materials commonly used are metals, ceramics, natural or
synthetic polymers and composites [12-16]. Hydroxyapatite, calcium phosphate and a wide variety
of ceramic matrices are appropriate for cell transport as they stimulate their differentiation and
bone growth. However, there are problems associated with biodegradability, inflammatory and
immunological reactions when they are used as carriers of osteoinductive factors. To overcome
these drawbacks, synthetic biodegradable polymers based on polylactic acid (PLA), polyglycolic
acid (PGA) and their polylactic-co-glycolic acid copolymers (PLGA) have been developed [17].
Polymers with an erodible surface (e.g. poly-ortho esters) may be beneficial in load bearing bone
applications because only the surface undergoes degradation, leaving the material that provides
mechanical strength, reducing the risk of implant failure [18]. In addition to appropriate
mechanical properties, the scaffold must also have the right internal micro-architecture with
interconnected pores of 200-400 μm diameter (the average size of the human osteon is
approximately of 223 µm) [19]. Pore size is known to affect cellular affinity and viability by
influencing cellular movement, binding and spreading, intracellular signaling, and transport of
nutrients and metabolites [20].
Moreover, because concentration gradients of bioactive signaling molecules guide tissue
formation and regeneration, and gradients in cellular and extracellular architecture as well as in
mechanical properties are readily apparent in native tissues, it is important to consider this aspect
in attempting to regenerate tissue by incorporating gradients into engineering design strategies
[21-23].
