Biomedical Engineering Reference
In-Depth Information
native osteochondral (cartilage-bone) interface provided the motivation for creating
techniques to fabricate multi-compartment collagen-glycosaminoglycan (GAG)
scaffolds (CG scaffolds); this structure contains region-specific compartments as
well as gradients of ECM proteins and soluble biomolecules (growth factors,
proteins, cytokines) across the interface. Second, the development of a tendon
regeneration strategy has required implementation of bioinspired composite
structures to generate bioactive, porous scaffolds that maintain sufficient
mechanical integrity. Although focused on orthopedic tissue engineering, the
methods discussed here have broader applicability to many other tissue systems.
Critically, both case studies provide valuable information regarding the integration
of defined layers, compartments, and gradations into a single biomaterial structure.
16.2 Collagen-GAG Scaffolds: History of Applications
The ECM is a fibrillar network of structural proteins (collagens, proteoglycans,
etc.), specialized proteins for cell adhesion (fibronectin, laminin, etc.), and other
tissue-specific materials such as hydroxyapatite in bone [
7
]. The ECM defines the
physical morphology of tissues and the local environment in which cells reside.
Tissue engineering scaffolds are used as 3D analogs of the native ECM to heal or
modify tissues in a controlled manner. In order to be successful, these scaffolds
must be able to recapitulate integral aspects of the ECM microenvironment while
supporting a range of physiological cell processes.
As analogs of the native ECM, collagen-GAG materials possess several vital
characteristics for successful tissue engineering scaffolds, including a 3D micro-
structure with a high degree of pore interconnectivity, tunable degradation and
resorption rates, surface ligands for cell adhesion, and mechanical integrity [
7
,
8
].
CG biomaterials were first developed in the 1970's through a collaborative effort
between Dr. Ioannis Yannas, a professor at Massachusetts Institute of Technol-
ogy, and John F. Burke, a surgeon at Massachusetts General Hospital. Originally
developed for regenerative repair of full-thickness skin wounds, CG biomaterials
have been utilized in a plethora of tissue engineering studies, both
in vivo
as
regenerative templates for skin, peripheral nerves, conjunctiva, and a range of
orthopedic tissues (bone, cartilage, tendon, intervertebral disk) [
9
-
12
]aswellas
in vitro
as 3D microenvironments to probe more fundamental questions about cell
behaviors and cell-matrix interactions [
13
-
15
]. Scaffold microstructure (poros-
ity, mean pore size, pore shape, interconnectivity, specific surface area) [
9
,
12
,
15
-
23
] and mechanical properties (Young's modulus, yield stress) [
24
-
33
]have
been shown to be key factors that can influence cell behaviors such as adhesion,
motility, contraction, stem cell differentiation, gene expression, and overall
bioactivity [
9
].
CG scaffolds are traditionally created from a suspension consisting of
co-precipitated collagen (typically type I) and glycosaminoglycan content in a
weak acetic acid solution [
9
]. The collagen backbone of this scaffold provides
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