Extracellular matrix in native tissue
Functions of scaffolds
Features of scaffold
– Provides structural support for cells
– Should provide structural support for in vitro seeded cells
– Should have binding sites for cells and with porous structure
– Contributes to the mechanical properties of tissue
– Should provide the shape and mechanical stability to the tissue defect
– With enough mechanical stability so that empty space of the defect could be filled up easily
– Provides bioactive support for cells
– Interacts with cells to facilitate proliferation and differentiation
– Biologically (carrying cell adhesiveness) and physically (surface topography) stable
– Is a reservoir for growth factors
– Serves as a delivery vehicle for in vitro applied growth factors
– With microstructures carrying bioactive agents in scaffold
– Creates such a flexible physical environment for the dynamic processes of the tissue
– Provides volume for new tissue formation and remodeling
– Porous microstructure for nutrients and metabolites diffusion
Firstly, ECM provides structural support and physical environment for the cells of that tissue to grow and respond to signals. Secondly, ECM gives the tissue its structural and also mechanical character, like elasticity or rigidity basically depending on the function of that tissue. Thirdly, ECM actively offers bioactive signals to the cells inside the matrix for cellular activities. Fourthly, ECM is also a reservoir of growth factors. Fifthly, ECM creates an optimum physical environment during degradation process during tissue dynamic processes like morphogenesis, homeostasis, and wound healing [6, 7].
So theoretically the best scaffold for “tissue engineering” should have the ECM of the target tissue. But the complex composition and the dynamic nature of ECM make it almost impossible to mimic the same. Therefore, the main strategy of scaffolding in tissue engineering is to mimic the functions of native ECM [8].
Scaffolds should have enough empty space for new tissue formation and remodeling after implantation. On the other hand, this scaffold consisting of porous structure for transport of nutrients and metabolites should be mechanically stable. And also, after implantation the speed of degradation of this biomaterial should match with the new matrix production of new tissue. The pore structures affect the cell responses and their further organization in the tissue. Hydrogel type scaffolds have water-filled channels and polymer networks, whereas there are space open channels for the general scaffolds. The porous structure relies basically on the fabrication and manufacturing. These methods include fiber bonding, solvent casting/particulate leaching, gas foaming, and phase separation [8, 9].
Scaffolds should be made of biocompatible biomaterial so that the cellular components of the engineered tissue and the cells of host tissue suit properly. Natural and synthetic polymers have excellent flexibility to adapt their shape to wanted forms via different manufacturing techniques [8].
The bioactivity level of the scaffold should be high enough to carry out and regulate the activity of native tissue cells and the cells inside the engineered ECM. The scaffold, at the same time, is a delivery vehicle for exogenous growth-stimulating signals such as growth factors. Hydrogels can be filled up with proteins, and the release of these proteins can be triggered via swelling of the scaffold [10].
Scaffolds, on the first hand, must provide mechanical and shape stability to the defective area of the native tissue defect. Therefore, mechanical properties of the scaffold should match that of the host tissue.
Regardless of the approach used for each clinical application, the objective is the same, specifically, the restoration of structure and function. Similarly, regardless of which strategy is selected, the response of the host to the implanted construct will dictate the success or failure of the eventual outcome.
5.2 Humoral Response to a Scaffold
It is a fact that all kind of materials implanted into a human recipient are subject to response by the host’s immune system. The host response to implanted materials is unavoidable. This response occurs immediately, and there are factors affecting the level of this response. These are directly related to the character of the material especially the constituents of the implant and also anatomical location of the implant.
We have a broad knowledge about the foreign body reaction for the classical biomaterials which are composed of nondegradable synthetic and metallic components and used for long-term implantation like hip and knee prosthesis. On the other hand, tissue engineering end products, scaffolds, trigger a different response than those preferred for long-term treatment like materials used for arthroplasty without degradation. There should be a balance between tissue reaction against the biomaterial implanted and the structural and mechanical properties of that biomaterial in vivo.
The foreign body response is known to have negative effects for material lifetime in the body and local tissue as well.
Immediately after implantation of biomaterial, a cascade of events regarding the host response starts. This starts from protein biofilm formation on the biomaterial then continues with acute inflammation then to chronic inflammation and granulation tissue formation and ends with fibrosis and capsule formation around the biomaterial [11, 12].
5.2.1 Blood Material Interaction and Biofilm Formation
Release of blood into the wound site during the surgical procedure results in degranulation of platelets and start of inflammatory process. With the blood, contact proteins (components of coagulation system or plasma-derived proteins) attach to the surface of the biomaterial within seconds of implantation. These proteins on the surface of biomaterial (or scaffold) serve as an anchor for the inflammatory cells migrating to the region. And finally a biofilm is formed around the scaffold [12, 13].
5.2.2 Acute Inflammation
Arrival of inflammatory cells, especially neutrophils, will start the process with the release of chemoattractant factors. However, as soon as neutrophils arrive, they interact with the proteins on the biomaterial surface. This will lead to phagocytosis by neutrophils and/or macrophages or destruction of the pathogen via the complement pathway. In both processes there will be an erosion of implanted material which is not favored in short term after implantation [12, 14].
5.2.3 Chronic Inflammation
The chronic inflammation is typically characterized by the presence of activated macrophages. This process may last from weeks to months depending on the nature of the implanted material and the anatomical location. Different from acute inflammation, angiogenic component is prominent in chronic inflammation, and there is new ECM formation in and around the scaffold. And also, unlike acute inflammation, the foreign body giant cells will replace macrophages [12].
5.2.4 Granulation Tissue Formation, Foreign Body Reaction, and Tissue Encapsulation
Chronic inflammation can progress to a granulation tissue phase, in which the deposition of new ECM and the growth of vasculature into the implantation eventually form a dense layer of connective tissue. This will end up with “foreign body reaction” and eventually encapsulation of the biomaterial within a dense layer of collagenous connective tissue will be seen [12, 15].
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