A majority of the previous and current biomaterial modifications continue to focus on a "magic bullet" approach for biomaterial healing. This unidirectional approach has yet to produce a clinically acceptable bioactive material, potentially due to the simplistic approach taken for such a complex phenomenon. The native tissue that these materials are implanted into possesses a multitude of functions that undergo various responses upon injury such as controlling thrombus formation and orchestrating controlled cellular regrowth. Therefore, the next generation of biomaterials must also possess several characteristics in order to better mimic some of the key functions inherent to native tissue. These individual functions, when incorporated into a single biomaterial surface, will act synergistically, resulting in a novel biomaterial with localized biologic activity to stimulate complete healing of the biomaterial.
Two essential areas will need to be addressed when designing a novel biomaterial: material design and surface biologic characteristics. Material design will permit simulation of the physical characteristics of the native tissue such as compliance and durability. The material must also be easy to handle, as well as to implant (suturability). For the base material, polyester could still be utilized due to the biodurability of the fiber and the potential for creating numerous variations in the material design (i.e., knitting, weaving). Additionally, polyester can be chemically modified, creating functional groups within the polymer structure [132-134]. For these reasons, polyester would be the ideal candidate for the base material due to its proven clinical history as well as the various knitting procedures that are available.
Creation of a polyester material that possesses specific biological properties directly at the material surface can be created via immobilization of various proteins. For example, prevention of surface thrombus formation could involve covalent linkage of the potent anti-thrombin agent rHir. Thrombin is a pivotal enzyme in the blood coagulation cascade that is primarily responsible for cleavage of fibrinogen to fibrin . During clot lysis, enzymatically active thrombin is released rendering the vessel susceptible to prompt rethrombosis [136, 137]. Even within a clot, thrombin functions as a smooth muscle cell mitogen  are chemotactic for monocytes and neutrophils [139, 140] and an aggregator of lymphocytes. Thus, thrombin that goes unregulated within a clot or pseudointima may lead to cellular infiltration and uncontrolled smooth muscle cell proliferation. rHir is the most potent direct inhibitor of thrombin , inhibiting the enzymatic, chemotactic, and mitogenic properties of thrombin [142, 143]. Additionally, rHir has also been shown to inhibit clot-bound thrombin . Thus, immobilization of rHir provides an attractive strategy to controlling surface thrombus formation prior to cellular healing.
Another example is a surface that propagates hemostasis and stimulates wound healing is a desired property for hernia repair mesh as well as wound-dressing materials. Activation of the coagulation cascade in order to promote thrombus formation in an effort to control excess bleeding at the injury site is the first step. Thrombin is a pivotal enzyme in the blood coagulation cascade that is primarily responsible for cleavage of fibrinogen to fibrin . During clot lysis, enzymatically active thrombin is released rendering the vessel susceptible to prompt rethrombosis [146, 147]. Even within a clot, thrombin functions as a smooth muscle cell mitogen  are chemotactic for monocytes and neutrophil [139, 140] and an aggregator of lymphocytes. Thus, immobilization of thrombin to hernia repair mesh or a wound dressing could expedite hemostasis by directing enzymatic fibrinogen cleavage at the biomaterial surface/injury interface as well as by activating additional clotting factors within the wound (e.g., platelets).
For cellular attachment and proliferation, VEGF, a 42 kDa homodimeric glycoprotein, has been shown to be a potent endothelial cell mitogen and va-sopermeability factor . VEGF, which is produced by many different cell types both in tissue culture and in vivo, binds to plasma membrane receptors on endothelial cells only with an extracellular transmembrane glycoprotein linked to an intracellular tyrosine kinase domain . This mitogen has also been implicated as a necessary component of wound healing [150, 151]. VEGF in these studies was being released from either a protein scaffold or a viral vector. Thus, covalent linkage of VEGF or another growth factor such as basic fibroblast growth factor to a vascular graft, hernia repair mesh, or a wound dressing would promote initial cellular growth followed by complete healing at the site of injury.
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