Abstract

Peripheral arterial disease and critical limb ischemia are common symptoms of cardiovascular disease. Vascular surgery is used to create a bypass around occluded blood vessels to improve blood flow to ischemic muscle, thus avoiding the need for amputation. Attempts to vascularize tissues by therapeutic angiogenesis using delivery of exogenous angiogenic agents are underwhelming. A material‐based approach that provides an endogenous stimulus capable of promoting angiogenesis and increased tissue perfusion would provide a paradigm shift in treatment options available. It is reported here that microporous biodegradable films produced using thermally induced phase separation provide a localized biophysical stimulus of proangiogenic genes in vivo that is associated with increased blood vessel density and restoration of blood flow to ischemic tissue. These findings show, for the first time, that acellular, nonfunctionalized biodegradable biomaterials can provide an innovative, material‐based approach for therapeutic angiogenesis to enhance tissue reperfusion in vivo.

Highlights

  • Introduction patients withPeripheral arterial disease (PAD);[6] concerns have been raised regarding the risk of oncogenic effects with this approach.[7]

  • Peripheral arterial disease (PAD) is often caused by the build-up delivery of proangiogenic agents, either as proteins or genes, in of atherosclerotic fat in the arteries, which, if left untreated, can the form of monotherapy does not replicate the plethora of factors develop into limb ischemia and other forms of cardiovascular that underlie the physiological process of angiogenesis in vivo, disease.[1]

  • Amorphous materials consisting of natural polymer gels, including fibrin and extracellular matrix (ECM)-derived hydrogels, as well as highly porous gelatin films, have been reported to result in processes associated with angiogenesis.[12,21,22,23]. Taken together these results suggest mechanically defined microenvironments created by implanting materials could be exploited to deliver local stimuli that translate into proangiogenic signals, providing new approaches for delivering therapeutic angiogenesis

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Summary

Results and Discussion

TIPS is a widely used technique for the fabrication of 3D polymeric tissue scaffolds with a range of geometries.[26,27] TIPS has been used extensively for the preparation of porous membranes and films from a variety of polymers, including poly(vinylidene fluoride) (PVDF), polyethylene, polypropylene, poly(methyl methacrylate), polystyrene, and poly(ethylene-covinyl alcohol),[28,29,30,31,32,33] for applications including filtration, quasisolid electrolytes for electrical devices, and dermal tissue engineering scaffolds.[34,35] The current study is the first to investigate the use of TIPS films composed of PLGA for use in therapeutic angiogenesis. Since the TIPS process is highly versatile, the method used to produce films in the current study provides scope to produce polymer films that exhibit different roughness and pore structures via adjustment of parameters including the polymer:solvent ratio, composition of PLGA (ratio of lactide to glycolide), solvent, and rate of quenching.[27] The ability to control these parameters through further refinement of the porous films provides greater opportunity to fine tune the proangiogenic effect achieved compared with other approaches investigated for therapeutic angiogenesis, such as gene-based therapy, lowering concerns over oncogenic risks. Patches for treatment of ischemia or films for dermal wounds and ulcers

Conclusion
Experimental Section
Conflict of Interest

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