Quickening: Translational design of resorbable synthetic vascular grafts

Abstract

Traditional tissue-engineered vascular grafts have yet to gain wide clinical use. The difficulty of scaling production of these cell- or biologic-based products has hindered commercialization. In situ tissue engineering bypasses such logistical challenges by using acellular resorbable scaffolds. Upon implant, the scaffolds become remodeled by host cells. This review describes the scientific and translational advantages of acellular, synthetic vascular grafts. It surveys in vivo results obtained with acellular synthetics over their fifty years of technological development. Finally, it discusses emerging principles, highlights strategic considerations for designers, and identifies questions needing additional research.

Keywords: Biodegradable; Degradable vascular graft; Host remodeling; In situ tissue engineering.

Figure 1.

Resorbable graft concept. An acellular, polymeric graft is implanted orthotopically. Host cells invade the graft, degrade the polymer, proliferate, and synthesize new ECM. The artificial graft is replaced by a living vascular conduit.

Figure 2.

Cellular and structural complexity of the artery. Replicating such an extraordinary design by tissue engineering is a challenge. (A) H&E staining of the sheep common carotid. (B) Second harmonic generation image of a rat aorta. Elastin autofluoresces in green, collagen autofluoresces in red, and the nucleic stain spills over into the green channel. Bars: 100 μm. Image in (B) courtesy of Piyusha S. Gade and Anne M. Robertson.

Figure 3.

Transformation is enabled by a balance between the rates of polymer degradation and neotissue synthesis. The polymer initially bears all the load of pressurization, but it contributes less as it degrades (gold). The load is taken up by newly deposited matrix (red). To prevent dilation, the sum of the mechanical contributions of the polymer and neotissue (grey) must always be greater than some critical level (dotted, black). Mechanics should ideally approach those of the native vessel (dashed, black). (Figure memorably presented by Frederick J. Schoen, M.D., Ph.D.)

Figure 4.

Idealized J-shaped pressure-diameter relationship exhibited by an artery under biaxial inflation.

Figure 5.

Proposed mechanisms of graft remodeling. Transanastomotic healing involves migration of SMCs (green) and ECs (yellow) from the adjacent arterial stubs. Fall-out healing involves adhesion, differentiation, and proliferation of various circulating stem/progenitor cells (purple, brown). Transmural healing involves migration of vascular cells (green, yellow) from adventitial capillaries or adventitial progenitors (blue) from the perivascular space. Remodeling is largely directed by macrophages (orange), which interpret material and chemical cues and coordinate the infiltrating cell responses through cytokine signaling (teal).