# Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts
## 3 Heparin Conjugation Methods
### Physical Conjugation
#### 3.1.3 Coaxial Electrospinning Technique
On the other hand, [PERSON]'s group hypothesized that a certain P(LLA-CL) blend, a blend of 60% PCL and 40% PLLA, could simulate native ECM and found that it could mimic natural blood vessels without the addition of natural materials [26]. They conducted an in vivo study by implanting heparin pre-endothelialized P(LLA-CL) grafts into canine femoral arteries. Heparin was conjugated by coaxial electrospinning as in the other group, but they employed a higher heparin solution concentration of 25%. Their heparin-bound graft was more than 85% patent compared to 37.5% patent for the control PLLA-CL after 24 weeks. They also noted that heparin binding to P(LLA-CL) decreased the maximum scaffold tensile strength and initial burst of heparin release, while increasing its elasticity and suture retention [30]. Not only is P(LLA-CL) useful, electrospun PCL also has its uses: [PERSON] et al. suggest that among the many bioabsorbable materials, PCL electrospun fibers can be used to increase the amount of release. Specifically, an 8% w/v solution of heparin in polyacrylamide (PCL) was spun with 7:3 dichloromethane:methanol to produce fibers with a smooth surface [44]. The sustained release of heparin was confirmed by fluorescent labeling, and after 14 days, about half of the encapsulated heparin was released from the heparin/PCL fiber by diffusion control, indicating good, sustained release. [PERSON] et al. fabricated tubular vascular tissue engineering scaffolds with fibers in a core-shell structure using a coaxial electrospinning method with an appropriate flow ratio of inner and outer solutions. PCL was used as the core to give the scaffold mechanical properties and integrity, and collagen was used as the shell to improve vascular cell attachment and proliferation due to its excellent biocompatibility [31]. Furthermore, the functional inner layer using a coaxial electrospinning technique is expected to prevent the acute thrombosis of non-bioabsorbable materials such as ePTFE and promote rapid endothelialization of artificial vascular grafts. Based on this finding, salvianolic acid B (SAB) promotes the proliferation and migration of endothelial cells. [PERSON] et al., fabricated the inner layer of an artificial graft using coaxial electrospinning and loaded it with heparin and SAB [45]. [PERSON] et al. reported that in situ implantation of ePTFE grafts coated with heparin/substance P-conjugated PLCL could ensure long-term patency by forming a proper endothelial layer and smooth muscle cells in the graft, resembling a native artery [46]. Based on the above, physical heparin conjugation can change a graft lumen's surface charge and solve the problem of early thrombosis. However, there are few reports on their effect in long-term animal studies. Physically conjugated heparin grafts may be pretreated first or blended with natural polymers to promote EC adhesion and proliferation. Furthermore, bioabsorbable materials with heparin could be used to increase the biocompatibility of existing nonbioabsorbable materials. Future reports in long-term large animal studies on the efficacy of grafts physically conjugated with heparin are awaited.