Pilot Experimental Study of Different Types of Vascular Grafts Remodeling in the Posterior Vena Cava System of Growing Primates

Study attrition: Animal No. 4 died at 28 months of follow-up from progressive chronic kidney disease associated with urolithiasis, which was unrelated to vascular graft function.

Somatic growth dynamics: During the 29-month observation period, significant growth of all experimental animals was recorded, confirming the adequacy of the chosen model of a growing organism. Mean body weight increased by 36.15% from 4850±840 g to 6603±898 g (p<0.01). Mean body length increment was 64.83 mm (p<0.01).

Analysis of individual linear growth trajectories revealed pronounced positive dynamics in all animals (Figure 2a). The rate of body length increase, assessed by linear regression, varied between individuals, reflecting natural biological variability. High coefficients of determination (R²), reaching 87.5% and 73.5% in animals No. 3 and No. 4, respectively, indicated stable and predictable somatic growth throughout the observation period.

Body weight dynamics also showed a consistent positive trend with significant interindividual variability (Figure 2b). Monthly weight gain rates ranged from 0.63% to 5.41%. The highest average monthly weight gain rate (5.41%/month) was observed in animal No. 4. Animals No. 3 and No. 4 exhibited high coefficients of determination (R²>0.90), confirming the linear and predictable nature of body weight gain. Thus, the documented positive dynamics of two key somatometric parameters-body length and body weight-confirm that the entire experimental period occurred during an active phase of somatic growth, a fundamental condition for valid assessment of vascular implant remodeling in a setting modeling the growing pediatric organism.

Summary analysis of vascular graft remodeling: To comparatively evaluate remodeling of different vascular implant types, key morphometric and hemodynamic parameters were analyzed. Figure 3 presents the results of direct intraoperative measurements of graft length and diameter at implantation and after explantation. Figure 4 reflects the long-term dynamics of these same parameters according to duplex ultrasound scanning (DUS). Figure 5 shows the dynamics of volumetric blood flow velocity, characterizing the hemodynamic load on the implants.

Autologous vein: The autologous vein graft demonstrated an exemplary balanced type of remodeling. Direct morphometry (Figure 3 a, b) showed a mean graft length increase of 20% (from 15.5 to 18.5 mm) and a diameter increase of 40–50%. Dynamic DUS confirmed a stable dilatational trend: functional diameter increased by 25–30% by the end of observation, and positive length dynamics were also recorded (Figure 4 a, b). Hemodynamic parameters remained stable, and the increase in volumetric blood flow velocity was minimal (Figure 5). Follow-up SCTA clearly demonstrated preserved patency in the autologous vein implantation zone (Figure 6 a, b). At explantation, the autologous vein macroscopically did not differ from the native vein (Figure 7 a, b). Histopathological examination revealed preservation of a three-layer wall structure close to native; inflammatory reaction was absent in all layers, except for minimal inflammatory infiltration in the anastomosis zone; no signs of intimal hyperplasia were detected (Fig. 8 a, b). These data morphologically substantiate the successful integration and functional integrity of the autologous vein.

Allogeneic grafts: Allogeneic implants exhibited significant but variable adaptive potential.

Single-group allograft. Direct morphometry recorded a substantial length increase (+58%, from 12 to 19 mm) with constrictive change in anatomical diameter (–22%, from 9 to 7 mm) (Figure 3 a, b). Conversely, dynamic DUS revealed an opposite trend—an increase in functional diameter by 16% during the observation period (Figure 4 a, b). This discrepancy highlights the difference between structural changes assessed ex vivo and functional status in vivo. Hemodynamic parameters remained stable (Figure 5). SCTA data confirmed preserved blood flow in the implantation zone (Figure 9a,b). Macroscopic examination of the explanted graft showed no differences from the native vein, no cicatricial deformation, and no signs of stenosis (Figure 10a,b). Histological analysis demonstrated preservation of a three-layer wall structure close to native, with minimal inflammatory reaction. In the anastomosis zone, a smooth transition of the native vein intima onto the allograft was observed, with no neointimal hyperplasia (Figure 11a,b). This explains the clinically acceptable integration of this graft type despite the variability in instrumental data.

Cross-group allograft. The maximum relative length increase (+67%, from 9 to 15 mm) and anatomical diameter increase of 50% (from 6 to 9 mm) were recorded by morphometry (Fig. 3 a, b). However, DUS showed that the functional lumen of the graft remained virtually unchanged (+0.2%) (Figure 4 a, b), likely related to the development of endothelial hyperplasia visualized as "small tubercles" (Figure 12 a). SCTA confirmed satisfactory contrast enhancement of the anastomosis zone (Figure 12 b, c). At explantation, macroscopic infiltration of perigraft tissues was noted (Figure 13 a, b). Histopathological examination revealed regression of smooth muscle cells in the media and their absence in the adventitia, indicating partial wall degradation due to immune response (Figure 14). Inflammatory reaction in the adventitia was minimal, and anastomotic zones showed a smooth transition of the native vein intima onto the implanted material without signs of hyperplasia.

Biodegradable polymer matrix (BPM): BPM demonstrated a unique, phased remodeling pattern fundamentally different from the other studied graft types.

The largest absolute length increase among all implants was recorded: +42% (from 19 to 27 mm), confirmed by both direct intraoperative morphometry and dynamic DUS monitoring (Figure 3 a, 4 a). This indicates the high adaptive capacity of the matrix to conditions of ongoing somatic growth. In the early postoperative period, constrictive remodeling was noted: anatomical diameter decreased by 33% (Figure 3 b), and the functional lumen according to DUS narrowed by approximately 15% (Figure 4 b). However, by the end of the observation period, a consistent trend towards diameter restoration to near-baseline values was observed. The identified constriction was transient and reversible, not a progressive stenotic process.

Initial increases in linear velocity and decreases in volumetric blood flow velocity were subsequently normalized (Figure 5). By the end of observation, the pressure gradient had stabilized, indicating the formation of compensatory-adaptive mechanisms and restoration of implant functional integrity. Follow-up SCTA demonstrated patency in the implantation zone without visible stenosis (Figure 15 a, b). Macroscopically, the matrix appearance was practically indistinguishable from the native vein. At explantation, signs of outer layer formation (neoadventitia) and graft surface neovascularization were noted. Matrix isolation from surrounding tissues was difficult due to integration, but no gross scarring, deformation, or aneurysmal changes were found (Figure 16).

Histopathological examination revealed that the tissue-engineered vascular implant wall consisted of three clearly differentiated layers: neointima, neomedia, and neoadventitia. In the anastomotic zone with the posterior vena cava, no signs of myointimal hyperplasia were detected. A smooth transition of the native vessel intima onto the implant was observed (Figure 17). Thus, BPM demonstrated a balanced adaptive response, key characteristics of which include: pronounced and confirmed growth potential, reversibility of early constrictive changes, absence of intimal hyperplasia and degenerative changes, and stabilization of hemodynamic parameters in the long term. These data allow the observed constrictive phenomenon to be considered not as implant failure, but as a reversible stage of remodeling overcome during integration, supporting the promise of further optimization of this material class.

PTFE prosthesis: The polytetrafluoroethylene prosthesis showed no signs of adaptive remodeling. Its length and diameter remained unchanged (Figure 3 a, b). According to DUS and SCTA, the graft lost patency early due to thrombosis (Figure 18 b), confirmed intraoperatively at explantation (Figure 19 c). Histopathological examination verified luminal thrombosis with focal recanalization and calcification in the absence of true vascular wall formation (Figure 20), morphologically explaining its complete functional failure.