Effect of platelet-derived growth factor-BB on tissue integration of cross-linked and non-cross-linked collagen matrices in a rat ectopic model

AimTo test whether or not the network structure and the addition of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to a chemically cross-linked collagen matrix (CCM)- and a non-cross-linked collagen matrix (NCCM)-influenced tissue integration, angiogenesis, and matrix degradation. Materials and methodsFour treatment modalities were randomly assigned to four unconnected pouches in the back of 50 rats: (i) CCM-S (soaked in saline), (ii) CCM-P (plus rhPDGF-BB), (iii) NCCM-S (soaked in saline), and (iv) NCCM-P (plus rhPDGF-BB). The animals were sacrificed at 2, 4, 8, 16, and 24weeks. Descriptive histology and histomorphometric assessments were performed thereby evaluating matrix thickness, the number of vessels (angiogenesis), and connective tissue formation. Means and standard deviations were calculated. Robust linear mixed modeling was used to test the effect of group (NCCM vs CCM), rhPDGF-BB, and time point of sacrifice (2, 4, and 8weeks). ResultsThe thickness of NCCM groups revealed stability (range 440-570m) over 8weeks, while the matrices were no longer present at 16 and 24weeks. CCM matrices demonstrated a maximal thickness at 2weeks (2689187m for CCM-S and 2693 +/- 389m for CCM-P), a decrease of roughly 40% at 8weeks, but were still present at 16 and 24weeks. Vascularization of NCCM gradually increased over time with a peak (mean 17.0; SD 1.7) for NCCM-S and NCCM-P (22.0 +/- 34.8) at 8weeks. Angiogenesis in CCM was significantly more pronounced at early time points with a peak at 2weeks (29.3 +/- 16.8 for CCM-S and 30.3 +/- 18.4 for CCM-P). No statistically significant effect of rhPDGF-BB was observed for any of the evaluated parameters (all P>0.05). ConclusionsThe compact layer (in NCCM) delayed angiogenesis and connective tissue formation, while the spongeous cross-linked matrix of CCM facilitated early vascularization and demonstrated network presence over a longer time span.