Neovascularization of poly(ether ester) block‐copolymer scaffolds in vivo: Long‐term investigations using intravital fluorescent microscopy

Abstract

Poly(ether ester) block-copolymer scaffolds of different pore size were implanted into the dorsal skinfold chamber of balb/c mice. Using intravital fluorescent microscopy, the temporal course of neovascularization into these scaffolds was quantitatively analyzed. Three scaffold groups (diameter, 5 mm; 220 -260 thickness, m; n ϭ 30) were implanted. Different pore sizes were evaluated: small (20 -75 m), medium (75-212 m) and large pores (250 -300 m). Measurements were performed on days 8, 12, 16, and 20 in the surrounding normal tissue, in the border zone, and in the center of the scaffold. Standard microcirculatory parameters were assessed (plasma leakage, vessel diameter, red blood cell velocity, and functional vessel density). The largepored scaffolds showed significantly higher functional vessel density in the border zone and in the center (days 8 and 12) compared with the scaffold with the small and mediumsized pores. These data correlated with a larger vessel diameter and a higher red blood cell velocity in the largepored scaffold group. Interestingly, during the evaluation period the microcirculatory parameters on the edge of the scaffolds returned to values similar to those found in the surrounding tissue. In the center of the scaffold, however, neovascularization was still active 20 days after implantation. Plasma leakage and vessel diameter were higher in the center of the scaffold. Red blood cell velocity and functional vessel density were 50% lower than in the surrounding tissue. In conclusion, the dorsal skinfold chamber model in mice allows long-term study of blood vessel growth and remodeling in porous biomedical materials. The rate of vessel ingrowth into poly(ether ester) block-copolymer scaffolds is influenced by pore size and was highest in the scaffold with the largest pores. The data generated with this model contribute to knowledge about the development of functional vessels and tissue ingrowth into biomaterials.

Bone Tissue Engineering with Multilayered Scaffolds—Part I: An Approach for Vascularizing Engineered Constructs In Vivo

“…[4][5][6][7][8] However, less than optimal scaffold architecture remains as one of the crucial factors, which affect the depth, rate of vascular ingrowth, and spatial distribution of vessels in the engineered construct. [9][10][11][12] Both angiogenesis, where the development of new vessels occurs from pre-existing blood vessels, and vasculogenesis, where blood vessels are formed through the de novo differentiation of stem cells into endothelial cells and/or their progenitors, have been studied by researchers to overcome the problem of inadequate vascularization of tissue-engineered constructs. 13 For functional vascularization of the construct, the role of material-driven properties such as compatibility, functionality, mechanical property, and degradation along with scaffold design parameters such as structure, porosity, pore size, and interconnectivity are important.…”

The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

“…Moreover, it is necessary that the tissues inside the chamber are not affected by the implanted chamber material itself. Therefore, chambers originally consisted of aluminium, which was covered with Tefl on S to guarantee low weight, low thermal conductivity and biological inertness (Endrich et al, 1980). Nowadays, the chambers are usually made of titanium, which also exhibits these material properties and additionally provides an improved stability .…”

“…The dorsal skinfold chamber model has been established in rats (Papenfuss et al, 1979), immuno-competent mice (Cardon et al, 1970), nude and severe combined immunodefi cient mice (Leunig et al, 1992;Lehr et al, 1993) as well as in hamsters (Endrich et al, 1980). In contrast to rats and mice, preparation of the dorsal skinfold chamber in hamsters bears the major advantage that the retractor muscle is only loosely attached to the underlying panniculus carnosus muscle without many vascular interconnections between the two muscle layers.…”

“…For such facial surgical procedures, patients often undergo perioperative steroid therapy to reduce postoperative oedema formation and to shorten recovery time (Kara and Gökalan, 1999;Kargi et al, 2003). However, it was found that Medpor ® implanted into the dorsal skinfold chamber of prednisolone-treated balb/c mice exhibits a signifi cantly reduced vascularisation when compared to vehicle-treated controls (Ehrmantraut et al, 2010). These fi ndings indicate that perioperative steroid therapy may be avoided in case of Medpor ® implantation to achieve a rapid incorporation of the material at the implantation site.…”

“…During the last few years, various scaffold types have been evaluated in terms of biocompatibility and vascularisation in dorsal skinfold chambers of mice. These scaffolds consisted of collagen (Ichioka et al, 2005), collagen-elastin (Ring et al, 2010a), collagen-chitosanhydroxyapatite hydrogel , acellular dentin (Rücker et al, 2008), hydroxyapatite (Rücker et al, 2008), β-tricalcium-phosphate , poly(ether ester) (Druecke et al, 2004), poly(L-lactideco-glycolide) (PLGA) , polyethylene glycol terephthalate/polybutylene terephthalate (PEGT/ PBT) (Ring et al, 2006a,b), lactocapromer terpolymer (Ring et al, 2010b(Ring et al, , 2011b, polyurethane (Laschke et al, 2009c(Laschke et al, , 2010a and supramolecular nanofi bres (Ghanaati et al, 2009). Notably, it was found that the initial vascularisation of the scaffolds is crucially dependent on their biocompatibility.…”