Microchannels Are an Architectural Cue That Promotes Integration and Vascularization of Silk Biomaterials in Vivo

Abstract

Functional integration of implanted biomaterials and bioengineered tissues in vivo requires effective and timely vascular ingrowth. While many vascularization strategies rely on delivery of angiogenic growth factors or endothelial cells to promote vascular ingrowth, the effect of physical and architectural features of biomaterials on the vascularization process is less well understood. Microchannels are a simple, accessible architectural feature frequently engineered into 3D biomaterials to promote mass transfer. In this study, the effect of microchannels on the integration and vascularization of 3D porous silk scaffolds was explored over a 14 week period. An array of 508 μm diameter microchannels spanning the length of critically sized, porous silk scaffolds significantly improved tissue ingrowth into the constructs. At week 6, all silk scaffolds (n = 8) with microchannels showed complete tissue infiltration throughout the construct, while only one of eight (12.5%) did so in the absence of microchannels. The presence of microchannels improved silk scaffold vascularization with significantly more vessels per unit area in the presence of microchannels. The vessel size distribution was similar in both scaffold types, but a shift in distribution toward smaller vessels was observed in the presence of microchannels. The blood vessels in silk scaffolds were perfused, functional and connected to the animal’s cardiovascular system, as demonstrated by the presence of red blood cells in the vessel lumens, and effective delivery of a contrast agent the vessels inside the scaffold. This study demonstrates the utility of microchannels as a simple architectural feature that significantly improves vascularization and integration of implanted biomaterials.

A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials

“…Silk scaffolds were implanted in subcutaneous pockets on the back of each mouse ( n = 8 per condition) for 6 weeks as previously established. [ 34,38 ] The incisions were closed with surgical clips that were removed at day 10 post‐surgery. At week 6 post‐surgery the mice were processed for either histological or magnetic resonance imaging (MRI) analyses.…”

Impact of sterilization on a conjugated polymer based bioelectronic patch

“…Thereafter, the sections were stained with haematoxylin and eosin (H&E), Masson's trichome as previously described. 39 Briefly, following rehydration, slides were stained with Harris haematoxylin for 5 min, followed by eosin for 4 min, before dehydration and mounting. Masson's trichrome staining was performed following manufacturer's standard procedure.…”

Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches

“…Analysis of blood vessel perfusion in silk scaffolds with: (g) Δ R maps of MRI imaging showed the relative blood volume inside the channeled scaffold implanted subcutaneously in mice for 6 weeks, (h) Δ R map overlaid over a corresponding histological section, and (i) Fluorescent images of lectin‐perfused blood vessels (red) inside a silk scaffold (green) implanted subcutaneously in mice for 6 weeks and imaged via light‐sheet microscopy (Dashed line: scaffold boundary, White arrow points to the silk scaffold, Scale bar is 1 mm). Reproduced with permission 120‐122 . Copyright 2018, Royal Society of Chemistry, 2010 and 2020, American Society of Chemistry…”

“…Cells can convert the biomaterial's biophysical features into intracellular biochemical signals via for example mechanosensing resulted in ultimate gene expression 123 . Therefore, the creation of specific morphologies and surface patterns along with optimization of pore size and pore morphology has been shown to influence the growth of interconnected blood vessels within the scaffold and also the degree of vascularization through the mechanisms involving the body's immune system 120,124 . In this regard, using biomaterials containing microchannel architecture, expanded fibrous morphologies, and 3D bioprinting systems can be considered as promising approaches due to their ability to 3D mimicking the native microenvironment of cells 34,60,120,124‐126 .…”

“…As an example, Tang et al studied the effect of microchannels on the integration and vascularization of host tissue into the 3D porous silk scaffolds containing 508 μm diameter microchannels. The in vivo test results (at 6 and 14 weeks) showed the formation of perfused and functional blood vessels within the microchanneled scaffold which were connected to the animal's cardiovascular system demonstrated by smooth delivery of either the contrast agent or dye through the vessels inside the scaffold 120 (Figure 4f,i).…”