Additive Manufacturing of Multi‐Scale Porous Soft Tissue Implants That Encourage Vascularization and Tissue Ingrowth

Abstract

Medical devices, such as silicone-based prostheses designed for soft tissue implantation, often induce a suboptimal foreign-body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the "liquid rope coil effect", is exploited via direct ink writing, to create a controlled macro open-pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture. The potential to tailor the degree of tissue integration and vascularization using these fabrication techniques is demonstrated through subdermal and submuscular implantation studies in rodent and porcine models respectively, illustrating the implant coating's potential applications in both traditional soft tissue prosthetics and active drug-eluting devices.

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

“…We previously examined novel additive manufacturing techniques to tailor multi-scale porosity on the surface of soft tissue implants. This study found that the degree of tissue integration and vascularity in proximity to the implant is shown to increase 2.5-fold with precisely controlled surface structural complexity [17]. This study proposed that the use of this topographical enhancement could promote the tissue integration and vascularization needed for macroencapsulated islet cell viability and efficacy.…”

“…Devices were composed of two micro-permeable inner membranes (average pore size 6 µm) sandwiched and bonded with an inner support structure. A macro texture was deposited across the outer surface of each membrane in the form of repeating loops (as described in Coulter et al [17]), and this macro-texture served a dual purpose of reinforcing the membrane and encouraging tissue on-growth.…”

“…Devices were placed sub-muscularly in the cavity following enlargement with a pair of scissors filled and sealed. We have previously demonstrated that sub-muscular implant sites in the anterior abdominal wall meet requirements for size, accessibility, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival [17,31]. Therefore, a submuscular implantation site was chosen due to its comparability and translatability for our future sites for clinically scaled devices.…”

“…The visualisation of blood vessels was facilitated by immunohistological staining of CD31 (ab28364, Abcam, UK), an endothelial cell marker. Using twenty images per sample, a stereological counting technique was used to obtain unbiased estimates of Numerical Density, Length Density and Radial Diffusion Distances [17,[34][35][36][37][38]. Each vessel that was counted was also measured for vessel diameter analysis (up to 700 vessels per animal).…”

“…A total of twenty fields of view, chosen randomly, were acquired within each fibrous capsule. αSMA+ vessels within the fibrous capsule were counted using the ImageJ Cell Counter and represented as a percentage of total blood vessels present [17,34].…”