Molded collagen scaffolds as an engineered replacement for biological-sourced materials in reconstructive urological applications

NIKOLAI SOPKO, DAVID LEE, XIAPOU LIU, MICHAEL BICKELL, RAFAELCARRION, ANIRUDHA SINGH, TRINITY BIVALACQUA

Background

Severe Peyronie’s disfigurement requires plaque incision/excision and grafting

Purpose of graft material is to replace tunica albuginea, prevent vascular leak, undergo minimal contraction, incite minimal inflammatory response

Grafting materials

Grafting materials include: tunica vaginalis, temporalis fascia, saphenous vein, Dacron, and Gore-Tex.

Commonly used materials include:

Tutoplast – Decellularized cadaveric pericardium (Coloplast)- 400uM thick multidirectional matrix- >>Collagen I- Mild inflammatory response- First reported use for Peyronie’s in 2000 (Hellstrom et al.)

SIS - Decellularized porcine small intestine submucosa (Surgisis ES, Cook Medical)- 4-layered extracellular matrix 80-100uM thick- >>Collagen I, fibronectin, glycosaminoglycans, proteoglycans, growth factors- Mild inflammatory response, usually replaced within 6 weeks- First reported use for Peyronie’s in 2001 (Knoll et al.)

Issues with Tutoplast and SISExpensive – cost hundreds to thousands of dollars per sheet

Theoretical risk of disease transmission

Tutoplast and SIS contract and therefore are oversized by 20-30% when grafting

Minor inconsistencies between batches may affect contraction rate and consistency of efficacy

Off the shelf with 5 year shelf-life

Robust

Low immunogenicity

Do not require additional surgical morbidity in order to obtain (vs. vein and fascia)

Question: Can we manufacturer a collagen based scaffold that performs similar to Tutoplast and SIS while being cheap, consistent, and safe.

Goal

To evaluate how a collagen based scaffold compares to Tutoplast and SIS

Collagen scaffold

Evaluated two different collagen I-based scaffolds formed by a novel vacuum-condensation technique

Anirudha Singh, PhD

Collagen I scaffold with pores - CPC

Collagen I scaffold that is heavily cross-linked – CLC

Study design

Tut SIS CPC CLC

Scanning Electron MicroscopyStress Strain Testing

Cellular Infiltration/Inflammation

Profile Tissue Response

3 day

7 day

14 day

28 day

Collect Tissues

Impant MaterialSubcutaneously

Sprague-Dawley

Mechanical properties

Decellularized Epicardium(Tutoplast - Tut)

Decellularized Small Intestinal Submucosa (SIS)

Cross-LinkedMolded Collagen (CLC)

PorousMolded Collagen (CPC)

ScanningElectron

Microscopy

Gross Imaging4 weeks

Post-Implantation

Tut

CPC

SIS

CLC

PCR characterization of graft cellularization – 28 Days

0

1

2

3

4

5

TGFb CD68 ITGB2 CD3e VEGF

Tut

SIS

CPC

CLC

Histology3-DaysPost-

Implantation

Histology28-Days

Post-Implantation

Conclusions

Collagen based scaffold can have mechanical properties similar to Tutoplast and SIS

Implanted collagen based scaffolds induce a similar tissue response as Tutoplast and SIS

Collagen based scaffolds may be suitable for reconstructive urological applications

Xiaopu Liu, BSHotaka Matsui, MD

Max Kates, MD

Bivalacqua Laboratory

Takahiro Yoshida, MD, PhD

Nikolai Sopko, MD, PhD

Trinity Bivalacqua, MD, PhD

Singh Laboratory

Anirudha Singh, PhD

David Lee, BSPraveena Sabnekar