Artificial Bladder: Filling the Void Alexander Kutikov, MD (talk prepared in 2002, reviewed in 2011) Alexander Kutikov, MD (talk prepared in 2002, reviewed

Artificial Bladder: Filling the VoidArtificial Bladder: Filling the Void

Alexander Kutikov, MD(talk prepared in 2002, reviewed in 2011)

Alexander Kutikov, MD(talk prepared in 2002, reviewed in 2011)

Bladder Regeneration: Overview Bladder Regeneration: Overview

• Introduction

• Use of GI Segments

• Approaches to Bladder Replacement•Alloplastic Bladders

• Tissue Engineered Bladders• In-Situ Regenerated • In-Vitro Regenerated

• Summary

• Introduction

• Use of GI Segments

• Approaches to Bladder Replacement•Alloplastic Bladders

• Tissue Engineered Bladders• In-Situ Regenerated • In-Vitro Regenerated

• Summary

Introduction: Bladder DiseaseIntroduction: Bladder Disease

• 400 Million Suffer from Bladder Dz Cancer Trauma Infection Inflammation Iatrogenic Injuries Congenital Anomalies

• Many Require Bladder Replacement

• 400 Million Suffer from Bladder Dz Cancer Trauma Infection Inflammation Iatrogenic Injuries Congenital Anomalies

• Many Require Bladder Replacement

Current TreatmentCurrent Treatment

• Bladder replacement w/ GI segments• > 100 year-old method• Remains the standard of care

• Bladder replacement w/ GI segments• > 100 year-old method• Remains the standard of care

Problems w/ Using BowelProblems w/ Using Bowel

GI Tissue - Designed to Absorb SolutesGU Tissue - Designed to Excrete SolutesGI Tissue - Designed to Absorb Solutes

GU Tissue - Designed to Excrete Solutes

==

Compliations of GI Neo-Bladders Compliations of GI Neo-Bladders

• Altered Electrolyte Metabolism• Altered Hepatic Metabolism• Abnormal Drug Metabolism• Infection• Calculus Formation• Nutritional Disturbances• Growth Retardation• Osteomalacia• Cancer

• Altered Electrolyte Metabolism• Altered Hepatic Metabolism• Abnormal Drug Metabolism• Infection• Calculus Formation• Nutritional Disturbances• Growth Retardation• Osteomalacia• Cancer

Ideal Bladder SubstituteIdeal Bladder Substitute

• Adequate Urine Storage• Complete Evacuation of Urine (volitional)• Preserve Renal Function

• Biocompatible• Resistant to Urinary Encrustation• Resistant to Bacterial Infection

• Adequate Urine Storage• Complete Evacuation of Urine (volitional)• Preserve Renal Function

• Biocompatible• Resistant to Urinary Encrustation• Resistant to Bacterial Infection

Must be superior to GI segments

Approaches to Bladder SubstitutionApproaches to Bladder Substitution

• Alloplastic Bladders

• Tissue Engineered Bladders• In-Situ Regenerated • In-Vitro Generated

• Alloplastic Bladders

• Tissue Engineered Bladders• In-Situ Regenerated • In-Vitro Generated

Alloplastic OrgansAlloplastic Organs

Alloplastic OrgansAlloplastic Organs

Alloplastic BladderAlloplastic Bladder

• First prosthetic bladder reported in 1960• Box-shaped silicone reservoir attached to anterior abdominal wall• Silicone tube brought out onto the skin served as outlet• Hydronephrosis due to ureteral prosthetic anastomosis main reason for failure• No dog survived more than 1 month

• First prosthetic bladder reported in 1960• Box-shaped silicone reservoir attached to anterior abdominal wall• Silicone tube brought out onto the skin served as outlet• Hydronephrosis due to ureteral prosthetic anastomosis main reason for failure• No dog survived more than 1 month

Alloplastic Bladder: Mayo Clinic ModelAlloplastic Bladder: Mayo Clinic Model

Rigid polysulfone shell

Distensible silicone shell

8 Fr siliconetubes in ureters

Fluid

• Implanted intraperitoneally• No dog survived > 10 wks

• Infections w/ abscess formation *• Urinary leaks at anastomoses *• Mechanical failure of device*• Urinary encrustation • Formation of constrictive capsule • RF 2o to Hydronephrosis

• Infections w/ abscess formation *• Urinary leaks at anastomoses *• Mechanical failure of device*• Urinary encrustation • Formation of constrictive capsule • RF 2o to Hydronephrosis

Alloplastic Bladder: Reasons for FailureAlloplastic Bladder: Reasons for Failure

* - Applies to Mayo Clinic Model* - Applies to Mayo Clinic Model

Alloplastic Bladder: Aachen ModelAlloplastic Bladder: Aachen Model

Subcutaneous compressiblereservoirs

Dacron-covered silicone tubesthrough renal parenchyma

Y-shaped Dacron-reinforcedsilicone reservoir drains intourethra

7 years to develop7 years to develop

Alloplastic Bladder: Aachen ModelAlloplastic Bladder: Aachen Model

• Implanted into 5 sheep

• Functioned effectively in 2 sheep for 18 mo

• Urinary leakage in 3 animals due to anastamotic

or material failure

• Kidney structure and function preserved in all

cases

• No further publications on use of Aachen Model

since 1996

• Implanted into 5 sheep

• Functioned effectively in 2 sheep for 18 mo

• Urinary leakage in 3 animals due to anastamotic

or material failure

• Kidney structure and function preserved in all

cases

• No further publications on use of Aachen Model

since 1996

Alloplastic Bladder: Lessons LearnedAlloplastic Bladder: Lessons Learned

• Minimize anastomoses btwn living tissue and alloplasts Transrenal-parenchymal insertion of urteral prosthesis

offers hope

• Infection is a major hurdle to overcome Antibiotic-coated solid materials under investigation

• Minimize anastomoses btwn living tissue and alloplasts Transrenal-parenchymal insertion of urteral prosthesis

offers hope

• Infection is a major hurdle to overcome Antibiotic-coated solid materials under investigation

TISSUE ENGINEERING: potential solution to both problems

Use of living cells to restore, maintain, or

enhance tissues or organs

Use of living cells to restore, maintain, or

enhance tissues or organs

Tissue Engineering: DefinitionTissue Engineering: Definition

Tissue Engineering: PrinciplesTissue Engineering: Principles

1. Implantation of freshly isolated or cultured cells

2. In Situ tissue regeneration

3. Implantation of tissues assembled in vitro from

cells and scaffolds




cells and scaffolds

Strategies for Treatment of Diseased/Injured Tissue: Strategies for Treatment of Diseased/Injured Tissue:





cells and scaffolds




cells and scaffolds


Tissue Engineering: In Situ RegenerationTissue Engineering: In Situ Regeneration






Tissue Engineering: In Situ RegenerationTissue Engineering: In Situ Regeneration • Numerous Materials Have been Tried as

Matrices

• Most Successful:

• Small bowel submucosa• Acellular submucola of porcine small bowel

• Bladder Acellular Matrix Grafts (BAMG)• Acellular collagen and elastin produced

by stripping stromal and epithelial cells

from bladder wall

• Numerous Materials Have been Tried as

Matrices

• Most Successful:

• Small bowel submucosa• Acellular submucola of porcine small bowel

• Bladder Acellular Matrix Grafts (BAMG)• Acellular collagen and elastin produced

by stripping stromal and epithelial cells

from bladder wall


7 mo post

Distended NormalBladder

S/p hemicystectomyof dome

BAMG graftedbladder


B/f Surgery S/p Surgery 7 mo s/p Surgery


Histology a/f 4 monthsHistology a/f 4 months


• Bladder wall structurally and functionally

nearly identical to native bladder • No significant rejection of graft seen

• Bladder wall structurally and functionally

nearly identical to native bladder • No significant rejection of graft seen

• Similar results obtained with SIS and BAMG grafts • Similar results obtained with SIS and BAMG grafts

• Human trials with BAMG and SIS being attempted• Human trials with BAMG and SIS being attempted




3. Implantation of tissues assembled in vitro



3. Implantation of tissues assembled in vitro


Tissue Engineering: In Vitro AssemblyTissue Engineering: In Vitro Assembly





SMOOTH MUSCLE

UROTHELIUM


• Potential for genetic/phenotypic screeing of harvested cells allows selection against transformed phenotypes • Potential for genetic/phenotypic screeing of harvested cells allows selection against transformed phenotypes


• Potential for genetic/phenotypic screening of harvested cells allows selection against transformed phenotypes

• Cells could also be genetically modified to acquire desired properties (e.g. antimicrobial, growth factors, etc.)

• Potential for genetic/phenotypic screening of harvested cells allows selection against transformed phenotypes

• Cells could also be genetically modified to acquire desired properties (e.g. antimicrobial, growth factors, etc.)


Bx to implant of graft = 5 weeks



Native bladder wall

Native bladder wall

Tissue-engineeredNeo-bladder

Tissue-engineeredNeo-bladder


• Function of Tissue Engineered Neo-Bladder:

• Mean bladder capacity was 95% of precystecomy volume

• Mean compliance was no different than preoperative values

• Function of Tissue Engineered Neo-Bladder:

• Mean bladder capacity was 95% of precystecomy volume

• Mean compliance was no different than preoperative values

SummarySummary

• GI Segments: employed as neobladders >100 years; it’s time for change.

• Alloplastic Neobladders: little hope w/ current materials.

• Tissue Engineering: hold much hope, but remains experimental. Human studies humbling to date.

• GI Segments: employed as neobladders >100 years; it’s time for change.

• Alloplastic Neobladders: little hope w/ current materials.

• Tissue Engineering: hold much hope, but remains experimental. Human studies humbling to date.

Documents

Artificial Bladder: Filling the Void Alexander Kutikov, MD (talk prepared in 2002, reviewed in 2011) Alexander Kutikov, MD (talk prepared in 2002, reviewed