Bioengineered Internal Anal Sphincter Constructs for Fecal Incontinence
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Solution Overview
Problem
Current treatments for fecal incontinence, such as biofeedback, sacral nerve stimulation, myoblast injections, and artificial anal sphincter implantations, focus on reinstating external anal sphincter function or mechanical closure, neglecting the restoration of internal anal sphincter function, which is crucial for coordinated rectal contraction and relaxation mediated by the enteric nervous system.
Innovation Solution
The development of bioengineered internal anal sphincter constructs using autologous neural progenitor cells and smooth muscle cells, isolated from patient biopsies, which are cultured and formed into a gel matrix to recreate the internal anal sphincter's muscle and nerve components, capable of being implanted to restore function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments (biofeedback, sacral nerve stimulation, myoblast injections, artificial anal sphincter implantation) are used to treat fecal incontinence, then external anal sphincter function or mechanical closure is reinstated, but internal anal sphincter function and coordinated rectal contraction/relaxation are neglected and not restored
Solution Approach 1:
The treatment is segmented into two distinct components: (1) bioengineered internal anal sphincter construct containing smooth muscle cells for basal tone, and (2) enteric neural crest-derived neurons for coordinated control. This segmentation allows each component to be optimized independently and implanted together to restore complete function.
Solution Approach 2:
Enteric neural crest-derived neurons serve as an intermediary that bridges the gap between mechanical sphincter function and neural control. These neurons are integrated into the smooth muscle construct and provide the missing neural coordination capability, enabling the sphincter to respond appropriately to rectal distension and maintain continence.
2Reliability
If bioengineered constructs with both smooth muscle cells and enteric neurons are developed, then complete internal anal sphincter function is restored, but treatment complexity increases
Solution Approach 1:
The smooth muscle cells and enteric neural crest-derived neurons are merged into a single integrated bioengineered construct. This combining allows the two cell types to work together synergistically within one implantable unit, restoring both basal tone and coordinated neural control simultaneously without requiring separate implantation procedures.
Solution Approach 2:
The construct uses a composite cellular architecture where smooth muscle cells provide the contractile element and enteric neurons provide the control element. This composite approach mirrors the natural internal anal sphincter structure and enables comprehensive functional restoration through a single integrated tissue engineering solution.
3Adaptability or versatility
If autologous cells are used for bioengineering, then patient-specific restoration is achieved, but biopsy and cell isolation procedures are required
Solution Approach 1:
The patient's own tissue serves as the source material for the bioengineered construct. Autologous smooth muscle cells and enteric neural crest-derived neurons are harvested from the patient's rectum, expanded in culture, and reimplanted. This self-service approach eliminates the need for allogeneic donors or synthetic materials, providing patient-specific customization while using the patient's own biological resources.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The bioengineered internal anal sphincter constructs effectively restore basal tone and rectoanal inhibitory reflex, significantly improving fecal continence by reestablishing the internal anal sphincter's muscle and neural functionality, as demonstrated by increased anal basal pressure and RAIR in clinical studies.
Implementation Method 1
steps of isolating can include a step of enzymatically digesting the mechanically disaggregated cell biopsy. In some embodiments, the step of enzymatically digesting can include a digesting media. In some embodiments, the digesting media can include a collagenase, e.g., Collagenase type II.
Implementation Method 2
In some embodiments, methods can further includes a step of preparing a smooth muscle cell gel and a neural progenitor cell gel. In some embodiments, methods can further include seeding the gels to form a matrix on a culture plate and/or mold.
Data Source
AI summary
The present disclosure provides methods of bioengineering sphincters having autologous smooth muscle cells isolated from human internal anal sphincter and autologous enteric neurospheres (neural progenitor cells) isolated from human small intestine (jejunum). The isolated neural progenitor cells and smooth muscle cells are co -cultured using dual layered hydrogels and allowed to form circular, intrinsically innervated internal anal sphincter constructs. Such innervated internal anal sphincter constructs, bioengineered internal anal sphincter constructs are useful as additive implants in the treatment of fecal incontinence.