3D Printed Bone Scaffold with Stem Cell Chambers

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Solution Overview

Problem

Current treatments for critical-sized bone defects, such as those caused by trauma or tumor resection, are inadequate due to high failure rates, donor site morbidity, and complications like infection, and existing bone grafts fail to regenerate complex bone structures effectively.

Innovation Solution

A bone regeneration product comprising a mesenchymal stem cell (MSC) formulation and a 3D-printed scaffold with hydroxyapatite (HA) and tricalcium phosphate (TCP) that includes a growth factor and a Smurf1 inhibitor, designed to promote dense or spongy bone regeneration by varying the ratio of cranial neural crest-derived MSCs to bone marrow-derived MSCs within the scaffold's chambers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If vascularized bone grafts are used to treat critical-sized bone defects, then blood supply and remodeling ability are improved, but mechanical stress and fracture risk increase

Engineering Contradiction:
Improvehealing success rateVSAvoidmechanical strength
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The scaffold is divided into multiple chambers (first chamber, second chamber, third chamber) that can be selectively filled with different stem cell formulations. This segmentation allows optimization of different regions for different functions - some chambers for osteogenic differentiation, others for chondrogenic differentiation, enabling simultaneous blood supply improvement and mechanical strength maintenance without relying on a single graft structure

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses composite stem cell formulations combining multiple types of stem cells (mesenchymal stem cells, adipose-derived stem cells, bone marrow-derived stem cells) in specific ratios within the scaffold chambers. This composite approach creates synergistic effects that improve both biological function (blood supply, remodeling) and mechanical properties through coordinated tissue regeneration

Inventive Principle:
Principle #40Composite materials

2Reliability

If fibular grafts are used for critical-sized defects in lower extremities, then bone regeneration is achieved, but fracture rates increase due to excessive mechanical stress

Engineering Contradiction:
Improvebone union rateVSAvoidfracture resistance
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

Different chambers of the scaffold are designed with different local qualities by filling them with specific stem cell formulations optimized for different tissue types. For example, chambers closer to load-bearing regions may contain formulations promoting cortical bone formation with higher mechanical strength, while other chambers promote trabecular bone or cartilage formation, creating spatially varying properties that match functional requirements

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The scaffold enables dynamic tissue regeneration by using stem cell formulations that can differentiate into multiple lineages (osteogenic, chondrogenic, adipogenic) based on local microenvironmental cues. This dynamic differentiation capability allows the regenerated tissue to adapt its mechanical properties during the healing process, transitioning from softer initial tissue to stronger mature bone, thereby improving fracture resistance over time

Inventive Principle:
Principle #15Dynamics

3Reliability

If traditional bone grafting methods are used, then bone healing is promoted, but donor site morbidity and infection risk occur

Engineering Contradiction:
Improvebone healing efficacyVSAvoiddonor site complications
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The scaffold acts as an intermediary carrier that delivers stem cells and growth factors directly to the defect site without requiring harvest from donor sites. The scaffold material itself (biocompatible polymer or ceramic) serves as a mediator that provides structural support while releasing bioactive molecules, eliminating the need for autologous bone harvesting and associated donor site morbidity and infection risks

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If existing bone grafts are used for critical-sized defects, then some healing is achieved, but complex bone structures are not regenerated effectively

Engineering Contradiction:
Improvehealing outcomeVSAvoidstructural complexity
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The multi-chambered scaffold design enables segmentation of the defect space, allowing each chamber to be optimized for specific structural requirements. Chambers can be designed with different geometries, pore sizes, and interconnectivity patterns to replicate complex native bone architectures such as cortical shells, trabecular interiors, or articular cartilage surfaces, achieving structural complexity that traditional homogeneous grafts cannot provide

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP3707240B1Stem cells and devices for bone regeneration
Publication Date: 2024.04.24 UNIV OF SOUTHERN CALIFORNIA
  • EP3707240B1 patent drawingFigure 1
  • EP3707240B1 patent drawingFigure 2
  • EP3707240B1 patent drawingFigure 3(A)~3(B)

AI summary

This invention relates to a bone regeneration product comprising at least one stem cell, at least one scaffold, and at least one stem cell. The stem cells suitable for this invention may comprise stem cells suitable for a dense bone regeneration, stem cells suitable for a spongy bone regeneration, or a combination thereof. The bone regeneration product may further comprise a growth factor. This invention also relates to a bone regeneration method and treatment of any bone that has a critical size defect. This invention also relates to a scaffold. This invention further relates to a 3D printed scaffold comprising hydroxyapatite(HA) and tricalcium phosphate(TCP). This invention also relates to a scaffold comprising a polymer. The polymer of this invention may be prepared by using photocurable polymers and/or monomers. The scaffold of this invention may comprise a growth factor and a small molecule. The small molecule may be a Smurf1 inhibitor.