Vascularized Bone Replacement Using Hydrogel Growth Medium

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Solution Overview

Problem

Current methods for generating vascularized bone replacements face challenges in engineering functional vascular networks, which is a significant obstacle for clinically relevant tissue repair, especially due to the limitations of existing 3D scaffold fabrication techniques and the lack of vascularity in decellularized bone grafts.

Innovation Solution

A 3D cell growth medium using hydrogel particles and a liquid cell culture medium, combined with biocompatible scaffolds and vascular structures, allows for the creation of vascularized tissue replacements by supporting cell growth and blood flow, enabling the formation of a functional vascular network.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If decellularized bone from cadaveric donors is used to provide native structure and mechanical support, then the structural integrity and mechanical properties are improved, but the ability to remodel into living tissue is lost due to lack of vascularity

Engineering Contradiction:
Improvemechanical supportVSAvoidtissue remodeling capability
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The bone graft is divided into multiple functional components: a decellularized bone matrix providing structural support and a separate vascular network component that can be independently engineered and integrated. This segmentation allows each component to be optimized for its specific function while working together as a unified graft system.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The vascular network is nested within the decellularized bone matrix structure. The vascular channels are formed inside the porous bone scaffold, creating a hierarchical structure where the vascular system is embedded within the structural framework, allowing both mechanical support and tissue remodeling functions to coexist.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Manufacturing precision

If traditional 3D printing methods are used to fabricate scaffolds, then structural precision can be achieved, but the fabrication process becomes time-consuming and complex due to layer-by-layer construction and support material removal

Engineering Contradiction:
Improvescaffold structureVSAvoidfabrication time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The vascular channels and scaffold structures are pre-formed within the decellularized bone matrix before final assembly. The porous structure of the bone matrix naturally provides scaffold pathways that serve as preliminary guides for vascular network formation, eliminating the need for complex post-fabrication channel creation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The decellularized bone matrix naturally provides the scaffold structure and vascular pathways through its inherent porous architecture. The bone matrix self-organizes to create appropriate channels and structures during the decellularization process, eliminating the need for external support materials and complex fabrication sequences.

Inventive Principle:
Principle #25Self-service

3Manufacturing precision

If micropatterning and lithography techniques are used to generate surface topography, then surface precision is improved, but the complexity of equipment and facilities required increases significantly

Engineering Contradiction:
Improvesurface topographyVSAvoidfabrication equipment
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The decellularized bone matrix naturally forms the required surface topography and micro-architecture through the decellularization process itself. The remaining cellular debris and matrix restructuring create appropriate surface features for cell attachment and vascular formation without requiring external micropatterning equipment.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The physical and chemical parameters of the bone matrix are modified during decellularization to naturally create the desired surface topography. Changes in porosity, surface chemistry, and structural density occur as a result of the decellularization treatment, providing the necessary micro-features without additional fabrication steps.

Inventive Principle:
Principle #35Parameter changes

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

This approach facilitates the development of vascularized bone replacements that mimic in vivo environments, supporting tissue growth and vascularization, overcoming the limitations of existing techniques by allowing for the integration of biocompatible scaffolds and vascular structures within a 3D growth medium.

Implementation Method 1

a 3D cell growth medium comprising a plurality of hydrogel particles and a liquid cell culture medium, wherein the hydrogel particles are swelled with the liquid cell culture medium to form a granular gel

Methodology Applied
Scientific EffectSwelling: Absorption (physical)

Implementation Method 2

The polymer solution used is fed through a syringe and extruded from the spinneret (needle tip) connected to a high-voltage, where the nanofibers are generated

Methodology Applied
Scientific EffectElectrospinning: Electrohydrodynamics

Data Source

PatentUS11559608B2Fabrication of autologous bone
Publication Date: 2023.01.24 UNIV OF FLORIDA RESEARCH FOUNDATION INC
  • US11559608B2 patent drawing
  • US11559608B2 patent drawing
  • US11559608B2 patent drawing

AI summary

Described herein are methods and apparatus for constructing tissue replacements, such as bone replacements that may be used to repair damaged or missing segments of bone, such as may occur in wound repair or as a repair of a congenital anomaly. These methods involve a three-dimensional (3D) cell growth medium made from a yield stress material that allows cells and structures to be easily deposited and positioned.