Structured Bone Grafts Using Stem Cells Without BMP

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Solution Overview

Problem

Existing bone graft substitutes face challenges such as inefficient bone remodeling, inflammation, and the risk of cancer due to the use of exogenous growth factors like BMP, and they often result in disordered bone growth or inadequate bone mass formation.

Innovation Solution

The development of novel methods and compositions that utilize bone marrow stromal cells (BMSCs) differentiated into osteoblast precursors, loaded into implant bodies made of porous, bio-compatible matrices functionalized with ascorbic acid, which promote the formation of structured, continuous bone tissue without the need for BMP or other growth factors, allowing for precise geometry and diverse bone structure creation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If BMP or other growth factors are included with cultured cells to promote bone formation, then bone mass formation is enhanced, but inflammation increases and cancer risk increases

Engineering Contradiction:
Improvebone mass formationVSAvoidinflammation and cancer risk
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent removes BMP and other growth factors from the bone graft composition, using only cultured osteoblasts within a collagen matrix. This extraction of harmful substances eliminates the associated inflammation and cancer risks while maintaining bone formation capability through the cultured cells alone.

Inventive Principle:
Principle #2Taking out (Extraction)

2Quantity of substance

If BMP is used to treat cells to promote bone growth, then bone formation is enhanced, but cells overgrow to form chaotic disordered structures

Engineering Contradiction:
Improvebone growthVSAvoidbone structure order
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

By removing BMP from the treatment protocol and using only cultured osteoblasts in a collagen matrix, the patent prevents the overgrowth and chaotic structure formation associated with BMP treatment while maintaining adequate bone mass formation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The cultured osteoblasts self-organize within the collagen matrix to form structured bone without external growth factor guidance, producing ordered bone structures through their inherent biological organization capabilities rather than BMP-directed chaotic growth.

Inventive Principle:
Principle #25Self-service

3Object-affected harmful factors

If transplanted osteoblasts without BMP treatment are used, then inflammation is reduced, but adequate bone mass is not formed

Engineering Contradiction:
Improveinflammation reductionVSAvoidbone mass
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

Osteoblasts are cultured and prepared in advance within the collagen matrix before transplantation, allowing them to proliferate and organize into bone-forming structures ex vivo. This preliminary culturing ensures adequate bone mass formation capability is established before implantation, eliminating the need for post-transplantation BMP treatment.

Inventive Principle:
Principle #10Preliminary action

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

These methods and compositions enable the robust, precise formation of functional bone structures that integrate with native bone, avoiding overgrowth and inflammation, while providing a controlled and efficient bone repair or augmentation solution.

Implementation Method 1

implant bodies made of porous, bio-compatible matrices functionalized with ascorbic acid, which promote the formation of structured, continuous bone tissue

Methodology Applied
Scientific EffectAscorbic acid functionalization:

Implementation Method 2

implant bodies made of porous, bio-compatible matrices

Methodology Applied
Scientific EffectPorosity: Porosity

Data Source

PatentUS10994050B2High yield and high precision bone graft substitute from stem cells
Publication Date: 2021.05.04 RGT UNIV OF CALIFORNIA
  • US10994050B2 patent drawing
  • US10994050B2 patent drawing
  • US10994050B2 patent drawing

AI summary

The invention comprises various materials and methods for the formation of bone within a patient using implanted bodies that are seeded with bone forming cells. The implants of the invention may comprise interlocking building blocks which allow for the formation of any desired structure. The geometry of the resulting bone structure can be tailored with great precision, and can be controllably integrated with native bone as desired. Advantageously, the methods result in the formation of functional, structured bone and avoid overgrowth, undergrowth, and the use of growth factors such as BMP-2.