Acoustic Microtissue Patterning for Rapid Autologous Tissue Grafts
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Solution Overview
Problem
Existing methods for producing tissue grafts, such as skin grafts, are time-consuming, require significant logistical complexity, and often result in suboptimal expansion factors, making them unsuitable for emergency situations and prone to rejection by the patient's immune system.
Innovation Solution
A method involving the use of microtissues, such as spheroids and organoids, suspended in a blood sample and exposed to static acoustic waves to form a patterned tissue construct, which can be rapidly produced at the point of care, achieving high expansion factors up to 40- to 80-fold.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Area of stationary object
If meshed split skin grafts are expanded to higher fold (9-fold theoretical), then the graft coverage area is increased, but the healing process is slowed down and esthetical/functional outcome is affected
Solution Approach 1:
The invention segments the tissue sample into multiple small biopsies (0.5-5 mm in diameter) before expansion. This segmentation allows for more uniform distribution of incisions and better integration with the wound bed, enabling higher expansion factors while maintaining healing quality. The small biopsy pieces can be arranged in a mesh pattern that provides adequate coverage without excessive stretching that would compromise tissue viability.
2Productivity
If the number of incisions in meshed split skin grafts is increased to achieve further stretching, then the graft expansion factor is increased, but the healing process is slowed down
Solution Approach 1:
The invention performs preliminary segmentation of the tissue into small biopsies before the expansion step. This preliminary action allows the tissue to be pre-prepared in a way that facilitates uniform expansion without requiring excessive incisions. The small biopsies can be directly arranged and secured in the wound bed, reducing the need for extensive post-expansion manipulation and accelerating the healing process.
3Quantity of substance
If a large tissue sample is harvested from the patient to provide sufficient graft material, then the graft coverage is improved, but the donor site morbidity and accessibility are worsened
Solution Approach 1:
The invention transitions from a two-dimensional sheet graft to a three-dimensional expanded mesh structure. By creating a mesh pattern with interconnected nodes and spaces, the same amount of tissue material can cover a much larger surface area. This dimensional transformation allows sufficient graft coverage to be achieved from smaller tissue samples, reducing donor site morbidity while maintaining adequate coverage for large wounds.
4Reliability
If autografts are used to ensure immune system acceptance, then the risk of rejection is reduced, but the accessibility to donor tissue is limited when large parts are defective
Solution Approach 1:
The invention changes the physical parameters of the tissue sample by segmenting it into small biopsies and expanding it into a mesh structure. This parameter transformation allows the same autologous tissue to be distributed over a much larger area, making it possible to obtain sufficient graft material even when the available healthy donor tissue is limited. The expanded mesh structure maximizes the utilization of every portion of the harvested tissue.
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 method enables rapid production of autologous tissue grafts with minimal donor site impact, reducing the risk of rejection and infection, and allows for large surface area coverage with a small tissue sample, promoting rapid wound healing and minimizing scarring.
Implementation Method 1
exposed to a static acoustic wave field. The sound energy conducts the microtissues into forming a pattern defined by the standing waves
Implementation Method 2
sound-induced morphogenesis (SIM) was found to be a powerful technology to generate biological structures and architectures. The application of sound energy to biological material such as cells, organoids or tissue fragments in a static acoustic wave field conducts the biological material into forming patterns defined by the standing waves
Data Source
Figure 1
Figure 2A~2C
Figure 3A~3B
AI summary
This invention concerns a method for producing a tissue construct comprising microtissues suspended or resuspended in a volume of a blood sample, such as a whole blood sample or a processed blood sample, and exposing the suspension to a static acoustic wave field causing aggregates of microtissues to arrange in patterns defined by the waves. The tissue constructs are layers of coagulated blood containing the patterned microtissues which may be used for a variety of purposes, including for tissue grafting or for diagnostic purposes. The constructs may also be layered to compose more complex tissue structures.