Engineered Cartilage via Autologous Cell Expansion
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Solution Overview
Problem
Current methods for reconstructing nasal cartilage after skin cancer treatment face challenges such as donor site morbidity, poor aesthetic and functional outcomes due to warping and shifting of grafts, and variability in cartilage quality, which are not adequately addressed by existing reconstructive techniques.
Innovation Solution
A method involving the expansion of autologous chondrocytes and chondroprogenitors by detecting specific surfaceome and secretome protein gene expressions, followed by culturing them in a medium with FGF-2 and TGFβ1, and co-culturing with mesenchymal stem cells to produce high-quality engineered cartilage grafts, utilizing 3D bioprinting for custom-shaped grafts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cartilage grafts are harvested from donor sites (ear concha or rib cartilage), then cartilage material is obtained for reconstruction, but donor site morbidity occurs including surgical site pain, infection, scarring, deformity, and life-threatening complications
Solution Approach 1:
The patent uses autologous chondrocytes as an intermediary substance. Instead of directly harvesting cartilage from donor sites, the method extracts chondrocytes from a small biopsy, expands them in vitro, and uses these cultured cells to generate cartilage grafts. This intermediary cellular approach eliminates the need for large donor site harvesting while still producing the required cartilage material for reconstruction
Solution Approach 2:
The patent applies preliminary action by expanding chondrocytes in vitro before transplantation. The chondrocytes are harvested from a small biopsy, then cultured and expanded in the laboratory to generate sufficient cell numbers for creating the required cartilage graft volume. This preliminary cell expansion eliminates the need for large-scale donor site harvesting at the time of surgery
2Shape
If cartilage grafts are carved to appropriate shape by surgeon, then custom-shaped grafts are obtained, but the procedure becomes extremely time consuming and technically challenging
Solution Approach 1:
The patent applies preliminary action by pre-shaping the cartilage grafts during the in vitro culture process. The chondrocytes are cultured in molds or scaffolds that define the desired final shape, allowing the cartilage to form its custom geometry during the expansion phase. This eliminates the need for time-consuming surgical carving while still achieving custom-shaped grafts tailored to the patient's anatomical needs
3Shape
If cartilage grafts are carved meticulously, then shape is achieved, but warping and shifting in position still occur due to scar contracture, leading to poor aesthetic and functional results
Solution Approach 1:
The patent applies preliminary action by pre-stressing or pre-positioning the cartilage grafts during the in vitro culture phase. The grafts are shaped and conditioned in their final configuration before implantation, allowing them to adapt to the implantation site in advance. This preliminary conditioning reduces the impact of subsequent scar contracture forces that would otherwise cause warping and position shifting
Solution Approach 2:
The patent applies parameter changes by modifying the mechanical properties of the cartilage grafts through controlled in vitro culture conditions. The culture medium composition, oxygen tension, and mechanical loading parameters are optimized to produce grafts with enhanced mechanical integrity and resistance to warping. These parameter changes during culture create grafts that are more resistant to the deforming forces of scar contracture
4Quantity of substance
If traditional reconstructive techniques are used, then cartilage replacement is achieved, but significant variability in histological and biochemical quality occurs between donors
Solution Approach 1:
The patent applies self-service by using the patient's own autologous chondrocytes to generate the cartilage grafts. The chondrocytes are harvested from the patient's nasoseptal cartilage, expanded in vitro, and used to create grafts that are transplanted back to the same patient. This self-service approach ensures perfect histological and biochemical compatibility while eliminating donor-to-donor variability, as the grafts are biologically identical to the patient's native tissue
Solution Approach 2:
The patent applies parameter changes by controlling the in vitro culture conditions to standardize the production of cartilage grafts. The culture medium composition, growth factors, oxygen tension, and mechanical loading parameters are precisely controlled to produce grafts with consistent histological and biochemical properties. This parameter control ensures reproducible cartilage quality regardless of variations in the initial biopsy sample
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 reduces donor-donor variability, enhances cartilage quality, and enables the production of high-fidelity, custom-shaped nasal cartilage grafts with improved mechanical integrity and reduced morbidity, addressing the limitations of traditional grafting methods.
Implementation Method 1
expanding autologous chondrocytes and/or chondroprogenitors from a donor patient
Implementation Method 2
culturing the selected expanded chondrocytes and/or chondroprogenitors in a culture medium allowing formation of a transplantable cartilage material
Implementation Method 3
selecting expanded chondrocytes and/or chondroprogenitors by detecting the expression of at least one surfaceome protein gene or secretome protein gene
Implementation Method 4
utilizing 3D bioprinting for custom-shaped grafts
Implementation Method 5
co-culturing with mesenchymal stem cells to produce high-quality engineered cartilage grafts
Data Source
AI summary
It is provided a method of producing high-quality engineered cartilage graft in a human of animal, such as nasal cartilage graft, comprising expanding chondrocytes and/or chondroprogenitors, e.g. autologous human nasoseptal chondrocytes (hNC,) from a donor patient by selecting expanded chondrocytes and/or chondroprogenitors by detecting the expression of at least one surfaceome protein gene or secretome protein gene, wherein the at least one surfaceome protein gene is ADGRG1, NPR3, SLC16A4, TSPAN13, FZD4 and SLC22A23 and the at least one secretome protein gene is ADGRG1, B3GNT7, COLGALT2, IGFBP3, STC2, SAA1, ANGPLT1, COL8A2, INHBB, ADAMTS9, ORM1, COL14A1, DCN, COL21A1, ENOX1, IL7, MXRA5 GAL, TFRC, SERPINA9, LIF, GDF6 and COL5A3.