Prototyping takes upon these integral and critical parts after designating the design criteria

  1. Essential Parts
    1. What is needed, and why
  2. Technology and Dimensions
    1. Technology that is supplied from companies
    2. Dimensions for our prototype to work
  3. Iterative Design Process
    1. Procedure of the inception of the idea to the testing of the application
    2. If issues exist, draw back to square one and improve on the flaws
  4. Design Testing
    1. How testing will be meticulous conducted and improved upon
  5. Alternatives Upon Failure.
    1. Prototype has failed. What can be salvaged and turned into an alternative design that can still perform the design criteria without sacrifice to the key goal.

1. Essential Parts

  1. Chitsoan Polysaccharide Scaffold 
    1. Acts as mechanical support
    2. Removes chances of infection
    3. Durable against premature wearing and biofluids’ interaction.
  2. Minimally Invasive Suture Devices (MISDs)
    1. Depends on which brand used (variable tips and sizes per procedure demands)
    2. Monumental in reducing harm and infection rates
    3. Least damage and tissue scarring possible
  3. Stem Cells 
    1. hiPSC more specifically, which are the best to induce tendon tissue regeneration [28]
    2. With faster time, there will be less immobility to the patient
    3. Needle gauges from biotech companies

2. Technology and Dimensions

Technology and Supplier: 

  • hiPSC (Stem Cells) Transplants Needles– Needles Gauges from 25-35 
    • Bioheart, Myocatch [12]
  • MISD from Medical Tech Brands:
    • AG, Medtronic, Stryker, etc. [11] 
  • Ultrafine Non-Animal Chitosan Polymers [13]
    •  Supplied from Millipore Sigma 
    • 2g powdery packaging, can be shaped and solidified

Although hiPSC isn’t technology, the needle gauges are more technologically advanced as some do use programming for proper reading and feedback of the extraction. [11]

Dimensions: 

  • (Variable) Surgical forcep, clamps, and devices for incisions and suture procedures.[14]  
    • Area of Interest assessed from 100-220 cubic cm [17]
      • Area of interest is the volume of the damaged tendon, which can be assessed by semielliptical or elliptical molds to create a polymer replication of the specialized areas [17]
      • Varies upon damage and needs via MISD tools.
        • Forceps, incision blades, clamps, etc. are all minimal and optimized for the least damage possible.
  • Chitsan Polymers Scaffolds are >1µm in overall size. [15]
    • Multiple will be used for tendon scaffolding. 
    • 5mm x 2mm shaping for the Achilles Tendon [15]
  • Approximately 300µm per stem cell culture.  [16]

Fig 6- 8: Chitosan Scaffold [16,20]

Fig 6- Relative Sizing of the polymer compared to the tendon (sizes increase left to right) [16]

Fig 7- Scaffold plate that will be used to compile the polymer to be shaped [16]

Fig 8- Microscopic imagery at 300µm and again at 100µm [20]

Fig 9: MISDs and the varying tips and tool sizes, hence no concrete dimensions upon prototyping. [18]

Fig.10 – hiPSC culture with fluorescent markers are 300 microns. [19]

 

3. Iterative Design Process

In order to create a successful design, we will need to first define the issue at hand– Achilles tendon rupture. Once we have a clear understanding of the condition, and the shortcomings of traditional methods, we can formulate design criteria for potential solutions to improve Achilles tendon healing. After choosing and designing the best solution, we will need to move on to testing the product in a variety of ways to ensure the safety and efficacy of the product. If, however, the product doesn’t perform up to standards, and the product design was suitable, we must modify the design and retest the product. Once, we reach a product that is effective and safe, we can finalize the design.

The procedure we will follow to test our design and implicate the design will be done in a test and examine results fashion. Firstly, we need to know what are the common treatments that currently exist. Find the effectiveness and flaws of those existing solutions.In our research we found the most common procedure was an invasive procedure. The benefits of repair came with heavy caveats of skin damage, pain, and immobility.  Find ways to improve or outright remove the flaws that pre-existed. Knowing of these factors of treatments and flaws, create a design criteria that hones in the most important needs and improvements of this design. As we know the flaws of ATR were damage to skin, pain and prolonged immobility, we sought to fix this with a safer methodology, faster healing time, and partial mobility rather than none.  Under more research and prototyping, develop a potential solution that seems to solve the problem and seems to be better over the current solution. Our MISD and chitosan polymer solves this problem with noninvasive procedure (less damage possible), partial mobility with the scaffolding, and the only need for faster regeneration. We sought after hiPSC to instigate faster healing with forced cellular interactions for natural tissue growth around the damaged tendon. Now in  practice, use your solution to resolve the issue. If failure occurs, examine faults and back to the drawing board and reevaluate issues and improvements. If successful, further on to more advanced and realistic testing. Again examine if the product solves just the issue at hand without sacrificing the design criteria. If an issue exists, modify it until it fulfills what was required. If successful again, send to the medical market and see how it performs and where to continue improving post-patent. We will examine our methods with Design Testing with this iterative design process.

Summary of the Iterative Design Process [1,2]

  • Biocompatibility testing → MTT assays & thrombogenicity tests (Biocompatibility Test Methods)
  • Test biodegradability rates and modify accordingly (Ramalho) 
  • Mechanical testing – tensile force, absorption and stiffness (Ramalho) 
  • Animal models to test the efficiency  scaffold in vivo 
  • Clinical trials to follow. 

 

4. Design Testing

Once we create prototypes for our design, we will need to do rigorous testing to ensure the efficacy and safety of our proposed chitosan scaffold. 

Firstly, we must test the biocompatibility of the product because poor biocompatibility can harm the Achilles tendon as well as the entire body. To test the cytotoxicity of the product, we can perform MTT assays. [1]. MTT assays use colorimetry to quantify the cellular reduction in a sample culture when exposed to the chitosan scaffold, which in turn allows us to determine its toxicity. [1]. Similarly, the acute system toxicity test can assess the toxicity in vivo by injecting small bits of the scaffold material into several mice and observing for toxicity signs by comparing the test mice to the controls. [1]. Lastly, since the scaffold will be in contact with blood, we should analyze the thrombogenicity of the scaffold material using Partial Thromboplastin Time (PTT) assay to detect anomalies.[1]

In addition to being biocompatible, the scaffold should be biodegradable to avoid complications due to deterioration over time. [2]. We will need to perform trials to determine the rate of degradation and then, if necessary, manipulate the composition of the scaffold so that the degradation rate is similar to the rate at which the Achilles tendon tissue grows back. [2]. 

Next, we will need to test the mechanical properties of the scaffold; for the scaffold to be effective, it must have mechanical properties very similar to that of the Achilles tendon. A scaffold with stronger mechanical properties than that of the Achilles tendon could result in stress shielding, thus increasing the likelihood of further injury. [2]. On the other hand, if the mechanical properties of the scaffold are much weaker than that of the native Achilles tendon tissue, then the scaffold will not be able to withstand the forces subjected to the Achilles tendon and will be ineffective. However, sometimes, scaffolds that are only slightly weaker than the native tissue are preferred so that if the tendon were overexerted, the scaffold would sustain the injury rather than the tissue. [2]. The most important mechanical properties to test are absorption, tensile force, and stiffness. [2]. Additionally, CT scans can be used to analyze the porosity of the scaffold and determine the cell adherence and proliferation on the scaffold, which in turn can predict its efficiency. [2].

5. Design Alternatives Upon Failure

If after testing our original hiPSC-seeded chitosan scaffold doesn’t perform satisfactorily, we will have to modify our design. If such a design failure occurs, we can stick to not using the hiPSC as this was used to create a benefit for the common patient’s desire for faster recovery. If the Chitosan scaffold itself has some issue with durability/mechanical properties, we can employ a plethora of other modifications to try and improve the design. For example, we can test collagen-based or other polysaccharide based scaffolds that have the same stiffness and tensile strength as the achilles tendon. Additionally, we could try a PLAGA (polyDL-lactide-co-glycolide) based scaffold. One study testing the efficiency of a PLAGA based scaffold in rat achilles showed an improvement in the repair; after eight weeks, the scaffold degraded appropriately and the repaired tissue demonstrated cell alignment, while the repaired tissue in the control group “appeared weak and contained gaps.” [40]. Another study indicated that and PLLA/coll-75/25 blend served as a good material for scaffolds since it had good mechanical properties and utilized some natural polymers, allowing for easier adhesion of new cells. [39]. If none of the biomaterials mentioned present the necessary mechanical properties, we can modify the design by changing the porosity of the scaffold. Additionally, we could test out different mixtures of biomaterials suitable for the scaffold.

It’s very difficult to see a scenario where the MISDs would fail as several corporations have their own branded MISDs that have been remarkably similar in purpose and effectiveness. If such an error would occur we would use the competitors MISD to make sure the design is foolproof. Simply said, the alternative is to not use hiPSC (as this is still a field of promise and expensive research and experimentation, but was not a focus of the design and merely a useful auxiliary to speed regeneration), use a competitors set of MISDs, and use another similar or promising type of polymer scaffold (as many exists with relations to chitosan polysaccharide or collagen types).