Diabetes related chronic wounds and subsequent lower limb amputation are major causes ofmorbidity in diabetic patients, incurring enormous medical, economic and social burden. The rigorous treatment regimes in clinics have had only modest success in lowering overall amputation rate. The major reason behind the failure is that diabetes affects all the wound healing cells not only functionally but also genetically. This molecular disarray is not completely understood yet, so treatment regimes aimed at rectifying the genetic problem are needed for tangible therapeutic benefit.

Researchers at the Network of Excellence for Functional Biomaterials (NFB) at NUI Galway are working on a project investigating the genetic dysregulation but also combined novel and complementary genes to normalise wound healing and found that success of the gene therapy depends largely on how it is delivered.

The gene delivery system developed gives a protective scaffold and also allows controlled delivery with components carrying different genes and degrading at different rates. The gene delivery method is, in effect, micron-size spheres embedded in mesh made from protein fibers, a tiny but very complex biomaterial product. Overall results are very encouraging with enhanced wound closure, complemented by increased blood vessel formation and reduced inflammation.

According to the NFB’s Mangesh Kulkarni, “We envision that the combined new gene therapy and delivery system can aid in reducing the amputation rate by enhancing wound healing. This has the potential to make a real change when applied to chronic diabetic wounds. Since the components of the system have a relatively good safety profile, clinical trials can be conducted to prove the therapeutic benefit in human patients.”

Acoustic cell separation
The transplantation of haematopoetic stem cells is an effective treatment for patients with malignant blood diseases, but the composition and quality of transplanted cells are crucial to the outcome. Researchers from Lund University, Sweden, have developed a method to improve transplanted cells quality using ultrasound for acoustic cell separation.

“The method was developed in the field of microtechnology and builds on basic engineering researchfrom Lund University,” explains Professor Thomas Laurell, research group leader at the Faculty of Engineering. The method is expected to facilitate improvements in the processing of blood stem cells.

Associate Professor Stefan Scheding, (left) senior consultant at the Department of Haematology at Skåne University Hospital and research group leader at the Stem Cell Centre at Lund University, is in charge of the preclinical development of the new method to effectively separate and possibly remove or concentrate cell populations normally found in standard blood stem cells products. The first step has shown that the method works, by separating out platelets from stem cell products.

“Our hope is that it will become possible to produce the optimal stem cell product for each individual transplant patient,” says Scheding. “This would give us a good chance of improving the treatment of patients who would otherwise be at risk of suffering from serious transplant complications, such as graft-versus-host (rejection) disease and infections. By optimising the quality of the transplanted cells, it may even be possible to better fight the leukaemia cells that remain in the body despite the transplant treatment”, he explains.

The project is part of the research programme CellCare, which is funded by the Swedish Governmental Agency for Innovation Systems (Vinnova) and coordinated by Thomas Laurell.

CAD for tissue reconstruction scaffolds
Biofabrication, researchers used computer-aided design (CAD) to create an extremely accurate mould of a breast that was used as a visual aid to surgeons in tissue reconstruction operations. CAD was also used to design and produce patient-specific physical scaffolds that could potentially be used in conjunction with one of the most promising areas of medicine – tissue engineering.

In theory, patients’ own cells could be harnessed and grown onto the highly specific scaffolds and then transferred to the affected area, avoiding the need to transfer tissue from other parts of the body which can cause large scars, result in considerable blood loss and require five to ten hours of anaesthesia.

Study co-author, Professor Dietmar Hutmacher of regenerative medicine at Queensland TechnologyUniversity said, “We would take a laser scan of the healthy breast and use the CAD modelling process to design a patient-specific scaffold in silico. We would then produce a scaffold of very high porosity and load it with the patient’s own cells in combination with a hydrogel. The construct would then be implanted.”

CAD allows the ability to work to full scale, examine the design from all angles and maintain absolute accuracy. After informed consent, 3D laser scanning was performed on three female patients who suffered from breast cancer. The images were then fed into a piece of CAD-software which produced a single image representing the patient’s breast and surrounding thorax region.

This image was then “printed” to form a 3D mould used as an operative aid for surgeons who performed autologous tissue reconstructions – the transferring of tissue from another part of the patient’s body – on each of the patients.
  
After each of the operations, surgeons observed a more perfect shape with a higher degree of symmetry between the breasts whilst, more importantly, the patients reported a higher satisfaction of the surgery outcomes than the control group, again with respect to breast shape and symmetry.  
The long-term study aim was on development of a material that could be used in tissue engineering and it shows CAD as an effective way of achieving this.

A function was created using the CAD software that enabled the creation of a mould for any scanned tissue with the ability to independently tailor the porosity and pore size – a property essential to the seeding and diffusing of cells throughout the structure, and something that limits modern technologies.