**4. Gene regulation**

both *in vitro* and *in vivo* [37]. This research surmised that it is likely that blood vessel walls may hold a reserve of mesenchymal-like stem cells that are involved in the repair and neovasculari-

Patient selection for harvesting is an important factor because biologic properties can be affected by systemic disease. Adipose tissue that is extracted from patients with diabetes is inferior to adipose tissue that has not been subjected to systemic disease. In tissue exposed to systemic illness, there is loss of cell differentiation ability, increased levels of failed division

There are few human clinical trials involving the applications of MSCs and even fewer evaluating the utilisation of adipose cells. The current use of ASCs in clinical practice remains limited to trials. A number of animal model studies have demonstrated the promising possibilities of adipose-derived stem cells and there are a number of small pilot clinical trials, which have been published in the literature recently with many new studies emerging frequently. This exciting data gives promise to the potential clinical applications of ASCs and with new information continuing to evolve, the routine use of stem cells in clinical practice remains a tangible prospect in the near future. This section of the chapter provides up to date

Nie et al. investigated the mechanisms of action of ASCs in wound healing [39]. ASCs were incorporated into full thickness excisional wounds in both diabetic and non-diabetic rats. The study showed that wound healing was accelerated and time taken to close wounds in both groups was shortened. There was increased re-epithelisation and advanced development of granulation tissue within the wound. Enhanced neovascularisation was also shown due to the

Park et al. recently investigated the role of allogenic ASCs in the treatment of complex perianal fistulas secondary to Crohn's disease [40]. In this small pilot multicentre, clinical trial participants had complex non-healing perianal fistulas, which had not healed by conventional techniques (surgery or infliximab treatment). The initial group of participants received a smaller dose of ASCs than the second group. At 6-month follow-up, 50% of participants had achieved complete closure of the fistula, which was maintained at the final follow-up at 8 months.

A phase one clinical trial demonstrated the effect of autologous-derived adipose stem cells in patients with severe peripheral arterial disease with chronic non-healing ulcer disease. All participants had non-vascularisable critical limb ischaemia with lower limb rest pain or ulcers and a low ankle systolic oxygen pressure. ASCs were injected intramuscularly into the ischaemic limb with no complications recorded. Most participants showed an increase in

Kim et al. studied the effectiveness of stem cell treatment in patients with chronic non-healing wounds following complications of soft tissue nasal fillers [42]. ASCs were harvested from the patient's subcutaneous adipose tissue. Following preparation in the laboratory, the adipose cell containing solution was injected into the dermis and subcutaneous layer around the wound. All participants experienced enhanced wound healing and at 6 months post treatment all wound sizes were reduced. These results lead the authors to propose that stem cells could be considered in the future for routine use as a treatment of complications of filler injections.

sation of wounds. However, the exact mechanisms and significance remains unknown.

and apoptosis and an overall reduction in the levels of growth factors secreted [38].

evidence and a summary of recent studies involving ASCs.

trans-cutaneous oxygen pressure and improved ulcer healing [41].

increased secretion of angiogenic growth factors.

56 Tissue Regeneration

Other novel tissue regeneration methods have been trialled in both animal and human studies. For example, genetics is an ever-evolving field when it comes to finding ways and methods of aiding tissue regeneration. Animal studies provide a starting point for future discoveries—for example, Kang et al. investigated tissue regeneration enhancer elements (TREEs), providing evidence that these elements trigger gene expression in injury sites [46]. The authors of this particular study felt that these findings could further be extrapolate in the future to assess their regenerative potential in vertebrate organs [46]. Gene regulation to aid tissue regeneration has been investigated in human studies, too. Recent studies by Finkel et al. and Mendell et al. showed promise in motor neurone diseases, specifically spinal muscular atrophy [47, 48]. Finkel et al. modified promoted increased production of the survival motor neurone (SMN) protein with an antisense oligonucleotide drug and showed that infants with spinal muscular atrophy receiving this drug were more likely to be alive and have improved motor function that the control group [47]. Patients in the Mendell et al. study received adeno-associated viral vector infusion containing DNA coding for SMN; these patients again, survived longer, achieved motor milestones better and had improved motor function than historical cohorts [48]. Musculoskeletal tissue regeneration is a great challenge for scientists and lots of studies have looked into potential options, in addition to the two mentioned already. Padilla et al. discuss a variety of techniques, including blood derived biological drug delivery therapies, which have significant potential for tissue regeneration [49]. For example, platelets release hepatocyte growth factor and stromal cell-derived growth factor 1, both known to be involved in wound healing and proliferation [49]. There is a significant need for further randomised trials and systematic reviews to assess if these therapies could be used routinely for the treatment of musculoskeletal conditions. These are just examples of how gene regulation can lead to significant changes in tissue regeneration and improved clinical outcomes; and future research will be needed to assess safety of such gene therapies for widespread use.

organ transplantation – the risk of immune rejection? Do et al. speaks about this in an article about 3D printed scaffolds and their potential applications [51]. The aim would be to create scaffolds that have properties of the native recipient microenvironment and the ability to promote angiogenesis and osteogenesis, and various tissue engineering techniques could be used in order to facilitate this process and this is still a work in progress, albeit an ever-expanding and promising field (see **Figure 6**). Other studies have suggested that 3D scaffolds could also exhibit bactericidal properties, and aid not only tissue regeneration, but also prevent the high risk of infection that comes with any foreign body or implant. Correiaa et al. have shown that silver nanoparticles could be a suitable way to achieve this [52]. The idea of 3D printing has attracted neuroscientists, too, and Zhu et al. hypothesised that the combination of 3D printed scaffolding and low-level light therapy could aid neural regeneration, and favourable results have been achieved in this in vitro neural stem cell study [53]. Further studies will be needed to assess how effective and useful the proposed 3D printing methods for tissue regeneration

This comprehensive chapter summarised the subject of tissue regeneration in a variety of different fields of surgery. We explored the use of acellular dermal matrices in plastic and reconstructive surgery (e.g., for treatment of burns), breast surgery (e.g., for immediate breast reconstruction after mastectomy) and general surgery (e.g., abdominal wall repair). Stem cellbased therapies were also discussed to reflect the promise they hold in aiding tissue regeneration in the coming years. Particular focus was placed on adipose tissue-derived stem cells and adult mesenchymal stem cells, both of which are a potentially revolutionary therapy in regenerative medicine. Finally, we discussed potential future benefits of using three-dimensional printed scaffolds and gene regulation—both of these fields are currently being investigated by scientists across the world to discover how best to adapt these techniques in day-to-day clinical practice.

, Shuchi Chaturvedi<sup>2</sup>

[1] DermaMatrix Acellular Dermis. Human dermal collagen matrix. Synthes® CMF. 2006. Available from: http://synthes.vo.llnwd.net/o16/LLNWMB8/US%20Mobile/Synthes%

1 Department of Surgery, Aberdeen Royal Infirmary, Aberdeen, United Kingdom

and Shailesh Chaturvedi1

Scaffold Biomaterials in Tissue Regeneration in Surgery http://dx.doi.org/10.5772/intechopen.73657 59

\*

in humans will actually be.

**6. Conclusion**

**Author details**

, Gabija Lazaraviciute1

\*Address all correspondence to: s.chaturvedi@nhs.net

2 Kings College, University of London, United Kingdom

Emma Iddles1

**References**
