Muholan Kanapathy

Tissue-engineered lymphatic graft for the treatment of lymphedema.

BACKGROUND Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. METHODS Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. RESULTS The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. CONCLUSIONS With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable.

Epidermal grafting for wound healing: a review on the harvesting systems, the ultrastructure of the graft and the mechanism of wound healing

Epidermal grafting for wound healing involves the transfer of the epidermis from a healthy location to cover a wound. The structural difference of the epidermal graft in comparison to the split‐thickness skin graft and full‐thickness skin graft contributes to the mechanism of effect. While skin grafting is an epidermal transfer, little is known about the precise mechanism of wound healing by epidermal graft. This paper aims to explore the evolution of the epidermal graft harvesting system over the last five decades, the structural advantages of epidermal graft for wound healing and the current hypotheses on the mechanism of wound healing by epidermal graft. Three mechanisms are proposed: keratinocyte activation, growth factor secretion and reepithelialisation from the wound edge. We evaluate and explain how these processes work and integrate to promote wound healing based on the current in vivo and in vitro evidence. We also review the ongoing clinical trials evaluating the efficacy of epidermal graft for wound healing. The epidermal graft is a promising alternative to the more invasive conventional surgical techniques as it is simple, less expensive and reduces the surgical burden for patients in need of wound coverage.

Development of a Tissue‐Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema

Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the worlds first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P < 0.001), favorable kink resistance, and excellent suture retention property (casted vs. coagulated, P < 0.05). Cytocompatibility study showed that the POSS-PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue-engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema.

The CelluTome epidermal graft-harvesting system: a patient-reported outcome measure and cost evaluation study

Conventional split skin grafts (SSG) require anaesthesia, specialist equipment and can have high donor site (DS) morbidity. The CelluTome epidermal graft‐harvesting device is a novel alternative, providing pain‐free epidermal skin grafts (ESG) in the outpatient setting, with projected minimal DS trauma and improved patient satisfaction. This study aimed to compare ESG with SSG by evaluating patient‐related outcome measures (PROMs) and the cost implications of both.

Upregulation of epidermal gap junctional proteins in patients with venous disease

Leg ulceration is a feared complication of venous insufficiency. It is not known whether varicose veins predispose skin to poor wound healing. The expression pattern of gap junctional protein connexin, a known marker of poor wound healing, was investigated across various stages of venous disease.

Systematic review of the efficacy of fat grafting and platelet‐rich plasma for wound healing

Adipose‐derived stem cells found in fat grafts may have significant healing properties. When fat is combined with autologous platelet‐rich plasma (PRP), there may be enhanced healing effects due to the pro‐angiogenic and anti‐inflammatory effects of PRP. This study aimed to evaluate the current evidence on fat grafting in combination with PRP for wound healing to establish the efficacy of this technique. A comprehensive search in the MEDLINE, EMBASE, CENTRAL, Science Citation Index, and Google Scholar databases (to March 2017) was conducted to identify studies on fat grafting and PRP for wound healing. Case series of less than 3 cases and studies only describing harvest technique were excluded. The database identified 571 articles, of which 3 articles that used a combination of fat and PRP for wound healing (1 RCT and 2 case series) were included in this review. A total of 69 wounds in 64 patients were treated with an average wound size of 36.32cm2. Of these, 67% of wounds achieved complete healing. When reported, the mean time to healing was 7.5 weeks for those who underwent a single treatment. There were no significant complications in any patients. The combination of fat grafting and PRP may achieve adequate wound healing with relatively quick wound healing time compared with standard wound management options. However, evidence is extremely limited, and further studies are required to evaluate its efficacy for wound healing.

Epidermal Graft Accelerates the Healing of Acute Wound: A Self-controlled Case Report

Summary: Wound care represents a significant socioeconomic burden, with over half of chronic wounds taking up to a year to heal. Measures to accelerate wound healing are beneficial to patients and also reduce the cost and burden of wound management. Epidermal grafting (EG) is an emerging option for autologous skin grafting in the outpatient setting to improve wound healing. Although several case series have previously reported good clinical outcome with EG, the healing rate in comparison to conservative wound management is not known. In this report, we compare the weekly healing rate of 2 separate wounds in the same patient, one treated with EG and the other with dressings. The treated wound showed accelerated healing, with the healing rate being the highest at the first 2 weeks after EG. The average healing time of the treated wound was 40% faster compared with the control wound. EG accelerates healing of acute wounds, potentially reducing the healthcare cost and surgical burden.

Diabetic foot ulcers in conjunction with lower limb lymphedema: pathophysiology and treatment procedures

Diabetic foot ulcers (DFUs) are complex, chronic, and progressive wounds, and have a significant impact on morbidity, mortality, and quality of life. A particular aspect of DFU that has not been reviewed extensively thus far is its management in conjunction with peripheral limb edema. Peripheral limb edema is a feature of diabetes that has been identified as a significant risk factor for amputation in patients with DFU. Three major etiological factors in development of lymphedema with concurrent DFU are diabetic microangiopathy, failure of autonomic regulation, and recurrent infection. This review outlines the pathophysiology of lymphedema formation in patients with DFU and highlights the cellular and immune components of impaired wound healing in lymphedematous DFU. We then discuss the principles of management of DFU in conjunction with lymphedema.