natural polymer-based bilayer adhesive skin substitute for infected burned wound healing

Thermal wounds are complex and lethal with irregular shapes, risk of infection, slow healing, and large surface area. The mortality rate in patients with infected burns is twice that of non-infected burns. Developing multifunctional skin substitutes to augment the healing rate of infected burns is vital. Herein, we 3D printed a hydrogel scaffold comprising carboxymethyl chitosan (CMCs) and oxidized alginate grafted catechol (O-AlgCat) on a hydrophobic electrospun layer, forming a bilayer skin substitute (BSS). The functional layer (FL) was fabricated by physiochemical crosslinking to ensure favorable biodegradability. The gallium-containing hydrophobic electrospun layer or backing layer (BL) could mimic the epidermis of skin, avoiding fluid penetration and offering antibacterial activity. 3D printed FL contains catechol, gallium, and biologically active platelet rich fibrin (PRF) to adhere to both tissue and BL, show antibacterial activity, encourage angiogenesis, cell growth, and migration. The fabricated bioactive BSS exhibited noticeable adhesive properties (P ≤ 0.05), significant antibacterial activity (P ≤ 0.05), faster clot formation, and the potential to promote proliferation (P ≤ 0.05) and migration (P ≤ 0.05) of L929 cells. Furthermore, the angiogenesis was significantly higher (P ≤ 0.05) when evaluated in vivo and in ovo. The BSS-covered wounds healed faster due to low inflammation and high collagen density. Based on the obtained results, the fabricated bioactive BSS could be an effective treatment for infected burn wounds.

In vitro comparison of human plasma-based and self-assembled tissue-engineered skin substitutes:two different manufacturing processes for the treatment of deep and difficult to heal injuries

Background:The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes(hbTESSs)designed for the treatment of severely burned patients.These are the scaffold-free self-assembled skin substitute(SASS)and the human plasma-based skin substitute(HPSS).Methods:Fibroblasts and keratinocytes from three humans were extracted from skin biopsies(N=3)and cells from the same donor were used to produce both hbTESS models.For SASS manu-facture,keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced(n=12),while for HPSS production,keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial(Fibrin),plasma combined with hyaluronic acid(Fibrin-HA)or plasma combined with collagen(Fibrin-Col)(n/biomaterial=9).The production time was 46-55 days for SASSs and 32-39 days for HPSSs.Substitutes were characterized by histology,mechanical testing,PrestoBlue™-assay,immunofluorescence(Ki67,Keratin(K)10,K15,K19,Loricrin,type IV collagen)and Western blot(type I and IV collagens).Results:The SASSs were more resistant to tensile forces(p-value<0.01)but less elastic(p-value<0.001)compared to HPSSs.A higher number of proliferative Ki67+cells were found in SASSs although their metabolic activity was lower.After epidermal differentiation,no significant difference was observed in the expression of K10,K15,K19 and Loricrin.Overall,the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs.Conclusions:This study demonstrates,for the first time,that both hbTESS models present similar in vitro biological characteristics.However,mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.

3D Bioprinted Skin Substitutes for Accelerated Wound Healing and Reduced Scar

The shortage of skin for grafting continues to be a major problem in the treatment of serious skin injuries.3D bioprinting provides a new way to solve this problem.However,current 3D printed skin is less effective in treatment of large wounds because of severe shrinkage and scarring.In this study,bionically designed bilayer skin was fabricated using an extrusion-based bioprinter and a gelatin/sodium alginate/gelatin methacrylate hydrogel with excellent physical and biological properties.Full-thickness skin wounds were created in the back of nude mice and treated with bioprinted skin or hydrogel.Bioprinted skin accelerated wound healing,reduced wound contraction and scarring,and facilitated wound skin epithelialization compared with the bioprinted hydrogel or untreated wound.The skin from the wound was collected 28 days after grafting for histology and immunofluorescence analysis.The thickness of the dermis and epidermis of the bioprinted skin was similar to that of nude mice.Microvascular formation in the dermis and dense keratinocytes in the epidermis of the bioprinted skin were observed.This study provides a potential treatment strategy for reducing skin contraction and scar in large skin wounds.

Dopamine hydrochloride and carboxymethyl chitosan coatings for multifilament surgical suture and their influence on friction during sliding contact with skin substitute

In order to reduce the damage to tissue and fill the interstices between fibers,multifilament sutures are frequently treated with certain coating materials.The objective of this study was to create and characterize dopamine hydrochloride(DA)and carboxymethyl chitosan(CMCS)coatings on surgical sutures and investigate their effects on the frictional performance of the surgical sutures during sliding through a skin substitute.The effects of the treatment on the physical and chemical characteristics of the surgical sutures were evaluated.The friction force of the surgical sutures during sliding through the skin substitute was experimentally determined using a penetration friction apparatus.The coefficient of friction(COF)was calculated using a linear elastic model and was used to estimate the frictional behavior of the surgical suture‐skin interactions.The results showed that the DA coating could evenly deposit on the surface of the etched multifilament surgical suture surfaces in a weakly alkaline buffer solution.The CMCS coating material could form a uniform film on the surface of the sutures.Minor changes in the surface roughness of the multifilament surgical sutures with different treatments occurred in this study.The friction force and the COF of the multifilament surgical sutures with DA and CMCS coating showed little change when compared with untreated multifilament surgical sutures.

FAILURE OF HERPES SIMPLEX VIRUS TYPE 2 TO SUBSTITUTE FOR DIMETHYL-BENZANTHRACENE IN TWO-STAGE SKIN CARCINOGENESIS

There are some Indications thtt herpes aimplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated In cultured cells infected with HSV. To further Investigate the mutagenic activity of HSV type 2 (HSV-2) we used mouse skin as a model system for cardnogenetls. Inoculation of the back skin of 4-week-old Sencar mke with live virus twice per week for one week or with Inactivated virus twice per week for two weeks was used to Initiate the mouse akin. After Initiation with HSV-2, 12-O-tetradecanoylphorbol-13-acetale(TPA) was applied twice weekly for 50 weeks as a promoter. During a period of 52 weeks, no skin carcinoma was found In the experimental groups, whereas 55% of control mice treated with 9, 10-dlmethy1-1, 2- benzanthracene (DMBA ) and then with TPA-developed skin carcinoma. The results demonstrate that HSV-2 could not substitute for DMBA in this animal model of two-stage skin carcinogenesis.

Tissue-Engineered Products for Skin Regenerative Medicine

In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer.

Treatment of infected soft tissue loss

Hand coverage in infected soft tissue loss(STL)is a challenging clinical condition.Appropriate and well-timed antibiotic therapy and careful debridement are crucial for the success of the subsequent reconstructive procedure.Debridement must be radical,and all nonviable or infected tissue should be removed.Strict medical control and multiple procedures can be required when infection recurrence is observed after primary procedure.Secondary healing of STL is usually necessary in these complex conditions.Negative pressure wound therapy(NPWT)is often used as a temporary instrument to reduce oedema and drainage,facilitating the attainment of a clean wound for subsequent reconstruction.According to the type and size of the defect,multiple options ranging from skin grafts and substitutes to local and free flaps can be selected for the treatment of infected STL.A reconstructive ladder approach and case-by-case decision making should always be considered.Due to the unique function and role of the hand,the surgical strategy must also take into account aesthetic and functional factors.Orthopedic and Plastic surgeons should manage this wide variety of treatment options in a multidisciplinary and high-specialized context including radiologists,microbiologists,infectious disease specialists and physiotherapists,customizing the treatment path to the specific patient's situation.

Development and use of biomaterials as wound healing therapies

There is a vast number of treatments on the market for the management of wounds and burns,representing a multi-billion dollar industry worldwide.These include conventional wound dressings,dressings that incorporate growth factors to stimulate and facilitate the wound healing process,and skin substitutes that incorporate patientderived cells.This article will review the more established,and the recent advances in the use of biomaterials for wound healing therapies,and their future direction.