Skin tissue engineering advances in severe burns:review and therapeutic applications

Current advances in basic stem cell research and tissue engineering augur well for the development of improved cultured skin tissue substitutes:a class of products that is still fraught with limitations for clinical use.Although the ability to grow autologous keratinocytes in-vitro from a small skin biopsy into sheets of stratified epithelium(within 3 to 4 weeks)helped alleviate the problem of insufficient donor site for extensive burn,many burn units still have to grapple with insufficient skin allografts which are used as intermediate wound coverage after burn excision.Alternatives offered by tissue-engineered skin dermal replacements to meet emergency demand have been used fairly successfully.Despite the availability of these commercial products,they all suffer from the same problems of extremely high cost,sub-normal skin microstructure and inconsistent engraftment,especially in full thickness burns.Clinical practice for severe burn treatment has since evolved to incorporate these tissue-engineered skin substitutes,usually as an adjunct to speed up epithelization for wound closure and/or to improve quality of life by improving the functional and cosmetic results long-term.This review seeks to bring the reader through the beginnings of skin tissue engineering,the utilization of some of the key products developed for the treatment of severe burns and the hope of harnessing stem cells to improve on current practice.

Recent advancements in applications of chitosan-based biomaterials for skin tissue engineering

The use of polymer based composites in the treatment of skin tissue damages,has got huge attention in clinical demand,which enforced the scientists to improve the methods of biopolymer designing in order to obtain highly efficient system for complete restoration of damaged tissue.In last few decades,chitosan-based biomaterials have major applications in skin tissue engineering due to its biocompatible,hemostatic,antimicrobial and biodegradable capabilities.This article overviewed the promising biological properties of chitosan and further discussed the various preparation methods involved in chitosan-based biomaterials.In addition,this review also gave a comprehensive discussion of different forms of chitosan-based biomaterials including membrane,sponge,nanofiber and hydrogel that were extensively employed in skin tissue engineering.This review will help to form a base for the advanced applications of chitosan-based biomaterials in treatment of skin tissue damages.

Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction

Craniomaxillofacial(CMF)reconstruction is a challenging clinical dilemma.It often necessitates skin replacement in the form of autologous graft or flap surgery,which differ from one another based on hypodermal/dermal content.Unfortunately,both approaches are plagued by scarring,poor cosmesis,inadequate restoration of native anatomy and hair,alopecia,donor site morbidity,and potential for failure.Therefore,new reconstructive approaches are warranted,and tissue engineered skin represents an exciting alternative.In this study,we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting(IOB),which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting.Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix(adECM)and stem cells(ADSCs),skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies.adECM,even at a very low concentration such as 2%or less,has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo.Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects,accomplishing near-complete wound closure within two weeks.More importantly,both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame.Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.

Antibacterial biomaterials for skin wound dressing

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health.And bacterial contamination could significantly menace the wound healing process.Considering the sophisticated wound healing process,novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients,antibacterial agents included,into biomaterials with different morphologies to improve cell behaviors and promote wound healing.However,a comprehensive review on antibacterial wound dressing to enhance wound healing has not been reported.In this review,various antibacterial biomaterials as wound dressings will be discussed.Different kinds of antibacterial agents,including antibiotics,nanoparticles(metal and metallic oxides,lightinduced antibacterial agents),cationic organic agents,and others,and their recent advances are summarized.Biomaterial selection and fabrication of biomaterials with different structures and forms,including films,hydrogel,electrospun nanofibers,sponge,foam and three-dimension(3D)printed scaffold for skin regeneration,are elaborated discussed.Current challenges and the future perspectives are presented in thismultidisciplinary field.We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.

Engineered artificial skins:Current construction strategies and applications

Skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic deficits.However,traditional treatments,such as skin grafting,have limitations including limited donor skin availability,poor aesthetics,and functional impairment.Skin tissue engineering provides a promising alternative,with engineered artificial skins offering a highly viable avenue.Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments,particularly for severe burns,chronic wounds,and other skin injuries or defects.These artificial skins aim to promote wound healing,provide temporary coverage,permanent skin replacement,and restore the skin’s barrier function.Artificial skins have diverse applications in medicine and wound care,addressing burns,chronic wounds,and traumatic injuries.They also serve as valuable tools for research in tissue engineering,offering experimental models for studying wound healing mechanisms,testing new biomaterials,and exploring innovative approaches to skin regeneration.This review provides an overview of current construction strategies for engineered artificial skin,including cell sources,biomaterials,and construction techniques.It further explores the primary application areas and future prospects of artificial skin,highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.

Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study

Bioprinting has exhibited remarkable promises for the fabrication of functional skin substitutes.However,there are some significant challenges for the treatment of full-thickness skin defects in clinical practice.It is necessary to determine bioinks with suitable mechanical properties and desirable biocompatibilities.Additionally,the key for printing skin is to design the skin structure optimally,enabling the function of the skin.In this study,the full-thickness skin scaffolds were prepared with a gradient pore structure constructing the dense layer,epidermis,and dermis by different ratios of bioinks.We hypothesized that the dense layer protects the wound surface and maintains a moist environment on the wound surface.By developing a suitable hydrogel bioink formulation(sodium alginate/gelatin/collagen),to simulate the physiological structure of the skin via 3D printing,the proportion of hydrogels was optimized corresponding to each layer.These results reveal that the scaffold has interconnected macroscopic channels,and sodium alginate/gelatin/collagen scaffolds accelerated wound healing,reduced skin wound contraction,and re-epithelialization in vivo.It is expected to provide a rapid and economical production method of skin scaffolds for future clinical applications.

Mechanical performance and cyocompatibility of PU/PLCL nanofibrous electrospun scaffolds for skin regeneration

Skin tissue engineering with considerable skin regeneration capability is an urgent need for the wound site.The current challenge for researchers is to develop a bionic scaffold that imitates the extracellular matrix for the regeneration of the damaged regions.In our study,poly(L-lactide-co-caprolactone)(PLCL)was blended with polyurethane(PU)to obtain nanofibrous scaffolds via electrospinning.The electrospun fibers with 50%PLCL content had a certain number of intersections and jointing points,and exhibited significantly enhanced mechani-cal properties combined with suitable porosity.Moreover,cell activities demonstrated that PU/PLCL membranes had significantly biological advantages in enhanced growth of human skin fibroblasts with spreading morphology compared with PU membranes,indicating good cytocompatibility of composite scaffolds.These findings proved that PU/PLCL electrospun membranes have great potential in applications of skin tissue engineering.

Antibacterial Electrospun Nanofibrous Materials for Wound Healing

One of the leading causes of wound healing delays is bacterial infection,which limits the process of restoring the histological and functional integrity of the skin.Electrospun nanofibrous materials(ENMs)are biocompatible and biodegradable,and they can provide specific physical,chemical,and biological cues to accelerate wound healing.Based on this fact,a series of multifunctional ENMs for complex clinical applications,particularly infected skin injuries,have been developed.Anti-biotics,antimicrobial peptides(AMPs),metals and metal oxides(MMOs),and antibacterial polymers have previously been incorporated into ENMs through advanced material processing techniques,endowing ENMs with enhanced and excellent antibacterial activity.This review summarizes wound healing issues and provides recent advances in antibacterial ENMs created by cutting-edge technology.The future of clinical and translational research on ENMs is also discussed.

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure.This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix.To this aim,the co-assembly behaviour of a carboxylated variant of xyloglucan(CXG)with a peptide amphiphile(PA-H3)has been investigated to generate hierarchical constructs with tuneable molecular composition,structure,and properties.Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks.At a higher concentration,CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by smallamplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios.A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.