Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.

BackgroundCompromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton’s jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown.MethodsWe performed mass spectrometry on acellular gelatinous Wharton’s jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo.ResultsSubjecting the acellular gelatinous Wharton’s jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton’s jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton’s jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton’s jelly exosomes on wound healing.ConclusionsExosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton’s jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0921-2) contains supplementary material, which is available to authorized users.

Wound healing is vital for patients with complex wounds including burns. While the gold standard of skin transplantation ensures a surgical treatment to heal wounds, it has its limitations, for example, insufficient donor sites for patients with large burn wounds and creation of wounds and pain when harvesting the donor skin. Therefore, tissue-engineered skin is of paramount importance. The aim of this study is to investigate and characterize an elastomeric acellular scaffold that would demonstrate the ability to promote skin regeneration. A hybrid gelatin-based electrospun scaffold is fabricated via the use of biodegradable polycarbonate polyurethane (PU). It is hypothesized that the addition of PU would enable a tailored degradation rate and an enhanced mechanical strength of electrospun gelatin. Introducing 20% PU to gelatin scaffolds (Gel80–PU20) results in a significant increase in the degradation resistance, yield strength, and elongation of these scaffolds without altering the cell viability. In vivo studies using a mouse excisional wound biopsy grafted with the scaffolds reveals that the Gel80–PU20 scaffold enables greater cell infiltration than clinically established matrices, for example, Integra (dermal regeneration matrix, DRM), a benchmark scaffold. Immunostaining shows fewer macrophages and myofibroblastic cells on the Gel80–PU20 scaffold when compared with the DRM. The findings show that electrospun Gel80–PU20 scaffolds hold potential for generating tissue substitutes and overcoming some limitations of conventional wound care matrices.

For the first time we used hybrid self-assembling peptide-carbon nanotube hybrid hydrogels (that we have recently introduced briefly in the "Carbon" journal in 2014) for tissue engineering and 3D tumor engineering. We showed the potential of these hybrid hydrogels to enhance the efficiency of the peptide hydrogels for tissue engineering application in terms of cell behavior (cell attachment, spreading and migration). This opens up new rooms for the peptide hydrogels and can expand their applications. Also our system (peptide and peptide-CNT hydrogels) was used for cancer cell spheroid formation showing the effect of both tumor microenvironment stiffness and cell-scaffold adhesion on cancer cell invasion. This was only possible based on the presence of CNTs in the hydrogel while the stiffness kept constant. Finally it should be noted that these hybrid hydrogels expand applications of peptide hydrogels through enhancing their capabilities and/or adding new properties to them.

We demonstrate the noncovalent modification of multiwalled carbon nanotubes (MWNTs) immersed in aqueous solution using the ionic-complementary peptide EFK16-II. This modification presumably arises through the interaction between the hydrophobic side of the EFK16-II and MWNT sidewalls and orients hydrophilic functional groups toward the solution phase and enables them to form highly stable dispersions in water. This stability can be attributed to the electrostatic repulsion between self-assembled peptides on the MWNTs. This repulsion as determined by ζ potential measurements increases as the pH diverges from the isoelectric point of ~6.7 for EFK16-II. This trend is confirmed by dynamic light scattering measurements of the suspensions showing a decrease in their particle size as the ζ potential increases. These EFK16-II-MWNT suspensions have been used to modify mica surfaces. Atomic force microscopy and scanning electron microscopy images show that this leads to a uniform distribution of individual modified MWNTs on the mica surfaces. Transmission electron microscopy reveals images of well-dispersed fibers with dimensions similar to those of individual MWNTs. Tissue culture plates previously contacted with EFK16-II-modified MWNTs have been shown to have enough biocompatibility for growth and attachment of cells. The biocompatibility and enhanced electrical conductivity that should result from the modification with these EFK16-II-MWNT suspensions opens up their use in a number of potential biomedical applications such as the design of bioelectrode interfaces and fabrication of biosensors with high sensitivity.

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Tissue-engineered dermal substitutes represent a promising approach to improve wound healing and provide more sufficient regeneration, compared with current clinical standards on care of large wounds, early excision, and grafting of autografts.However, inadequate regenerative capacity, impaired regeneration/degradation profile, and high cost of current commercial tissue-engineered dermal regeneration templates hinder their utilization, and the development of an efficient and costeffective tissue-engineered dermal substitute remains a challenge. Inspired from our previously reported data on a pullulan/gelatin scaffold, here we present a new generation of a porous pullulan/gelatin scaffold (PG2) served as a dermal substitute with enhanced chemical and structural characteristics. PG2 shows excellent biocompatibility (viability, migration, and proliferation), assessed by in vitro incorporation of human dermal fibroblasts in comparison with the Integra® dermal regeneration template (Control). When applied on a mouse full-thickness excisional wound, PG2 shows rapid scaffold degradation, more granulation tissue, more collagen deposition, and more cellularity in comparison with Control at 20 days post surgery. The faster degradation is likely due to the enhanced recruitment of inflammatory macrophages to the scaffold from the wound bed, and that leads to earlier maturation of granulation tissue with less myofibroblastic cells. Collectively, our data reveal PG2's characteristics as an applicable dermal substitute with excellent dermal regeneration, which may attenuate scar formation.