Biological Coatings: Advanced Strategies Driving Multifunctionality and Clinical Potential in Dermal Substitutes

Naliyadhara N., Trujillo F.J.

Lam M., Baudoin M., Mougin B., Falentin‐Daudré C.

ABSTRACTMelt‐blown, an environmentally friendly technique, is widely used to create high‐quality non‐woven fabrics by extruding molten polymer resins into interlaced fibers. In the realm of biomedical textiles, its unique microstructure makes it ideal for filtration and wound dressings. Our study focuses on modifying the surfaces of polypropylene melt‐blown membranes. An effective, one‐step, suitable, and reliable method to graft a bioactive polymer, sodium polystyrene sulfonate—PolyNaSS, onto the membranes has been developed. The process involves UV irradiation to initiate direct and progressive growth of NaSS over the surface through radical polymerization. To assess the efficiency of the grafting, techniques like colorimetry, water contact angle measurements, Fourier‐transformed infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used. Outcomes related to the grafting were demonstrated by a change in wettability and quantitatively calculated sulfonate groups. Subsequently, grafted PolyNaSS promoted cell adhesion, as evidenced by improved cell morphology. On grafted membranes, fibroblasts exhibited a stretched shape, while non‐grafted ones showed inactive round shapes. These findings underscore the chemical and biological reactivity of polypropylene materials, opening exciting possibilities for various applications of melt‐blown materials.

Kohestani A.A., Xu Z., Baştan F.E., Boccaccini A.R., Pishbin F.

Recent interest in tissue engineering (TE) has focused on electrically conductive biomaterials. This has been inspired by the characteristics of the cells' microenvironment where signalling is supported by electrical stimulation. Numerous studies have demonstrated the positive influence of electrical stimulation on cell excitation to proliferate, differentiate, and deposit extracellular matrix. Even without external electrical stimulation, research shows that electrically active scaffolds can improve tissue regeneration capacity. Tissues like bone, muscle, and neural contain electrically excitable cells that respond to electrical cues provided by implanted biomaterials. To introduce an electrical pathway, TE scaffolds can incorporate conductive polymers, metallic nanoparticles, and ceramic nanostructures. However, these materials often do not meet implantation criteria, such as maintaining mechanical durability and degradation characteristics, making them unsuitable as scaffold matrices. Instead, depositing conductive layers on TE scaffolds has shown promise as an efficient alternative to creating electrically conductive structures. A stratified scaffold with an electroactive surface synergistically excites the cells through active top-pathway, with/without electrical stimulation, providing an ideal matrix for cell growth, proliferation, and tissue deposition. Additionally, these conductive coatings can be enriched with bioactive or pharmaceutical components to enhance the scaffold's biomedical performance. This review covers recent developments in electrically active biomedical coatings for TE. The physicochemical and biological properties of conductive coating materials, including polymers (polypyrrole, polyaniline and PEDOT:PSS), metallic nanoparticles (gold, silver) and inorganic (ceramic) particles (carbon nanotubes, graphene-based materials and Mxenes) are examined. Each section explores the conductive coatings' deposition techniques, deposition parameters, conductivity ranges, deposit morphology, cell responses, and toxicity levels in detail. Furthermore, the applications of these conductive layers, primarily in bone, muscle, and neural TE are considered, and findings from in vitro and in vivo investigations are presented. Tissue engineering (TE) scaffolds are crucial for human tissue replacement and acceleration of healing. Neural, muscle, bone, and skin tissues have electrically excitable cells, and their regeneration can be enhanced by electrically conductive scaffolds. However, standalone conductive materials often fall short for TE applications. An effective approach involves coating scaffolds with a conductive layer, finely tuning surface properties while leveraging the scaffold's innate biological and physical support. Further enhancement is achieved by modifying the conductive layer with pharmaceutical components. This review explores the under-reviewed topic of conductive coatings in tissue engineering, introducing conductive biomaterial coatings and analyzing their biological interactions. It provides insights into enhancing scaffold functionality for tissue regeneration, bridging a critical gap in current literature.

Safin Kaosar Saad K., Saba T., Bin Rashid A.

Physical vapor deposition (PVD) coating is a versatile and well-liked method for depositing thin films of materials onto surfaces in a range of industries. Due to their numerous functional and aesthetic benefits, PVD coatings are beneficial in several applications, from electronics and optics to automotive and medical equipment. PVD coating technology dramatically improves the effectiveness and quality of medical implants. PVD-coated medical implants improve osseointegration, lower wear and friction, increase corrosion resistance, and have antibacterial properties, which lead to better patient outcomes, fewer complications, and overall higher quality of life for people who need implantable medical devices. The essential concepts of PVD coating and the numerous deposition techniques and materials used are covered at the study's outset. The specific uses of PVD-coated medical implants are then highlighted, including those for orthopedic and dental implants and cardiovascular and neurosurgical devices. The review also emphasizes the critical contribution of PVD coatings to reducing wear and friction, improving corrosion resistance, augmenting biocompatibility, enhancing osseointegration, and aesthetic appeal. The challenges and prospects of PVD coating technologies were further addressed in this article. This review is invaluable for academics, doctors, and businesspeople interested in the beneficial combination of PVD coating and medical implantology.

Almonte L., Fernandez M., Cortés-Ossa J.D., Blesio P., Juan-Bordera L., Sabater C., Cortajarena A.L., Calvo M.R.

Ramli N.A., Adam F., Ries M.E., Ibrahim S.F.

CNCs are intensively studied to reinforce biocomposites. However, it remains a challenge to homogeneously disperse the CNC in biocomposites for a smooth film surface. Mechanochemical treatment via ultrasonication in deep eutectic solvent (DES) generated a stable dispersion of CNC before incorporation into carrageenan biocomposite. Shifted peaks of choline chloride (ChCl) methylene groups to 3.95-3.98 ppm in

Kang Y., Liu K., Chen Z., Guo J., Xiang K., Wu X., Jiang T., Chen J., Yan C., Jiang G., Wang Y., Zhang M., Xiang X., Dai H., Yang X.

Chronic skin wounds, especially infected ones, pose a significant clinical challenge due to their increasing incidence and poor outcomes. The deteriorative microenvironment in such wounds, characterized by reduced extracellular matrix, impaired angiogenesis, insufficient neurogenesis, and persistent bacterial infection, has prompted the exploration of novel therapeutic strategies. In this study, we developed an injectable multifunctional hydrogel (GEL/BG@Cu + Mg) incorporating Gelatin-Tannic acid/ N-hydroxysuccinimide functionalized polyethylene glycol and Bioactive glass doped with copper and magnesium ions to accelerate the healing of infected wounds. The GEL/BG@Cu + Mg hydrogel composite demonstrates good biocompatibility, degradability, and rapid formation of a protective barrier to stop bleeding. Synergistic bactericidal effects are achieved through the photothermal properties of BG@Cu + Mg and sustained copper ions release, with the latter further promoting angiogenesis. Furthermore, the hydrogel enhances neurogenesis by stimulating axons and Schwann cells in the wound bed through the beneficial effects of magnesium ions. Our results demonstrate that the designed novel multifunctional hydrogel holds tremendous promise for treating infected wounds and allowing regenerative neurogenesis at the wound site, which provides a viable alternative for further improving clinical outcomes.

Kamaraj M., Moghimi N., Chen J., Morales R., Chen S., Khademhosseini A., John J.V.

Electrospinning technology has garnered wide attention over the past few decades in various biomedical applications including drug delivery, cell therapy, and tissue engineering. This technology can create nanofibers with tunable fiber diameters and functionalities. However, the 2D membrane nature of the nanofibers, as well as the rigidity and low porosity of electrospun fibers, lower their efficacy in tissue repair and regeneration. Recently, new avenues have been explored to resolve the challenges associated with 2D electrospun nanofiber membranes. This review discusses recent trends in creating different electrospun nanofiber microstructures from 2D nanofiber membranes by using various post-processing methods, as well as their biotechnological applications.

Nagano H., Mizuno N., Sato H., Mizutani E., Yanagida A., Kano M., Kasai M., Yamamoto H., Watanabe M., Suchy F., Masaki H., Nakauchi H.

AbstractAutologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos’ dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos’ dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.

Moors J.J., Xu Z., Xie K., Rashad A., Egger J., Röhrig R., Hölzle F., Puladi B.

Abstract Background The radial forearm free flap (RFFF) serves as a workhorse for a variety of reconstructions. Although there are a variety of surgical techniques for donor site closure after RFFF raising, the most common techniques are closure using a split-thickness skin graft (STSG) or a full-thickness skin graft (FTSG). The closure can result in wound complications and function and aesthetic compromise of the forearm and hand. The aim of the planned systematic review and meta-analysis is to compare the wound-related, function-related and aesthetics-related outcome associated with full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) in radial forearm free flap (RFFF) donor site closure. Methods A systematic review and meta-analysis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed. Electronic databases and platforms (PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI)) and clinical trial registries (ClinicalTrials.gov, the German Clinical Trials Register, the ISRCTN registry, the International Clinical Trials Registry Platform) will be searched using predefined search terms until 15 January 2024. A rerun of the search will be carried out within 12 months before publication of the review. Eligible studies should report on the occurrence of donor site complications after raising an RFFF and closure of the defect. Included closure techniques are techniques that use full-thickness skin grafts and split-thickness skin grafts. Excluded techniques for closure are primary wound closure without the use of skin graft. Outcomes are considered wound-, functional-, and aesthetics-related. Studies that will be included are randomized controlled trials (RCTs) and prospective and retrospective comparative cohort studies. Case-control studies, studies without a control group, animal studies and cadaveric studies will be excluded. Screening will be performed in a blinded fashion by two reviewers per study. A third reviewer resolves discrepancies. The risk of bias in the original studies will be assessed using the ROBINS-I and RoB 2 tools. Data synthesis will be done using Review Manager (RevMan) 5.4.1. If appropriate, a meta-analysis will be conducted. Between-study variability will be assessed using the I2 index. If necessary, R will be used. The quality of evidence for outcomes will eventually be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion This study's findings may help us understand both closure techniques' complication rates and may have important implications for developing future guidelines for RFFF donor site management. If available data is limited and several questions remain unanswered, additional comparative studies will be needed. Systematic review registration The protocol was developed in line with the PRISMA-P extension for protocols and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 September 2023 (registration number CRD42023351903).

Alizadeh S., Majidi J., Jahani M., Esmaeili Z., Nokhbedehghan Z., Aliakbar Ahovan Z., Nasiri H., Mellati A., Hashemi A., Chauhan N.P., Gholipourmalekabadi M.

AbstractAn ideal antibacterial wound dressing with strong antibacterial behavior versus highly drug‐resistant bacteria and great wound‐healing capacity is still being developed. There is a clinical requirement to progress the current clinical cares that fail to fully restore the skin structure due to post‐wound infections. Here, we aim to introduce a novel two‐layer wound dressing using decellularized bovine skin (DBS) tissue and antibacterial nanofibers to design a bioactive scaffold with bio‐mimicking the native extracellular matrix of both dermis and epidermis. For this purpose, polyvinyl alcohol (PVA)/chitosan (CS) solution was loaded with antibiotics (colistin and meropenem) and electrospun on the surface of the DBS scaffold to fabricate a two‐layer antibacterial wound dressing (DBS‐PVA/CS/Abs). In detail, the characterization of the fabricated scaffold was conducted using biomechanical, biological, and antibacterial assays. Based on the results, the fabricated scaffold revealed a homogenous three‐dimensional microstructure with a connected pore network, a high porosity and swelling ratio, and favorable mechanical properties. In addition, according to the cell culture result, our fabricated two‐layer scaffold surface had a good interaction with fibroblast cells and provided an excellent substrate for cell proliferation and attachment. The antibacterial assay revealed a strong antibacterial activity of DBS‐PVA/CS/Abs against both standard strain and multidrug‐resistant clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Our bilayer antibacterial wound dressing is strongly suggested as an admirable wound dressing for the management of infectious skin injuries and now promises to advance with preclinical and clinical research.

Al-Musawi M.H., Mahmoudi E., Kamil M.M., Almajidi Y.Q., Mohammadzadeh V., Ghorbani M.

Wound dressing materials such as nanofiber (NF) mats have gained a lot of attention in recent years owing to their wonderful effect on accelerating the healing process and protection of wounds. In this regard, three different types of NF mats were fabricated using pure polyvinylpyrrolidone (PVP), PVP/κ-carrageenan (KG), and ursolic acid (UA) in the optimal PVP/KG ratio by electrospinning method to apply them as wound dressings. The morphology, chemical structure, degradation, porosity, mechanical properties and antioxidant activity of the produced NFs were investigated. Moreover, cell studies (e.g., cell proliferation, adhesion, and migration) and their antibacterial properties were evaluated. Adding KG and UA reduced the mean diameter size of the PVP-based NFs to ∼98 nm in the optimal sample, with defect-free morphology. The PVP/KG/UA 0.25 % exhibited the highest porosity, hydrophilicity, and degradation rate and a wound closure rate of 60 %, 2.5 times higher than that of the control group. Furthermore, this sample's proliferation and antibacterial ability were significantly higher than the other groups. These findings confirmed that the produced UA-loaded NFs have excellent properties as wound dressing.

Shahriari-Khalaji M., Sattar M., Cao R., Zhu M.

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.

YASTI A.Ç., ÇOLAK B., ÖZCAN F., KISMET K., SÜREL A.A., Akgün A.E., AKIN M.

Oxygen is required for cell migration into the scaffold and for the survival of the overlying graft in the use of a single-layer scaffold. In the absence of diffusion from the avascular wound base, such as in areas above the bone/tendon, oxygen delivery from the lateral edges of the scaffold is important. This study compared the oxygen permeability of skin scaffolds, currently commercially available in Turkey (Nevelia®, MatriDerm®, and Pelnac®), in the lateral plane.To measure oxygen permeability, an interconnected closed system was created. Oxygen permeability was evaluated based on the color change that occurred as a result of the reaction of iron with oxygen. After the dermal matrices placed in the closed system were exposed to oxygen, the color change on the surface of the dermal matrices was measured, and electron microscopic images were recorded to compare deformation before and after the procedure.Two scaffolds did not show deformation after the procedure while Pelnac® had minimal deformation. The oxygen rates on the nitrogen side of the test apparatus were found to be 29%, 34%, and 27% for Nevelia®, MatriDerm®, and Pelnac®, respectively; and the oxygen transmission lengths (length of color change) of these scaffolds in the lateral plane were 1, 2, and 0.5 cm, respectively.Although none of the scaffolds showed significant deformation, and all continued to exhibit their scaffold properties after the procedure, MatriDerm® was determined to be the most suitable scaffold for use in avascular areas, with a 2-cm oxygen transmission length in terms of lateral oxygenation.

Zhang G., Zhang Z., Cao G., Jin Q., Xu L., Li J., Liu Z., Xu C., Le Y., Fu Y., Ju J., Li B., Hou R.

Tissue-engineered skin is ideal for clinical wound repair. Restoration of skin tissue defects using tissue-engineered skin remains a challenge owing to insufficient vascularisation. In our previous study, we developed a 3D bioprinted model with confined force loading and demonstrated that the confined force can affect vascular branching, which is regulated by the YAP signalling pathway. The mechanical properties of the model must be optimised to suture the wound edges. In this study, we explored the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularisation and wound healing. The shape of the GelMA-HAMA-fibrin scaffold containing 3% GelMA was affected by the confined forces produced by the embedded cells. The GelMA-HAMA-fibrin scaffold was easy to print, had optimal mechanical properties, and was biocompatible. The constructs were successfully sutured together after 14 d of culture. Scaffolds seeded with cells were transplanted into skin tissue defects in nude mice, demonstrating that the cell-seeded GelMA-HAMA-fibrin scaffold, under confined force loading, promoted neovascularisation and wound restoration by enhancing blood vessel connections, creating a patterned surface, growth factors, and collagen deposition. These results provide further insights into the production of hydrogel composite materials as tissue-engineered scaffolds under an internal mechanical load that can enhance vascularisation and offer new treatment methods for wound healing. STATEMENT OF SIGNIFICANCE: Tissue-engineered skin is ideal for use in clinical wound repair. However, treatment of tissue defects using synthetic scaffolds remains challenging, mainly due to slow and insufficient vascularization. Our previous study developed a 3D bioprinted model with confined force loading, and demonstrated that confined force can affect vascular branching regulated by the YAP signal pathway. The mechanical properties of the construct need to be optimized for suturing to the edges of wounds. Here, we investigated the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularization in vitro and wound healing in vivo. Our findings provide new insight into the development of degradable macroporous composite materials with mechanical stimulation as tissue-engineered scaffolds with enhanced vascularization, and also provide new treatment options for wound healing.