Severe Skin Wounds Research Articles

Antibacterial and wound healing stimulant nanofibrous dressing consisting of soluplus and soy protein isolate loaded with mupirocin

Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of the Sol/SPI/Mp nanofibers were measured as 3.61 ± 0.29 MPa, 39.15 ± 5.08 MPa, and 59.11 ± 1.94%, respectively. Additionally, 85.90 ± 6.02% of Mp loaded in the nanofibers was released in 5 days in vitro, and by applying the Mp-loaded nanofibers, 93.06 ± 5.40% and 90.40 ± 5.66% of S. aureus and E. coli bacteria were killed, respectively. Human keratinocyte cells (HaCat) demonstrated notable biocompatibility with the prepared nanofibers. Furthermore, compare to other groups, Sol-SPI-Mp nanofibers caused the fastest re-epithelialization and wound healing in a rat model. The findings of this study present a novel nanofiber-based wound dressing that accelerates the healing of severe skin wounds with the risk of infection.

Psychosocial Impact of Suspected Xylazine-Associated Skin Wounds Among People Using Fentanyl, Philadelphia, 2022 to 2023.

The United States opioid crisis has been worsened by the emergence of fentanyl adulterated or associated with the veterinary sedative xylazine. Designated by the White House as an "emerging threat to the US" in 2023, xylazine use is associated with severe skin wounds. This research explored beliefs, concerns, and treatment behaviors for skin wounds among 93 participants recruited outside of a Philadelphia, Pennsylvania harm reduction agency who reported past-6-month history of a skin wound via a cross-sectional survey administered August-September 2022 (group 1; n = 33). Following a December 2022 Philadelphia Department of Public Health Report that indicated xylazine was becoming more prevalent in the Philadelphian drug supply, additional data was collected with new participants from February-March 2023 (group 2; n = 60) using the same survey. Participants were ≥18 years old, reported past-year fentanyl use, and spoke English. Our 17-item tool measured skin wound-related beliefs, concerns, treatment behaviors, and treatment sources. An open-response item explored why participants self-treat skin wounds. Participants averaged 41 years old (SD = 9), slightly more than half were men (n = 54, 58%), 31% (n = 29) were non-White, and most (n = 66, 71%) were unhoused. Overall, 79% of participants self-treated skin wounds. Participants endorsed worry about limb loss (n = 77; 83%), wound shame (n = 76; 82%), and appearance changes (n = 80; 86%). Sixty participants (65%) reported waiting to see wound severity before seeking care. Forty-one participants (44%) delayed wound care because of withdrawal fears. People with probable xylazine-associated skin wounds have psychosocial concerns about and self-treat these wounds. Findings may be a harbinger of skin wound harm in other regions of the United States and internationally where xylazine is increasing.

Strontium ranelate-loaded human hair keratin-hyaluronic acid hydrogel accelerates wound repair with anti-inflammatory and antioxidant properties

Inflammation and reactive oxygen species (ROS) production often accompany the repair of severe skin wounds, and the management of wounds has always been a clinical challenge, so the design of a hydrogel wound dressing with antioxidant and anti-inflammatory properties is of significant importance. This work incorporated strontium ranelate (SrR) into the keratin/hyaluronic acid (K/HA) hydrogel, which could scavenge ROS and reduce inflammation. The optimized hydrogel exhibits large pore size (217.2 μm), high porosity (57 %), high swelling rate (1759.52 %), and an elastic modulus (3.41 kPa). In the in vitro study, incorporating SrR into hydrogel effectively inhibited oxidative damage in mouse fibroblasts (L929) and improved anti-inflammatory effect in RAW264.7 cells stimulated by lipopolysaccharide. The in vivo study showed that, compared with the control group, the expression of ROS, IL-6 and TNF - α in the K/HA/0.5 mM SrR group were significantly reduced to 31.6 %, 39.7 % and 61.1 %, respectively. The in vivo evaluation in a full-thickness wound defect model demonstrated that K/HA/0.5 mM SrR hydrogel promotes wound healing by attenuating ROS levels, reducing inflammation, and promoting microangiogenesis. In summary, the excellent ROS scavenging and anti-inflammatory properties of SrR make the K/HA/SrR hydrogel a promising and effective strategy for wound healing.

Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment

Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities for Staphylococcus aureus (S. aureus). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity against S. aureus. Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β from macrophage inflammatory cells. This was achieved through downregulating the activation of NF-κB, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth of S. aureus in the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.

Antibiotics against Pseudomonas aeruginosa on Human Skin Cell Lines: Determination of the Highest Non-Cytotoxic Concentrations with Antibiofilm Capacity for Wound Healing Strategies.

Pseudomonas aeruginosa is one of the most common microorganisms causing infections of severe skin wounds. Antibiotic or antiseptic treatments are crucial to prevent and curb these infections. Antiseptics have been reported to be cytotoxic to skin cells and few studies evaluate the impact of commonly used antibiotics. This study evaluates how clinical antibiotics affect skin cells' viability, proliferation, migration, and cytokine secretion and defines the highest non-cytotoxic concentrations that maintain antibacterial activity. Cell proliferation, viability, and migration were evaluated on cell monolayers. Cytokines related to the wound healing process were determined. The minimum inhibitory concentrations and the impact on bacterial biofilm were assessed. Results showed that 0.02 mg/mL ciprofloxacin and 1 mg/mL meropenem are the highest non-cytotoxic concentrations for fibroblasts and keratinocytes while 1.25 mg/mL amikacin and 0.034 mg/mL colistin do not affect fibroblasts' viability and cytokine secretion but have an impact on keratinocytes. These concentrations are above the minimum inhibitory concentration but only amikacin could eradicate the biofilm. For the other antibiotics, cytotoxic concentrations are needed to eradicate the biofilm. Combinations with colistin at non-cytotoxic concentrations effectively eliminate the biofilm. These results provide information about the concentrations required when administering topical antibiotic treatments on skin lesions, and how these antibiotics affect wound management therapies. This study set the basis for the development of novel antibacterial wound healing strategies such as antibiotic artificial skin substitutes.

Biocompatible and antimicrobial multilayer fibrous polymeric wound dressing with optimally embedded silver nanoparticles

The demand for advanced, biocompatible wound dressings with antibacterial properties is increasing in order to treat people with severe skin wounds, such as burn victims or those suffering from ulcers. We have developed an ultrafine three-layer polymer nanofiber mesh using electrospinning that is able to kill bacteria (Escherichia coli; E. coli and Staphylococcus aureus; S. aureus) but also has cytocompatibility properties. The first layer was generated with polystyrene (PS) for strength and functions as a carrier layer. The second layer consisted of polycaprolactone (PCL) with silver nanoparticles (Ag NPs) that were added to the spinning solution, which had antibacterial properties. Finally, the third layer comprised of polyethylene oxide (PEO) acting as a hydrophilic, barrier layer that was also non-adhesive, with the potential to further assist in wound healing. Systematic physicochemical and biological characterization was performed including dynamic light scattering (DLS), UV spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP-OES), scanning electron microscopy (SEM), water contact angles, evaluation of antibacterial properties, and cell attachment and proliferation assays. The cumulative Ag ion release was optimized for a period up to 84 days in physiologically similar media at physiological temperature. Chemical, mechanical, and biological analysis demonstrated that incorporation of Ag NPs at higher quantities into the PCL fibers layer providing excellent antimicrobial activity with minimal toxicity at low concentration. The findings highlight the importance of optimizing the properties of Ag based antibacterial meshes to find the balance between high antibacterial activity and low toxicity.

One ternary nucleic acid delivery system with smart dextran-peptide coating enables in vivo and ex vivo wound therapy

<h2>Summary</h2> Apart from the superiority in supplementing cytokines in wound healing, gene therapy faces several critical obstacles, including the substantial exudation in wounds and difficult-to-transfect primary cells. Herein, a ternary nucleic acid delivery system (HPD) was constructed through the assembly of polyhexamethylene biguanide, DNA, and dextran-peptide conjugate (Dex-H2E5), which are prepared by the highly reproducible reaction of dextran and peptide. The proposed Dex-H2E5 forms a smart coating of HPD and acts as the "propellant" for the nucleic acid delivery. <i>In vitro</i> results confirmed that HPD realized low toxicity and high transfection performance in cell lines/primary cells and favorable serum stability/dosage independence. <i>In vivo</i> and <i>ex vivo</i> therapy of severe skin wounds further demonstrated the excellent performance of HPD after loading a therapeutic plasmid. Our work offers a highly efficient, reproducible delivery system for wound gene therapy. It could be extended to other clinical scenarios in which superior gene therapy is urgently demanded.

Ferrous iron-induced formation of glycyrrhizic acid hydrogels for Staphylococcus aureus-infected wound healing

Severe skin wound healing is mainly hindered by bacterial infection and uncontrolled inflammatory reaction. As a wound dressing, multifunctional hydrogel is expected to offer the potential possibility for overcoming current barriers in wound therapeutics. Herein, a natural drug molecule (glycyrrhizic acid, GA) and metal ion (Fe2+) were used to achieve the metal coordination-induced gelation. This as-prepared Fe2+-induced GA hydrogel showed excellent injectability, self-healing property, and sustained release behavior at a relatively lower concentration of GA, thereby reducing the high dose-caused cytotoxicity. In addition to acting as an inducer of gelation, Fe2+ promoted the antibacterial performance of hydrogel against Escherichia coli and Staphylococcus aureus through causing lipid peroxidation, membrane damage, and DNA degradation. Moreover, the released GA from hydrogel significantly accelerated cell migration and inhibited the inflammatory reaction by mediation of NF-κB signaling pathway to downregulate levels of important inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells. Using a mouse skin infected model, we revealed that the Fe2+/GA hydrogel applied to the wound resulted in the rapid wound healing. It is believed that the construction of natural drug molecule-derived hydrogel with antibacterial and anti-inflammatory capabilities may shed a new light to serve as a promising dressing for managing the severe skin wounds.

Initial Steps towards Spatiotemporal Signaling through Biomaterials Using Click-to-Release Chemistry.

The process of wound healing is a tightly controlled cascade of events, where severe skin wounds are resolved via scar tissue. This fibrotic response may be diminished by applying anti-fibrotic factors to the wound, thereby stimulating regeneration over scarring. The development of tunable biomaterials that enable spatiotemporal control over the release of anti-fibrotics would greatly benefit wound healing. Herein, harnessing the power of click-to-release chemistry for regenerative medicine, we demonstrate the feasibility of such an approach. For this purpose, one side of a bis-N-hydroxysuccinimide-trans-cyclooctene (TCO) linker was functionalized with human epidermal growth factor (hEGF), an important regulator during wound healing, whereas on the other side a carrier protein was conjugated—either type I collagen scaffolds or bovine serum albumin (BSA). Mass spectrometry demonstrated the coupling of hEGF–TCO and indicated a release following exposure to dimethyl-tetrazine. Type I collagen scaffolds could be functionalized with the hEGF–TCO complex as demonstrated by immunofluorescence staining and Western blotting. The hEGF–TCO complex was also successfully ligated to BSA and the partial release of hEGF upon dimethyl-tetrazine exposure was observed through Western blotting. This work establishes the potential of click-to-release chemistry for the development of pro-regenerative biomaterials.

Mammalian organ regeneration in spiny mice.

Fibrosis-driven solid organ failure is a major world-wide health burden with few therapeutic options. Spiny mice (genus: Acomys) are terrestrial mammals that regenerate severe skin wounds without fibrotic scars to evade predators. Recent studies have shown that spiny mice also regenerate acute ischemic and traumatic injuries to kidney, heart, spinal cord, and skeletal muscle. A common feature of this evolved wound healing response is a lack of formation of fibrotic scar tissue that degrades organ function, inhibits regeneration, and leads to organ failure. Complex tissue regeneration is an extremely rare property among mammalian species. In this article, we discuss the evidence that Acomys represents an emerging model organism that offers a unique opportunity for the biomedical community to investigate and clinically translate molecular mechanisms of scarless wound healing and regeneration of organ function in a mammalian species.

Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis

SummaryFibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the Acomys genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.

One nanosystem with potent antibacterial and gene-delivery performances accelerates infected wound healing

Growth factor delivery has attracted high attention for the treatment of severe skin wounds, while it is still desirable to develop new delivery systems with superiority for both antibacterial and delivery performances. In this work, one bifunctional nanosystem (HPT-RP) was constructed for the anti-bacterial and gene-delivery (plasmid encoding epidermal growth factor (EGF)) treatment of infected wound through the one-pot dual conjugation of photosensitizer and bacterium/cell-affinity phenylboronic acid onto hyperbranched polyaminoglycosides. HPT-RP realized high anti-bacterial ability owing to the receptor-mediated photodynamic therapy. The nanoparticle morphology and phenylboronic acid conjugation endowed HPT-RP with high gene transfection. In a rat infected-skin-defect model, HPT-RP exhibited the remarkable performance of anti-infective/EGF-delivery and accelerated healing. More importantly, a new sight into rat-EGF production revealed the underlying mechanism of extraneous EGF delivery and endogenous EGF production. This work sheds light on the rational design of growth factor delivery systems for infected wound therapy.

Injectable hydrogel wound dressing based on strontium ion cross-linked starch

Severe skin wounds cause great problems and sufferings to patients. In this study, an injectable wound dressing based on strontium ion cross-linked starch hydrogel (SSH) was developed and evaluated. The good inject-ability of SSH made it easy to be delivered onto the wound surface. The good tissue adhesiveness of SSH ensured a firm protection of the wound. Besides, SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Importantly, SSH exhibited strong antibacterial effects on Staphylococcus aureus (S. aureus), which could prevent wound infection. These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.

Auto Micro Atomization Delivery of Human Epidermal Organoids Improves Therapeutic Effects for Skin Wound Healing.

Severe skin wounds are often associated with large areas of damaged tissue, resulting in substantial loss of fluids containing electrolytes and proteins. The net result is a vulnerability clinically to skin infections. Therapies aiming to close these large openings are effective in reducing the complications of severe skin wounds. Recently, cell transplantation therapy showed the potential for rapid re-epithelialization of severe skin wounds. Here, we show the improved effects of cell transplantation therapy using a robust protocol of efficient expansion and delivery of epidermal cells for treatment of severe skin wounds. Human skin tissues were used to generate human epidermal organoids maintained under newly established culture conditions. The human epidermal organoids showed an improved capacity of passaging for at least 10 rounds, enabling organoids to expand to cell numbers required for clinical applications. A newly designed auto micro-atomization device (AMAD) was developed for delivery of human epidermal organoids onto the sites of severe skin wounds enhancing uniform and concentrated delivery of organoids, facilitating their engraftment and differentiation for skin reconstitution. With the optimal design and using pneumatic AMAD, both survival and functions of organoids were effectively protected during the spraying process. Cells in the sprayed human epidermal organoids participated in the regeneration of the epidermis at wound sites in a mouse model and accelerated wound healing significantly. The novel AMAD and out new protocol with enhanced effects with respect to both organoid expansion and efficient transplantation will be used for clincal treatments of complex, uneven, or large-area severe skin wounds.

Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1

The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF®, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAF® does not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF®. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAF® induced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAF® to clinical application in cases of severe skin injury.

Large-scale expansion of human skin-derived precursor cells (hSKPs) in stirred suspension bioreactors.

Human skin-derived precursor cells (hSKPs) are multipotent adult stem cells found in the dermis of human skin. Incorporation of hSKPs into split-thickness skin grafts (STSGs), the current gold standard to treat severe burns or tissue resections, has been proposed as a treatment option to enhance skin wound healing and tissue function. For this approach to be clinically viable substantial quantities of hSKPs are required, which is the rate-limiting step, as only a few thousand hSKPs can be isolated from an autologous skin biopsy without causing donor site morbidity. In order to produce sufficient quantities of clinically viable cells, we have developed a bioprocess capable of expanding hSKPs as aggregates in stirred suspension bioreactors (SSBs). In this study, we found hSKPs from adult donors to expand significantly more (P < 0.05) at 60 rpm in SSBs than in static cultures. Furthermore, the utility of the SSBs, at 60 rpm is demonstrated by serial passaging of hSKPs from a small starting population, which can be isolated from an autologous skin biopsy without causing donor site morbidity. At 60 rpm, aggregates were markedly smaller and did not experience oxygen diffusional limitations, as seen in hSKPs cultured at 40 rpm. While hSKPs also grew at 80 rpm (0.74 Pa) and 100 rpm (1 Pa), they produced smaller aggregates due to high shear stress. The pH of the media in all the SSBs was closer to biological conditions and significantly different (P < 0.05) from static cultures, which recorded acidic pH conditions. The nutrient concentrations of the media in all the SSBs and static cultures did not drop below acceptable limits. Furthermore, there was no significant build-up of waste products to limit hSKP expansion in the SSBs. In addition, hSKP markers were maintained in the 60 rpm SSB as demonstrated by immunocytochemistry. This method of growing hSKPs in a batch culture at 60 rpm in a SSB represents an important first step in developing an automated bioprocess to produce substantial numbers of clinically viable hSKPs aimed at regenerating the dermis to improve healing of severe skin wounds. Biotechnol. Bioeng. 2016;113: 2725-2738. © 2016 Wiley Periodicals, Inc.

A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds

Topically applied opioids are an option to induce efficient analgesia in patients with severe skin wounds. For ongoing pain reduction, the vehicle should provide sustained drug release in order to increase the intervals during the regular wound dressing changes. In addition, the formulation should not impair wound healing. Hydrogels provide a moist wound environment, which is known to facilitate the healing process. Investigating poloxamer hydrogels as a carrier system for morphine in terms of release behavior and (per-)cutaneous absorption, poloxamer 407 25wt.% hydrogel sustained morphine release up to 24h. The drug release rate decreased with increasing concentration of the gel forming triblock copolymer. Poloxamer 407 25wt.% hydrogel retarded morphine uptake into reconstructed human skin and percutaneous drug absorption compared to a hydroxyethyl cellulose reference gel. The results of our in vitro study indicate that the thermosensitive poloxamer 407 25wt.% hydrogel is an appropriate carrier system for the topical application of morphine with regard to sustained drug release and ongoing analgesia.

Common features of optimal collagen scaffolds that disrupt wound contraction and enhance regeneration both in peripheral nerves and in skin

The adult mammal responds to severe injury of most organs spontaneously by wound contraction and scar formation, rather than by regeneration. In severe skin wounds, the ability of porous collagen scaffolds to induce regeneration was found to correlate strongly with a reduction in wound contraction rate. Here, we present quantitative evidence of a similar positive relationship between the extent of disruption of tissue contraction and quality of peripheral nerve regeneration in transected rat peripheral nerves. Our observations suggest that porous collagen scaffolds enhance regeneration both in injured adult skin and peripheral nerves by disrupting the formation of a contractile cell capsule at the edges of the wound. Preliminary observations made with other injured organs support the hypothesis that capsules or clusters of contractile cells impose a universal mechanical barrier during wound healing which, if disrupted appropriately, enhances the quality of induced regeneration in a wider range of organs.

3D-Wound healing model: Influence of morphine and solid lipid nanoparticles

For efficient pain reduction in severe skin wounds, topically applied opioids may be a new option. Moreover, by stimulating keratinocyte migration opioids may also accelerate wound healing. Yet, conventional formulations failed to consistently provide sufficient pain control in patients which may be due to local drug degradation or insufficient concentrations at the target site. After having excluded major morphine glucuronidation by keratinocytes and fibroblasts, we next aimed for an optimised formulation. Since long intervals for painful wound dressing changes are intended, the formulations should allow for prolonged opioid release and should not impair the healing process. We developed morphine-loaded solid lipid nanoparticles (SLN, mean size about 180nm), and tested improvement of wound closure in a new human-based 3D-wound healing model. Standardised wounds were induced by CO2-laser irradiation of reconstructed human full-thickness skin equivalents (EpiDermFT™). Morphine, morphine-loaded and unloaded SLN accelerated reepithelialization. Keratinocytes almost completely covered the dermis equivalent after 4 days, which was not the case when applying the vehicle. In conclusion, acceleration of wound closure, low cytotoxicity and irritation as well as possible prolonged morphine release make SLN an interesting approach for innovative wound management.

Influences of opioids and nanoparticles on in vitro wound healing models

For efficient pain reduction in severe skin wounds, topical opioids may be a new option – given that wound healing is not impaired and the vehicle allows for slow opioid release, since long intervals of painful wound dressing changes are intended. We investigated the influence of opioids on the wound healing process via in vitro models, migration assay and scratch test. In fact, morphine, hydromorphone, fentanyl and buprenorphine increased the number of migrated HaCaT cells (spontaneously transformed keratinocytes) twofold. In the scratch test, morphine accelerated the closure of a monolayer wound (scratch). As possible slow release application forms are nanoparticulate systems like solid lipid nanoparticles (SLN) and dendritic core-multishell (CMS) nanotransporters, we evaluated the effect of unloaded nanoparticles on HaCaT cell migration, too. CMS nanotransporters did not inhibit migration, SLN even enhanced it (twofold). Applying morphine plus unloaded nanoparticles reduced morphine effects possibly due to uptake into CMS nanotransporters and adsorption to the surface of SLN. In contrast to SLN, TGF-β1 was taken up by CMS nanotransporters, too. Both nanoparticles are tolerable by skin and eye as derived from Episkin-SM TM skin irritation test and HET-CAM assay. No acute toxic effects were observed either. In conclusion, opioids as well as the investigated nanoparticulate carriers conform the essential conditions for topical pain reduction.