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The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium-carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m2 h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care.
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Objective: Collagen, a widely used natural biomaterial polymer in skin tissue engineering, can be innovatively processed into nanocollagen through cryogenic milling to potentially enhance skin tissue healing. Although various methods for fabricating nanocollagen have been documented, there is no existing study on the fabrication of nanocollagen via cryogenic milling, specifically employing graphene oxide as separators to prevent agglomeration. Methods: In this study, three research groups were created using cryogenic milling: pure nanocollagen (Pure NC), nanocollagen with 0.005% graphene oxide (NC + 0.005% GO), and nanocollagen with 0.01% graphene oxide (NC+0.01% GO). Characterization analyses included transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, x-ray diffraction (XRD), zeta potential (ZP), and polydispersity index (PDI). Results: TEM and SEM analysis revealed that nanocollagen groups alone exhibited particle sizes of less than 100 nm. FTIR spectroscopic investigations indicated the presence of amide A, B, and I, II, and III (1800 to 800 cm-1) in all nanocollagen study groups, with the characteristic C-O-C stretching suggesting the incorporation of graphene oxide (GO). XRD data exhibited broadening of the major peak as the proportion of GO increased from pure NC to the nanocollagen groups with GO. Zeta potential measurements indicated electrostatic attraction of the samples to negatively charged surfaces, accompanied by sample instability. PDI results depicted size diameters ranging from 800 to 1800 nm, indicating strong polydispersity with multiple size populations. Conclusion: This research demonstrated that collagen can be successfully fabricated into nanoparticles with sizes smaller than 100 nm.
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Colágeno , Grafite , Tamanho da Partícula , Grafite/química , Colágeno/química , Espectroscopia de Infravermelho com Transformada de Fourier , Materiais Biocompatíveis/química , Difração de Raios X , Engenharia Tecidual/métodos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de TransmissãoRESUMO
Regenerative medicine represents a paradigm shift in healthcare, aiming to restore tissue and organ function through innovative therapeutic strategies. Among these, bioprinting and extracellular vesicles (EVs) have emerged as promising techniques for tissue rejuvenation. EVs are small lipid membrane particles secreted by cells, known for their role as potent mediators of intercellular communication through the exchange of proteins, genetic material, and other biological components. The integration of 3D bioprinting technology with EVs offers a novel approach to tissue engineering, enabling the precise deposition of EV-loaded bioinks to construct complex three-dimensional (3D) tissue architectures. Unlike traditional cell-based approaches, bioprinted EVs eliminate the need for live cells, thereby mitigating regulatory and financial obstacles associated with cell therapy. By leveraging the synergistic effects of EVs and bioprinting, researchers aim to enhance the therapeutic outcomes of skin regeneration while addressing current limitations in conventional treatments. This review explores the evolving landscape of bioprinted EVs as a transformative approach for skin regeneration. Furthermore, it discusses the challenges and future directions in harnessing this innovative therapy for clinical applications, emphasizing the need for interdisciplinary collaboration and continued scientific inquiry to unlock its full therapeutic potential.
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Conditioned media refers to a collection of the used cell culture media. The goal of this study was to evaluate the possible impacts of different conditioned media collected across a number of cycles on the fibroblast proliferation, migration, and profiles of protein release. Human dermal fibroblast (HDF) cells and Wharton jelly mesenchymal stem cells (WJMSC) were cultured and incubated for 3 days prior to being harvested as cycle-1 using the serum-free media F12:DMEM and DMEM, respectively. The procedures were repeatedly carried out until the fifth cycle of conditioned media collection. An in-vitro scratch assay was conducted to measure the effectiveness of wound healing. Collagen hydrogel was combined separately with both the Wharton jelly-conditioned medium (WJCM) and the dermal fibroblast-conditioned medium (DFCM) in order to evaluate the protein release profile. The conditioned medium from many cycles had a lower level of fibroblast attachment than the control (complete medium); however, the growth rate increased from 100 to 250 h-1, when supplemented with a conditioned medium collected from multiple cycles. The wound scratch assay showed that fibroblast cell migration was significantly increased by repeating cycles up to cycle-5 of DFCM, reaching 98.73 ± 1.11%. This was faster than the rate of migration observed in the cycle-5 of the WJCM group, which was 27.45 ± 5.55%. Collagen hydrogel from multiple cycles of DFCM and WJCM had a similar protein release profile. These findings demonstrate the potential for employing repeated cycles of DFCM- and WJCM-released proteins with collagen hydrogel for applications in wound healing.
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The treatment of various types of wounds such as dermal wounds, multidrug resistant bacteria-infected wounds, and chronic diabetic wounds is one of the critical challenges facing healthcare systems. Delayed wound healing can impose a remarkable burden on patients and health care professionals. In this case, given their unique three-dimensional porous structure, biocompatibility, high hydrophilicity, capability to provide a moist environment while absorbing wound exudate, permeability to both gas and oxygen, and tunable mechanical properties, hydrogels with antibacterial function are one of the most promising candidates for wound healing applications. Polylysine is a cationic polymer with the advantages of inherent antibacterial properties, biodegradability, and biocompatibility. Therefore, its utilization to engineer antibacterial hydrogels for accelerating wound healing is of great interest. In this review, we initially discuss polylysine properties, and then focus on the most recent advances in polylysine-containing hydrogels (since 2016) prepared using various chemical and physical crosslinking methods for hemostasis and wound healing applications. Finally, the challenges and future directions in the engineering of these antibacterial hydrogels for wound healing are discussed.
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Antibacterianos , Hidrogéis , Polilisina , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Polilisina/química , Polilisina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Animais , Hemostáticos/farmacologia , Hemostáticos/química , Hemostáticos/administração & dosagem , Hemostasia/efeitos dos fármacosRESUMO
Wounds are breaks in the continuity of the skin and underlying tissues, resulting from external causes such as cuts, blows, impacts, or surgical interventions. Countless individuals suffer minor to severe injuries, with unfortunate cases even leading to death. In today's scenario, several commercial products are available to facilitate the healing process of wounds, although chronic wounds still present more challenges than acute wounds. Nevertheless, the huge demand for wound-care products within the healthcare sector has given rise to a rapidly growing market, fostering continuous research and development endeavors for innovative wound-healing solutions. Today, there are many commercially available products including those based on natural biopolymers, stem cells, and microRNAs that promote healing from wounds. This article explores the recent breakthroughs in wound-healing products that harness the potential of natural biopolymers, stem cells, and microRNAs. A comprehensive exploration is undertaken, covering not only commercially available products but also those still in the research phase. Additionally, we provide a thorough examination of the opportunities, obstacles, and regulatory considerations influencing the potential commercialization of wound-healing products across the diverse markets of Europe, America, and Asia.
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Skin tissue engineering has gained significant attention as a promising alternative to traditional treatments for skin injuries. In this study, we developed 3D hydrogel-based scaffolds, Alginate, incorporating different concentrations of Curcumin and evaluated their properties, including morphology, swelling behavior, weight loss, as well as hemo- and cytocompatibility. Furthermore, we investigated the therapeutic potential of Alginate hydrogel containing different amounts of Curcumin using an in vitro wound healing model. The prepared hydrogels exhibited remarkable characteristics, SEM showed that the pore size of hydrogels was 134.64 µm with interconnected pores, making it conducive for cellular infiltration and nutrient exchange. Moreover, hydrogels demonstrated excellent biodegradability, losing 63.5% of its weight over 14 days. In addition, the prepared hydrogels had a stable release of curcumin for 3 days. The results also show the hemocompatibility of prepared hydrogels and a low amount of blood clotting. To assess the efficacy of the developed hydrogels, 3T3 fibroblast growth was examined during various incubation times. The results indicated that the inclusion of Curcumin at a concentration of 0.1 mg/mL positively influenced cellular behavior. The animal study showed that Alginate hydrogel containing 0.1 mg/mL curcumin had high wound closure(more than 80%) after 14 days. In addition, it showed up-regulation of essential wound healing genes, including TGFß1 and VEGF, promoting tissue repair and angiogenesis. Furthermore, the treated group exhibited down-regulation of MMP9 gene expression, indicating a reduction in matrix degradation and inflammation. The observed cellular responses and gene expression changes substantiate the therapeutic efficacy of prepared hydrogels. Consequently, our study showed the healing effect of alginate-based hydrogel containing Curcumin on skin injuries.
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Curcumina , Hidrogéis , Animais , Hidrogéis/farmacologia , Curcumina/farmacologia , Alginatos/farmacologia , Cicatrização , Perfilação da Expressão GênicaRESUMO
Recent breakthroughs in developing human-relevant organotypic models led to the building of highly resemblant tissue constructs that hold immense potential for transplantation, drug screening, and disease modeling. Despite the progress in fine-tuning stem cell multilineage differentiation in highly controlled spatiotemporal conditions and hosting microenvironments, 3D models still experience naive and incomplete morphogenesis. In particular, existing systems and induction protocols fail to maintain stem cell long-term potency, induce high tissue-level multicellularity, or drive the maturity of stem cell-derived 3D models to levels seen in their in vivo counterparts. In this review, we highlight the use of extracellular matrix (ECM)-derived biomaterials in providing stem cell niche-mimicking microenvironment capable of preserving stem cell long-term potency and inducing spatial and region-specific differentiation. We also examine the maturation of different 3D models, including organoids, encapsulated in ECM biomaterials and provide looking-forward perspectives on employing ECM biomaterials in building more innovative, transplantable, and functional organs.
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Chronic wounds are challenging to heal and increase global mortality. The effectiveness of skin graft is limited by rejection, fibrosis, and inadequate donor site. Multifunctionalised-hydrogel skin substitutes promoted higher wound healing by maintaining the moisture microenvironment and permit gas exchange/nourishment in prolong cell viability/activity. The purpose of this study was to evaluate a skin substitute using two strategies; via injectable and 3D bioprinting technique. New hydrogel formulations that composed of gelatin (GE) and polyvinyl-alcohol (PVA) were constructed using a pre-mix crosslinking approach with genipin (GNP) to generate the biodegradable and biocompatible skin substitute with reduced secondary traumatic wound. GPVA5_GNP (6% GE: 5% PVA crosslinked with GNP) was the most stable hydrogel for wound healing application with the longest enzymatic degradation and stable hydrogel for absorption of excess wound exudates. Primary human dermal fibroblasts (HDFs) migrated extensively through 3D bioprinted hydrogels with larger average pore sizes and interconnected pores than injectable hydrogels. Moreover, 3D bioprinted GPVA hydrogels were biocompatible with HDFs and demonstrated > 90% cell viability. HDFs maintained their phenotype and positively expressed collagen type-I, vinculin, short and dense F-actin, alpha-smooth muscle actin, and Ki67. Additionally, the presence of GNP demonstrated antioxidant capacity and high-ability of angiogenesis. The utilisation of the 3D bioprinting (layer-by-layer) approach did not compromise the HDFs' growth capacity and biocompatibility with selected bioinks. In conclusion, it allows the cell encapsulation sustainability in a hydrogel matrix for a longer period, in promoting tissue regeneration and accelerating healing capacity, especially for difficult or chronic wound.
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Bioimpressão , Pele Artificial , Humanos , Gelatina , Álcool de Polivinil , Bioimpressão/métodos , Hidrogéis , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
BACKGROUND: Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. The lack of effective diabetic wound dressings has been a significant problem in DFU management. In this study, we aim to establish a phlorotannin-incorporated nanofibre system and determine its potential in accelerating hyperglycaemic wound healing. METHODS: The effective dose of Ecklonia cava phlorotannins (ECP) for hyperglycaemic wound healing was determined prior to phlorotannin nanofibre fabrication using polyvinyl-alcohol (PVA), polyvinylpyrrolidone (PVP), and ECP. Vapour glutaraldehyde was used for crosslinking of the PVA/PVP nanofibres. The phlorotannin nanofibres were characterised, and their safety and cytocompatibility were validated. Next, the wound healing effect of phlorotannin nanofibres was determined with 2D wound scratch assay, whereas immunofluorescence staining of Collagen-I (Col-I) and Cytokeratin-14 (CK-14) was performed in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK), respectively. RESULTS: Our results demonstrated that 0.01 µg/mL ECP significantly improved hyperglycaemic wound healing without compromising cell viability and proliferation. Among all nanofibres, PVA/PVP/0.01 wt% ECP nanofibres exhibited the best hyperglycaemic wound healing effect. They displayed a diameter of 334.7 ± 10.1 nm, a porosity of 40.7 ± 3.3%, and a WVTR of 1718.1 ± 32.3 g/m2/day. Besides, the FTIR spectra and phlorotannin release profile validated the successful vapour glutaraldehyde crosslinking and ECP incorporation. We also demonstrated the potential of phlorotannin nanofibres as a non-cytotoxic wound dressing as they support the viability and proliferation of both HDF and HEK. Furthermore, phlorotannin nanofibres significantly ameliorated the impaired hyperglycaemic wound healing and restored the hyperglycaemic-induced Col-I reduction in HDF. CONCLUSION: Taken together, our findings show that phlorotannin nanofibres have the potential to be used as a diabetic wound dressing.
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Diabetes Mellitus , Hiperglicemia , Nanofibras , Humanos , Glutaral/farmacologia , Cicatrização , Diabetes Mellitus/tratamento farmacológico , Colágeno Tipo IRESUMO
Introduction: A regenerative strategy employing extracellular matrix (ECM)-based biomaterials and stem cells provide a better approach to mimicking the three-dimensional (3D) microenvironment of intervertebral disc for endogenous tissue regeneration. However, there is currently limited understanding regarding the human Wharton Jelly derived-mesenchymal stem cells (hWJ-MSCs) towards nucleus pulposus (NP)-like cells. Our study focused on the development of 3D bioengineered hydrogel based on the predominant ECM of native NP, including type II collagen (COLII) and hyaluronic acid (HA), which aims to tailor the needs of the microenvironment in NP. Methods: We have fabricated a 3D hydrogel using from COLII enriched with HA by varying the biomacromolecule concentration and characterised it for degradation, stability and swelling properties. The WJ-MSC was then encapsulated in the hydrogel system to guide the cell differentiation into NP-like cells. Results: We successfully fabricated COLII hydrogel (2 mg/ml) and HA 10 mg/ml at a weight ratio of HA and COLII at 1:9 and 4.5:9, and both hydrogels physically maintained their 3D sphere-shaped structure after complete gelation. The higher composition of HA in the hydrogel system indicated a higher water intake capacity in the hydrogel with a higher amount of HA. All hydrogels showed over 60% hydrolytic stability over a month. The hydrogel showed an increase in degradation on day 14. The hWJ-MSCs encapsulated in hydrogel showed a round morphology shape that was homogenously distributed within the hydrogel of both groups. The viability study indicated a higher cell growth of hWJ-MSCs encapsulated in all hydrogel groups until day 14. Discussion: Overall, our findings demonstrate that HA/COLII hydrogel provides an optimal swelling capacity, stability, degradability, and non-cytotoxic, thus mimics the NP microenvironment in guiding hWJ-MSCs towards NP phenotype, which is potentially used as an advanced cell delivery system for intervertebral disc regeneration.
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Respiratory diseases have a major impact on global health. The airway epithelium, which acts as a frontline defence, is one of the most common targets for inhaled allergens, irritants, or micro-organisms to enter the respiratory system. In the tissue engineering field, biomaterials play a crucial role. Due to the continuing high impact of respiratory diseases on society and the emergence of new respiratory viruses, in vitro airway epithelial models with high microphysiological similarities that are also easily adjustable to replicate disease models are urgently needed to better understand those diseases. Thus, the development of biomaterial scaffolds for the airway epithelium is important due to their function as a cell-support device in which cells are seeded in vitro and then are encouraged to lay down a matrix to form the foundations of a tissue for transplantation. Studies conducted in in vitro models are necessary because they accelerate the development of new treatments. Moreover, in comparatively controlled conditions, in vitro models allow for the stimulation of complex interactions between cells, scaffolds, and growth factors. Based on recent studies, the biomaterial scaffolds that have been tested in in vitro models appear to be viable options for repairing the airway epithelium and avoiding any complications. This review discusses the role of biomaterial scaffolds in in vitro airway epithelium models. The effects of scaffold, physicochemical, and mechanical properties in recent studies were also discussed.
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Materiais Biocompatíveis , Doenças Respiratórias , Humanos , Materiais Biocompatíveis/química , Células Epiteliais/metabolismo , Epitélio , Sistema Respiratório , Engenharia Tecidual , Doenças Respiratórias/metabolismo , Alicerces Teciduais/químicaRESUMO
Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to address the dilemma in current dental treatments faced by clinicians in order to repair or replace injured and diseased tissues. The exploration of 3D bioprinting technology provides high reproducibility and precise control of the bioink containing the desired cells and biomaterial over the architectural and dimensional features of the scaffolds in fabricating functional tissue constructs that are specific to the patient treatment need. In recent years, the dental applications of different 3D bioprinting techniques, types of novel bioinks, and the types of cells used have been extensively explored. Most of the findings noted significant challenges compared to the non-biological 3D printing approach in constructing the bioscaffolds that mimic native tissues. Hence, this review focuses solely on the implementation of 3D bioprinting techniques and strategies based on cell-laden bioinks. It discusses the in vitro applications of 3D-bioprinted scaffolds on cell viabilities, cell functionalities, differentiation ability, and expression of the markers as well as the in vivo evaluations of the implanted bioscaffolds on the animal models for bone, periodontal, dentin, and pulp tissue regeneration. Finally, it outlines some perspectives for future developments in dental applications.
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Materiais Biocompatíveis , Bioimpressão , Animais , Reprodutibilidade dos Testes , Diferenciação Celular , Sobrevivência CelularRESUMO
The skin is known to be the largest organ in the human body, while also being exposed to environmental elements. This indicates that skin is highly susceptible to physical infliction, as well as damage resulting from medical conditions such as obesity and diabetes. The wound management costs in hospitals and clinics are expected to rise globally over the coming years, which provides pressure for more wound healing aids readily available in the market. Recently, nanomaterials have been gaining traction for their potential applications in various fields, including wound healing. Here, we discuss various inorganic nanoparticles such as silver, titanium dioxide, copper oxide, cerium oxide, MXenes, PLGA, PEG, and silica nanoparticles with their respective roles in improving wound healing progression. In addition, organic nanomaterials for wound healing such as collagen, chitosan, curcumin, dendrimers, graphene and its derivative graphene oxide were also further discussed. Various forms of nanoparticle drug delivery systems like nanohydrogels, nanoliposomes, nanofilms, and nanoemulsions were discussed in their function to deliver therapeutic agents to wound sites in a controlled manner.
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Introduction: Plenty of biomaterials have been studied for their application in skin tissue engineering. Currently, gelatin-hydrogel is used to support three-dimensional (3D) skin in vitro models. However, mimicking the human body conditions and properties remains a challenge and gelatin-hydrogels have low mechanical properties and undergo rapid degradation rendering them not suitable for 3D in vitro cell culture. Nevertheless, changing the concentration of hydrogels could overcome this issue. Thus, we aim to investigate the potential of gelatin hydrogel with different concentrations crosslinked with genipin to promote human epidermal keratinocytes and human dermal fibroblasts culture to develop a 3D-in vitro skin model replacing animal models. Methods: Briefly, the composite gelatin hydrogels were fabricated using different concentrations as follows 3%, 5%, 8%, and 10% crosslinked with 0.1% genipin or non-crosslinked. Both physical and chemical properties were evaluated. Results and discussion: The crosslinked scaffolds showed better properties, including porosity and hydrophilicity, and genipin was found to enhance the physical properties. Furthermore, no alteration was prominent in both formulations of CL_GEL 5% and CL_GEL8% after genipin modification. The biocompatibility assays showed that all groups promoted cell attachment, cell viability, and cell migration except for the CL_GEL10% group. The CL_GEL5% and CL_GEL8% groups were selected to develop a bi-layer 3D-in vitro skin model. The immunohistochemistry (IHC) and hematoxylin and eosin staining (H&E) were performed on day 7, 14, and 21 to evaluate the reepithelization of the skin constructs. However, despite satisfactory biocompatibility properties, neither of the selected formulations, CL_GEL 5% and CL_GEL 8%, proved adequate for creating a bi-layer 3D in-vitro skin model. While this study provides valuable insights into the potential of gelatin hydrogels, further research is needed to address the challenges associated with their use in developing 3D skin models for testing and biomedical applications.
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3D bioprinting technology is a well-established and promising advanced fabrication technique that utilizes potential biomaterials as bioinks to replace lost skin and promote new tissue regeneration. Cutaneous regenerative biomaterials are highly commended since they benefit patients with larger wound sizes and irregular wound shapes compared to the painstaking split-skin graft. This study aimed to fabricate biocompatible, biodegradable, and printable bioinks as a cutaneous substitute that leads to newly formed tissue post-transplantation. Briefly, gelatin (GE) and polyvinyl alcohol (PVA) bioinks were prepared in various concentrations (w/v); GE (6% GE: 0% PVA), GPVA3 (6% GE: 3% PVA), and GPVA5 (6% GE: 5% PVA), followed by 0.1% (w/v) genipin (GNP) crosslinking to achieve optimum printability. According to the results, GPVA5_GNP significantly presented at least 590.93 ± 164.7% of swelling ratio capacity and optimal water vapor transmission rate (WVTR), which is <1500 g/m2/h to maintain the moisture of the wound microenvironment. Besides, GPVA5_GNP is also more durable than other hydrogels with the slowest biodegradation rate of 0.018 ± 0.08 mg/h. The increasing amount of PVA improved the rheological properties of the hydrogels, leading the GPVA5_GNP to have the highest viscosity, around 3.0 ± 0.06 Pa.s. It allows a better performance of bioinks printability via extrusion technique. Moreover, the cross-section of the microstructure hydrogels showed the average pore sizes >100 µm with excellent interconnected porosity. X-ray diffraction (XRD) analysis showed that the hydrogels maintain their amorphous properties and were well-distributed through energy dispersive X-ray after crosslinking. Furthermore, there had no substantial functional group changes, as observed by Fourier transform infrared spectroscopy, after the addition of crosslinker. In addition, GPVA hydrogels were biocompatible to the cells, effectively demonstrating >90% of cell viability. In conclusion, GPVA hydrogels crosslinked with GNP, as prospective bioinks, exhibited the superior properties necessary for wound healing treatment.
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Skin tissue engineering possesses great promise in providing successful wound injury and tissue loss treatments that current methods cannot treat or achieve a satisfactory clinical outcome. A major field direction is exploring bioscaffolds with multifunctional properties to enhance biological performance and expedite complex skin tissue regeneration. Multifunctional bioscaffolds are three-dimensional (3D) constructs manufactured from natural and synthetic biomaterials using cutting-edge tissue fabrication techniques incorporated with cells, growth factors, secretomes, antibacterial compounds, and bioactive molecules. It offers a physical, chemical, and biological environment with a biomimetic framework to direct cells toward higher-order tissue regeneration during wound healing. Multifunctional bioscaffolds are a promising possibility for skin regeneration because of the variety of structures they provide and the capacity to customise the chemistry of their surfaces, which allows for the regulated distribution of bioactive chemicals or cells. Meanwhile, the current gap is through advanced fabrication techniques such as computational designing, electrospinning, and 3D bioprinting to fabricate multifunctional scaffolds with long-term safety. This review stipulates the wound healing processes used by commercially available engineered skin replacements (ESS), highlighting the demand for a multifunctional, and next-generation ESS replacement as the goals and significance study in tissue engineering and regenerative medicine (TERM). This work also scrutinise the use of multifunctional bioscaffolds in wound healing applications, demonstrating successful biological performance in the in vitro and in vivo animal models. Further, we also provided a comprehensive review in requiring new viewpoints and technological innovations for the clinical application of multifunctional bioscaffolds for wound healing that have been found in the literature in the last 5 years.
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Wound care management is incredibly challenging for chronic injuries, despite the availability of various types of wound care products in the market. However, most current wound-healing products do not attempt to mimic the extracellular matrix (ECM) and simply provide a barrier function or wound covering. Collagen is a natural polymer that involves a major constituent of the ECM protein, thus making it attractive to be used in skin tissue regeneration during wound healing. This study aimed to validate the biological safety assessments of ovine tendon collagen type-I (OTC-I) in the accredited laboratory under ISO and GLP settings. It is important to ensure that the biomatrix will not stimulate the immune system to produce any adverse reaction. Therefore, we successfully extracted collagen type-I from the ovine tendon (OTC- I) using a method of low-concentration acetic acid. The three-dimensional (3D) skin patch of spongy OTC-I was a soft and white colour, being tested for safety and biocompatibility evaluations based on ISO 10993-5, ISO 10993-10, ISO 10993-11, ISO 10993-23, USP 40 <151>, and OECD 471. For the dermal sensitisation and acute irritation test, none of the tested animals displayed any erythema or oedema effects (p > 0.005). In addition, there were no abnormalities detected in the organ of the mice after being exposed to OTC-I; additionally, no morbidity and mortality were observed in the acute systemic test under the guideline of ISO 10993-11:2017. The grade 0 (non-reactive) based on ISO 10993-5:2009 was graded for the OTC-I at 100% concentration and the mean number of the revertant colonies did not exceed 2-fold of the 0.9% w/v sodium chloride compared to the tester strains of S. typhimurium (TA100, TA1535, TA98, TA1537), and E. coli (WP2 trp uvrA). Our study revealed that OTC-I biomatrix does not present any adverse effects or abnormalities in the present study's condition of induced skin sensitization effect, mutagenic and cytotoxic towards cells and animals. This biocompatibility assessment demonstrated a good agreement between in vitro and in vivo results regarding the absence of skin irritation and sensitization potential. Therefore, OTC-I biomatrix is a potential medical device candidate for future clinical trials focusing on wound care management.
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Burns are a widespread global public health traumatic injury affecting many people worldwide. Non-fatal burn injuries are a leading cause of morbidity, resulting in prolonged hospitalization, disfigurement, and disability, often with resulting stigma and rejection. The treatment of burns is aimed at controlling pain, removing dead tissue, preventing infection, reducing scarring risk, and tissue regeneration. Traditional burn wound treatment methods include the use of synthetic materials such as petroleum-based ointments and plastic films. However, these materials can be associated with negative environmental impacts and may not be biocompatible with the human body. Tissue engineering has emerged as a promising approach to treating burns, and sustainable biomaterials have been developed as an alternative treatment option. Green biomaterials such as collagen, cellulose, chitosan, and others are biocompatible, biodegradable, environment-friendly, and cost-effective, which reduces the environmental impact of their production and disposal. They are effective in promoting wound healing and reducing the risk of infection and have other benefits such as reducing inflammation and promoting angiogenesis. This comprehensive review focuses on the use of multifunctional green biomaterials that have the potential to revolutionize the way we treat skin burns, promoting faster and more efficient healing while minimizing scarring and tissue damage.
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Numerous biomaterials have been developed over the years to enhance the outcomes of endoscopic sinus surgery (ESS) for patients with chronic rhinosinusitis. These products are specifically designed to prevent postoperative bleeding, optimize wound healing, and reduce inflammation. However, there is no singular material on the market that can be deemed the optimal material for the nasal pack. We systematically reviewed the available evidence to assess the functional biomaterial efficacy after ESS in prospective studies. The search was performed using predetermined inclusion and exclusion criteria, and 31 articles were identified in PubMed, Scopus, and Web of Science. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess each study's risk of bias. The studies were critically analyzed and categorized into types of biomaterial and functional properties, according to synthesis without meta-analysis (SWiM) guidelines. Despite the heterogeneity between studies, it was observed that chitosan, gelatin, hyaluronic acid, and starch-derived materials exhibit better endoscopic scores and significant potential for use in nasal packing. The published data support the idea that applying a nasal pack after ESS improves wound healing and patient-reported outcomes.