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.
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.
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.