Type I collagen is commonly recognized as the gold standard biomaterial for the manufacturing of medical devices for health-care related applications. In recent years, with the final aim of developing scaffolds with optimal bioactivity, even more studies focused on the influence of processing parameters on collagen properties, since processing can strongly affect the architecture of collagen at various length scales and, consequently, scaffolds macroscopic performances. The ability to finely tune scaffold properties in order to closely mimic the tissues' hierarchical features, preserving collagen's natural conformation, is actually of great interest. In this work, the effect of the pepsin-based extraction step on the material final properties was investigated. Thus, the physico-chemical properties of fibrillar type I collagens upon being extracted under various conditions were analyzed in depth. Correlations of collagen structure at the supramolecular scale with its microstructural properties were done, confirming the possibility of tuning rheological, viscoelastic and degradation properties of fibrillar type I collagen.
Collagen Type I , Pepsin A , Horses , Animals , Pepsin A/metabolism , Collagen/chemistry , Fibrillar Collagens/chemistry , Tendons/chemistry
Soft tissues diseases significantly affect patients quality of life and usually require targeted, costly and sometimes constant interventions. With the average lifetime increase, a proportional increase of age-related soft tissues diseases has been witnessed. Due to this, the last two decades have seen a tremendous demand for minimally invasive one-step resolutive procedures. Intensive scientific and industrial research has led to the recognition of injectable formulations as a new advantageous approach in the management of complex diseases that are challenging to treat with conventional strategies. Among them, collagen-based products are revealed to be one of the most promising among bioactive biomaterials-based formulations. Collagen is the most abundant structural protein of vertebrate connective tissues and, because of its structural and non-structural role, is one of the most widely used multifunctional biomaterials in the health-related sectors, including medical care and cosmetics. Indeed, collagen-based formulations are historically considered as the "gold standard" and from 1981 have been paving the way for the development of a new generation of fillers. A huge number of collagen-based injectable products have been approved worldwide for clinical use and have routinely been introduced in many clinical settings for both aesthetic and regenerative surgery. In this context, this review article aims to be an update on the clinical outcomes of approved collagen-based injectables for both aesthetic and regenerative medicine of the last 20 years with an in-depth focus on their safety and effectiveness for the treatment of diseases of the integumental, gastrointestinal, musculoskeletal, and urogenital apparatus.
Collagen is one of the most widely used biomaterials in health-related sectors. The industrial production of collagen mostly relies on its extraction from mammals, but several issues limited its use. In the last two decades, marine organisms attracted interest as safe, abundant, and alternative source for collagen extraction. In particular, the possibility to valorize the huge quantity of fish industry waste and byproducts as collagen source reinforced perception of fish collagen as eco-friendlier and particularly attractive in terms of profitability and cost-effectiveness. Especially fish byproducts from eco-sustainable aquaponics production allow for fish biomass with additional added value and controlled properties over time. Among fish species, Oreochromis niloticus is one of the most widely bred fish in large-scale aquaculture and aquaponics systems. In this work, type I collagen was extracted from aquaponics-raised Tilapia skin and characterized from a chemical, physical, mechanical, and biological point of view in comparison with a commercially available analog. Performed analysis confirmed that the proprietary process optimized for type I collagen extraction allowed to isolate pure native collagen and to preserve its native conformational structure. Preliminary cellular studies performed with mouse fibroblasts indicated its optimal biocompatibility. All data confirmed the eligibility of the extracted Tilapia-derived native type I collagen as a biomaterial for healthcare applications.
Urethral stenosis is a pathological condition that consists in the narrowing of the urethral lumen because of the formation of scar tissue. Unfortunately, none of the current surgical approaches represent an optimal solution because of the high stricture recurrence rate. In this context, we preliminarily explored the potential of an insoluble type-I collagen from horse tendon as scaffolding material for the development of innovative devices for the regeneration of injured urethral tracts. Non-porous collagen-based substrates were produced and optimized, in terms of crosslinking density of the macromolecular structure, to either provide mechanical properties compliant with the urinary tract physiological stress and better sustain tissue regeneration. The effect of the adopted crosslinking strategy on the protein integrity and on the substrate physical-chemical, mechanical and biological properties was investigated in comparison with a decellularized matrix from porcine small intestinal submucosa (SIS patch), an extensively used xenograft licensed for clinical use in urology. The optimized production protocols allowed the preservation of the type I collagen native structure and the realization of a substrate with appealing end-use properties. The biological response, preliminarily investigated by immunofluorescence experiments on human adult renal stem/progenitor cells until 28 days, showed the formation of a stem-cell monolayer within 14 days and the onset of spheroids within 28 days. These results suggested the great potential of the collagen-based material for the development of scaffolds for urethral plate regeneration and for in vitro cellular studies.
Biological materials found in living organisms, many of which are proteins, feature a complex hierarchical organization. Type I collagen, a fibrous structural protein ubiquitous in the mammalian body, provides a striking example of such a hierarchical material, with peculiar architectural features ranging from the amino acid sequence at the nanoscale (primary structure) up to the assembly of fibrils (quaternary structure) and fibers, with lengths of the order of microns. Collagen plays a dominant role in maintaining the biological and structural integrity of various tissues and organs, such as bone, skin, tendons, blood vessels, and cartilage. Thus, "artificial" collagen-based fibrous assemblies, endowed with appropriate structural properties, represent ideal substrates for the development of devices for tissue engineering applications. In recent years, with the ultimate goal of developing three-dimensional scaffolds with optimal bioactivity able to promote both regeneration and functional recovery of a damaged tissue, numerous studies focused on the capability to finely modulate the scaffold architecture at the microscale and the nanoscale in order to closely mimic the hierarchical features of the extracellular matrix and, in particular, the natural patterning of collagen. All of these studies clearly show that the accurate characterization of the collagen structure at the submolecular and supramolecular levels is pivotal to the understanding of the relationships between the nanostructural/microstructural properties of the fabricated scaffold and its macroscopic performance. Several studies also demonstrate that the selected processing, including any crosslinking and/or sterilization treatments, can strongly affect the architecture of collagen at various length scales. The aim of this review is to highlight the most recent findings on the development of collagen-based scaffolds with optimized properties for tissue engineering. The optimization of the scaffolds is particularly related to the modulation of the collagen architecture, which, in turn, impacts on the achieved bioactivity.
Type I collagen has always aroused great interest in the field of life-science and bioengineering, thanks to its favorable structural properties and bioactivity. For this reason, in the last five decades it has been widely studied and employed as biomaterial for the manufacture of implantable medical devices. Commonly used sources of collagen are represented by bovine and swine but their applications are limited because of the zoonosis transmission risks, the immune response and the religious constrains. Thus, type-I collagen isolated from horse tendon has recently gained increasing interest as an attractive alternative, so that, although bovine and porcine derived collagens still remain the most common ones, more and more companies started to bring to market a various range of equine collagen-based products. In this context, this work aims to overview the properties of equine collagen making it particularly appealing in medicine, cosmetics and pharmaceuticals, as well as its main biomedical applications and the currently approved equine collagen-based medical devices, focusing on experimental studies and clinical trials of the last 15 years. To the best of our knowledge, this is the first review focusing on the use of equine collagen, as well as on equine collagen-based marketed products for healthcare.
In the last two decades, marine collagen has attracted great scientific and industrial interest as a 'blue resource', with potential for use in various health-related sectors, such as food, medicine, pharmaceutics and cosmetics. In particular, the large availability of polluting by-products from the fish processing industry has been the key factor driving the research towards the conversion of these low cost by-products (e.g. fish skin and scales) into collagen-based products with high added value and low environmental impact. After addressing the extraction of collagen from aquatic sources and its physicochemical properties, this review focuses on the use of marine collagen and its derivatives (e.g. gelatin and peptides) in different healthcare sectors. Particular attention is given to the bioactive properties of marine collagen that are being explored in preclinical and clinical studies, and pave the way to an increased demand for this biomaterial in the next future. In this context, in addition to the use of native collagen for the development of tissue engineering or wound healing devices, particularly relevant is the use of gelatin and peptides for the development of dietary supplements and nutraceuticals, specifically directed to weight management and glycemic control. The marine collagen market is also briefly discussed to highlight the opportunities and the most profitable areas of interest.
Collagen/chemistry , Animals , Aquatic Organisms/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Collagen/metabolism , Collagen/pharmacology , Cosmetics , Dietary Supplements , Humans , Protein Stability , Tissue Engineering , Wound Healing/drug effects
The aim of this work is to evaluate the effects of different extraction and material processing protocols on the collagen structure and hierarchical organization of equine tendons. Wide and Small Angle X-ray Scattering investigations on raw powders and thin films revealed that not only the extraction and purification treatments, but also the processing conditions may affect the extent of the protein crystalline domain and induce a nanoscale "shield effect." This is due to the supramolecular fiber organization, which protects the atomic scale structure from the modifications that occur during fabrication protocols. Moreover, X-ray analyses and Fourier Transform Infrared spectroscopy performed on the biomaterial sheds light on the relationship between processing conditions, triple helical content and the organization in atomic and nanoscale domains. It was found that the mechanical homogenization of the slurry in acidic solution is a treatment that ensures a high content of super-organization of collagen into triple helices and a lower crystalline domain in the material. Finally, mechanical tensile tests were carried out, proving that the acidic solution is the condition which most enhances both mechanical stiffness and supramolecular fiber organization of the films.
