Health care and medicine were revolutionized in recent years by the development of biomaterials, such as stents, implants, personalized drug delivery systems, engineered grafts, cell sheets, and other transplantable materials. These materials not only support the growth of cells before transplantation but also serve as replacements for damaged tissues in vivo. Among the various biomaterials available, those made from natural biological sources such as extracellular proteins (collagen, fibronectin, laminin) have shown significant benefits, and thus are widely used. However, routine biomaterial-based research requires copious quantities of proteins and the use of pure and intact extracellular proteins could be highly cost ineffective. Gelatin is a molecular derivative of collagen obtained through the irreversible denaturation of collagen proteins. Gelatin shares a very close molecular structure and function with collagen and thus is often used in cell and tissue culture to replace collagen for biomaterial purposes. Recent technological advancements such as additive manufacturing, rapid prototyping, and three-dimensional printing, in general, have resulted in great strides toward the generation of functional gelatin-based materials for medical purposes. In this review, the structural and molecular similarities of gelatin to other extracellular matrix proteins are compared and analyzed. Current strategies for gelatin crosslinking and production are described and recent applications of gelatin-based biomaterials in cell culture and tissue regeneration are discussed. Finally, recent improvements in gelatin-based biomaterials for medical applications and future directions are elaborated. Impact statement In this study, we described gelatin's biochemical properties and compared its advantages and drawbacks over other extracellular matrix proteins and polymers used for biomaterial application. We also described how gelatin can be used with other polymers in creating gelatin composite materials that have enhanced mechanical properties, increased biocompatibility, and boosted bioactivity, maximizing its benefits for biomedical purposes. The article is relevant, as it discussed not only the chemistry of gelatin, but also listed the current techniques in gelatin/biomaterial manufacturing and described the most recent trends in gelatin-based biomaterials for biomedical applications.

Engineering and Functionalization of Gelatin Biomaterials: From Cell Culture to Medical Applications.

https://hal.archives-ouvertes.fr/hal-02991710/document

3D Extracellular Matrix Mimics: Fundamental Concepts and Role of Materials Chemistry to Influence Stem Cell Fate

Due to its unique properties, collagen is used in the growing fields of pharmaceutical and biomedical devices, as well as in the fields of nutraceuticals, cosmeceuticals, food and beverages. Collagen also represents a valid resource for bioplastics and biomaterials, to be used in the emerging health sectors. Recently, marine organisms have been considered as promising sources of collagen, because they do not harbor transmissible disease. In particular, fish biomass as well as by-catch organisms, such as undersized fish, jellyfish, sharks, starfish, and sponges, possess a very high collagen content. The use of discarded and underused biomass could contribute to the development of a sustainable process for collagen extraction, with a significantly reduced environmental impact. This addresses the European zero-waste strategy, which supports all three generally accepted goals of sustainability: sustainable economic well-being, environmental protection, and social well-being. A zero-waste strategy would use far fewer new raw materials and send no waste materials to landfills. In this review, we present an overview of the studies carried out on collagen obtained from by-catch organisms and fish wastes. Additionally, we discuss novel technologies based on thermoplastic processes that could be applied, likewise, as marine collagen treatment.

Marine Collagen from Alternative and Sustainable Sources: Extraction, Processing and Applications.

There is a vast number of treatments on the market for the management of wounds and burns, representing a multi-billion dollar industry worldwide. These include conventional wound dressings, dressings that incorporate growth factors to stimulate and facilitate the wound healing process, and skin substitutes that incorporate patient-derived cells. This article will review the more established, and the recent advances in the use of biomaterials for wound healing therapies, and their future direction.

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/221874/Development and use of biomaterials as wound healing therapies.pdf

Development and use of biomaterials as wound healing therapies.

Significance: A 2018 retrospective analysis of Medicare beneficiaries identified that ∼8.2 million people had wounds with or without infections. Medicare cost estimates for acute and chronic wound treatments ranged from $28.1 billion to $96.8 billion. Highest expenses were for surgical wounds followed by diabetic foot ulcers, with a higher trend toward costs associated with outpatient wound care compared with inpatient. Increasing costs of health care, an aging population, recognition of difficult-to-treat infection threats such as biofilms, and the continued threat of diabetes and obesity worldwide make chronic wounds a substantial clinical, social, and economic challenge. Recent Advances: Chronic wounds are not a problem in an otherwise healthy population. Underlying conditions ranging from malnutrition, to stress, to metabolic syndrome, predispose patients to chronic, nonhealing wounds. From an economic point of view, the annual wound care products market is expected to reach $15-22 billion by 2024. The National Institutes of Health's (NIH) Research Portfolio Online Reporting Tool (RePORT) now lists wounds as a category. Future Directions: A continued rise in the economic, clinical, and social impact of wounds warrants a more structured approach and proportionate investment in wound care, education, and related research.

Human Wounds and Its Burden: An Updated Compendium of Estimates

Collagen is a fibrillar protein that conforms the conjunctive and connective tissues in the human body, essentially skin, joints, and bones. This molecule is one of the most abundant in many of the living organisms due to its connective role in biological structures. Due to its abundance, strength and its directly proportional relation with skin aging, collagen has gained great interest in the cosmetic industry. It has been established that the collagen fibers are damaged with the pass of time, losing thickness and strength which has been strongly related with skin aging phenomena [Colageno para todo. 60 y mas. 2016. http://www.revista60ymas.es/InterPresent1/groups/revistas/documents/binario/ses330informe.pdf.]. As a solution, the cosmetic industry incorporated collagen as an ingredient of different treatments to enhance the user youth and well-being, and some common presentations are creams, nutritional supplement for bone and cartilage regeneration, vascular and cardiac reconstruction, skin replacement, and augmentation of soft skin among others [J App Pharm Sci. 2015;5:123-127]. Nowadays, the biomolecule can be obtained by extraction from natural sources such as plants and animals or by recombinant protein production systems including yeast, bacteria, mammalian cells, insects or plants, or artificial fibrils that mimic collagen characteristics like the artificial polymer commercially named as KOD. Because of its increased use, its market size is valued over USD 6.63 billion by 2025 [Collagen Market By Source (Bovine, Porcine, Poultry, Marine), Product (Gelatin, Hydrolyzed Collagen), Application (Food & Beverages, Healthcare, Cosmetics), By Region, And Segment Forecasts, 2014 - 2025. Grand View Research. http://www.grandviewresearch.com/industry-analysis/collagen-market. Published 2017.]. Nevertheless, there has been little effort on identifying which collagen types are the most suitable for cosmetic purposes, for which the present review will try to enlighten in a general scope this unattended matter.

Collagen: A review on its sources and potential cosmetic applications.

Skin wounds have been extensively studied as their healing represents a critical step towards achieving homeostasis following a traumatic event. Dependent on the severity of the damage, wounds are categorized as either acute or chronic. To date, chronic wounds have the highest economic impact as long term increases wound care costs. Chronic wounds affect 6.5 million patients in the United States with an annual estimated expense of $25 billion for the health care system. Among wound treatment categories, active wound care represents the fastest-growing category due to its specific actions and lower costs. Within this category, proteases from various sources have been used as successful agents in debridement wound care. The wound healing process is predominantly mediated by matrix metalloproteinases (MMPs) that, when dysregulated, result in defective wound healing. Therapeutic activity has been described for animal secretions including fish epithelial mucus, maggot secretory products and snake venom, which contain secreted proteases (SPs). No further alternatives for use, sources or types of proteases used for wound healing have been found in the literature to date. Through the present review, the context of enzymatic wound care alternatives will be discussed. In addition, substrate homology of SPs and human MMPs will be compared and contrasted. The purpose of these discussions is to identify and propose the stages of wound healing in which SPs may be used as therapeutic agents to improve the wound healing process.

/pdf/practical-context-of-enzymatic-treatment-for-wound-healing-a-2e6q10jgdj.pdf

María Isabela Avila Rodríguez

Papers

Collagen: A review on its sources and potential cosmetic applications.

Practical context of enzymatic treatment for wound healing: A secreted protease approach (Review).