Biotechnological Production and Application of Hyaluronan

Schiraldi, Chiara; Gatta, Annalisa La; Rosa, Mario De

doi:10.5772/10271

Cited by 49 publications

(64 citation statements)

References 88 publications

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“…HA is prevalently distributed around cells, where it forms a pericellular coating, and in the extracellular matrix (ECM) of connective tissues [61,82]. Approximately the 50% of the total HA resides in the skin, both in the dermis and the epidermis [82]. Synovial joint fluid and eye vitreous body, being mainly composed of ECM, contain important amount of hyaluronan: 3-4 mg/mL and 0.1 mg/mL (wet weight), respectively [61,82].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

“…), endogenous HA sustains wound healing and reepithelialization processes thanks to several actions including the promotion of fibroblast proliferation, migration, and adhesion to the wound site, and the stimulation of collagen production [210]. For this reason, HA is used in topical formulations (such as Connettivina® by Fidia) to treat skin irritations and wounds such as abrasions, post-surgical incisions, metabolic and vascular ulcers, and burns [82,[210][211][212][213]. Currently, HA derivatives [173,182,214,215] and HAbased wound dressings, films or hydrogels enriched with other therapeutic agents [216,217] are being evaluated in order to understand if the cicatrisation process could be further enhanced.…”

Section: Wound Treatmentmentioning

confidence: 99%

“…Approximately the 50% of the total HA resides in the skin, both in the dermis and the epidermis [82]. Synovial joint fluid and eye vitreous body, being mainly composed of ECM, contain important amount of hyaluronan: 3-4 mg/mL and 0.1 mg/mL (wet weight), respectively [61,82]. Moreover, HA is also abundant in the umbilical cord (4 mg/mL), where it represents the major component of Wharton's jelly together with chondroitin sulfate [87,88].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

“…Hyaluronan is widely diffused in nature: it is present in humans, animals -such as, rabbits, bovines, roosters-, bacteria -such as Streptococcus equi, Streptococcus zooepidermicus, Streptococcus equisimilis, Streptococcus pyogenes, Streptococcus uberis, Pasteurella multocida- [49,[80][81][82], algae -such as the green algae Chlorella sp. infected by the Chlorovirus [49,83]-, yeasts such as Cryptococcus neoformans- [49] and molluscs [84].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

See 4 more Smart Citations

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Wound Treatmentmentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

See 3 more Smart Citations

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Production of glucuronic acid‐based polysaccharides by microbial fermentation for biomedical applications

Cimini

Rosa

Schiraldi

2011

Biotechnology Journal

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This review provides an overview of the properties, different biosynthetic machineries, and biotechnological production processes of four microbially derived glucuronic acid-based polysaccharides that are of interest for diverse biomedical purposes. In particular, the utilization of hyaluronic acid and heparin sulfate in high-value medical applications is already well established, whereas chondroitin sulfate and alginate show high potential within this ever-growing field. Furthermore, new strategies exploiting genetically engineered microorganisms generated through improving naturally existing pathways or de novo designed ones are described. These new developments result in increased fermentation titers, and thereby, pave the way towards feasible, or at least improved, process economy. Moreover, these strategies also allow for the future possibility of producing tailor-made biopolymers with specified characteristics, even novel molecules.

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Hyaluronan dermal fillers via crosslinking with 1,4‐butandiol diglycidyl ether: Exploitation of heterogeneous reaction conditions

et al. 2015

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Most of hyaluronan (HA)-based dermal fillers currently available on the market are produced through biopolymer crosslinking with 1,4-butandiol diglycidyl ether (BDDGE). Chemical modification is usually performed on the biopolymer dissolved in a highly alkaline aqueous medium (homogeneous conditions). Heterogeneous conditions for HA reaction with BDDGE were exploited here to obtain competitive HA fillers and to assess potential improvements in production process. Optimal parameters for effective reaction accomplishment were evaluated (e.g., medium composition, temperature and time of reaction). HA was modified with increasing BDDGE/HA equivalents (7-14%) achieving 66-74% (w/w) biopolymer insolubility. Hydrogels exhibited high swelling extent and outstanding resistance to enzymatic degradation decreasing and improving according to crosslinking degree, respectively. Once suspended in physiological solution (20 mg/mL), these products directly formed easy-to-extrude gels through 27-29 G needles. Gel particle dimensions were in the range 10-1000 µm. Rheological analyses revealed decreasing viscosity with the shear rate and G' values in the range 1200-1700 Pa. Overall, results of the in vitro characterization demonstrated the attainment of crosslinked HA particles suitable for application as dermal fillers. These new gels proved superior to similar commercialized products in terms of stability to enzymatic hydrolysis. Further, the protocol assessed allowed interesting improvements over conventional manufacturing procedures.

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Biotechnological Production and Application of Hyaluronan

Cited by 49 publications

References 88 publications

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Production of glucuronic acid‐based polysaccharides by microbial fermentation for biomedical applications

Hyaluronan dermal fillers via crosslinking with 1,4‐butandiol diglycidyl ether: Exploitation of heterogeneous reaction conditions

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