Biomedical Chemistry: Research and Methods 2025, 8(4), e00289

SOME METHODS FOR MANAGING THE DEGRADATION OF BIOMEDICAL IMPLANTABLE MATERIALS BASED ON COLLAGEN AND HYALURONIC ACID

I.S. Rudik*1, A.V. Vasiliev 1,2, A.V. Mironov 3, V.S. Kuznetsova 1, F.F. Losev 1,2

1Central Research Institute of Dentistry and Maxillofacial Surgery, 16 Timur Frunze str., Moscow, 119021; *e-mail: rudik_is@cniis.ru

2Sechenov First Moscow State Medical University, 8 Trubetskaya str., Moscow, 119048 Russia
3National Research Centre “Kurchatov Institute”, 1 Academician Kurchatov sq., Moscow, 123182 Russia

Keywords:hyaluronic acid; degradation; collagen; polymer matrix

DOI:10.18097/BMCRM00289

The whole version of this paper is available in Russian.

The review considers modern approaches to modifying the in vitro degradation kinetics of implantable matrices based on collagen and hyaluronic acid. It includes data presented in 24 of approximately one hundred articles on similar topics found. Special attention is paid to the effect of polymer additives in collagen- and hyaluronic acid-based materials on their degradation rates in hydrolytic and enzymatic environments. The mechanisms of interaction of components and the impact of their structure on degradation processes are described. Approaches to the development of implantable medical devices based on biopolymers with controlled degradation and biocompatibility properties are proposed.

Table 1.  In vitro degradation of collagen and hyaluronic acid based matrices

Main component

Сoncentration of the main component

Modifying components

Modification conditions

Degradation solution

Time, days

t ºС

Reference

Type I collagen (bovine, “Sigma Aldrich”, USA)

2 mg/mL

Crosslinking agent – PEG-DA (20 kDa, “Sigma Aldrich”, USA) 10%.

Photoinitiator (Sigma Aldrich, USA) 0.1%.

Collagen hydrogel was mixed with PEG-DA and photoinitiator solution, and then crosslinked by exposure it to long-wave UV light (365 nm, 5 min).

RPMI-1640 medium with the addition of 10% fetal bovine serum, 2 mmol/L glutamine and 1% antibiotics.

8

37

[11, 24]

Type I collagen (bovine tendon microfibrillar, “Integra LifeSciences”, USA)

6 mg/mL

Hyaluronic acid (Streptococcus zooepidermicus; “Sigma Chemical”, USA) 10 mg/mL (1% масс.)

Crosslinking agent – 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC, “Sigma Chemical”, USA)

The rated quantities of components were mixed and lyophilized at -40ºС. Chemical cross-linking of the scaffold discs was performed using a water-soluble carbodiimide.

Culture medium with the addition of 10% fetal bovine serum and 1% penicillin.

21

37

[12]

Commercial equine type I collagen (“Euroresearch”, Italy)

sponge

Tetrabutylammonium salt of hyaluronic acid

The sponge soaked in 1% wt. HA-TBA aqueous solution was lyophilized. The sponge was then continuously refluxed for 8 hours using acetone.

Сollagenase from Clostridium hystolyticum solution (0.0004% wt.) in Tris–HCl (pH  7.4).

3

37

[9]

Type I bovine telocollagen (“Advanced Biomatrix”, USA)

5 mg/mL

Photoinitiator – riboflavin 5′-phosphate sodium salt hydrate (“Sigma Aldrich”, USA) 0.25 mmol/L

The photoinitiator was added to the collagen solution, and then, was exposed to UV light (365 nm, 1.8 mW/cm2, 10 min, 15 min and 30 min).

Сollagenase from Clostridium type I solution (0.4% wt.) in medium KSFM.

6

25

[13]

Absorbable collagen membranes (“Lando Biomaterials”, China)

membrane

Crosslinking agent – polycaprolactone methacryloyl (3200 Da, “Engineering For Life”, China)

Photoinitiator – 2,4,6-trimethylbenzoyldiphenylphosphinate (TPO, “Engineering For Life”, China) 0.5% wt.

The membrane was impregnated with a solution of TPO in PCLMA and photocured using a 405-nm light source.

Collagenase PBS solution (0.01% wt.), pH  7.4.

28

25

[10]

Methacrylated hyaluronic acid (250 kDa, “Bioiberica”, Spain)

1% wt.

Photoinitiator – Irgacure 2959 (“Sigma Aldrich”, USA) 1% wt.

The rated amount of Irgacure 2959 in HAMA solution was applied to porous scaffolds consisting of poly(D, L-lactide-co-glycolide) and PEG-DA and cured using a photoreactor equipped with five UV lamps (313 nm, 0.095 mW/cm2, 5 min).

PBS (pH  7.4).

10

37

[21]

Methacrylated hyaluronic acid (100 kDa, “LifeCore Biomedical”, USA)

5% wt.

Gallic acid-functionalized hyaluronic acid 5% wt.

Photoinitiator – Irgacure 2959 (“Merck”, Germany) 0.5% wt.

Irgacure 2959 was added to HAMA and mixed with HAGA in a 1:1 ratio. The mixture was crosslinked by exposure it to UV light (365 nm, 25 mW/cm2, 2 min).

Hyaluronidase DPBS solution (50 U/mL), pH 7.4.

7

37

[23]

Methacrylated hyaluronic acid (80–100 kDa, “Biosynth”, USA)

1%, 3%, 5% wt.

Methacrylated gelatin (type B, from bovine skin, “Sigma Aldrich”, USA) 2, 6, 10% wt.

Photoinitiator – Irgacure 2959 (“Sigma Aldrich”, USA) 0.5% wt.

HAMA (DoM = 11%), GelMA (DoM = 40%) were mixed with Irgacure 2959, and then, cured with UV light (365 nm, 4 W/cm2, 10 min).

Collagenase type II PBS solution (0.001% wt.), pH 7.4.

1

37

[19]

Methacrylated hyaluronic acid (2000 kDa, “Kikkoman”, Japan)

1% wt.

Methacrylated gelatin (type B, from porcine skin, “Sigma Aldrich”, USA) 10% wt.

Crosslinking agent – 3-acryloxypropyl silanetriol-functionalized nSi 0.1–1% wt.

Photoinitiator – lithium phenyl-2,4,6-trimethyl-benzoyl phosphinate (LAP, “Sigma Aldrich”, USA) 0.3% wt.

HAMA (DoM = 85 ± 10%), GelMA (DoM = 95 ± 5%) in a 2:1 ratio, crosslinking agent and LAP were mixed. Crosslinking was performed using a UV-photoreactor (280–400 nm, 2 min).

Hyaluronidase PBS solution (2.5 U/mL), pH 7.4.

30

37

[20]

Thiolated hyaluronic acid (400 kDa, “Blafar”, Ireland)

4% wt.

Hyperbranched PEG-DA (10 – 20 kDa, “Sigma Aldrich”, UK) 40% wt.

Solutions of the components in PBS were mixed in a 1:1 ratio. The hydrogel was formed as a result of the reaction of acrylate groups of PEG-DA with thiol groups of hyaluronic acid via the Michael addition reaction.

PBS (pH 7.4).

64

37

[22]

Acrylated hyaluronic acid (10 kDa и 50 kDa, “Lifecore Biomedical”, USA)

0.3 mol/L

Crosslinking agent – poly(ethylene glycol) tetra-thiol

(10 kDa, “Sun Bio”, USA)

0.03 mol/L

Gel formation of acrylated hyaluronic acid and PEG-SH4 occurred as a result of the Michael reaction at a temperature of 37 ºC.

PBS (pH 7.4).

45

37

[17]

Hyaluronidase PBS solution (100 U/mL), pH = 7.4.

45

37

Note. RPMI-1640 medium – mixture of inorganic salts, amino acids, vitamins, glucose and phenol red dissolved in purified water, and sterilized by membrane filtration (pH from 7.0 to 7.4). HA-TBA – tetrabutylammonium salt of hyaluronic acid. PCLМА – polycaprolactone methacryloyl. PBS – phosphate-buffered saline. HAMA – methacrylated hyaluronic acid. PEG-SH4 – poly(ethylene glycol) tetra-thiol. HAGA – gallic acid-functionalized hyaluronic acid. DPBS – Dulbecco's phosphate-buffered saline. DoM – degree of methacrylation. GelMA – methacrylated gelatin.

 

FUNDING

This work was supported by the framework of the state assignment No. 1023021300027-9-3.2.14 (WLGC-2024-0001) of the Ministry of Health of the Russian Federation.

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