BOC Sciences produces hyaluronic acid (HA) products with different crosslinking densities using a variety of crosslinking technologies (such as BDDE, DVS, PEGDE, etc.). We can customize HA hydrogels or HA microspheres with different properties using different crosslinking agents and crosslinking methods according to customer needs. We also provide a series of in vitro cell testing and in vivo testing to evaluate the biocompatibility, cytotoxicity of crosslinked HA and its effects on cell adhesion, proliferation and differentiation at different concentrations and formulations. We can further enhance the moisturizing, anti-aging and repair capabilities of HA preparations by providing services for the addition of various bioactive ingredients such as vitamins, amino acids, peptides and antioxidants. All raw materials, excipients and functional ingredients provided are strictly tested and screened in accordance with international standards (ISO and cGMP), and are accompanied by detailed quality inspection reports and relevant certification documents.
Hyaluronic acid (HA) is a linear polysaccharide that exists in vertebrate tissues and has a wide range of biological functions, especially its applications in the fields of medicine, beauty and biotechnology. However, its rapid metabolism limits its application, so its properties are improved by cross-linking technology. The cross-linking of HA refers to the intermolecular cross-linking reaction between HA and a cross-linking agent with relevant functional groups; or the cross-linking agent is used as a catalyst to undergo an intramolecular cross-linking reaction to obtain a molecular network structure with different cross-linking degrees, thereby increasing the HA molecular chain, increasing the average molecular weight, enhancing viscoelasticity, relatively weakening water solubility, and improving mechanical strength. Currently known cross-linking agents include BDDE (1,4-butanediol diglycidyl ether), DVS (divinyl sulfone), ADH (oxalic acid dihydrazide), EDC (carbodiimide), GMA (glycidyl methacrylate), non-toxic amino acids, etc. Among them, the most mature process is the BDDE and DVS cross-linking method.
BOC Sciences uses multiple cross-linking technologies such as BDDE, DVS, PEGDE to produce cross-linked HA with different cross-link densities. We have established an exhaustive quality control framework to ensure the consistency, purity and safety of our cross-linked HA products. This framework covers rigorous testing protocols at every stage of production, from raw material sourcing to final product packaging, using advanced analytical techniques to verify product specifications (such as HPLC, NMR and GPC). In addition, our production adheres to international quality standards and regulatory guidelines such as ISO and cGMP certification.
1,4-Butanediol diglycidyl ether (BDDE) is the most commonly used cross-linking agent in the production of cross-linked HA, especially in dermal fillers for the cosmetic industry. BDDE cross-linked HA exhibits excellent stability, preventing rapid degradation of HA under physiological conditions, making it ideal for long-lasting dermal fillers. BOC Sciences has state-of-the-art facilities and a team of experts dedicated to optimizing the BDDE cross-linking process, which ensures a continuous supply of high-quality cross-linked HA to meet the stringent requirements of customers around the world.
Divinyl sulfone (DVS) rapidly cross-links with the hydroxyl groups of HA at room temperature to produce gels with different properties. The degree of cross-linking of the gel can be varied by controlling the HA concentration, molecular weight, HA/DVS ratio and pH of the reaction medium. DVS cross-linked HA exhibits significant resistance to enzymatic degradation, ensuring long-term performance in biological environments. At BOC Sciences, the DVS cross-linking process is carefully managed to produce high-quality, robust cross-linked HA. Their commitment to research and innovation ensures they remain at the forefront of crosslinking technology, continually improving processes to meet emerging market demands.
Polyethylene glycol diglycidyl ether (PEGDE) is another key crosslinker used by BOC Sciences to create enhanced HA products. PEGDE is highly regarded for its ability to form hydrogels that are highly biocompatible and versatile. PEGDE imparts hydrophilicity to HA, enhancing its potential in applications where water retention and hydration are critical, such as in ophthalmic solutions and wound healing products. Additionally, the PEGDE crosslinking process reduces immunogenic responses, making it particularly suitable for injectable and implantable devices.
BOC Sciences can use different cross-linking agents and cross-linking methods to customize HA hydrogels with different properties according to customer needs. For example, with the help of chemical cross-linking agents such as BDDE, we can achieve efficient cross-linking of HA to prepare high-viscosity and high-elasticity hydrogels, which are widely used in skin filling, joint lubrication and other fields. In addition, BOC Sciences has developed a variety of cross-linking parameter optimization schemes to significantly improve the durability and biocompatibility of HA hydrogels. Our customized hydrogel solutions can be used in tissue engineering, drug delivery, wound healing and cosmetics.
HA microspheres are spherical particles with diameters ranging from nanometers to micrometers. Their size, surface properties, and encapsulation efficiency make them highly valuable in a variety of biomedical applications. BOC Sciences' HA microsphere preparation service is based on advanced microsphere manufacturing technologies such as emulsification-solvent evaporation, spray drying, and electrospinning nanotechnology. These methods ensure uniform particle size distribution and high drug loading rate of microspheres, thereby improving the controlled release effect and bioavailability of drugs. In addition, our research team is proficient in HA chemical modification and functionalization, and can modify HA according to customer requirements to give it better physicochemical properties and biological properties. Our HA microsphere testing projects include particle size analysis, surface morphology observation, drug loading determination, and in vitro release characteristics experiments. Throughout the service process, BOC Sciences always adheres to customer-oriented, providing flexible and efficient solutions. Whether in the initial project consultation or in the product development and mass production stages, we maintain close communication with customers to ensure that the project goes smoothly and achieves the best results.
At BOC Sciences, cellular testing services encompass a range of in vitro studies designed to evaluate the biocompatibility, cytotoxicity, and cellular responses of cross-linked HA. These studies utilize a variety of human cell lines to assess factors such as cell adhesion, proliferation, and differentiation in response to different concentrations and formulations of HA. In addition to cell-based studies, BOC Sciences also offers robust in vivo testing services. These animal studies are essential to assess the safety and efficacy of cross-linked HA in various applications, such as injectable dermal fillers or tissue engineering scaffolds. Our team follows strict ethical guidelines and regulatory standards to ensure animal welfare while obtaining valuable data on pharmacokinetics, biodistribution, and potential side effects.
BOC Sciences has extensive experience and technical accumulation in the field of cross-linked HA preparations, providing customers with high-quality raw materials, excipients and functional ingredients configuration services. Our services cover the entire process from raw material selection to final application, ensuring that the products fully meet market needs in terms of safety, effectiveness and functionality. In terms of the configuration of functional ingredients, we provide a variety of bioactive ingredients that can enhance the functions of HA preparations. For example, various vitamins, amino acids, peptides and antioxidants can be added to HA preparations to improve their moisturizing, anti-aging and repair capabilities. In addition, BOC Sciences also provides customized formulation services to optimize the combination of different ingredients according to the specific needs of customers to achieve the best product efficacy. All raw materials, excipients and functional ingredients we provide are strictly tested and screened before being put into use to ensure that they meet international standards (ISO and cGMP). In addition, all BOC Sciences products are accompanied by detailed quality inspection reports and relevant certification documents so that customers can use them with confidence.
| Excipients | |||
| Peptides | Collagen | Polyethylene glycol | Retinol |
| Vitamin C | Vitamin E | Vitamin B5 | Salicylic acid |
| Botulinum toxin | Glutathione | Tranexamic acid | N-acetyl cysteine |
| Ceramides | Xanthan gum | Carbomer | Oligonucleotides |
| Argireline | Glycerin | Arbutin | Niacinamide |
Cross-linked HA is a cross-linked bridge between HA molecules through chemical reactions, thus forming a network structure. This cross-linking effect greatly improves the stability and viscoelasticity of HA, slows down its degradation rate, and thus stays in the body longer. This makes cross-linked HA very suitable for scenarios where the effect needs to be maintained for a long time, such as facial filling, wrinkle filling or shaping. Cross-linked HA has a higher hardness and can provide a more obvious and lasting filling effect. Non-cross-linked HA, also known as free HA, does not contain cross-linked bridges and does not form a network structure between molecules, so its physical and chemical properties are relatively unstable. It degrades relatively quickly in the skin, but its moisturizing ability and absorbability are still excellent. Non-cross-linked HA is usually used in scenarios where rapid hydration and moisturizing are required, such as skin moisturizers, HA essences, etc. This type of HA is more suitable for products that urgently need moisturizing or improve skin texture in the short term.
The preparation process of cross-linked HA involves combining hyaluronic acid with a cross-linking agent through a chemical reaction to form a more stable three-dimensional network structure with special physical properties. The following is a simplified description of the steps:
Step 1: Select high-purity sodium hyaluronate and an appropriate cross-linking agent, such as 1,4-butanediol diglycidyl ether (BDDE), diisocyanate (DIC) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC).
Step 2: Dissolve HA in an appropriate solvent (such as water or phosphate buffer) and then gradually add the cross-linking agent. The cross-linking agent will form bridges under specific conditions to connect HA molecules to each other.
Step 3: Control the temperature, pH value and reaction time to ensure the smooth cross-linking process. Usually, the reaction takes several hours to one day under mild conditions, such as room temperature or slightly above room temperature (25-37 °C).
Step 4: After the reaction is completed, remove the unreacted cross-linking agent and by-products by dialysis or other methods. Finally, the resulting cross-linked HA is dried into a powder or gel state.
