Home Tissue EngineeringExploring Hydrogels: Key Materials for Biomedical Applications

Exploring Hydrogels: Key Materials for Biomedical Applications

Close-up of clear hydrogels with bubbles in a turquoise liquid, showcasing their texture and transparency

Section Overview

Introduction
Key Material Types
Crosslinking Methods
Key Applications
Recent Advances
Additives for Hydrogel
Related Products

Introduction

Hydrogels are three-dimensional networks of hydrophilic polymers with the ability to retain a large amount of water, closely mimicking the properties of natural tissue. Another key property of these materials is their biocompatibility, ensuring minimal adverse reactions when in contact with biological tissues¹. These distinctive properties render them highly useful in biomedical applications. Hydrogels can be derived from natural sources like collagen and alginate or can be chemically produced from polymers such as PEG and PVA. The natural versatility in composition and structure permits the customization of mechanical strength, biodegradability, and bioactivity to meet the requirements for targeted applications.

Key Material Types

Based on the source, hydrogels can be broadly classified into natural and synthetic categories. Each type has unique properties, advantages, and applications in biomedical fields. Comparative properties of natural and synthetic hydrogel polymers are summarized in Table 1.

Table 1.Comparative properties of natural and synthetic polymers
Property	Natural Polymers	Synthetic Polymers
Source	Derived from biological materials (e.g., collagen, alginate)	Chemically synthesized (e.g., PEG, PVA)
Biocompatibility	Generally high, mimicking natural tissues	Varies; can be engineered for specific applications
Customization	Limited to natural variability	Highly customizable in terms of properties
Mechanical Strength	Typically, lower mechanical strength	Can be designed for high strength and durability
Biodegradability	Often biodegradable	Varies; some are designed for controlled degradation
Cost	Can be more expensive due to extraction	Generally, more cost-effective due to mass production

Natural Polymers

Natural polymers such as collagen, gelatin, and alginate are favored for biomedical applications due to their excellent biocompatibility and biodegradability. Collagen supports cell growth and is widely used in tissue engineering; gelatin offers easy modification and gelation properties for drug delivery; and alginate forms biocompatible hydrogels ideal for cell encapsulation and wound healing.

Synthetic Polymers

Polyethylene glycol (PEG) is renowned for its biocompatibility and hydrophilicity and is widely used in drug delivery and tissue engineering hydrogels. Polyvinyl alcohol (PVA) offers excellent mechanical strength, biocompatibility, and moisture retention, making it ideal for wound dressings and scaffolds. Polyacrylic acid (PAA) is valued for its water absorption and pH-responsive gelation, suited for controlled drug release and tissue regeneration.

Crosslinking Methods

Hydrogels can be crosslinked using physical methods (e.g., hydrogen bonding) or chemical methods (e.g., covalent bonds), depending on the desired application. These advances enhance the applicability of hydrogels through improved interaction with biological systems, making them more effective in therapeutic and regenerative medicine. Representative hydrogel recipes with monomers, cross-linkers, initiators, and key biomedical applications are presented in Table 2.

Table 2.Hydrogel Formulations: Composition, Crosslinking, and Uses
Hydrogels (Name & Type)	Monomers/Polymers	Crosslinking Agents & Method	Initiators	Applications
pHEMA (Synthetic)	2-Hydroxyethyl methacrylate (HEMA)	Ethylene glycol dimethacrylate (EGDMA); UV/thermal crosslinking	Azobisisobutyronitrile (AIBN)	Contact lenses; ocular drug delivery
Silicone-based Hydrogel (Hybrid)	3-[Tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS), N,N-Dimethylacrylamide, 1-Vinyl-2-pyrrolidinone	Poly(ethylene glycol) dimethacrylate (PEGDMA); UV curing	Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) or Irgacure^®819 Photoinitiator	High-oxygen-permeable contact lenses
PEG Hydrogel (Synthetic)	Poly(ethylene glycol) diacrylate PEGDA / tetra-PEG	Self-crosslink via thiol-Michael or UV	UV photoinitiators like, Irgacure ^®2959, Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP)	Surgical sealants; anti-adhesion
PVA Hydrogel (Synthetic)	Poly(vinyl alcohol)	Freeze–thaw or glutaraldehyde crosslinking	None (physical) / acid-catalyzed (chemical)	Wound dressings; cartilage replacement
Alginate Hydrogel (Natural)	Sodium alginate	Ionic gelation with Ca²⁺	Not required	Wound dressings; cell encapsulation
Hyaluronic Acid Hydrogel (Natural)	Hyaluronic acid	Carbodiimide/UV crosslinking	Photoinitiator like Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP)	Dermal fillers; wound healing, microneedles
Collagen/Gelatin Hydrogel (Natural)	Type I collagen/gelatin	Self-assembly or N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide / N-hydroxysuccinimide (NHS) crosslinking	Carbodiimide activation	Wound matrices; tissue scaffolds
Chitosan Hydrogel (Natural)	Chitosan	Genipin (covalent) or Sodium tripolyphosphate (TPP) (ionic)	None (ionic); genipin reaction	Antimicrobial dressings; derma care
PVP Hydrogel (Synthetic)	Polyvinylpyrrolidone	N,N′-Methylenebisacrylamide (MBAA) (UV crosslink) or grafting	Irgacure ^®2959 / Benzophenone	Lubricious coatings; personal care
PNIPAM Hydrogel (Smart, Synthetic)	N-Isopropylacrylamide (NIPAM)	N,N’-Methylenebisacrylamide (BIS); free-radical polymerization	Ammonium persulfate (APS) + N,N,N′,N′-Tetramethylethylenediamine (TEMED)	Thermoresponsive systems, smart polymers

Key Applications

Hydrogels offer versatile solutions across the biomedical field due to their unique ability to retain water and adapt to biological environments. They enable developments in wound healing, medical devices, and tissue engineering by supporting advanced therapies, drug delivery, and 3D cell culture solutions.

Medical Devices

Wound Healing

Hydrogels support wound healing by maintaining moisture, promoting cell growth, and delivering antimicrobial agents. Integrating smart polymers allows continuous health monitoring, enabling real-time tracking of metrics like pH, glucose, or infection status for better care².

Contact Lenses and Dental Applications

Hydrogels are used in contact lenses for their oxygen permeability, softness, and ability to retain moisture—enhancing comfort during wear. In dentistry, the durability of hydrogels supports sustained drug release, stable tissue regeneration support, and periodontal repair with structural integrity and therapeutic function retained over long-term clinical use. Their biocompatibility and versatility make them valuable in both optical and oral care fields³.

Tissue Engineering

Hydrogels provide a scaffold that supports cell attachment, growth, and differentiation, crucial for tissue regeneration. They mimic the extracellular matrix (ECM) structure, allowing for the integration of cells and growth factors to form new tissues. Applications include cartilage repair, bone regeneration, and vascular tissue engineering.

3D Bioprinting

Hydrogels play a crucial role in 3D bioprinting as bioinks due to their high water content, biocompatibility, and customizable properties. They support cell encapsulation, maintain viability, and mimic the extracellular matrix. This facilitates the precise construction of tissues and organs, aiding regenerative medicine and personalized therapeutic solutions⁴.

Controlled Release Mechanisms

Hydrogels can encapsulate drugs and release them in a controlled manner, improving therapeutic efficacy and reducing side effects. They are particularly useful for localized delivery, where the drug is released at the target site over an extended period⁵. By regulating the drug's half-life, hydrogels enable sustained delivery for applications like cancer therapy or chronic wound management, improving therapeutic efficacy and patient compliance.

Personal Care – Cosmetic Industry

Hydrogels play a pivotal role in personal care due to their hydration, biocompatibility, and tunable properties. With respect to formulations, they stabilize and control the release of active ingredients in creams and serums. Dermal fillers, which are primarily hyaluronic acid-based hydrogels, provide volume restoration, elasticity, and long-lasting effects. A key factor behind their durability is 1,4-butanediol diglycidyl ether (BDDE), the gold-standard crosslinking agent.⁶ BDDE covalently links HA chains, strengthening the hydrogel structure, improving elasticity, and reducing enzymatic breakdown. This translates to longer-lasting fillers, fewer retreatments, and enhanced patient satisfaction. Beyond fillers, BDDE-crosslinked hydrogels are enabling next-generation cosmetic solutions. They provide a stable matrix for smart, responsive systems that deliver antioxidants, peptides, or UV filters precisely when needed, supporting skin health and rejuvenation. In high-end plastic surgery, injectable hydrogels support tissue regeneration and contouring with minimal invasiveness. Advanced personal care solutions utilize smart hydrogels, which are responsive to pH, temperature, or enzymes, enabling targeted delivery of antioxidants, peptides, or UV filters for enhanced skin health and rejuvenation.

Recent Advances

Recent innovations in hydrogel technology focus on enhancing their functional properties and are summarized in Table 3.

Table 3.Cutting-Edge Hydrogel Materials: Composition, Crosslinkers, and Their Biomedical Applications
Types of Hydrogels	Monomers/Polymers Used	Crosslinking Agents	Key Applications
Self-Healing Hydrogels	Chitosan, Tannic acid, Polyethylene glycol, 4-(Diethoxymethyl)benzaldehyde, 4-Aminophenylboronic acid hydrochloride , Poly(vinyl alcohol)	Hydrogen bonding, Ionic interactions, Imine bonds (benzaldehyde–amine) + Borate ester bonds (boronic acid–diol)	Wound dressings, tissue scaffolds⁷
Stimuli-Responsive Hydrogels	TOChN@PNIPAm - TEMPO oxidized nanochitin (TOChN) and Poly(N-isopropylacrylamide) (PNIPAm), 2-(Dimethylamino)ethyl methacrylate (DMAEMA), PEDOT:PSS, Carboxymethyl cellulose, polythiophene, Acid-hydrolyzed cellulose	Dynamic boric acid ester bonds, hydrogen bonds, π–π stacking between DA groups and PEDOT:PSS, Covalent crosslinking, Electrostatic interactions	Tissue engineering, biosensors, Polymeric wearable sensors⁸
Clay–Polymer Hybrid Hydrogels	Sodium alginate, Ethylene glycol , Acrylic acid, Silver nitrate	Chemical or physical crosslinking	Enhanced mechanical strength for wound healing, tissue engineering⁹
ULAS Hydrogels		Chemical crosslinking via free radical copolymerization process	Biosensing, ECG monitoring, wearable biomedical devices¹⁰
Injectable Hydrogels	GelMA, Methacrylated Alginate	Radical photopolymerization	Designed for minimally invasive delivery, forming in situ to fill irregular defects and deliver cells or drugs¹¹

Additives for Hydrogel

Additives are widely employed in hydrogel systems to enhance their performance and expand the functionality of hydrogel-based contact lenses. For instance, incorporating photo-absorbers like 2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate into the hydrogel matrix can regulate light penetration during photopolymerization. This not only improves crosslinking control, spatial resolution, and mechanical robustness of the hydrogel but also enables the integration of UV and blue light filtering capabilities. Such enhancements are particularly valuable for protecting the eyes from harmful radiation, reducing digital eye strain, and improving overall comfort and safety for users in both medical and personal care applications.

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