How Do Collagen Peptides Act on the Skin? From Surface Hydration and Percutaneous Delivery to Fibroblasts and Collagen Homeostasis

Introduction

Collagen peptides in skincare products are often understood as being able to directly replenish collagen lost from the skin. In reality, the process does not involve filling the dermis with exogenous collagen, but instead operates at two distinct levels:

① Larger hydrolyzed collagen fragments act mainly on the skin surface and within the stratum corneum, where they provide moisture-binding and film-forming effects and improve the appearance of dry skin texture;

② Short peptides with specific amino acid sequences, provided that they can be released from the formulation, cross the stratum corneum, and remain structurally intact, may further influence extracellular matrix metabolism in keratinocytes or dermal fibroblasts.

The skincare effects of collagen peptides do not result from the direct replenishment of exogenous collagen into the dermis. Instead, they are jointly determined by the type of raw material, percutaneous delivery capacity, the cellular activity of specific peptide sequences, and the balance between collagen synthesis and degradation. Their principal pathways of action are illustrated below.

 

Larger collagen molecules and hydrolyzed fragments act mainly on the skin surface through moisture binding and film formation. Short peptides with defined sequences may act on cells in the viable epidermis or dermis only after being released from the formulation, crossing the stratum corneum, and maintaining structural stability. Their ultimate effects depend on the dynamic balance among collagen production, maturation, and degradation.

1 Collagen, Collagen Hydrolysates, and Bioactive Short Peptides

1.1 Dermal collagen is synthesized and assembled by fibroblasts

The extracellular matrix (ECM) of the dermis is composed primarily of collagen, elastin, glycosaminoglycans, and various adhesive proteins. Type I collagen constitutes the main fibrous framework of the dermis, whereas type III collagen contributes to the regulation of fiber organization and the mechanical properties of the tissue.

Dermal collagen formation is not a simple accumulation of free amino acids or protein fragments, but a continuous cellular biosynthetic process:

Procollagen polypeptide-chain synthesis → proline and lysine hydroxylation → triple-helix folding → procollagen secretion → removal of terminal propeptides → collagen-molecule alignment → fibril assembly and cross-linking

Exogenous collagen lacks the intracellular processes of hydroxylation, folding, and secretion and cannot independently complete oriented extracellular organization. Therefore, topically applied collagen does not act by directly integrating into existing collagen fibers.

1.2 Collagen peptide raw materials include different types

Commercial raw materials described as “collagen peptides” may be complex mixtures produced by collagen hydrolysis or individual short peptides with defined sequences. These two types differ in composition, delivery capacity, and mechanism of action.

Raw material type	Compositional characteristics	Primary direction of action
Intact collagen or soluble collagen	Large molecular size, with much of the protein structure retained	Surface film formation, moisture binding, and improvement of skin feel
Hydrolyzed collagen	Contains polypeptides and oligopeptides of different lengths, as well as free amino acids	Primarily moisturization and film formation; some short peptides may possess cellular activity
Collagen-derived peptides with defined sequences	Defined amino acid sequence, molecular weight, and addition concentration	May regulate cells by acting as extracellular matrix-derived signals
Lipidated collagen-derived peptides	Short peptides conjugated to fatty-acid chains	Alter formulation partitioning, affinity for the stratum corneum, and skin retention

2 Why Intact Collagen Is Difficult to Deliver Directly into the Dermis

2.1 The stratum corneum restricts the entry of large hydrophilic proteins

The stratum corneum consists of corneocytes and continuously arranged intercellular lipids. Exogenous substances must first be released from the formulation and then partition into the stratum corneum before they can diffuse toward the viable epidermis and dermis.

Intact collagen is a large and relatively hydrophilic protein that may also form triple helices, aggregates, or fibrous structures. It has a low capacity to partition into stratum-corneum lipids, and its diffusion rate is also limited by molecular size. Even oligopeptides with much lower molecular weights are substantially affected by hydrophilicity, charge, and molecular conformation during percutaneous delivery. Studies of peptide delivery through the skin have shown that reducing charge and modifying molecular structure can enhance skin permeation, demonstrating that molecular weight is not the only determining factor.[2]

2.2 Entry into the skin does not mean formation of collagen fibers

Collagen-fiber formation depends on fibroblast-mediated procollagen synthesis, followed by hydroxylation, folding, secretion, enzymatic cleavage, and cross-linking. Even if a small quantity of exogenous collagen fragments enters the skin, these fragments lack the cellular processes required for their reassembly into normal dermal collagen fibers.

Topically applied collagen-related ingredients are more likely to affect the dermis through the following pathway:

Specific peptides reach viable skin layers → interact with cell membranes or extracellular structures → alter cellular signaling and gene expression → regulate fibroblast synthesis or remodeling of the extracellular matrix

This is a process of cellular regulation rather than physical filling.

3 Conditions Required for the Percutaneous Delivery of Collagen Peptides

For a short peptide to reach target cells in the skin from a formulation, it must pass through a continuous delivery pathway:

Total peptide in the formulation → release from the carrier or aqueous phase → partitioning into the stratum corneum → diffusion within the skin → resistance to enzymatic and chemical degradation → arrival at the target skin layer → establishment of an effective local concentration

Low efficiency at any stage will reduce the amount of intact peptide that ultimately reaches the target cells.

3.1 Molecular weight and actual molecular state

A smaller molecular size generally favors diffusion through the skin, but there is no fixed penetration threshold applicable to all peptides. Peptides with the same molecular weight may display markedly different percutaneous behaviors because of differences in charge, hydrophobicity, and conformation.

Hydrolyzed collagen also presents the issue of molecular-weight distribution. Two raw materials with the same average molecular weight may have entirely different compositions:

① One may consist primarily of oligopeptides of similar sizes;

② The other may simultaneously contain large quantities of free amino acids and longer polypeptides.

Short peptides may also form aggregates through hydrogen bonding, electrostatic interactions, or hydrophobic interactions, resulting in an actual diffusion particle size larger than the theoretical size of an individual peptide molecule. Raw-material evaluation should therefore focus on molecular-weight distribution and aggregation state. For systems that may form aggregates or carrier particles, particle size in aqueous solution may be further evaluated.

3.2 Amino acid sequence, net charge, and hydrophobicity

The peptide sequence determines the following properties:

① The number of acidic and basic amino acids;

② Net charge at the formulation pH;

③ Hydrogen-bonding capacity;

④ Solubility in the aqueous phase;

⑤ Affinity for stratum-corneum lipids;

⑥ Tendency toward self-assembly and aggregation;

⑦ Susceptibility to peptidase degradation.

Highly hydrophilic and strongly charged peptides dissolve readily in the aqueous phase but do not easily enter stratum-corneum lipids. Excessively hydrophobic peptides may enter stratum-corneum lipids but may also be retained excessively in the oil phase or stratum corneum, making further diffusion toward the viable epidermis difficult.

Percutaneous delivery requires an appropriate balance among aqueous solubility, release from the formulation, and partitioning into the stratum corneum, rather than the simple pursuit of high hydrophilicity or high lipophilicity.

3.3 Effects and limitations of lipidation

Conjugating a fatty-acid chain, such as a palmitoyl group, to a short peptide can enhance interactions between the peptide and lipid phases. For example, palmitoyl pentapeptide-4 is a lipidated derivative of the KTTKS sequence.

Lipidation may produce the following changes:

Reduced peptide water solubility + increased affinity for stratum-corneum lipids + increased retention on the skin surface + potential changes in resistance to peptidase degradation

These changes may sometimes facilitate skin delivery, but they may also cause peptide aggregation, incorporation into micelles, or retention within the stratum corneum. Dermal delivery of lipidated peptides still requires verification through quantitative layer-by-layer analysis of human skin and cannot be inferred directly from structural modification alone.

3.4 Formulation release determines the bioavailable concentration

Peptides may exist in a free state within a formulation, or they may bind to thickening polymers, surfactants, emulsified interfaces, or lipid carriers.

A high amount of raw material added to a formulation does not necessarily produce a corresponding increase in the concentration of free peptide within the target skin layer. If a peptide is excessively encapsulated by a carrier or binds strongly to formulation components, its release rate may be restricted.

3.5 Stability within the skin

Various peptidases are present on the skin surface, within the stratum corneum, and in the viable epidermis. After entering the skin, short peptides may undergo:

① Progressive cleavage from the amino or carboxyl terminus;

② Internal hydrolysis of the peptide chain;

③ Oxidation of sulfur-containing or aromatic amino acids;

④ Deamidation of asparagine and glutamine;

⑤ Cleavage at the lipidation linkage or oxidation of the fatty-acid chain.

Detection of a fluorescent signal within the skin does not necessarily indicate that the intact peptide has reached the corresponding depth. The fluorescent group may become detached from the peptide or remain attached to degradation fragments. A more reliable evaluation method is to separately sample the stratum corneum, viable epidermis, and dermis, followed by liquid chromatography–mass spectrometry detection of the intact characteristic sequence.

4 Effects Differ among Skin Layers

Whether collagen peptides need to enter the dermis depends on their intended effect.

Site reached	Possible effects	Evidence required
Skin surface and superficial stratum corneum	Moisture binding, film formation, and reduction of dryness and roughness	Stratum-corneum hydration, transepidermal water loss, and surface texture
Viable epidermis	Regulation of keratinocyte status and epidermal–dermal signaling	Quantitative epidermal-layer analysis and keratinocyte or skin-model experiments
Epidermal–dermal junction and superficial dermis	Direct effects on fibroblasts and extracellular matrix metabolism	Quantification of intact peptide in the dermis, comparison with effective concentrations, and fibroblast-related indicators

4.1 Surface moisturization does not require entry into the dermis

Larger collagen polypeptides can form a hydrophilic film on the skin surface and improve stratum-corneum softness by binding water. As stratum-corneum hydration increases, fine lines and roughness caused by dryness may be temporarily reduced.

This effect represents a surface-level improvement of the epidermis and is distinct from dermal collagen synthesis.

4.2 Direct effects on fibroblasts require evidence of dermal delivery

Fibroblasts are located primarily in the dermis. If a peptide is described as directly increasing the production of type I collagen, type III collagen, or fibronectin by fibroblasts, the intact active sequence must reach the vicinity of dermal fibroblasts and establish a biologically meaningful local concentration. This concentration should then be compared with the concentration–response relationship observed in cell experiments.

In cell-culture experiments, peptides are added directly to the culture medium, bypassing the stratum corneum and epidermal barriers. Such studies demonstrate what may occur after a peptide comes into contact with cells, but they cannot independently prove that an ordinary topical formulation can achieve the same delivery.

4.3 The epidermis may also indirectly influence the dermis

Peptides do not necessarily have to enter the dermis directly to influence the dermal environment. Certain ingredients may first act on keratinocytes in the viable epidermis and subsequently affect underlying fibroblasts through cytokines and growth factors.

Such epidermal–dermal communication requires support from three-dimensional skin models, co-culture models, or tissue experiments. Fibroblast experiments alone cannot distinguish direct effects from indirect effects mediated by the epidermis.

5 How Specific Collagen-Derived Peptides Regulate Fibroblasts

5.1 Collagen fragments can carry extracellular matrix signals

The extracellular matrix not only provides mechanical support but also participates in the regulation of cellular behavior. Some short peptides generated during collagen-precursor processing or collagen degradation can induce specific cellular responses. These biologically active extracellular matrix fragments are commonly referred to as matrix-derived peptides.

KTTKS is one of the earliest extensively studied collagen-derived pentapeptides. Its amino acid sequence is:

Lys–Thr–Thr–Lys–Ser

Lysine–threonine–threonine–lysine–serine

Studies have shown that KTTKS can increase the production of extracellular matrix components, including type I collagen, type III collagen, and fibronectin, in cultured fibroblasts.[1]

5.2 Different peptide sequences produce different cellular responses

Prolyl-hydroxyproline (Pro-Hyp) is a collagen-derived dipeptide. In studies using cultured human dermal fibroblasts, Pro-Hyp increased cell proliferation and hyaluronic acid synthesis and upregulated the expression of hyaluronan synthase 2.[3]

This result demonstrates that Pro-Hyp possesses cellular activity, but two limitations should be noted:

1. Pro-Hyp was added directly to the cell-culture medium, and delivery across the stratum corneum was not evaluated;

2. The study focused on cell proliferation and hyaluronic acid metabolism and cannot be directly interpreted as evidence of increased mature collagen-fiber formation.

The GEKG tetrapeptide has been shown to promote collagen and other extracellular matrix-related indicators in cultured human dermal fibroblasts, and small-scale human studies have also observed improvements in skin roughness.[4] Because the sample sizes and delivery data were limited, these results are appropriately regarded as evidence of the cellular regulatory potential of peptides with defined sequences rather than as a general conclusion applicable to all topically applied collagen peptides.

5.3 From increased gene expression to collagen-fiber formation

An increase in the expression of collagen-related genes in fibroblasts indicates only that part of the collagen-synthesis program has changed. The formation of mature collagen requires multiple additional processing steps:

Transcription of collagen genes such as COL1A1 and COL1A2 → translation of procollagen polypeptide chains → hydroxylation of proline and lysine → triple-helix folding → procollagen secretion → propeptide cleavage → fibril alignment → covalent cross-linking

COL1A1 and COL1A2 encode the α1 and α2 chains of type I collagen, respectively. An increase in the messenger RNA levels of these genes alone does not prove that an increased quantity of mature, properly organized collagen fibers has formed within the dermis.

A more comprehensive evaluation of the extracellular matrix should simultaneously examine:

① Collagen-related gene expression;

② Procollagen-protein secretion;

③ Collagen deposition;

④ Fibril structure and organization;

⑤ Changes in fibronectin, elastin, and hyaluronic acid;

⑥ Mechanical connections between cells and the matrix.

6 Collagen Synthesis and MMP-Mediated Degradation Jointly Determine Collagen Homeostasis

6.1 Collagen homeostasis is a dynamic balance between production and degradation

Changes in the amount of collagen in the skin can be summarized as follows:

Net change in collagen = procollagen synthesis and maturation − enzymatic collagen degradation and nonenzymatic damage

Stimulation of collagen synthesis represents only one side of this balance. When ultraviolet radiation, oxidative stress, and chronic inflammation persist, newly formed collagen may still undergo accelerated degradation.

6.2 Ultraviolet radiation simultaneously reduces synthesis and increases degradation

Ultraviolet radiation can increase reactive oxygen species (ROS) and activate mitogen-activated protein kinase-related signaling and activator protein-1 (AP-1). AP-1 can increase the expression of matrix metalloproteinase (MMP)-related genes.[11]

The process can be represented as follows:

Ultraviolet radiation → increased ROS → enhanced AP-1 and other stress-related signaling → increased MMP-1 expression → initial cleavage of type I and type III collagen

MMP-1 can initially cleave the triple helices of fibrillar collagen at specific sites, generating fragments approximately three-quarters and one-quarter of the original collagen length.[12] After triple-helix stability decreases, other proteases may continue to degrade these fragments.

At the same time, ultraviolet radiation can inhibit transforming growth factor-β (TGF-β)-related signaling, thereby reducing type I procollagen synthesis.[5]

6.3 Collagen fragmentation impairs fibroblast function

In normal dermis, fibroblasts attach to collagen fibers through integrins and other adhesion structures and exert tensile forces on the surrounding matrix. An intact collagen network provides cells with an extended morphology and mechanical signals.

After extensive collagen fragmentation, fibroblasts lose stable attachment sites, resulting in reduced cellular spreading and mechanical tension. Studies of aged human skin and collagen models have found that collagen fragmentation is accompanied by further increases in ROS, AP-1, and MMP-1 in fibroblasts, creating a continuing cycle of matrix damage.[6]

Collagen fragmentation → reduced fibroblast attachment and tension → increased oxidative stress and MMP-1 → further collagen degradation

This cycle indicates that collagen-related anti-aging strategies require not only the regulation of new collagen synthesis by fibroblasts but also a reduction in repeated damage to the existing collagen network.

6.4 Collagen peptides are not equivalent to MMP inhibitors

Whether specific collagen-derived peptides can indirectly affect MMP expression must be determined according to the individual peptide sequence and experimental results.

MMPs also participate in normal matrix renewal. For example, in postnatal mouse dermis and three-dimensional cross-linked type I collagen models, the membrane-type matrix metalloproteinase MMP-14 participates in pericellular collagen remodeling by fibroblasts and is associated with β1-integrin signaling and fibroblast survival.[10]

Collagen homeostasis requires moderate and controlled matrix remodeling rather than the suppression of all MMP activity to low levels.

7 Mechanistic Basis for Combination with Vitamin C and Retinol

The following section primarily describes how different ingredients act at complementary stages of collagen metabolism. It does not indicate that synergistic effects have been demonstrated for any specific combination system.

7.1 Combination with vitamin C: cellular signaling and procollagen maturation

During procollagen synthesis, proline and lysine residues are hydroxylated by prolyl hydroxylases and lysyl hydroxylases, respectively. Both enzyme classes are Fe²⁺- and α-ketoglutarate-dependent dioxygenases. Vitamin C supports the continuation of these hydroxylation reactions by helping maintain the iron at the enzyme active site in its reduced state.

The simplified reaction is:

Proline or lysine residues in procollagen + α-ketoglutarate + O₂ → hydroxyproline or hydroxylysine + succinate + CO₂

The enzymatic reaction requires ferrous ions, and vitamin C helps maintain the reducing state required for enzymatic activity. Hydroxyproline helps stabilize the collagen triple helix, whereas hydroxylysine participates in glycosylation and subsequent collagen-structure formation.[7]

The functional roles of the two types of ingredients can be summarized as follows:

Specific collagen-derived peptides → regulate fibroblast extracellular matrix responses

Vitamin C → supports procollagen hydroxylation, folding, and maturation

Human studies of topical vitamin C have reported improvements in wrinkles and the formation of new collagen in biopsy samples. However, these findings correspond to specific formulations and cannot be directly extrapolated to all forms and concentrations of vitamin C.[8]

The following factors should be examined when the ingredients are combined:

① Peptide integrity under acidic conditions;

② Oxidative stability of L-ascorbic acid;

③ Effects of metal ions on oxidation and peptide structure;

④ Binding of peptides to thickeners and emulsifiers;

⑤ Peptide-sequence integrity and vitamin C content after storage.

7.2 Combination with retinol: nuclear-receptor regulation and matrix signaling

After entering the skin, retinol can be progressively oxidized to retinaldehyde and retinoic acid. Retinoic acid binds to nuclear receptors and regulates epidermal differentiation, fibroblast function, and the expression of extracellular matrix-related genes.

Human skin studies have shown that topical retinol can induce histological changes in the epidermis and dermis and increase the expression of type I and type III collagen-related markers.[9]

The rationale for the combination is as follows:

Retinol → regulates cellular transcription and skin renewal through nuclear receptors

Specific collagen-derived peptides → regulate fibroblast responses through extracellular matrix-derived signals

Formulation design must address the light, oxygen, and thermal stability of retinol while avoiding damage to peptide structure during high-temperature emulsification. Retinol may cause dryness and desquamation. Hydrolyzed collagen, glycerol, and barrier lipids may improve hydration and skin feel, but this does not mean that they can eliminate retinol-related irritation.

7.3 Sunscreen reduces the input of collagen-damaging stimuli

Ultraviolet radiation can simultaneously inhibit procollagen synthesis and increase MMP-related degradation. Sunscreen reduces ultraviolet-induced damage, whereas collagen peptides, vitamin C, and retinol act on cellular signaling, collagen maturation, and transcriptional regulation, respectively.

8 Classification and Research Applications of Representative Chemicals Related to Percutaneous Delivery, Collagen Synthesis, and Homeostatic Regulation of Collagen Peptides

Table 1. Collagen Matrices, Characteristic Amino Acids, and Collagen-Derived Peptides

Classification	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Type I collagen matrix	9007-34-5	B475465	Bovine Collagen Solution	Moligand™, ≥95%, Type I, sterile filtered, BSE-Free, suitable for biomedical research	Type I collagen extracellular matrix material; used in three-dimensional collagen gels, fibroblast culture, cell adhesion and migration, matrix contraction, and collagen-remodeling studies.
Denatured collagen structural control	9000-70-8	G108396	Gelatin	PharmPure™, USP, BP, European Pharmacopoeia (Ph. Eur.), gel strength ~240 g Bloom	Thermally denatured collagen product; used to compare gel formation, protease degradation, cell adhesion, and delivery-carrier performance following loss of the triple-helical structure.
Collagen backbone amino acid	56-40-6	A110749	Glycine	Moligand™, ≥99%	Highly abundant amino acid in the repetitive collagen sequence; used in collagen-composition analysis, amino acid quantification, culture-system supplementation, and procollagen-synthesis-related controls.
Collagen backbone amino acid	147-85-3	L476193	L-Proline	UltraBio™, ≥99.5%	Constituent amino acid of collagen polypeptide chains; used in collagen amino acid composition analysis, cell-culture supplementation, proline metabolism, and studies of substrate supply for collagen synthesis.
Characteristic collagen amino acid	51-35-4	H111005	L-Hydroxyproline	Moligand™, ≥99%	Characteristic hydroxylated amino acid of collagen; used for hydroxyproline quantification in collagen and collagen hydrolysates, estimation of collagen content, and analysis of collagen degradation products.
Collagen backbone amino acid	56-87-1	L598932	L-Lysine	Moligand™, ≥98%, Metal <500 ppm	Constituent amino acid of collagen polypeptide chains; used in collagen amino acid composition analysis, cell-culture supplementation, lysine metabolism, and studies of substrate supply for collagen synthesis.
Collagen-derived dipeptide	18684-24-7	H332495	4-Hydroxy-1-L-prolyl-L-proline	≥98%	Collagen-derived prolyl-hydroxyproline dipeptide; used in studies of fibroblast proliferation, hyaluronic acid synthesis, collagen degradation products, and peptide-sequence activity.
Procollagen-derived signaling peptide	149128-48-3	P1020219	Pentapeptide-4	—	Procollagen-derived pentapeptide with a defined sequence; used in studies of fibroblast responses, type I and type III collagen production, fibronectin production, and percutaneous delivery.

Table 2. Research Products for Collagen Hydroxylation, Fibroblast Signaling, and Vitamin A Compounds

Classification	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Collagen hydroxylation cofactor	50-81-7	L432790	L-Ascorbic Acid	UltraBio™, ultrapure grade, ≥99.5% (RT)	Used in prolyl hydroxylase and lysyl hydroxylase reactions, procollagen hydroxylation, triple-helix stabilization, and studies of collagen synthesis in fibroblasts.
Glycosylated vitamin C derivative	129499-78-1	O160006	2-O-α-D-Glucopyranosyl-L-Ascorbic Acid	≥98% (HPLC)	Used in comparative studies of vitamin C derivative stability, enzymatic conversion, antioxidant activity, and collagen-related indicators.
Ethylated vitamin C derivative	86404-04-8	O159940	3-O-Ethyl-L-Ascorbic Acid	Moligand™, ≥98% (HPLC) (T)	Used in studies of formulation stability, skin conversion, antioxidant activity, and collagen-related expression of vitamin C derivatives.
Phosphorylated vitamin C derivative	66170-10-3	S304311	Trisodium L-Ascorbate-2-Phosphate	≥96%	Water-soluble phosphorylated ascorbic acid derivative; used in studies of enzymatic dephosphorylation, oxidative stability, and collagen-related responses in fibroblasts.
Collagen hydroxylase cosubstrate	328-50-7	K105571	α-Ketoglutaric Acid	Moligand™, ≥98%	Cosubstrate for prolyl and lysyl hydroxylase reactions; used in studies of dioxygenase reactions, procollagen hydroxylation, and metabolic conditions.
Ferrous-ion source	7720-78-7	F709863	Ferrous Sulfate Standard Solution	0.25 mol/L in H₂O	Provides a quantitative source of ferrous ions; used in ferrous-ion content analysis and studies of metal-ion effects and oxidative stability.
Transforming growth factor-β pathway inhibitor	301836-41-9	S1371574-GMP	SB-431542	Moligand™, ≥99%	Used to inhibit transforming growth factor-β type I receptor kinase and to elucidate the effects of this signaling pathway on procollagen, fibronectin, and fibroblast phenotypes.
Vitamin A aldehyde	116-31-4	A122355	All-trans-Retinal	Moligand™, ≥98%	Used in studies of vitamin A metabolic conversion, epidermal renewal, fibroblast responses, and collagen-related expression.
Vitamin A ester	79-81-2	R106319	Vitamin A Palmitate	1,700,000 USP units/g	Used in studies of vitamin A ester hydrolysis, conversion to retinol, oil-phase stability, storage degradation, and skin renewal.
Vitamin A alcohol	68-26-8	R755730	Retinol	BioReagent, ≥97.5% (HPLC), ~3100 U/mg	Used in studies of retinol metabolism, epidermal renewal, fibroblast function, collagen-related expression, and photoaged-skin models.

Table 3. Research Products for Oxidative Stress, Photodamage, and Matrix Metalloproteinases

Classification	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Lipid-phase antioxidant	59-02-9	T433011	(+)-α-Tocopherol	From Type V vegetable oil, approximately 1000 IU/g	Used in studies of lipid peroxidation, oxidative damage to cell membranes, and formulation antioxidation, as well as in photoprotection evaluations involving combinations with vitamin C and ferulic acid.
Thiol antioxidant	616-91-1	A105421	N-Acetyl-L-Cysteine (NAC)	PharmPure™, USP, Moligand™, European Pharmacopoeia (Ph. Eur.), ≥98.5%	Used in studies of glutathione metabolism, reactive oxygen species scavenging, oxidative injury in fibroblasts, and intervention controls for matrix metalloproteinase expression.
Oxidative-stress inducer	7722-84-1	H755825	Hydrogen Peroxide Solution	Suitable for microbiology, 3%	Following quantitative dilution and preliminary optimization of experimental conditions, used to establish fibroblast oxidative-stress and premature-senescence models and to assess cell viability, collagen expression, reactive oxygen species, and changes in matrix metalloproteinases.
Broad-spectrum matrix metalloproteinase inhibitor	142880-36-2	G274767	GM 6001, Broad-Spectrum MMP Inhibitor	Moligand™, ≥98%	Used to inhibit multiple matrix metalloproteinases and verify protease-dependent processes involved in collagen degradation, cell migration, and extracellular matrix remodeling.
Phenolic-acid antioxidant	1135-24-6	F103701	Ferulic Acid	Moligand™, ≥99%	Used in studies of reactive oxygen species scavenging, ultraviolet-induced damage, antioxidant-system stability, and photoprotection in combination with vitamin C and vitamin E.

Table 4. Research Products for Skin Hydration, Barrier Lipids, and Formulation Delivery

Classification	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Low-molecular-weight hyaluronate	9067-32-7	H293513	Low-Molecular-Weight Sodium Hyaluronate (HA-TLLM)	1% solution	Used in studies of hyaluronic acid molecular-weight effects, skin hydration, diffusion behavior, fibroblast responses, and formulation rheology.
Hyaluronic acid matrix material	9004-61-9	H131007	Hyaluronic Acid	Moligand™, from rooster comb	Used as an extracellular matrix control and in evaluations of water retention and viscoelasticity, as well as in studies of collagen–hyaluronic acid composite matrices and cell migration.
Polyol humectant	56-81-5	G274225	Glycerol	Proteomics grade	Used as a stratum-corneum moisturization control and in studies of protein and peptide solution stability, osmotic-pressure regulation, and formulation water activity.
Barrier- and cellular-metabolism-conditioning ingredient	98-92-0	N108086	Niacinamide	≥99.5% (HPLC)	Used in studies of the stratum-corneum barrier, cellular energy metabolism, inflammation, and oxidative stress, as well as in evaluations of barrier tolerance in combination systems containing vitamin A compounds.
Stratum-corneum barrier lipid	57-88-5	C104032	Cholesterol	≥99%	Component of stratum-corneum intercellular lipids; used with ceramides to construct barrier-lipid models and to study lamellar structures and percutaneous diffusion.
Stratum-corneum ceramide system	100403-19-8	C647629	Ceramide Mixture	≥95%	Used in studies of the stratum-corneum lipid barrier, lamellar structures, transepidermal water loss, and the delivery environment for collagen peptides.
Oil-phase emollient and carrier material	111-01-3	S141278	Squalane	≥95%	Used as an oil-phase carrier and skin emollient and in studies of the dissolution, partitioning, and formulation stability of oil-soluble vitamin A compounds and antioxidants.

Note: The products listed above are representative Aladdin products related to scientific research and formulation studies. Additional product specifications, grades, and certificates of analysis may be retrieved from the Aladdin website using the product name, CAS number, or catalog number.

References

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[2] Lim SH, Sun Y, Madanagopal TT, Rosa V, Kang L. Enhanced skin permeation of anti-wrinkle peptides via molecular modification. Scientific Reports. 2018;8:1596. doi:10.1038/s41598-017-18454-z.

[3] Ohara H, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima S. Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. Journal of Dermatology. 2010;37(4):330-338. doi:10.1111/j.1346-8138.2010.00827.x.

[4] Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, et al. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Experimental Dermatology. 2011;20(7):602-604. doi:10.1111/j.1600-0625.2011.01307.x.

[5] Quan T, He T, Kang S, Voorhees JJ, Fisher GJ. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling. American Journal of Pathology. 2004;165(3):741-751. doi:10.1016/S0002-9440(10)63337-8.

[6] Fisher GJ, Quan T, Purohit T, Shao Y, Cho MK, He T, et al. Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. American Journal of Pathology. 2009;174(1):101-114. doi:10.2353/ajpath.2009.080599.

[7] Boyera N, Galey I, Bernard BA. Effect of vitamin C and its derivatives on collagen synthesis and cross-linking by normal human fibroblasts. International Journal of Cosmetic Science. 1998;20(3):151-158. doi:10.1046/j.1467-2494.1998.171747.x.

[8] Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatologic Surgery. 2002;28(3):231-236. doi:10.1046/j.1524-4725.2002.01129.x.

[9] Kong R, Cui Y, Fisher GJ, Wang X, Chen Y, Schneider LM, Majmudar G. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. Journal of Cosmetic Dermatology. 2016;15(1):49-57. doi:10.1111/jocd.12193.

[10] Sabeh F, Li XY, Olson AW, Botvinick E, Kurup A, Gimenez LE, Cho JS, Weiss SJ. Mmp14-dependent remodeling of the pericellular–dermal collagen interface governs fibroblast survival. Journal of Cell Biology. 2024;223(9):e202312091. doi:10.1083/jcb.202312091.

[11] Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature. 1996;379(6563):335-339. doi:10.1038/379335a0.

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