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Compared Analysis of Non-Hydrolyzed and Hydrolyzed Collagen in Wound Healing

HBS Blog March 3, 2021

COLLAGEN’S Importance in Wound Healing

Collagen is a novel triple helix protein molecule that constitutes an essential portion of the extracellular matrix (ECM). In all stages of wound healing, the ECM plays a crucial role. In the advanced wound care market, there are numerous collagen-based technologies.

The objective of collagen technology dressings is to decrease protease activity while promoting wound healing. Collagen advanced wound care dressings are proving to be a catalyst for wound chronicity by stimulating tissue growth, promoting autolysis, encouraging angiogenesis, collagen deposition, and reepithelializing wounds.

MMP modulating dressings or collagen technology dressings are ideal for chronic wounds because they inhibit matrix metalloproteinases (MMPs), enzymes that degrade viable and non-viable collagen. We currently lack a device for measuring MMP levels in a wound bed. What we do know is that MMPs must be present in the proper quantity, location, and time frame for a wound to progress along a healing trajectory.
Approximately 70-80% of the extracellular matrix (ECM) of skin is composed primarily of collagen types I and II. Collagen can be extracted from any animal, but most commonly from bovine, porcine, equine, Piscesan, and avian sources. In its matrix structure, collagen serves as the blueprint for new tissue growth, and its primary structure continues to attract fibroblasts to the site. It is hypothesized that when the healing process reaches the maturation stage, it promotes the deposition of oriented collagen fibers to increase the tensile strength of the new tissue.

Collagen is a novel triple-

helix protein molecule and an essential component of the extracellular matrix (ECM). 

The ECM participates in all stages of wound healing. 

In the field of advanced wound care, there are a number of collagen-based technologies. 

Dressings utilizing collagen technology are intended to inhibit protease activity while the wound transitions to a healing state. 

Collagen advanced wound care dressings promote tissue growth, autolysis, angiogenesis, collagen deposition, and wound re-epithelialization, acting as a catalyst in wound chronicity.

MMP regulating dressings, also known as collagen technology dressings, are suitable for chronic wounds because they inhibit matrix metalloproteinases (MMPs) that degrade viable and non-viable collagen. 

Currently, we lack the technology to measure MMP levels in a wound bed. 

For a wound to heal properly, MMPs must be present in the correct quantity, at the correct time, and in the correct location. 

70-80 percent of the ECM of skin is composed of collagen, particularly types I and II.

Collagen can be derived from any species, but it is most commonly discovered in bovine, porcine, equine, fish, and bird tissues. 

In its matrix structure, collagen serves as a template for future tissue formation, and the primary structure continues to attract fibroblasts to the region. 

When the healing process reaches the maturation stage, it is believed to stimulate the deposition of aligned collagen fibers, thereby increasing the tensile strength of the new tissue.


Non-Hydrolyzed Collagen is the “purest form” of collagen. Non-hydrolyzed collagen retains significantly more of its native triple helical protein structure, allowing for greater molecular and scaffolding stability during wound healing. To improve thermal stability, mechanical strength, and the ability to engage in precise interactions with other biomolecules, it is essential that collagen maintains its triple helix structure.
When fragmentation causes collagen molecules to lose their triple helix structure, the role shifts to a more rejuvenated state by activating monocytes, thereby generating more macrophages, etc. Nonhydrolyzed collagen particles or powders may improve scaffolding and cell migration for developing granulation tissue.

Collagen in its “purest form” is collagen that has not been hydrolyzed. 

Non-hydrolyzed collagen preserves a greater proportion of its native triple helix protein structure, resulting in increased molecular and scaffold stability during wound healing. 

To enhance thermal resistance, mechanical strength, and the capacity to engage in precise interactions with other biomolecules, collagen must preserve its triple helix structure.

When collagen molecules fragment, their triple helix structure is lost, the function changes to a more rejuvenated state by activating monocytes, resulting in the production of more macrophages, etc. 

Collagen particles or powders that have not been hydrolyzed may enhance scaffolding and cell migration during the formation of granulation tissue.


Due to the low molecular weight of its peptides, hydrolyzed collagen cannot form scaffolds on its own, but it can be combined with other copolymers such as cellulose and chitosan to form scaffolds. It consists of “dead-protein.” This type of collagen is produced primarily from nonbioavailable connective tissue. The derived source must undergo hydrolysis and an aggressive chemical process; consequently, it is composed of “post-collagen” amino acids.

Hydrolyzed Collagen is broken down into its constituent amino acids, glycine, proline, and hydroxyproline, and thus no longer possesses its native triple helical structure or “purest form.” Hydrolyzed collagen fragments in the form of particles or powder generate more active sites in the wound bed for fibronectin binding and enhanced fibroblast activity.

Due to the low molecular weight of the peptides, hydrolyzed collagen is incapable of forming scaffolds on its own, but it can be combined with other copolymers such as cellulose and chitosan. 

It is known as “dead-protein.” 

This type of collagen is primarily derived from connective tissue that is not bioavailable. 

Because the derived source is subjected to hydrolysis and a harsh chemical process, it contains post-collagen amino acids.

Because hydrolyzed collagen is broken down into its component amino acids, glycine, proline, and hydroxyproline, it no longer exists in its “purest form” 

Hydrolyzed collagen fragments in the form of particles or powder generate more active sites in the wound bed, promoting fibronectin binding and fibroblast activity.

Although not all collagen dressings are created equal, the objective is to hasten wound healing. 

Wound healing involves a series of steps that must be carried out in a logical sequence. 

Hemostasis, inflammation, proliferation, and remodeling are all possible bodily conditions. 

In order for wounds to heal, the damaged tissue is repaired spontaneously by the body. 

When this cascade healing process is not followed, the wound becomes chronic or difficult to heal. 

Chronic inflammation increases metalloproteases (MMPs), with biofilm formation in the wound also contributing. 

Collagen dressings can help maintain an optimally moist environment, stimulate the deposition of new collagen fibers, and promote new tissue regeneration during the healing process.

Using different Collagen technology dressings in conjunction with wound bed preparation, moist-wound healing, offloading/redistribution, and education has been shown to advance chronic complex wounds along the wound healing trajectory. 

When selecting advanced wound care products, healthcare professionals should consider product quality, product features, cost, and availability.

Utilize the wound assessment and clinical data to select a collagen dressing. 

Consider the type and quantity of collagen in an advanced wound care collagen dressing, as well as the method of production, cost-effectiveness, user-friendliness, and bioactive technology. 

The moist wound healing environment created by bioactive collagen materials aids in wound healing. 

According to clinical evidence, collagen-based dressings may be capable of influencing wound biochemistry and addressing chronic wound imbalances.

The blog of Human BioSciences, Inc. provides education and advice; however, the information provided by this website or company is not intended to replace medical treatment or advice.


In conjunction with wound bed preparation, moist-wound healing, offloading/redistribution, and education, various Collagen technology dressings have been demonstrated to advance chronic complex wounds along the wound healing trajectory. When selecting advanced wound care products, healthcare professionals should consider quality, product properties, cost, and availability.

Work Cited :

Brenner M, Albert P, Raminfard A. Collagen Treatment in the Diabetic Foot. The Diabetic Foot. 2019 November/December. Podiatry Management. last accessed July 30, 2020.

Gibson DJ, Schultz GS. Molecular Wound Assessments: Matrix Metalloproteinases. Adv Wound Care (New Rochelle). 2013;2(1):18-23. doi: 10.1089/wound.2011.0359

Chattopadhyay S, Raines RT. Review collagen-based biomaterials for wound healing. Biopolymers. 2014;101(8):821-833. doi: 10.1002/bip.22486Xenogeneic extracellular matrix as a scaffold for tissue reconstruction.

Badylak SF Transpl Immunol. 2004 Apr; 12(3-4):367-77.Westgate, S., Cutting, K. F., Deluca, G., & Assad, K. (n.d.). Collagen dressings Made Easy (page 1 of 3) › Made Easy › Wounds UK. Retrieved March 26, 2018, from

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