Extracellular Matrix Modulation: Optimizing Skin Care and Rejuvenation Procedures

April 2016 | Volume 15 | Issue 4 | Supplement Individual Articles | 63 | Copyright © April 2016

Alan D. Widgerow MBBCh MMed FCS FACS,a Sabrina G. Fabi MD FAAD FAACS,b
Roberta F. Palestine MD,c Alexander Rivkin MD,d Arisa Ortiz MD FAAD,b Vivian W. Bucay MD FAAD,e
Annie Chiu, MD,f Lina Naga MD,g Jason Emer MD,h and Paul E. Chasan MD FACSi

aChief Medical Officer ALASTINTM Skincare Inc., Carlsbad, CA
bDepartment of Dermatology, University of California San Diego, San Diego, CA
cThe Dermatology Center, Bethesda, MD
dDavid Geffen, UCLA School of Medicine, Los Angeles, CA
eBucay Center for Dermatology and Aesthetics, San Antonio, TX
fThe Derm Institute, Redondo Beach, CA
gWashington Institute of Dermatologic Laser Surgery, Washington, DC
hThe Roxbury Institute, Beverly Hills, CA
iRanch & Coast Plastic Surgery, Del Mar, CA

Normal aging and photoaging of the skin are chronic processes that progress gradually. The extracellular matrix (ECM), constituting over 70% of the skin, is the central hub for repair and regeneration of the skin. As such, the ECM is the area where changes related to photodamage are most evident. Degradation of the ECM with fragmentation of proteins significantly affects cross talk and signaling between cells, the matrix, and its constituents. The accumulation of collagen fragments, amorphous elastin agglutinations, and abnormal cross-linkages between the collagen fragments impedes the ECM from its normal repair and regenerative capacity, which manifests as wrinkled, non-elastic skin. Similar to how the chronic wound healing process requires wound bed preparation before therapeutic intervention, treatment of chronic aging of the skin would likely benefit from a “skin bed preparation” to optimize the outcome of rejuvenation procedures and skin maintenance programs. This involves introducing agents that can combat stress-induced oxidation, proteasome dysfunction, and non-enzymatic cross linkages involved in glycation end products, to collectively modulate this damaged ECM, and upregulate neocollagenesis and elastin production. Agents of particular interest are matrikines, peptides originating from the fragmentation of matrix proteins that exhibit a wide range of biological activities. Peptides of this type (tripeptide and hexapeptide) are incorporated in ALASTIN™ Skin Nectar with TriHex™ technology (ALASTIN Skincare, Inc., Carlsbad, CA), which is designed to target ECM modulation with a goal of optimizing results following invasive and non-invasive dermal rejuvenating procedures.

J Drugs Dermatol. 2016;15(Suppl 4):s63-s71.


The extracellular matrix (ECM) is the largest component of the dermal skin layer and its synthesis and function is essential to wound healing and dermal regeneration. “The major structural components of the dermal ECM are collagen I and III, accounting for over 70% and 15%, respectively, of skin dry weight, providing the dermis with tensile strength and stability.”1 In addition, elastin fibers provide the elasticity and tonality to the skin that allows adaptation to intrinsic physiologic and extrinsic environmental stresses. The ECM creates an environment that encourages cross talk and signaling between cells and proteins that modulate function and cell biology. 2 These extra- or intracellular proteins are subject to degradation and modification. Metalloproteinases (MMPs) are the most significant enzymes in the ECM remodeling process but other significant matrix clearing mechanisms exist.

Extrinsic and Intrinsic Aging

“In areas exposed to ultraviolet light, acute or ‘extrinsic’ aging processes are superimposed on underlying chronic or ‘intrinsic’ aging mechanisms” with direct cosmetic and structural consequences for the aging skin.3 Fragmentation of the elastic and collagenous protein components of the ECM transform the smoother, fine-lined appearance of intrinsically aged skin to the roughened, deeply wrinkled appearance of moderately photoaged skin, characterized histologically by the loss of elastin fibrillin microfibrils and fibulin from the papillary dermis together with collagen fragmentation and ECM disruption.3 “In severely photoaged skin, abundant deposits of highly disorganized elastic fiber material are distributed throughout the dermis.”3
One of the main mechanisms responsible for intrinsic and extrinsic aging of the cells is the accumulation of damaged