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Mechanism of Action: Extracellular Matrix (ECM)-based Allograft Technology

Primer: Tissue Engineering and Regenerative Medicine Basics:

Tissue Structure:

The majority of living tissue’s volume is comprised of extracellular space between groups of tightly packed cells. This void is filled with a complex meshwork called the Extracellular Matrix.

Extracellular Matrix (ECM):

A dynamic, physiologically active structure of molecules secreted by cells that provides structural and biochemical support to surrounding cells and is a component of all living tissues.

  • Provides structural support for the adhesion of cells within tissues.
  • Influences cells’ division, growth, and development.
  • Determines how tissues look and function.

next generation of infused allografts
Stem Cells – Powerful Agents of Healing:

Tissue repair requires the recruitment of properly functioning stem cells to the wound location. They release growth factor proteins that speed up and enhance healing.

The ability of stem cells to regenerate and differentiate into different types of cells (pluripotency) offers incredible therapeutic potential for tissue engineering.

Both ECM and Stem Cells are essential for growth and wound healing processes.

Addressing a Need in the Regenerative Medicine Market:

Other allograft products serve only as temporary tissue “void fillers” and do not actively promote healing nor do they specify the particular cellular regeneration needed (such as bone vs. skin) at the wound/surgical site.  Because these products do not actively promote regeneration, they depend solely on the quality of the patients’ own stem cells for healing, which is often ineffective.

By contrast, Lattice Biologics’ modified Extracellular Matrix (ECM) is directed scaffold technology derived from native ECM secreted by human Mesenchymal Stem Cells (hMSC) that has been enhanced for optimal regeneration, differentiation, homing, and engraftment. This dramatically improves healing capacity and reduces surgical recovery times.

Benefits of Lattice Biologics’ Next Generation ECM-based Allografts:

Lattice’s Next Generation Allografts dramatically improve healing and reduce recovery times.  Our decellularized technology derived from native ECM secreted by human Mesenchymal Stem Cells (hMSC):

  • Actively promote patient healing and specific cellular regeneration.
  • Provides a microenvironment custom engineered to promote the ability of patients’ stem cells to adhere to the allograft and thrive.
  • Utilizes specific proteins, growth factors, and signaling markers that attract patients’ stem cells to the injury site to promote healing.
  • Allows regenerating cells to strategically differentiate as bone, skin, or cartilage.

Differentiation:

Lattice infuses human-sourced (as opposed to porcine) ECM into allograft materials to synergize the stem cells’ healing potential.  HMSCs possess the powerful potential to differentiate into any type of tissue.  Undirected allograft products do not harness this potential.

Lattice strategically applies modifiers of MSC gene expression to ECM to create directed scaffolds that direct hMSCs to differentiate and regenerate as the intended bone, skin, or cartilage cells. This creates optimized growth conditions to promote propagation, vascularization, and intentional differentiation for ideal healing.

Homing and Engraftment:

Our decellularized cement provides a microenvironment that is engineered to enhance the ability of stem cells to adhere (engraft) and thrive.  Lattice’s ECM technology serves as a reservoir of proteins and growth factors that provide targeted tissue engineering treatment through the use of signaling markers that attract hMSCs to the site of injury (homing).  Homing delivers hMSCs where they need to do their healing work and help ensures the grafts “take” properly.

Mechanisms of ECM function

Figure: Mechanisms of ECM function. “The versatile functions of the ECM depend on its diverse physical, biochemical, and biomechanical properties. Anchorage to the basement membrane is essential for various biological processes, including asymmetric cell division in stem cell biology and maintenance of tissue polarity (stage 1). Depending on contexts, the ECM may serve to block or facilitate cell migration (stages 2 and 3). In addition, by binding to growth factor signaling molecules and preventing their otherwise free diffusion, the ECM acts as a sink for these signals and helps shape a concentration gradient (stage 4). Certain ECM components, including heparan sulfate proteoglycans and the hyaluronic acid receptor CD44, can selectively bind to different growth factors and function as a signal coreceptor (stage 5) or a presenter (stage 6) and help determine the direction of cell–cell communication (Lu et al., 2011). The ECM also direct signals to the cell by using its endogenous growth factor domains (not depicted) or functional fragment derivatives after being processed by proteases such as MMPs (stage 7). Finally, cells directly sense the biomechanical properties of the ECM, including its stiffness, and change a wide variety of behaviors accordingly (stage 8).”1

1Source: Pengfei Lu, Valerie M. Weaver, and Zena Werb. “The extracellular matrix: A dynamic niche in cancer progression.” The Rockefeller University Press J. Cell Biol. Vol. 196 No. 4 395–406 www.jcb.org/cgi/doi/10.1083/jcb.201102147.

ECM Mechanisms

Testimonial

“Everything went great… Lattice’s allografts worked really well and I liked using them. I also think they were more pliable than Alloderm.”

- Plastic Surgeon (Lattice Biologics client)