A New Approach To Using Growth Factors In Wound Healing

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Understanding The Nature Of Wound Healing

As we all know, the four phases of wound healing include the hemostatic phase, the inflammatory phase, the proliferative phase and tissue remodeling.

The hemostatic phase begins immediately following tissue injury. Platelets migrate and bind to the wound site, reducing or stopping blood flow. Fibrinogen is converted to fibrin by thrombin and a complex platelet/fibrin structure is formed. Growth factors released from platelets trapped in this structure initiate the wound healing process.

The inflammatory phase, which can last up to seven days, involves the infiltration of white cells into the wound site. This phase facilitates the removal of foreign material and the release of additional growth factors. Subsequently, the proliferative phase, which is also known as the fibroblastic phase, involves tissue regeneration, angiogenesis, matrix formation and epithelialization.5 The final phase of wound healing, remodeling, can last up to 24 months after the proliferative phase. In this phase of wound healing, enzyme complexes proteolytically remove excess tissue matrix while there is a continual process of collagen synthesis and breakdown.6 It is important to note these phases of wound healing overlap each other and are not separately identifiable chronological events.

Human platelets play an important role in controlling bleeding. They interact with the fibrin network and create a platelet/fibrin “plug” that achieves hemostasis. Perhaps more importantly, alpha granules on the surface of human platelets store most of the growth factors needed to start the healing process. These growth factors are immediately released from platelets activated by the clotting process occurring in the wound. These growth factors are involved in every phase of wound healing and are critical for any wound to heal.5

Researchers have identified a number of growth factors, including: PDGF (platelet-derived growth factor); EGF (epidermal growth factor); TGF-Beta (transforming growth factor-beta); VEGF (vascular endothelial growth factor); and IGF-I (insulin growth factor-I). Platelet-derived growth factors affect chemotaxis and migration (recruiting stem cells to the wound site). They also attach to cell receptors and control the genetic expression of stem cells via modulation of signal transduction pathways of secondary proteins, resulting in cellular division and differentiation. They promote angiogenesis and start the tissue regeneration and remodeling process.5

Using the Harvest double syringe applicator, you will see the APC+ form a gel via activation with a calcium chloride/thrombin mixture upon applying it to the wound.
This patient’s wound (see Case Study Two) was completely closed in 35 days after three autologous grafts using APC+.
Another view of the healed patient in Case Study Two.
This wound (see Case Study Three) was successfully closed with two treatments of autologous platelet concentrate in 21 days.
Here you can see the patient in Case Study Three, three weeks after beginning treatment.
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Author(s): 
By Stephen L. Barrett, DPM, CWS

There has been a plethora of advances, especially within the last several years, for the treatment of chronic wounds. One of the more notable advancements is the use of autologous platelet-derived growth factors. Not only have platelet-derived growth factors gained notoriety in specialties such as orthopedic, maxillofacial and plastic surgery, the technology is increasingly being recognized as an important modality for accelerating healing in chronic wounds.1-3
Human epidermal growth factor (EGF) has been shown to enhance wound healing in diabetic ulcers.4 Researchers have used various names to describe autologous platelet derived growth factors, including: APC+ (autologous platelet concentrate); PRP (platelet rich plasma); PC (platelet concentrate); and PG (platelet gel). However, while these terms are often interchanged in the literature, they are not necessarily clinically and biologically equivalent. In order to fully appreciate the impact of autologous platelet-derived growth factors, one must have a strong understanding of the wound healing process (see “Understanding The Nature Of Wound Healing” below).
Ongoing research continues to identify, investigate and explain more growth factors, their cellular mechanisms and the ways they interact with other proteins to affect the healing of both hard and soft tissue types.
Some of the complex interaction and function of platelet-derived growth factors have been reported in the literature. The use of platelet concentrates has enhanced osseous repair of bone grafts.2 Degranulation (release of growth factors from the alpha granules) of the platelet at the wound site is known to initiate and enhance the healing cascade.

Reviewing The Benefits Of Autologous Platelet Concentrate
By processing the patient’s own blood to derive a platelet concentrate, the surgeon can then use this autograft to treat both hard and soft tissue wounds. One may apply autologous platelet concentrate to an osteotomy site or combine it with a bone graft to fill a large defect and/or accelerate and enhance soft tissue wound healing.

Kevy and Jacobson, from the Center for Blood Research Laboratories, have shown that platelets concentrated with the SmartPReP™ system (Harvest Technologies) maintain normal functionality and are not activated or damaged during the separation process.7 They also reported that as platelet concentration increases, so does the concentration of growth factors released from those platelets. Autologous platelet concentrate prepared with the SmartPReP resulted in four to six times greater concentration of platelets than normal baseline platelet levels.
While there are other methods to process a patient’s blood in order to make a platelet concentrate, Kevy and Jacobson have shown that the SmartPReP system results in a greater platelet yield, greater platelet concentration and increased growth factor levels than these in other devices.7

How APC+ Differs From Procuren And Regranex
Some wound care clinicians have drawn the erroneous conclusion that using autologous platelet concentrate is similar to using Procuren® or that it is like using a recombinant growth factor preparation such as Regranex®. However, unlike a single growth factor recombinant preparation, APC+ results in the release of a multiplicity of growth factors synergistically working together in the wound site to enhance healing. It is not limited to a single regeneration pathway, but provides a more complete biologic event that is able to affect the entire healing cascade.
Procuren is a manufactured pharmaceutical material of extracted wound healing proteins that is suspended and diluted in a biological carrier. The product is devoid of all cellular components and their receptor sites. Although blood is drawn from the patient to produce Procuren and it is processed at a remote laboratory, there is no similarity between autologous platelet concentrate and Procuren or other recombinant single growth factor preparations.

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