What You Should Know About Wound Healing And Hyalofill

By Alan J. Cantor, DPM

The last decade has seen a tremendous evolution in the field of advanced wound management, both as a discipline and in regard to the development of wound healing therapies. New dressings, human skin equivalents, and barometric intervention all compete for utilization in the wound healing process. While each of these options is a viable intervention, there still needs to be more recognition of how wound biology and histo-cellular function affect wound healing.
Indeed, understanding the process of healing wounds is essential for the clinician dedicated to wound medicine. Often, it is stated that understanding wound biology and physiology in the 21st century will be as mandatory as reading and writing if you wish to be a competent wound healer. It is generally accepted that the next few years will feature new agents and therapies designed and devoted to regulating specific biological and cellular functions.
It is necessary to recognize the differences between an acute wound and a chronic wound in the biological-cellular response. An acute wound is understood to be an “acute disturbance of previous intact skin by external force.”1 The acute injury, which you would see with the immunocompetent elective surgical candidate, is an injury in which you can anticipate the normal wound healing cellular response. This cellular response is the classic multi-phase response of hemostasis, inflammation, granulation, reepithelialaization and remodelling.
Early granulation has heavy inflammatory activity (due to macrophage and neutrophil proliferation), which leads to a more fragile and unstable wound. However, once you’ve resolved the inflammation, a more stable environment emerges. This allows for a matrix which permits a new epidermal layer to be formed from epithelial cells migrating from surrounding intact periwound skin. Ultimately, a new protective epidermal barrier is established over the granulation tissue.
Significantly different from the acute wound is the chronic, non-healing wound. These are the wounds you’ll see with immunosuppressed hosts (diabetics) and these wound result from “internal forces.”1 With these patients, the normal wound healing cascade is disoriented and there is a prolonged inflammatory phase.
The inability of the host to deactivate the inflammatory response creates an environment unable to organize a normal, sequential cellular response. This results in the wound’s inability to create a healthy granulating bed. Furthermore, multiple destructive byproducts are formed, obstructing the formation of a healthy wound matrix, establishing a chronic wound that is unable to organize the choreographed, orderly cellular response that you would see in an acute wound.

Understanding The Makeup Of Hyaluronan
Hyaluronic acid (now formally known as hyaluronan) is a carbohydrate substance (a glycosaminoglycan). The material is a linear polymer of D-glucuronic acid and N-acetyl glucosamine. It is found in all vertebrates, in some marine organisms and in some bacteria. In the human body, it is present in many organs, including the vitrous humour of the eye, synovial fluid and the skin. With the exception of molecular weight variations, the molecule is identical among species in which it is found. Therefore, native hyaluronan, whether derived from mammalian, avian, amphibian or bacterial sources, is biocompatible, since the material is not recognized as a foreign body, even if it is derived from a different species.
Hyaluronan is an extremely hygroscopic molecule, which is capable of absorbing up to 3,000 times its own weight in water. While absorbing, the material swells to form viscous hydrogel. This hydrogel has unique viscoelastic and osmotic properties as well as cushioning possibilities.
Given this and other unique physical and biological properties, physicians have used hyaluronic acid materials in biomedical applications, such as ophthalmic surgery and for treating arthritic joints.2
Unmodified, native hyaluronan is very difficult to handle because of its gel properties and the limited physical stability. Sheer forces easily degrade the material. Esterification with benzyl alcohol of the carboxyl groups on the hyaluronan backbone produces a semi-synthetic family of biopolymers called Hyaff. Hyaff has several physical properties, including the water solubility and the speed of biodegradation, which are determined by the degree of esterification.
Therefore, this technology produces materials that can be produced into a range of medical products with different physical properties. One of these materials is called Hyalofill, a non-woven fleece dressing made entirely of Hyaff, which is specifically aimed at wound management.
When in contact with (wound) fluid, the Hyalofill dressing, is degraded through hydrolysis. The dressing is slowly de-esterified into its original components, hyaluronan and benzyl alcohol. In this form, hyaluronan is not distinguishable from endogenous hyaluronan and will not elicit a foreign body reaction.

How You Should Use Hyalofill
You should use Hyalofill primarily for treating indolent, “difficult to heal” ulcers. These ulcers include indolent venous leg ulcers, many diabetic foot ulcers and, in general, skin lesions that, with “regular” good therapy, do not show clear signs of wound closure. Since an ulcer could be defined as a “gradual disturbance of previously intact skin by internal forces,” it is important to realize that you have to properly manage the “internal forces.”1
For example, when treating a patient with a venous leg ulcer and massive edema of the leg, managing the edema with compression is absolutely necessary. Similarly, a diabetic foot ulcer in a patient with severe arterial occlusion cannot be expected to heal property, unless you ensure better circulation. Therefore, Hyalofill should be part of an overall treatment regimen, which takes the entire patient as well as the local circumstances into account.
Thoroughly preparing the wound is necessary to obtain the best results with Hyalofill. For example, in infected wounds, you should first treat the infection itself. Thorough debridement is also necessary. Necrosis prevents intimate contact between the wound surface and the dressing.
You can use different types of dressings over Hyalofill. These dressings include plain gauze, but also more sophisticated materials such as Aquacel or occlusive dressings.
The interval between dressing changes will depend upon the state of the wound. In heavily exuding wounds or wounds with a large amount of slough, it may be necessary to do more frequent dressing changes. After all, in an environment in which much fluid is released, hydrolysis and breakdown of hyaluronic acid will be more rapid. In extremely dry wounds, it may be
recommended to moisten Hyalofill before applying it. In general, when Hyalofill therapy is successful, you may gradually extend the interval between dressing changes.
In a comparative trial, Edmonds, et. al., evaluated patients with complicated diabetic foot ulcers.3 The control group patients were managed with a standard, extensive, wound care regimen, which included a foam as the primary dressing.3 A second group of patients were managed with exactly the same regimen, except for the primary dressing, which was Hyalofill.
Of the 13 patients in the Hyalofill group who had sinuses associated with the ulcer, 12 obtained complete closure of the sinus. In the control group, only one of nine patients with sinuses obtained complete closure. There was also significant differences between the two groups when it came to complete wound closure. Ten out of 15 patients in the Hyalofill group achieved complete wound closure whereas only three of 15 patients in the control group achieve complete wound closure.

Case Study: Treating A Venous Ulcer Of Five Years’ Duration
A 44-year-old male came into my practice with a venous ulcer on the lateral side of his left leg. The primary reason for the ulceration had been IV drug use, complicated by several periods of phlebitis and infection. Comorbidities were HIV, alcoholism, morbid obesity, hypertension and non-insulin dependent diabetes mellitus.
The leg ulcer had been present for five years. Over that period, it had been managed with an Unna Boot (changed weekly) and a plethora of topical and systemic drugs, including several types of antibiotics.
Upon inspecting the ulcer, we saw a granulating lesion. There was significant drainage but no pus. The drainage was probably caused by the considerable amount of edema. The patient had extensive fungal infection on the foot and nail mycosis. The entire ulcer area was very tender.
We initiated thorough debridement, combining it with the administration of Sporanox. We started topical use of becaplermin in combination with compression, but had to stop after the first application because of hyperaesthesia in the form of an “extreme burning sensation.”
Instead, we combined a Hyalofill dressing, covered with an Aquacel Hydrofiber dressing, with sustained compression. The dressings were changed twice a week. This approach resulted in a rapid response. After two weeks, the beginning of re-epithelialization had become apparent. By week five, the entire lesion was re-epithelialized.
Case Study: Treating A Long-Standing Plantar Ulcer Of A Rheumatoid Arthritis Patient
A 64-year-old female with severe rheumatoid arthritis had a history of hypertension, a cardiovascular accident, marked pedal joint contractures and atrophic skin. Multiple surgeries had been performed, including bilateral total hip, total knee and metacarpal joint replacements. They were all necessary given the consequences of rheumatoid arthritis. The patient was also using long-standing immunosuppression therapy, as a result of the arthritis.
Her orthopedic surgeon and rheumatologist referred her to our clinic. The patient had a long-standing (six month) plantar ulceration (0.5cm x 0.5cm) over the first metatarsal-phalangeal joint. The ulcer was deep, extending down to the bone. Previous physicians had used becaplermin (recombinant platelet-derived growth factor BB) gel therapy for six months without significant improvement.
The ulcer was the result of a pedal joint contracture and the complete loss of the protective fat pads. There was heavy serous drainage from the ulcer and we had a strong suspicion of osteomyelitis. The plantar skin was very atrophic. An MRI series revealed no evidence of osteomyelitis, and vascular assessment demonstrated adequate circulation to the foot.
To manage the ulcer, we implemented aggressive surgical debridement to remove necrotic tissue. After debridement, we covered the ulcer with Aquacel and DuoDerm CGF Border dressings to manage the high level of wound exudate. This regimen was continued until there was a reduction in the level of wound fluid production.
At this point, we added Hyalofill as a wound contact layer and changed the dressing at three- or four-day intervals. We used Aquacel over the Hyalofill layer (to control exudate and maintain a moist environment), and DuoDERM CGF Border as a top dressing. For offloading, the patient was given an ankle-foot brace.
By week four, steady progression had occurred. By week six, the ulcer was fully epithelialized.

In Conclusion
Wound management in general, but particularly the treatment of ulcers, requires a broad understanding of systemic and local pathophysiology. You have to address the systemic conditions that have led to the occurrence or caused the deterioration of an ulcer in order to close a wound.
On the local level, it is essential to understand the physiology of healing and implement steps to assist the natural wound healing process. These steps include managing edema and infection, using offloading techniques in patients with diabetic foot ulcers, and implementing proper debridement measures. However, even when you implement these steps correctly, a number of ulcers still do not heal properly. They become indolent or stagnant.
For these types of ulcers, Hyalofill seems to offer extended possibilities for wound management. When you combine Hyalofill with other good wound management techniques, you’ll find a number of ulcers (that had previously been managed for months with other materials) will start to progress toward complete healing. In my clinical experience, I have found Hyalofill to be an ideal choice for managing hard-to-heal wounds.

Dr. Cantor is in private practice at Meadowbrook Foot and Ankle Care in East Meadow, New York. He is an Attending Surgeon within the Department of Surgery at the Nassau University Medical Center in East Meadow. He is also an invited lecturer at Oxford University’s Wound Healing Summer School in the United Kingdom.


1. Hermans M. Hyalofill: innovations in wound care. In: Chen j, ed. Monograph. London: Bristol-Myers Squibb Company, 1997.

2. Balasz E. The viscoelastic matrix and control of cell function by hyaluronan. In: Laurant T, ed. The chemistry, biology and medical applications of hyaluronan and its derivatives. Vol. Wenner-Gren International Series. London: Portland press, 1998.

3. Edmonds M, Foster, A. Hyalofill: a new product for chronic wound management. The diabetic foot 2000; 3:29-30.

For related articles on wound healing, see the Wound Care Q&A column “Essential Tips On Managing Chronic Ulcer Pain” in the November, 2001 issue; “Unlocking The Secrets To Growth Factors” in the July, 2001 issue; or “Finding Diagnostic Clues Of Osteomyelitis” in the June, 2001 issue.

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