Publications  

ROLE OF POLYHEAL MICROSPHERES IN WOUND HEALING IN PATIENTS WITH CHRONIC ULCERS
V. M. Ritter, Ph.D, G. Rosenblat, Ph.D., Sh. Maretski ,Ph.D, A. Lazarovich  M.Sc. Ritter M, MD,  Tendler, M, MD ,Ph.D, l. Faitelberg, MD, Shamovski, V, M.Sc., Polyheal Ltd.

POLYHEAL-1 A NEW PRODUCT FOR THE TREATMENT OF RECALCITRANT ULCERS IN PATIENTS WITH NECROBIOSIS LIPOIDICA DIABETICORUM

R. Ahrahami, MD., T. Tamir, MD., * L. Kogan, MD **

Department of Vascular Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva, *Department of Plastic Surgery, Sheba Medical Center, Sacker School of Medicine, Tel Aviv University, Tel Aviv, and **Department of Plastic Surgery, Nahariya Medical Center, Israel

ULCERATING NECROBIOSIS LIPOIDICA DIABETICORUM TREATED WITH POLYHEAL-1

R. Avrahami¹,   B. Bsharah¹, A. Zelikovsky¹

¹Department of Vascular Surgery, Rabin Medical Center, Beilinson Campus, Petah Tiqva; Zammenhof Community Clinic, General Health Services, Tel Aviv;

POLYHEAL-1, A NOVEL TREATMENT FOR CHRONIC ULCERS WITH EXPOSED BONE & TENDON: A PRELIMINARY REPORT

J. Tamir MD, R. Avrahami* MD, L. Kogan** MD, PhD.

Plastic Surgery Department, Sheba Medical Center, Israel. *Vascular Surgery Clinic, Zamenhoff Clinic, General Health Fund, Tel Aviv, Israel. ** Plastic Surgery Unit, Nahariya Medical Center, Israel. 

POLYHEAL-1 FOR THE TREATMENT OF RECALCITRANT DIABETIC FOOT ULCERS: A PRELIMINARY REPORT

Dr. Leonid Kogan, Plastic Surgery Unit, Western Galillee Hospital, Nahariya, Israel

THE ROLE OF POLYHEAL MICROSPHERES IN WOUND HEALING IN PATIENTS WITH CHRONIC ULCERS

V. M. Ritter, Ph.D, G. Rosenblat, Ph.D., Sh. Maretski ,Ph.D, A. Lazarovich  M.Sc. Ritter M, MD,  Tendler, M, MD ,Ph.D, l. Faitelberg, MD, Shamovski, V, M.Sc., Polyheal Ltd., Israel

Introduction: The care of chronic recalcitrant wounds is a problem that haunts patients, potential patients and the medical staff that should care for them.  Polyheal Ltd presents a technology based on topical application of chemically inert non-biodegradable microspheres for treatment of  chronic ulcers.  

The first commercially available product, Polyheal 1® has been tested in leading Israeli hospitals.  Polyheal 1® has been used in treatment of stagnated recalcitrant ulcers, which resulted in the development of wound granulations, epithelization or preparation of the wound bed for a skin graft.

From previous data ^{1, 2} 30 patients with ulcers with exposed bones/tendons were treated. 

In 28 patients (93.3%), total coverage of exposed bones or tendons with healthy granulation tissue was achieved within 2.5 weeks on the average (minimum 0.5 weeks, maximum 6 weeks). Size of exposed bone/tendon varied from 0.5 cm² up to 30 cm².   In two patients (one with diabetic gangrene and other with a radiated scull) the treatment did not show any benefit. No complications related to Polyheal-1 were observed. Some aspects of the Polyheal activity have been studied in vitro.

Methods: Various biochemical, molecular and cell biology methods have been applied in order to investigate the interaction of cells with the microspheres.

Results: In vitro and in vivo studies employing myoblasts, inflammatory cells, fibroblasts and keratinocytes suggested that the action of the microspheres was dependent on their direct contact with cell surface. 

Such contact triggers several types of cellular responses. These entail changes in cell functions, including proliferation, enhancement of collagen production (in human foreskin fibroblasts) at a rate of about 150% and significant changes in gene expression of a number of cytokines in inflammatory cells.

Initial clinical and biochemical studies of venous stasis ulcers demonstrated a dramatic decrease in the amount of exudates (within one week), 48 h after the beginning of wound treatment with Polyheal 1.

Discussion: The detailed mechanism of the action of Polyheal 1 microspheres in wound is not fully elucidated at present.  Topical application of Polyheal microspheres may change the balance of cytokines in the wound space, influencing the structure and composition of the wound bed, and these seem to constitute an important trigger that terminates wound stagnation, as was observed in our clinical studies. The possible role of Polyheal treatment in different stages of the healing process was discussed.

1. J. Yehudain-Govrin, MD., R. Shafir, MD – unpublished data

2. J. Tamir J, MD, R. Avrahami MD, L. Kogan, MD

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POLYHEAL-1 A NEW PRODUCT FOR THE TREATMENT OF RECALCITRANT ULCERS IN PATIENTS WITH NECROBIOSIS LIPOIDICA DIABETICORUM

R. Ahrahami, MD., T. Tamir, MD., * L. Kogan, MD **

Department of Vascular Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva, *Department of Plastic Surgery, Sheba Medical Center, Sacker School of Medicine, Tel Aviv University, Tel Aviv, and **Department of Plastic Surgery, Nahariya Medical Center, Israel

Introduction: Necrobiosis lipoidica diabeticus (NLD) is a disorder of collagen degeneration in diabetic patients.  One-third of the lesions progress to ulcers, and management is often difficult.  Polyheal-1 is a water-based suspension of polymer microspheres intended for treatment of various types of chronic ulcers.  The dressing is placed over the surface of the wound and covered with gauze pads. The aim of this work is to describe the use of Polyheal-1 in a patient with NLD.

Methods: A 51 year-old woman with uncontrolled Type I diabetes mellitus presented with 4 (1-3cm²) unhealed ulcers in both legs for 5 months in duration. The patient was also a heavy smoker. Various types of local treatment had proven unsuccessful. A treatment regimen consisting of twice-daily placements of Polyheal-1 dressings was started. 

Results: Immediate granulation response was noted during the first week of treatment. Complete wound closure of all ulcers was achieved 8 weeks after the initiation of treatment with Polyheal-1.

Discussion: The underlying mechanism of Polyheal-1 activity is not fully understood. Apparently, the microspheres provide additional surface area for cell attachment. The resultant multi-point contact between the microspheres and the cell membranes facilitate the normal process of wound healing.

UP 

ULCERATING NECROBIOSIS LIPOIDICA DIABETICORUM TREATED WITH POLYHEAL-1

R. Avrahami¹,   B. Bsharah¹, A. Zelikovsky¹

¹Department of Vascular Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva; Zammenhof Community Clinic, General Health Services, Tel Aviv;

Introduction  

Necrobiosis lipoidica diabeticorum (NLD) is an inflammatory dermopathy strongly associated with Type-I diabetes mellitus and less frequently with Type-II diabetes mellitus[1] [2].  One-third of these lesions progress to ulcers which often fail to respond to either topical or systemic therapy.

Varying degrees of benefit have recently been reported from different treatment regimens such as pharmaceuticals that act on the haemostatic mechanisms, corticosteroid therapy (topical, intralesional and systemic), enhancers of wound healing, surgery and immunomodulating therapies (including photochemotherapy).  However, effective treatment of NLD related ulcers is rarely observed. We describe here the treatment of NLD ulcers with Polyheal-1â, a novel wound healing product.  The active ingredient  of Polyheal 1 are specially designed non biodegradable microspheres that have previously been  reported to be useful in the treatment of diabetic,  ischemic  and other recalcitrant chronic, ulcers with definite effects on appearance and development of healthy granulation tissue in  very  stubborn conditions and in preparation of chronic wounds for skin graft.   

CASE REPORT 

A 51-year-old woman with uncontrolled Type 1 diabetes mellitus and an 8-year history of biopsy-confirmed NLD lesions in both pretibial areas presented with unhealed ulcerations at the NLD sites, despite 5 months of treatment with topical antibiotics and corticosteroid agents. On examination, 4 ulcers measuring 1-3 cm² each were noted on the skin surface of both legs.  

The patient was ambulatory treated and tested weekly at an outpatient clinic.   The treatment regimen consisted of once a day topical application followed by a gauze pad dressing moistened with Polyheal and a dry regular dressing. (morning treatment)  Each evening all dressings, except for the layer containing the Polyheal preparation, were changed while the pad contacting the wound was re-moistened with Polyheal 1 ad libitum.

Results:  In the first week of treatment a granulation response was noted and the patient reported an absence of pain.   Complete wound closure of all ulcers was achieved at 8 weeks after initiation of treatment.

DISCUSSION 

Various treatment regimens^{[3] ,[4]}, have been used in treating NLD with differing degrees of success,.   Topical or systemic corticosteroids, cyclosporine, nicotinamide, microangiopathic pentoxifylline, acetylsalicylic acid, ticlopidine, and chloroquine have all been applied as immunosuppressive and antiinflammatory agents. ^{[5] [6] [7]}      

There are a number of reports on the use of a variety of topical preparations that are thought to act by promoting wound healing in ulcerated NLs. These include recombinant human granulocyte-macrophage colony-stimulating factors (GM-CSF), in ulcerating NLs on leg ulcers of two patients suffering from diabetes^[8]

Physical modification of the wound microenvironment may also be beneficial in promoting wound repair.[9]  Other reported therapies include topical PUVA photochemotherapy, topically applied GM-CSF, bovine collagen, topical tretinoin, and mycophenolate mofetil. However, there is no treatment for NL that has proven efficacy in double-blind, placebo-controlled studies.

The common trait in all of the above treatments is that they supply an external biological agent to the wound. In contrast, the present study of Polyheal-1, uses a microsphere-based product for wound healing, that does not supply any biological components. The use of Polyheal-1 produced a positive response after a few changes of dressing, and full closure of the ulcers was achieved within 2 months. . 

Polyheal 1 contains as an active ingredient five micron  microspheres synthesized from modified polystyrene that are negatively  charged and  non biodegradable. Some  aspects of interaction of microspheres with different types of cells have been investigated earlier. It was observed, that total collagen production was stimulated after interaction of human foreskin fibroblasts and myofibroblasts with Polyheal’s microspheres in vitro. 

Apparently, the microspheres provide additional surface area for cell attachment that may, in turn, be responsible for a cascade of cellular events including changes in cell membrane, cytoskeletons, cytokines and altered gene regulation.   In conclusion, this case report demonstrates promising results in the treatment of a chronic NLD lesion with Polyheal-1.