Matthew Regulski - Academia.edu (original) (raw)

Papers by Matthew Regulski

Research paper thumbnail of Giant Cell Tumor within the Tibialis Anterior Tendon: A Case Report

SVOA orthopaedics, May 10, 2024

Giant cell tumors of tendon sheath (GCT-TS) also characterized as giant cell tumors of low malign... more Giant cell tumors of tendon sheath (GCT-TS) also characterized as giant cell tumors of low malignant potential (GCT-TS LMP) are extremely rare entities found most frequently in the extremities. It appears as an enlarging painless mass and has a synovial origin. GCT-TS is approximately 1.6% of all soft tissue tumors. 1 The GCT-TS of the tibialis anterior tendon is very rare, and recurrence has not been reported in the literature. The authors present a rare case of a 71-year-old male with a GCT-TS within the Anterior Tibialis tendon. The soft tissue mass is characterized by a mix of giant cell reaction & gouty tophus occurring within the Tibialis Anterior Tendon.

Research paper thumbnail of A Case Series Examining the Use of Extracorporeal Shockwave Therapy (ESWT) to Treat Non-healing Venous Leg Ulcers

Stem cell and regenerative medicine, Jun 29, 2023

With their complex pathogenesis, many wounds, such as venous leg ulcers (VLUs) and diabetic foot ... more With their complex pathogenesis, many wounds, such as venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs), place a significant burden on the global healthcare system [1]. 93% of venous leg ulcers (VLUs) are open for more than a year due to a variety of factors such as comorbidities, lifestyle, and work demands. The most common causes are venous disease, arterial disease, and neuropathy. To avoid inappropriate treatment that could worsen the wound, delay healing, or harm the patient, a correct diagnosis is required. Wound chronicity can lead to complications such as infections, amputation, and even death. The purpose of this study is to determine the efficacy of ESWT therapy in patients with chronic non-healing venous leg ulcers who have not shown any signs of healing for more than a year [2].

Research paper thumbnail of Biofilm and Hospital-Acquired Infections in Older Adults

Critical Care Nursing Clinics of North America, Jul 1, 2023

Research paper thumbnail of Application of Dehydrated Amniotic Membrane Allografts in Advanced Diabetic Foot Ulceration: Case Report and Review of Literature

Reports, Jul 20, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Open-label Extension Phase of a Chronic Diabetic Foot Ulcer Multicenter, Controlled, Randomized Clinical Trial Using Cryopreserved Placental Membrane

PubMed, Sep 1, 2018

Objective: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved... more Objective: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved placental membrane; CPM; Osiris Therapeutics, Inc, Columbia, MD) multicenter, blinded, randomized, controlled clinical trial for chronic diabetic foot ulcers (DFUs) is reported. Materials and methods: Twenty-six patients in the standard wound care (SWC) arm whose DFUs did not close in the blinded phase chose to receive weekly applications of the CPM in an open-label extension phase. Results: In the extension phase, 17 (65.4%) patients closed their wounds in a median of 34 days and 3 visits. There were fewer total adverse events (AEs) (24 CPM vs. 52 SWC) and index wound-related infections (5 CPM vs. 12 SWC) during the CPM application compared with the number of AEs for the same patients during the SWC treatment in the blinded phase of the trial. Conclusions: These results corroborate the benefits of this CPM combined with SWC over SWC alone for chronic DFUs previously reported for the blinded randomized phase of the trial, which directly relate to lower health care costs.

Research paper thumbnail of Understanding Diabetic Induction of Cellular Senescence: A Concise Review

PubMed, Apr 1, 2018

Objective: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemos... more Objective: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. Materials and methods: Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for histopathological evaluation. Results: After 8 weeks, the extent of wound healing was similar between SCBS and ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds exhibited a greater depth of thermal effect over the first 3 weeks despite a shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory markers at early time points but healed more slowly, with scores that lagged behind ES for collagen deposition, fibrous tissue maturity, extracellular matrix, and stage of healing. Myofiber regeneration notably increased in SCBS-treated wounds at weeks 2, 3, and 8. By the end of the 8-week recovery period, there were no significant differences in healing parameters between the 2 groups. Conclusions: Overall, both devices elicited similar progression of healing by 8 weeks. The SCBS produced a deeper thermal effect in a shorter treatment time and improved myofiber regeneration compared with ES and had an equivalent overall course of healing.

Research paper thumbnail of Management of a chronic radiation necrosis wound with lyopreserved placental membrane containing viable cells

Clinical Case Reports, Jan 28, 2019

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Research paper thumbnail of Mesenchymal Stem Cells: "Guardians of Inflammation

PubMed, 2017

Human mesenchymal stem cells (MSCs) are a unique progenitor cell that can be recovered from most ... more Human mesenchymal stem cells (MSCs) are a unique progenitor cell that can be recovered from most vascularized tissues in the human body. In addition to their capability of differentiating into tissues of mesenchymal lineage, perhaps their most salient features are immunomodulation and trophic capabilities. A chronic wound is characterized by an overzealous immune response that leads to a corrosive extracellular matrix, deficiency of regulatory growth factors, hypoxia, and cellular senescence. Human MSCs are a potential therapeutic modality to recapitulate the healing paradigm through their capacity to modulate both the innate and the adaptive immune responses. They are capable of secreting specific proteins, as dictated by the microenvironment they are placed into, that will have anti-inflammatory and growth restorative effects on all cellular factions. Their low immunogenicity suggests MSCs can be transplanted without the need for matching between donor and recipient. The current understanding of the cellular mechanisms underlying their immunomodulatory effects is summarized in this review.

Research paper thumbnail of Cellular Senescence: What, Why, and How

PubMed, Jun 1, 2017

Cellular senescence is a process that results from a variety of stresses and leads to a state of ... more Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis; however, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. The pathways for the proteins p53/p21 and p16Ink4a/retinoblastoma protein are important for irreversible growth arrest and senescent cells. Senescent cells secrete numerous biologically active factors; the specific secretion phenotype by senescent cell contributes to physiological and pathological consequences in organisms. The purpose of this article is to review the molecular basis of cell-cycle arrest and the senescent-associated secretory phenotype within these cells contributing to pathological consequences.

Research paper thumbnail of The efficacy and safety of Grafix <sup>®</sup> for the treatment of chronic diabetic foot ulcers: results of a multi‐centre, controlled, randomised, blinded, clinical trial

International Wound Journal, Jul 21, 2014

In a randomised, controlled study, we compared the efficacy of Grafix®, a human viable wound matr... more In a randomised, controlled study, we compared the efficacy of Grafix®, a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase. The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix (62%) compared with controls (21%, P = 0·0001). The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls (P = 0·019). There were fewer Grafix patients with adverse events (44% versus 66%, P = 0·031) and fewer Grafix patients with wound‐related infections (18% versus 36·2%, P = 0·044). Among the study subjects that healed, ulcers remained closed in 82·1% of patients (23 of 28 patients) in the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0·419). Treatment with Grafix significantly improved DFU healing compared with standard wound therapy. Importantly, Grafix also reduced DFU‐related complications. The results of this well‐controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than standard wound therapy.

Research paper thumbnail of Anti-Biofilm Efficacy of Commonly Used Wound Care Products in In Vitro Settings

Antibiotics, Mar 8, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Utilization of a Viable Human Amnion Membrane Allograft in Elderly Patients With Chronic Lower Extremity Wounds of Various Etiologies

PubMed, Mar 1, 2018

ntroduction. Chronic nonhealing wounds are a growing health care problem in the United States, af... more ntroduction. Chronic nonhealing wounds are a growing health care problem in the United States, afflicting more than 6.5 million patients annually. In particular, diseases that compromise skin integrity and impair normal wound healing processes, such as diabetes and peripheral vascular diseases, are becoming more common in the aging population and leading to ever-increasing incidence of these chronic nonhealing wounds. Objective: The aim of this study is to evaluate a viable human amnion membrane allograft (vHAMA) for the treatment of chronic nonhealing wounds in elderly patients (aged > 65 years) with multiple comorbidities. Materials and methods: Four patients (age range, 69-85 years) with 5 chronic wounds of varying etiologies and sizes (2 traumatic wounds, 2 diabetic foot ulcers, and 1 venous leg ulcer) that persisted for at least 4 weeks and failed previous treatment with standard of care were included in this study. Comorbidities included diabetes mellitus, obesity, polymyalgia rheumatica, lymphedema, peripheral vascular disease, steroid use, and neuropathy. All patients received vHAMA once weekly or as deemed appropriate. Results: All patients reached complete wound closure with no complications or adverse events. Mean time to closure was 4.8 weeks (range, 2-8 weeks) with an average of 4.2 grafts (range, 1-8). There was no wound recurrence. Conclusions: Successful closure of wounds indicates the use of vHAMA may be beneficial for treatment of chronic wounds in elderly patients with comorbidities.

Research paper thumbnail of A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds

PubMed, Dec 1, 2013

Despite the introduction of advanced wound care modalities over the last 15 years, chronic wounds... more Despite the introduction of advanced wound care modalities over the last 15 years, chronic wounds are an increasing problem. Few single options are available for clinicians to treat recalcitrant wounds such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). A retrospective, single-center study was conducted at an outpatient wound care center to evaluate the clinical effect of a human cellular repair matrix (h-CRM) on chronic wounds that had failed to heal. Data from all patients who had received this treatment modality during a period of 2 years were abstracted. Standard care included weekly visits, regular debridement, offloading DFUs, compression for VLUs, and h-CRM for wounds >4 weeks duration. A total of 66 patients (30 male, 36 female, mean age 71.1 [± 8.8] years) received h-CRM treatment for 67 wounds (34 VLUs, 27 DFUs, and six other chronic wounds). The average wound size at baseline was 6.65 (± 9.68) cm2, and the average wound duration before h-CRM treatment was 38 (±70.8) weeks. Fifty (50) patients (74.6%) had failed to heal using other advanced therapies. After 12 weeks of care, 51 of the 67 wounds (76.1%) were healed: 23 of 34 (67.6%) VLUs and 23 of 27 (85.2%) DFUs. Average time to closure in these wounds was 5.8 (±2.5) weeks. No significant differences were found between proportions of VLUs and DFUs healed. No adverse events or recurrences occurred during an average follow-up time of 20.4 months (range 11 to 32 months). Overall, patients received an average of 3.8 applications of h-CRM, and 3.2 applications were used among patients that healed. The study results suggest h-CRM may benefit patients with chronic wounds. Prospective, randomized clinical studies are warranted.

Research paper thumbnail of Wound Closure Outcomes Suggest Clinical Equivalency Between Lyopreserved and Cryopreserved Placental Membranes Containing Viable Cells

Advances in wound care, Nov 1, 2019

Objective: To evaluate the clinical outcomes of lyopreserved placental membrane containing viable... more Objective: To evaluate the clinical outcomes of lyopreserved placental membrane containing viable cells (vLPM) in the treatment of nonhealing wounds of various etiologies, and to compare them to those previously reported for cryopreserved placental membrane containing viable cells (vCPM). Approach: Patients with nonhealing wounds who qualified to receive advanced wound therapies were consecutively enrolled and treated weekly with vLPM plus standard of care (SOC) at five centers. Data were de-identified and retrospectively analyzed. Outcomes included closure, time to closure, number of vLPM applications, and adverse events (AEs). Results: Seventy-eight patients with 98 wounds (41 diabetic foot ulcers [DFUs], 19 venous leg ulcers [VLUs], 10 surgical, and 28 others) with an average size of 13.3 cm 2 and 8.7 months duration were treated. Fifty-eight of the 98 wounds (59.2%) achieved complete closure with median time to closure of 63 days and 6 vLPM applications. The closure by wound etiology was 63% for DFUs, 47% for VLUs, 70% for surgical wounds, and 57% for other types of wounds. Similar closure rates have been previously demonstrated for vCPM. Wound duration was the main predictor of closure: 65.8% versus 30.0% (p = 0.004) closure was achieved for wounds of £12 and >12 months duration, respectively. There were no AEs related to vLPM application. Innovation: This is the first multicenter case series evaluating the clinical outcomes of vLPM in a real-world setting. Conclusion: These results support clinical equivalency between the two placental membrane formulations with the added convenience of room-temperature storage for vLPM, allowing it to be used in any wound-care setting.

Research paper thumbnail of Activated collagen accelerates wound repair and modulates cytokine production in whole blood and PBMC cultures

Cytokine, Oct 1, 2009

Several reports have shown that exogenous collagen fragments enhance wound repair through poorly ... more Several reports have shown that exogenous collagen fragments enhance wound repair through poorly understood mechanisms. CellerateRX is an activated (fragmented) product derived from Type I Collagen that is applied topically as a gel or powder on open wounds that are often infected or colonized with bacteria. In three case series, topical CellerateRX in conjunction with standard care healed infected surgical wounds and diabetic ulcers more rapidly than standard therapy alone. We conducted an interim analysis of 16 patients with lower extremity diabetic ulcers. Eight patients received CellerateRX in addition to standard treatment, and 8 received standard treatment alone. A quantitative analysis of wound healing at 14 weeks showed that CellerateRX-treated wounds were 100 0% healed, compared to 59 13.5% healing in control subject wounds. To examine possible mechanisms by which CellerateRX enhances wound healing, cytokine production was assessed in 24 hr cultures of whole blood and peripheral blood mononuclear cells (PBMC) from 10 healthy subjects. These cultures were

Research paper thumbnail of Biofilm and Hospital-Acquired Infections in Older Adults

Critical Care Nursing Clinics of North America

Research paper thumbnail of Anti-Biofilm Efficacy of Commonly Used Wound Care Products in In Vitro Settings

Antibiotics

Considering the prevalence and pathogenicity of biofilms in wounds, this study was designed to ev... more Considering the prevalence and pathogenicity of biofilms in wounds, this study was designed to evaluate the anti-biofilm capabilities of eight commercially available wound care products using established in vitro assays for biofilms. The products evaluated included dressings with multiple delivery formats for ionic silver including nanocrystalline, gelling fibers, polyurethane (PU) foam, and polymer matrix. Additionally, non-silver-based products including an extracellular polymeric substance (EPS)-dissolving antimicrobial wound gel (BDWG), a collagenase-based debriding ointment and a fish skin-based skin substitute were also evaluated. The products were evaluated on Staphylococcus aureus and Pseudomonas aeruginosa mixed-species biofilms grown using colony drip flow reactor (CDFR) and standard drip flow reactor (DFR) methodologies. Anti-biofilm efficacy was measured by viable plate counts and confocal scanning laser microscopy (CSLM). Four of the eight wound care products tested wer...

Research paper thumbnail of Application of Amniotic Membrane Allografts in Advanced Venous Leg Ulcer: A Case Study and Literature Review

Chronic venous insufficiency (CVI) is a lifelong, moribund, and debilitating disease process with... more Chronic venous insufficiency (CVI) is a lifelong, moribund, and debilitating disease process with tremendous personal and financial costs. At its core, CVI involves blood pooling in the lower extremities secondary to inadequate venous blood return, resulting in venous hypertension and incompetence of the one-way valves in the lower extremity veins. As venous circulation slows, metabolic demands of the cells in the lower extremities increase, leading to stasis dermatitis, infection, cellular death, and venous ulceration. This case study aims to report the efficacy of dehydrated amniotic membrane allograft (DAMA) applications to a chronic right lateral ankle ulcer resulting from chronic venous insufficiency. The patient in this study received DAMA applications weekly for six weeks. Upon examination at the initial application, the wound was wet and macerated due to drainage with significant hemosiderosis and lipodermatosclerosis consistent with a Venous Clinical Severity Score (VCSS) o...

Research paper thumbnail of Application of Dehydrated Amniotic Membrane Allografts in Advanced Diabetic Foot Ulceration: Case Report and Review of Literature

Reports

The management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wo... more The management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound-care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18-month duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrat...

Research paper thumbnail of Understanding Diabetic Induction of Cellular Senescence: A Concise Review

Wounds : a compendium of clinical research and practice, 2018

OBJECTIVE This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemost... more OBJECTIVE This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. MATERIALS AND METHODS Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for histopathological evaluation. RESULTS After 8 weeks, the extent of wound healing was similar between SCBS and ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds exhibited a greater depth of thermal effect over the first 3 weeks despite a shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory markers at early time points but healed more slowly,...

Research paper thumbnail of Giant Cell Tumor within the Tibialis Anterior Tendon: A Case Report

SVOA orthopaedics, May 10, 2024

Giant cell tumors of tendon sheath (GCT-TS) also characterized as giant cell tumors of low malign... more Giant cell tumors of tendon sheath (GCT-TS) also characterized as giant cell tumors of low malignant potential (GCT-TS LMP) are extremely rare entities found most frequently in the extremities. It appears as an enlarging painless mass and has a synovial origin. GCT-TS is approximately 1.6% of all soft tissue tumors. 1 The GCT-TS of the tibialis anterior tendon is very rare, and recurrence has not been reported in the literature. The authors present a rare case of a 71-year-old male with a GCT-TS within the Anterior Tibialis tendon. The soft tissue mass is characterized by a mix of giant cell reaction & gouty tophus occurring within the Tibialis Anterior Tendon.

Research paper thumbnail of A Case Series Examining the Use of Extracorporeal Shockwave Therapy (ESWT) to Treat Non-healing Venous Leg Ulcers

Stem cell and regenerative medicine, Jun 29, 2023

With their complex pathogenesis, many wounds, such as venous leg ulcers (VLUs) and diabetic foot ... more With their complex pathogenesis, many wounds, such as venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs), place a significant burden on the global healthcare system [1]. 93% of venous leg ulcers (VLUs) are open for more than a year due to a variety of factors such as comorbidities, lifestyle, and work demands. The most common causes are venous disease, arterial disease, and neuropathy. To avoid inappropriate treatment that could worsen the wound, delay healing, or harm the patient, a correct diagnosis is required. Wound chronicity can lead to complications such as infections, amputation, and even death. The purpose of this study is to determine the efficacy of ESWT therapy in patients with chronic non-healing venous leg ulcers who have not shown any signs of healing for more than a year [2].

Research paper thumbnail of Biofilm and Hospital-Acquired Infections in Older Adults

Critical Care Nursing Clinics of North America, Jul 1, 2023

Research paper thumbnail of Application of Dehydrated Amniotic Membrane Allografts in Advanced Diabetic Foot Ulceration: Case Report and Review of Literature

Reports, Jul 20, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Open-label Extension Phase of a Chronic Diabetic Foot Ulcer Multicenter, Controlled, Randomized Clinical Trial Using Cryopreserved Placental Membrane

PubMed, Sep 1, 2018

Objective: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved... more Objective: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved placental membrane; CPM; Osiris Therapeutics, Inc, Columbia, MD) multicenter, blinded, randomized, controlled clinical trial for chronic diabetic foot ulcers (DFUs) is reported. Materials and methods: Twenty-six patients in the standard wound care (SWC) arm whose DFUs did not close in the blinded phase chose to receive weekly applications of the CPM in an open-label extension phase. Results: In the extension phase, 17 (65.4%) patients closed their wounds in a median of 34 days and 3 visits. There were fewer total adverse events (AEs) (24 CPM vs. 52 SWC) and index wound-related infections (5 CPM vs. 12 SWC) during the CPM application compared with the number of AEs for the same patients during the SWC treatment in the blinded phase of the trial. Conclusions: These results corroborate the benefits of this CPM combined with SWC over SWC alone for chronic DFUs previously reported for the blinded randomized phase of the trial, which directly relate to lower health care costs.

Research paper thumbnail of Understanding Diabetic Induction of Cellular Senescence: A Concise Review

PubMed, Apr 1, 2018

Objective: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemos... more Objective: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. Materials and methods: Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for histopathological evaluation. Results: After 8 weeks, the extent of wound healing was similar between SCBS and ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds exhibited a greater depth of thermal effect over the first 3 weeks despite a shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory markers at early time points but healed more slowly, with scores that lagged behind ES for collagen deposition, fibrous tissue maturity, extracellular matrix, and stage of healing. Myofiber regeneration notably increased in SCBS-treated wounds at weeks 2, 3, and 8. By the end of the 8-week recovery period, there were no significant differences in healing parameters between the 2 groups. Conclusions: Overall, both devices elicited similar progression of healing by 8 weeks. The SCBS produced a deeper thermal effect in a shorter treatment time and improved myofiber regeneration compared with ES and had an equivalent overall course of healing.

Research paper thumbnail of Management of a chronic radiation necrosis wound with lyopreserved placental membrane containing viable cells

Clinical Case Reports, Jan 28, 2019

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Research paper thumbnail of Mesenchymal Stem Cells: "Guardians of Inflammation

PubMed, 2017

Human mesenchymal stem cells (MSCs) are a unique progenitor cell that can be recovered from most ... more Human mesenchymal stem cells (MSCs) are a unique progenitor cell that can be recovered from most vascularized tissues in the human body. In addition to their capability of differentiating into tissues of mesenchymal lineage, perhaps their most salient features are immunomodulation and trophic capabilities. A chronic wound is characterized by an overzealous immune response that leads to a corrosive extracellular matrix, deficiency of regulatory growth factors, hypoxia, and cellular senescence. Human MSCs are a potential therapeutic modality to recapitulate the healing paradigm through their capacity to modulate both the innate and the adaptive immune responses. They are capable of secreting specific proteins, as dictated by the microenvironment they are placed into, that will have anti-inflammatory and growth restorative effects on all cellular factions. Their low immunogenicity suggests MSCs can be transplanted without the need for matching between donor and recipient. The current understanding of the cellular mechanisms underlying their immunomodulatory effects is summarized in this review.

Research paper thumbnail of Cellular Senescence: What, Why, and How

PubMed, Jun 1, 2017

Cellular senescence is a process that results from a variety of stresses and leads to a state of ... more Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis; however, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. The pathways for the proteins p53/p21 and p16Ink4a/retinoblastoma protein are important for irreversible growth arrest and senescent cells. Senescent cells secrete numerous biologically active factors; the specific secretion phenotype by senescent cell contributes to physiological and pathological consequences in organisms. The purpose of this article is to review the molecular basis of cell-cycle arrest and the senescent-associated secretory phenotype within these cells contributing to pathological consequences.

Research paper thumbnail of The efficacy and safety of Grafix <sup>®</sup> for the treatment of chronic diabetic foot ulcers: results of a multi‐centre, controlled, randomised, blinded, clinical trial

International Wound Journal, Jul 21, 2014

In a randomised, controlled study, we compared the efficacy of Grafix®, a human viable wound matr... more In a randomised, controlled study, we compared the efficacy of Grafix®, a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase. The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix (62%) compared with controls (21%, P = 0·0001). The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls (P = 0·019). There were fewer Grafix patients with adverse events (44% versus 66%, P = 0·031) and fewer Grafix patients with wound‐related infections (18% versus 36·2%, P = 0·044). Among the study subjects that healed, ulcers remained closed in 82·1% of patients (23 of 28 patients) in the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0·419). Treatment with Grafix significantly improved DFU healing compared with standard wound therapy. Importantly, Grafix also reduced DFU‐related complications. The results of this well‐controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than standard wound therapy.

Research paper thumbnail of Anti-Biofilm Efficacy of Commonly Used Wound Care Products in In Vitro Settings

Antibiotics, Mar 8, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Utilization of a Viable Human Amnion Membrane Allograft in Elderly Patients With Chronic Lower Extremity Wounds of Various Etiologies

PubMed, Mar 1, 2018

ntroduction. Chronic nonhealing wounds are a growing health care problem in the United States, af... more ntroduction. Chronic nonhealing wounds are a growing health care problem in the United States, afflicting more than 6.5 million patients annually. In particular, diseases that compromise skin integrity and impair normal wound healing processes, such as diabetes and peripheral vascular diseases, are becoming more common in the aging population and leading to ever-increasing incidence of these chronic nonhealing wounds. Objective: The aim of this study is to evaluate a viable human amnion membrane allograft (vHAMA) for the treatment of chronic nonhealing wounds in elderly patients (aged > 65 years) with multiple comorbidities. Materials and methods: Four patients (age range, 69-85 years) with 5 chronic wounds of varying etiologies and sizes (2 traumatic wounds, 2 diabetic foot ulcers, and 1 venous leg ulcer) that persisted for at least 4 weeks and failed previous treatment with standard of care were included in this study. Comorbidities included diabetes mellitus, obesity, polymyalgia rheumatica, lymphedema, peripheral vascular disease, steroid use, and neuropathy. All patients received vHAMA once weekly or as deemed appropriate. Results: All patients reached complete wound closure with no complications or adverse events. Mean time to closure was 4.8 weeks (range, 2-8 weeks) with an average of 4.2 grafts (range, 1-8). There was no wound recurrence. Conclusions: Successful closure of wounds indicates the use of vHAMA may be beneficial for treatment of chronic wounds in elderly patients with comorbidities.

Research paper thumbnail of A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds

PubMed, Dec 1, 2013

Despite the introduction of advanced wound care modalities over the last 15 years, chronic wounds... more Despite the introduction of advanced wound care modalities over the last 15 years, chronic wounds are an increasing problem. Few single options are available for clinicians to treat recalcitrant wounds such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). A retrospective, single-center study was conducted at an outpatient wound care center to evaluate the clinical effect of a human cellular repair matrix (h-CRM) on chronic wounds that had failed to heal. Data from all patients who had received this treatment modality during a period of 2 years were abstracted. Standard care included weekly visits, regular debridement, offloading DFUs, compression for VLUs, and h-CRM for wounds >4 weeks duration. A total of 66 patients (30 male, 36 female, mean age 71.1 [± 8.8] years) received h-CRM treatment for 67 wounds (34 VLUs, 27 DFUs, and six other chronic wounds). The average wound size at baseline was 6.65 (± 9.68) cm2, and the average wound duration before h-CRM treatment was 38 (±70.8) weeks. Fifty (50) patients (74.6%) had failed to heal using other advanced therapies. After 12 weeks of care, 51 of the 67 wounds (76.1%) were healed: 23 of 34 (67.6%) VLUs and 23 of 27 (85.2%) DFUs. Average time to closure in these wounds was 5.8 (±2.5) weeks. No significant differences were found between proportions of VLUs and DFUs healed. No adverse events or recurrences occurred during an average follow-up time of 20.4 months (range 11 to 32 months). Overall, patients received an average of 3.8 applications of h-CRM, and 3.2 applications were used among patients that healed. The study results suggest h-CRM may benefit patients with chronic wounds. Prospective, randomized clinical studies are warranted.

Research paper thumbnail of Wound Closure Outcomes Suggest Clinical Equivalency Between Lyopreserved and Cryopreserved Placental Membranes Containing Viable Cells

Advances in wound care, Nov 1, 2019

Objective: To evaluate the clinical outcomes of lyopreserved placental membrane containing viable... more Objective: To evaluate the clinical outcomes of lyopreserved placental membrane containing viable cells (vLPM) in the treatment of nonhealing wounds of various etiologies, and to compare them to those previously reported for cryopreserved placental membrane containing viable cells (vCPM). Approach: Patients with nonhealing wounds who qualified to receive advanced wound therapies were consecutively enrolled and treated weekly with vLPM plus standard of care (SOC) at five centers. Data were de-identified and retrospectively analyzed. Outcomes included closure, time to closure, number of vLPM applications, and adverse events (AEs). Results: Seventy-eight patients with 98 wounds (41 diabetic foot ulcers [DFUs], 19 venous leg ulcers [VLUs], 10 surgical, and 28 others) with an average size of 13.3 cm 2 and 8.7 months duration were treated. Fifty-eight of the 98 wounds (59.2%) achieved complete closure with median time to closure of 63 days and 6 vLPM applications. The closure by wound etiology was 63% for DFUs, 47% for VLUs, 70% for surgical wounds, and 57% for other types of wounds. Similar closure rates have been previously demonstrated for vCPM. Wound duration was the main predictor of closure: 65.8% versus 30.0% (p = 0.004) closure was achieved for wounds of £12 and >12 months duration, respectively. There were no AEs related to vLPM application. Innovation: This is the first multicenter case series evaluating the clinical outcomes of vLPM in a real-world setting. Conclusion: These results support clinical equivalency between the two placental membrane formulations with the added convenience of room-temperature storage for vLPM, allowing it to be used in any wound-care setting.

Research paper thumbnail of Activated collagen accelerates wound repair and modulates cytokine production in whole blood and PBMC cultures

Cytokine, Oct 1, 2009

Several reports have shown that exogenous collagen fragments enhance wound repair through poorly ... more Several reports have shown that exogenous collagen fragments enhance wound repair through poorly understood mechanisms. CellerateRX is an activated (fragmented) product derived from Type I Collagen that is applied topically as a gel or powder on open wounds that are often infected or colonized with bacteria. In three case series, topical CellerateRX in conjunction with standard care healed infected surgical wounds and diabetic ulcers more rapidly than standard therapy alone. We conducted an interim analysis of 16 patients with lower extremity diabetic ulcers. Eight patients received CellerateRX in addition to standard treatment, and 8 received standard treatment alone. A quantitative analysis of wound healing at 14 weeks showed that CellerateRX-treated wounds were 100 0% healed, compared to 59 13.5% healing in control subject wounds. To examine possible mechanisms by which CellerateRX enhances wound healing, cytokine production was assessed in 24 hr cultures of whole blood and peripheral blood mononuclear cells (PBMC) from 10 healthy subjects. These cultures were

Research paper thumbnail of Biofilm and Hospital-Acquired Infections in Older Adults

Critical Care Nursing Clinics of North America

Research paper thumbnail of Anti-Biofilm Efficacy of Commonly Used Wound Care Products in In Vitro Settings

Antibiotics

Considering the prevalence and pathogenicity of biofilms in wounds, this study was designed to ev... more Considering the prevalence and pathogenicity of biofilms in wounds, this study was designed to evaluate the anti-biofilm capabilities of eight commercially available wound care products using established in vitro assays for biofilms. The products evaluated included dressings with multiple delivery formats for ionic silver including nanocrystalline, gelling fibers, polyurethane (PU) foam, and polymer matrix. Additionally, non-silver-based products including an extracellular polymeric substance (EPS)-dissolving antimicrobial wound gel (BDWG), a collagenase-based debriding ointment and a fish skin-based skin substitute were also evaluated. The products were evaluated on Staphylococcus aureus and Pseudomonas aeruginosa mixed-species biofilms grown using colony drip flow reactor (CDFR) and standard drip flow reactor (DFR) methodologies. Anti-biofilm efficacy was measured by viable plate counts and confocal scanning laser microscopy (CSLM). Four of the eight wound care products tested wer...

Research paper thumbnail of Application of Amniotic Membrane Allografts in Advanced Venous Leg Ulcer: A Case Study and Literature Review

Chronic venous insufficiency (CVI) is a lifelong, moribund, and debilitating disease process with... more Chronic venous insufficiency (CVI) is a lifelong, moribund, and debilitating disease process with tremendous personal and financial costs. At its core, CVI involves blood pooling in the lower extremities secondary to inadequate venous blood return, resulting in venous hypertension and incompetence of the one-way valves in the lower extremity veins. As venous circulation slows, metabolic demands of the cells in the lower extremities increase, leading to stasis dermatitis, infection, cellular death, and venous ulceration. This case study aims to report the efficacy of dehydrated amniotic membrane allograft (DAMA) applications to a chronic right lateral ankle ulcer resulting from chronic venous insufficiency. The patient in this study received DAMA applications weekly for six weeks. Upon examination at the initial application, the wound was wet and macerated due to drainage with significant hemosiderosis and lipodermatosclerosis consistent with a Venous Clinical Severity Score (VCSS) o...

Research paper thumbnail of Application of Dehydrated Amniotic Membrane Allografts in Advanced Diabetic Foot Ulceration: Case Report and Review of Literature

Reports

The management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wo... more The management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound-care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18-month duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrat...

Research paper thumbnail of Understanding Diabetic Induction of Cellular Senescence: A Concise Review

Wounds : a compendium of clinical research and practice, 2018

OBJECTIVE This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemost... more OBJECTIVE This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. MATERIALS AND METHODS Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for histopathological evaluation. RESULTS After 8 weeks, the extent of wound healing was similar between SCBS and ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds exhibited a greater depth of thermal effect over the first 3 weeks despite a shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory markers at early time points but healed more slowly,...