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Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra leading to disabling deficits. Dopamine neuron grafts may provide a significant therapeutic advance over current therapies. We have generated midbrain dopamine neurons from human embryonic stem cells and manufactured large-scale cryopreserved dopamine progenitors for clinical use. After optimizing cell survival and phenotypes in short-term studies, the cell product, MSK-DA01, was subjected to an extensive set of biodistribution, toxicity, and tumorigenicity assessments in mice under GLP conditions. A large-scale efficacy study was also performed in rats with the same lot of cells intended for potential human use and demonstrated survival of the grafted cells and behavioral amelioration in 6-hydroxydopamine lesioned rats. There were no adverse effects attributable to the grafted cells, no obvious distribution outside the brain, and no cell overgrowth or tumor formation, thus paving the way for a future clinical trial.

Background. Chronic lower extremity (LE) wounds frequently require significant interventions to close. The success of any method depends on an adequately prepared wound bed, while factors including wound size, perfusion, contamination, or exposed tissue structures can thwart efforts. We propose a standardized algorithm of care utilizing an acellular dermal matrix, split-thickness skin graft (STSG), and negative pressure wound therapy (NPWT) for the treatment of LE wounds. Methods. This was a single-center, retrospective cohort study examining patients who underwent LE wound debridement, placement of fetal bovine dermis (FBD), and STSG between 2016 and 2022. The primary outcome was wound closure, while secondary outcomes were wound infection and amputation-free survival. Results. Twenty patients (mean age 59 years, M:F 12:8)--including 24 LE venous ulcers (29.4%), amputation sites (29.4%), diabetic foot ulcers (25.0%), and atypical wounds (16.7%) with an average area of 39.15 cm²--underwent debridement and FBD placement followed by STSG a median of 61 days thereafter. Of these patients, 83.3% received NPWT after FBD and STSG with 86% closure. There was successful engraftment in 92% of wounds whose FBD placement was within 2 months of STSG. Of wounds that had <50% engraftment, 75% had a STSG placed over 2 months after FBD placement. Of those patients with post-STSG infection, 75% had the graft placed >2 months after FBD placement, one of which required proximal amputation. Conclusions. By following a treatment plan including debridement with treatment of infection, application of FBD with placement of STSG within 2 months thereafter, and reinforcing NPWT, chronic wounds will have an increased rate of successful reepithelialization. Many cases experienced delays from FBD engraftment until STSG application due to schedule and insurance impediments, which led to less favorable outcomes. Therefore, a protocol that involves scheduling the placement of STSG 4 weeks after successful engraftment of FBD has been adopted. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy of Acellular Fish Skin (AFS) in the closure of Wagner 1 and 2 Diabetic foot ulcer (DFU) when compared to a commercial collagen dressing. Therefore, a prospective randomized trial was initiated which included a total of 102 patients that randomized to best clinical practices (BCP)or weekly treatment with AFS. Method: Patient's with the hemoglobin A1c less than 12 with good arterial perfusion to the lower extremity with a diabetic foot wound greater than 1 sq cm and less than 12 sq cm were evaluated. Sharp debridement was carried out and 2 weeks of active offloading therapy was mandated. If the patient did not have a greater than 20% wound area reduction in the first 2 weeks, they were randomized to receive offloading in the form of a knee-high patellar weight-bearing brace. Then either AFS secured with surgical adhesive strips and covered with a non-adherent dressing applied weekly, or placing a collagen alginate dressing 3 times a week covered with gauze and stretch gauze with self-adherent wrap 3 times a week (BCP). Results / Discussion: At 12 weeks 57% (29/51) of the AFS group were closed while 31% (16/51) of the BCP group were closed. AFS closed relatively 80% more DFUs than BCP. The mean time to closure was 7 weeks, and the median number of applications was six. Conclusion: A clinically and statistically significant difference in healing was observed between patients treated with AFS and those treated with BCP. [ABSTRACT FROM AUTHOR]

Aim: Acellular fish skin (AFS) can be used to re-inforce suture lines, or cover bone in patients undergoing partial foot amputations or bone resections. Other utility is in the setting of a ray amputation. In all cases the post-surgical wounds have a portion of hard to fill potential space. Method: Seventeen patients that underwent bone resection, debridement or amputation had AFS placed over the bone, filling the dead space prior to primary closure of the skin and soft tissue. These operations were done as single stage operations, all patients were maintained as in patients post operatively for at least 4 days (median 6 days). Results / Discussion: Two of the 17 required further surgical intervention to close the wounds. However none of the patient's went on to further amputation or bone loss. Primary closure was obtained in 15 of the patients within 30 days of the primary index procedure. All patients regained ambulatory status in conjunction with appropriate accommodative footwear. Negative pressure wound therapy was not used in these patients. Conclusion: Acellular fish skin appears to be a viable adjunct for filling dead space and patients undergoing bony resection of their weight-bearing foot. A randomized controlled trial may elucidate whether AFS is superior to other methods to fill that space. [ABSTRACT FROM AUTHOR]

Aim: The overall cost of using of cellular or tissue-based therapies to close diabetic foot wounds is usually misrepresented. The cost of treating a cohort of patients must include the cost of success and the cost of failure. Method: The real costs of treating 102 DFU's over 12 weeks of wound that were randomized to treatment with acellular fish skin (AFS) or a collagen alginate dressing (CAT) is assessed. Results / Discussion: The real cost in 2022 U.S. Dollars is exhibited below.Cost to heal (0r not) an ulcer = weekly cost x number of weeks x number of (un) healed patients AFS cost = Total cost of care / 29 healed patients = $9235; CAT cost = Total cost of care / 16 healed patients = $6124. According to Medicare*, the total cost of care for ulcer in 1 year = $29,347; weekly cost = $29,347/52 = $564.37. Assuming nonhealed ulcers would stay open for the year. Cost of care for CAT = 35 patients x 40 weeks x $564.37 = $790,118 versus Cost of care for FSG = 22 patients x 40 weeks x $564.37 = $496,646 • Annual cost per therapy = total cost of care in study + cost of care rest of the year • Annual cost per therapy per patient = Annual cost per therapy / 51 • FSG annual life cost per individual = $13,926 • CAT annual life cost per individual = $16,744 Conclusion: Including the cost of complications of the unclosed DFU, treatment of Wagner 2 DFUs with AFS saves $2818 in the first year of therapy. [ABSTRACT FROM AUTHOR]

Aim: Acellular fish skin (AFS) is usually used on very well prepared lower extremity ulcers. However, some patients do not allow for good wound cleaning. Acellular fish skin was used an 18 patients who had significant comorbidities and only marginally adequate debridement of their lower leg ulcers. Method: Patients with lower extremity ulcers primarily of venous or atypical etiology with ultrasound tests consistent with some form of venous pathology, but adequate ankle brachial indices of with greater than 0.7 were approached. The patient then underwent 5 sequential weekly applications of AFS. The patient then underwent 3 further weeks of observation with non-stick dressings and multilayer compression. Of note none of these patients had particularly aggressive debridement. Results / Discussion: A 40% decrease in wound surface area (P < 0.05) and a 48% decrease in wound depth was seen with 5 weekly applications of the fish-skin graft and secondary dressing (P < 0.05). Complete closure was seen in 3 of 18 patients by the end of the study phase. The patients had a much steeper wound healing trajectory during the weekly application of the AFS then afterwards. Once AFS application was stopped, the wound healing trajectory became flat line. Conclusion: This fish-skin product appears to provide promise as an effective wound closing adjunctive ECM. This is true when used in this compassionate setting, where many other products fail. This study lacks a control arm and an aggressive application schedule, but the investigators believe it represents real-world practice. [ABSTRACT FROM AUTHOR]

NPWT has probably been the most important addition to wound care in the current century. Despite this fact, its use in the treatment of VLUs remains very limited. This review first examines the documented and potential VLU wound environment changes that can be facilitated by NPWT. The data supporting the use of NPWT for VLU wound bed preparation, the management of fluid drainage, and the bolstering of skin grafts are evaluated. The similarities and differences between suNPWT, traditional NPWT, and NPWTi are outlined. Included in this review is when and where each therapy may have a place in the treatment of VLUs. Finally, a brief algorithm to enhance the use of NPWT in the treatment of VLUs is presented.