Publications by authors named "Danielle M Minteer"

10 Publications

  • Page 1 of 1

Patient Selection for Pedal Soft Tissue Augmentation.

Aesthet Surg J Open Forum 2020 Sep 24;2(3):ojaa031. Epub 2020 Jun 24.

School of Medicine and the Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA.

Background: Pedal fat grafting has been shown to improve pain and functional impairment from forefoot fat pad atrophy.

Objectives: The authors aimed to determine if patient demographics and foot characteristics play a role in the level of impact that is achieved following surgery.

Methods: The authors performed a retrospective review of patients who received forefoot autologous fat injections for the treatment of pedal fat pad atrophy. Patient improvement of pain and functional impairment were evaluated for correlation with patient characteristics, including gender, age, BMI, unilateral vs bilateral injections, flexible vs rigid arch, previous foot deformity or surgery, and presence of callus.

Results: Forty-four patients received fat injections into the ball of their foot; 73% of them were women; their mean age was 61 years, and mean BMI was 26.6 kg/m; 75% had injections performed bilaterally; 41% had a flexible arch, 73% had a past history of pedal deformity or surgery, and 43% had callus. Only female gender was found to correlate with an improvement in pain from the time of surgery to 12 months later ( = 0.02).

Conclusions: Bilateral rigid, high arched foot type is a risk factor for foot pain and disproportionately represented among these patients. The only patient characteristic found to be correlated with improvement in pain at 12 months post-surgery was female gender. BMI and laterality of injections impacted the course of improvement after surgery. Given current data, all patients with suspected pedal fat pad atrophy should be considered for soft tissue augmentation.

Level Of Evidence 4:
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http://dx.doi.org/10.1093/asjof/ojaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671290PMC
September 2020

Clinical Evaluation of an Off-the-Shelf Allogeneic Adipose Matrix for Soft Tissue Reconstruction.

Plast Reconstr Surg Glob Open 2020 Jan 27;8(1):e2574. Epub 2020 Jan 27.

Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pa.

Biomaterials derived from human adipose extracellular matrix have shown promise in vitro and in animal studies as an off-the-shelf adipogenic matrix for sustained volume replacement. Herein, we report the results of a randomized prospective study conducted with allograft adipose matrix (AAM) grafted into the pannus of presurgical abdominoplasty patients 3 or 6 months before scheduled surgery. This is the first report of a longitudinal histologic analysis of AAM in clinical use.

Methods: Ten healthy patients undergoing elective abdominoplasty were recruited to receive AAM before surgery. Enrolled subjects were randomized into either a 3-month follow-up cohort or a 6-month follow-up cohort. Subjects were monitored for adverse events associated with AAM grafting in addition to undergoing serial biopsy. Following surgical excision of the pannus, representative samples from the AAM surgical sites were stained and evaluated with hematoxylin and eosin for tissue morphology, Masson's trichrome for collagen, and perilipin for adipocytes.

Results: All subjects tolerated AAM with no severe adverse events reported. At 3 months following implantation, AAM remained visible within the confines of the subjects' native surrounding adipose tissue with sparse adipocytes apparent within the matrix. By 6 months, AAM had remodeled and was primarily composed of perilipin-positive adipocytes. Histologic analysis confirmed tissue remodeling (hematoxylin and eosin), adipogenesis (perilipin), and angiogenesis (Masson's trichrome) occurred with the presence of AAM.

Conclusions: AAM is a safe, allogeneic, off-the-shelf regenerative matrix that is adipogenic and noninflammatory and promotes angiogenesis.
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http://dx.doi.org/10.1097/GOX.0000000000002574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015604PMC
January 2020

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates.

Sci Transl Med 2020 01;12(527)

Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and -ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm) compared to autograft (4.62 ± 3.99 μm) and PCL/Empty (4.52 ± 5.16 μm) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.
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http://dx.doi.org/10.1126/scitranslmed.aav7753DOI Listing
January 2020

Pressure Ulcer Monitoring Platform-A Prospective, Human Subject Clinical Study to Validate Patient Repositioning Monitoring Device to Prevent Pressure Ulcers.

Adv Wound Care (New Rochelle) 2020 01 6;9(1):28-33. Epub 2019 Dec 6.

Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

The objective of this prospective clinical study was to validate two prototype pressure ulcer monitoring platform (PUMP) devices, (PUMP1 and PUMP2), to promote optimal bed repositioning of hospitalized patients to prevent pressure ulcers (PUs). PUMP1 was a wearable electronic device attached to the patient gown with no skin contact. PUMP2 was a set of four identical electronic devices placed under the patient's bed wheels. A video camera recorded events in the patient room while measurements from the PUMP devices were correlated with true patient repositioning activity. The performance of these PUMP devices developed by our research team were evaluated and compared by both clinicians and engineers. Ten mobility-restricted patients were enrolled into the study. Repositioning movement was recorded by both PUMP devices for 10 ± 2 h and corroborated with video capture. One hundred thirty-seven movements in total were detected by both PUMP1 and PUMP2 over 105 h of capture. Two false positives were detected by the sensors and 11 movements were missed by the sensors. PUMP1 and PUMP2 never conflicted in data collection. The presented study evaluated two different sensors' abilities to capture accurate patient repositioning to eventually prevent PU formation. Importantly, detection of patient motion was completed without contact to patient skin. The clinical study demonstrated successful capture of patient repositioning movement by both PUMP1 and PUMP2 devices with 85% reliability, 2 false positives, and 11 missed movements. In future studies, the PUMP devices will be combined with a SMS-based mobile phone alert system to improve caregiver repositioning behavior.
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http://dx.doi.org/10.1089/wound.2018.0934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922059PMC
January 2020

Volumetric Analysis in Autologous Fat Grafting to the Foot.

Plast Reconstr Surg 2019 09;144(3):463e-470e

Pittsburgh, Pa.

Background: Pedal fat grafting is a safe, minimally invasive approach to treat pedal fat pad atrophy. Prior randomized controlled trials demonstrate that the fat as measured directly under the metatarsal heads disappears between 2 and 6 months after fat grafting, despite patients having relief for 2 years. The authors aim to use magnetic resonance imaging to further assess three-dimensional volume of fat in the foot after autologous fat grafting to help explain the mechanism for improved pain.

Methods: A prospective study was performed using magnetic resonance imaging before and at 6 months after pedal fat grafting to assess changes in the three-dimensional morphology of the fat.

Results: Seventeen patients (six men and 11 women) underwent injections with a mean volume of 5.8 cc per foot. At 6 months, patients demonstrated increased tissue thickness (p = 0.008) and volume (p = 0.04). Improvements were seen in pain (p < 0.05) and activity (p < 0.05). Foot pressures and forces were significantly decreased and positively correlated with increased fat pad volume (p < 0.05).

Conclusions: Pedal fat grafting significantly increases metatarsal fat pad volume. The distribution of the fat may contribute to lasting clinical relief in these patients.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000005956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716614PMC
September 2019

Fat Grafting for Pedal Fat Pad Atrophy in a 2-Year, Prospective, Randomized, Crossover, Single-Center Clinical Trial.

Plast Reconstr Surg 2018 12;142(6):862e-871e

From the Department of Plastic Surgery, University of Pittsburgh.

Background: By age 60, 30 percent of Americans suffer from fat pad atrophy of the foot. Forefoot fat pad atrophy results from long-term aggressive activity, genetically dictated foot type, multiple forefoot steroid injections, surgery, and foot trauma.

Methods: The authors present data from a 2-year, prospective, randomized crossover study performed to assess pain and disability indexes, fat pad thickness, forces, and pressures of stance and gait. Group 1 underwent fat grafting with 2 years of follow-up, and group 2 underwent conservative management for 1 year, then underwent fat grafting with 1 year of follow-up.

Results: Eighteen subjects (14 women and four men) constituted group 1. Thirteen subjects (nine women and four men) constituted group 2. Group 1 reported the worst pain at baseline and group 2 experienced the worst pain at 6- and 12-month standard-of-care visits; pain for both groups improved immediately following fat grafting and lasted through study follow-up (p < 0.05). Group 1 demonstrated functional improvements at 12, 18, and 24 months postoperatively (p < 0.05), whereas group 2 demonstrated the highest function at 12 months postoperatively (p < 0.05). Pedal fat pad thickness of subjects in group 1 increased postoperatively and returned to baseline thickness at 2 months postoperatively; subjects in group 2 experienced return to baseline thickness at 6 months postoperatively (p < 0.01). Forces and pressures of stance and gait increased over the 2 years of follow-up for group 1 (p < 0.05).

Conclusion: Pedal fat grafting provides long-lasting improvements in pain and function, and prevents against worsening from conservative management.

Clinical Question/level Of Evidence: Therapeutic, I.
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http://dx.doi.org/10.1097/PRS.0000000000005006DOI Listing
December 2018

Combining micro-computed tomography with histology to analyze biomedical implants for peripheral nerve repair.

J Neurosci Methods 2015 Nov 20;255:122-30. Epub 2015 Aug 20.

Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, United States. Electronic address:

Background: Biomedical implants used in tissue engineering repairs, such as scaffolds to repair peripheral nerves, can be too large to examine completely with histological analyses. Micro-computed tomography (micro-CT) with contrast agents allows ex vivo visualization of entire biomaterial implants and their interactions with tissues, but contrast agents can interfere with histological analyses of the tissues or cause shrinkage or loss of antigenicity.

New Method: Soft tissue, ex vivo micro-CT imaging using Lugol's iodine was compatible with histology after using a rapid (48 h) method of removing iodine.

Results: Adult normal and repaired rat sciatic nerves were infiltrated ex vivo with iodine, imaged with micro-CT and then the iodine was removed by incubating tissues in sodium thiosulfate. Subsequent paraffin sections of normal nerve tissues showed no differences in staining with hematoxylin and eosin or immunostaining with multiple antibodies. Iodine treatment and removal did not alter axonal diameter, nuclear size or relative area covered by immunostained axons (p>0.05). Combining imaging modalities allowed comparisons of macroscopic and microscopic features of nerve tissues regenerating through simple nerve conduits or nerve conduits containing a titanium wire for guidance.

Comparison With Existing Methods: Quantification showed that treatment with iodine and sodium thiosulfate did not result in tissue shrinkage or loss of antigenicity.

Conclusions: Because this combination of treatments is rapid and does not alter tissue morphology, this expands the ex vivo methods available to examine the success of biomaterial implants used for tissue engineering repairs.
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http://dx.doi.org/10.1016/j.jneumeth.2015.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604061PMC
November 2015

Adipose stem cells: biology, safety, regulation, and regenerative potential.

Clin Plast Surg 2015 Apr;42(2):169-79

Department of Bioengineering, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Plastic Surgery, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15213, USA. Electronic address:

This article discusses adipose-derived stem cell (ASC) biology, describes the current knowledge in the literature for the safety and regulation of ASCs, and provides a brief overview of the regenerative potential of ASCs. It is not an exhaustive listing of all available clinical studies or every study applying ASCs in tissue engineering and regenerative medicine, but is an objective commentary of these topics.
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http://dx.doi.org/10.1016/j.cps.2014.12.007DOI Listing
April 2015

Bioreactors addressing diabetes mellitus.

J Diabetes Sci Technol 2014 Nov 26;8(6):1227-32. Epub 2014 Aug 26.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA

The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies.
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http://dx.doi.org/10.1177/1932296814548215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455464PMC
November 2014

Adipogenesis of human adipose-derived stem cells within three-dimensional hollow fiber-based bioreactors.

Tissue Eng Part C Methods 2012 Jan 18;18(1):54-61. Epub 2011 Oct 18.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.

To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes and create three-dimensional (3D) adipose tissue in vitro, we applied multicompartment hollow fiber-based bioreactor technology with decentral mass exchange for more physiological substrate gradients and integral oxygenation. We hypothesize that a dynamic 3D perfusion in such a bioreactor will result in longer-term culture of human adipocytes in vitro, thus providing metabolically active tissue serving as a diagnostic model for screening drugs to treat diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose tissue and then inoculated into dynamic 3D culture bioreactors to undergo adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D-bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture displayed multiple mature adipocyte markers with more unilocular morphologies as compared with two-dimensional (2D) cultures. Results of real-time polymerase chain reaction showed 3D-bioreactor treatment had more efficient differentiation in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted in increased glucose uptake, with a return to baseline between testing. Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic activity of the tissue. 3D bioreactors allow more mature adipocyte differentiation of ASCs compared with traditional 2D culture and generate adipose tissue in vitro for up to 2 months. Reproducible metabolic activity of the adipose tissue in the bioreactor was demonstrated, which is potentially useful for drug discovery. We present here, to the best of our knowledge for the first time, the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro.
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http://dx.doi.org/10.1089/ten.TEC.2011.0216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245673PMC
January 2012