Publications by authors named "Jack E Brooker"

8 Publications

  • Page 1 of 1

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

Cone-Beam Computed Tomography Incidental Findings in Individuals With Cleft Lip and Palate.

Cleft Palate Craniofac J 2020 04 22;57(4):404-411. Epub 2020 Jan 22.

UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Objectives: The use of cone-beam computed tomography (CBCT) is well-established in clinical practice. This study seeks to categorize and quantify the incidental finding (IF) rate on CBCT in patients with cleft lip and palate (CLP) prior to orthodontic or surgical treatment.

Methods: This is systematic retrospective review of head and neck CBCTs in patients with nonsyndromic CLP taken between 2012 and 2019 at a single tertiary referral center. All assessments were performed independently by 4 observers (a head and neck radiologist and 3 orthodontists, including 2 fellowship-trained cleft-craniofacial orthodontists ). The images were divided into 9 anatomical areas and screened using serial axial slices and 3D reconstructions. The absolute number of IFs was reported for each area and statistical analysis was performed.

Results: Incidental findings were found in 106 (95.5%) of the 111 patients. The most common sites were the maxilla (87.4%, principally dental anomalies), paranasal sinuses (46.8%, principally inflammatory opacification), and inner ear cavities (18.9%, principally inflammatory opacification). Eleven patients had skull malformations. Thirty-three patients had IFs in 1 anatomical area, 49 patients in 2 anatomical areas, 19 patients in 3 areas, and 5 patients presented with IFs in 4 of the 9 anatomical areas.

Discussion: In patients with CLP, IFs on CBCT exam were present in the majority of cases. Most patients with IFs had them in multiple anatomical areas of the head and neck. The maxillary dental-alveolar complex was the most common area. Inflammatory changes in the inner ear cavities and paranasal sinuses were also common; however, cervical spine and skull abnormalities were also identified. Clinicians caring for patients with CLP should be aware of IFs, which may warrant further investigation and treatment.
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http://dx.doi.org/10.1177/1055665619897469DOI Listing
April 2020

Interleukin-10 Does Not Augment Osseous Regeneration in the Scarred Calvarial Defect Achieved with Low-Dose Biopatterned BMP2.

Plast Reconstr Surg 2019 06;143(6):1215e-1223e

From the Department of Plastic Surgery, University of Pittsburgh; Biomedical Engineering and Biological Sciences and The Robotics Institute, Carnegie Mellon University; and The Ohio State University College of Medicine.

Background: Large calvarial defects represent a major reconstructive challenge, as they do not heal spontaneously. Infection causes inflammation and scarring, further reducing the healing capacity of the calvaria. Bone morphogenetic protein-2 (BMP2) has been shown to stimulate osteogenesis but has significant side effects in high doses. BMP2 has not been tested in combination with antiinflammatory cytokines such as interleukin-10.

Methods: Sixteen New Zealand White rabbits underwent 15 × 15-mm flap calvarectomies. The flap was incubated in Staphylococcus aureus and replaced, and infection and scarring were allowed to develop. The flap was subsequently removed and the wound débrided. A 15 × 15-mm square of acellular dermal matrix biopatterned with low-dose BMP2, interleukin-10, or a combination was implanted. Computed tomographic scans were taken over 42 days. Rabbits were then killed and histology was performed.

Results: Defects treated with BMP2 showed significantly (p < 0.05) greater osseous regeneration than untreated controls. Interleukin-10 did not significantly augment the healing achieved with BMP2, and interleukin-10 alone did not significantly increase healing compared with controls. Histology showed evidence of bone formation in defects treated with BMP2. Untreated controls and defects treated with interleukin-10 alone showed only fibrous tissue in the defect site.

Conclusions: Low-dose BMP2 delivered directly to the scarred calvarial defect augments bony healing. Interleukin-10 at the dose applied did not significantly augment healing alone or in combination with BMP2. Healing had not finished at 42 days and analysis at later time points or the use of higher doses of BMP2 may yield greater healing.
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http://dx.doi.org/10.1097/PRS.0000000000005640DOI Listing
June 2019

The Future of Facial Fat Grafting.

J Craniofac Surg 2019 May/Jun;30(3):644-651

Department of Plastic Surgery.

Fat grafting was first described in the early 20th century but for many years remained a relatively underused technique due to the unreliability of long-term volume expansion. Significant improvements in reliability have been made in the last 2 decades and there is a large body of literature pertaining to extraction, processing and injection methods to obtain more lasting effects. However, volume loss and graft resorption remain a major challenge in the long term and lead to unpredictability in results. Enriching adipose graft with stromal vascular fraction, ex vivo cultured adipose stem cells and platelet-derived growth factor among others is one method under active investigation which may assist graft survival through a range of mechanisms including increased angiogenesis. Breaking adipose graft into smaller fragments such that engrafted cells have greater access to donor-site oxygenation and nutrition is another method which in theory may promote survival. Presently, adipose grafting in the face is usually for the addition of volume to fill defects. However, the stem-cell containing fraction of adipose grafting (stromal vascular fraction) appears to exert a rejuvenating effect on overlying skin and soft tissue when administered alone. The application of these low-volume injections represents a significant shift in thinking away from mere volume expansion. These techniques have been tested in a range of animal models and some human studies. In this review, the authors provide a broad overview of present research and highlight both limitations in previous research and current areas of investigation.
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http://dx.doi.org/10.1097/SCS.0000000000005274DOI Listing
July 2019

Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor.

J Craniofac Surg 2019 Jan;30(1):260-264

Department of Plastic Surgery, University of Pittsburgh.

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.
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http://dx.doi.org/10.1097/SCS.0000000000004779DOI Listing
January 2019

Cervical Spine Injury From Unrecognized Craniocervical Instability in Severe Pierre Robin Sequence Associated With Skeletal Dysplasia.

Cleft Palate Craniofac J 2018 05 28;55(5):773-777. Epub 2018 Feb 28.

1 Division of Pediatric Plastic Surgery, University of Pittsburgh School of Medicine, Pennsylvania, PA, USA.

Pierre Robin Sequence (PRS) can be associated with skeletal dysplasias, presenting with craniocervical instability and devastating spinal injury if unrecognized. The authors present the case of an infant with PRS and a type II collagenopathy who underwent multiple airway-securing procedures requiring spinal manipulation before craniocervical instability was identified. This resulted in severe cervical cord compression due to odontoid fracture and occipitoatlantoaxial instability. This case highlights the importance of early cervical spine imaging and cautious manipulation in infants with PRS and suspected skeletal dysplasia.
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http://dx.doi.org/10.1177/1055665618758102DOI Listing
May 2018

Costal bone abnormalities: an unusual cause of spontaneous bilateral breast implant deflation†.

J Surg Case Rep 2014 Dec 21;2014(12). Epub 2014 Dec 21.

Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Augmentation mammoplasty is the most common aesthetic surgical procedure performed in the USA. Prosthetic failure is a major reason for surgical reintervention. A number of causes for this have been documented, but costal bone abnormalities leading to perforation of the prosthesis are very unusual. We present the case of a woman who experienced spontaneous deflation of both saline implants in close succession, and who was found to have sharp bony spicules on both sides of her chest. Pathology examination reported reactive changes, suggestive of heterotopic bone. Examination of the implants showed no defects besides small punctures on the back wall, which coincided with the position of the spicules of bone. There are a number of possible causes for these bony growths which we examine in turn. The chest wall should be examined in all cases where unexplained implant deflation has occurred.
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http://dx.doi.org/10.1093/jscr/rju138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273103PMC
December 2014

Spontaneous late haematomas at latissimus dorsi flap donor sites: an unusual complication of breast reconstruction.

J Plast Reconstr Aesthet Surg 2015 Feb 13;68(2):e40-2. Epub 2014 Oct 13.

Department of Plastic & Reconstructive Surgery, Cambridge University Hospitals NHS Foundation Trust, United Kingdom; Cambridge Breast Unit, United Kingdom; Postgraduate Medical Institute, Anglia Ruskin University (Chelmsford & Cambridge), United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.bjps.2014.09.050DOI Listing
February 2015