Publications by authors named "Christopher M Mahoney"

3 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

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

Front Pharmacol 2018 17;9:507. Epub 2018 May 17.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.
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http://dx.doi.org/10.3389/fphar.2018.00507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966552PMC
May 2018

Adipose derived delivery vehicle for encapsulated adipogenic factors.

Acta Biomater 2017 08 19;58:26-33. Epub 2017 May 19.

Department of Bioengineering, University of Pittsburgh, United States; Department of Plastic Surgery, School of Medicine, University of Pittsburgh, United States; McGowan Institute of Regenerative Medicine, University of Pittsburgh, United States. Electronic address:

Hydrogels derived from adipose tissue extracellular matrix (AdECM) have shown potential in the ability to generate new adipose tissue in vivo. To further enhance adipogenesis, a composite adipose derived delivery system (CADDS) containing single- and double-walled dexamethasone encapsulated microspheres (SW and DW Dex MS) has been developed. Previously, our laboratory has published the use of Dex MS as an additive to enhance adipogenesis and angiogenesis in adipose tissue grafts. In the current work, AdECM and CADDS are extensively characterized, in addition to conducting in vitro cell culture analysis. Study results indicate the AdECM used for the CADDS has minimal cellular and lipid content allowing for gelation of its collagen structure under physiological conditions. Adipose-derived stem cell (ASC) culture studies confirmed biocompatibility with the CADDS, and adipogenesis was increased in experimental groups containing the hydrogel scaffold. In vitro studies of AdECM hydrogel containing microspheres demonstrated a controlled release of dexamethasone from SW and DW formulations. The delivery of Dex MS via an injectable hydrogel scaffold combines two biologically responsive components to develop a minimally, invasive, off-the-shelf biomaterial for adipose tissue engineering.

Statement Of Significance: Scientists and doctors have yet to develop an off-the-shelf product for patients with soft tissue defects. Recently, the use of adipose derived extracellular matrix (adECM) to generate new adipose tissue in vivo has shown great promise but individually, adECM still has limitations in terms of volume and consistency. The current work introduces a novel composite off-the-shelf construct comprised of an adECM-based hydrogel and dexamethasone encapsulated microspheres (Dex MS). The hydrogel construct serves not only as an injectable protein-rich scaffold but also a delivery system for the Dex MS for non-invasive application to the defect site. The methods and results presented are a progressive step forward in the field of adipose tissue engineering.
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http://dx.doi.org/10.1016/j.actbio.2017.05.046DOI Listing
August 2017