Kinetic degradation and biocompatibility evaluation of polycaprolactone‐based biologics delivery matrices for regenerative engineering of the rotator cuff

Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here...

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Bibliographic Details
Published inJournal of biomedical materials research. Part A Vol. 109; no. 11; pp. 2137 - 2153
Main Authors Prabhath, Anupama, Vernekar, Varadraj N., Vasu, Vignesh, Badon, Mary, Avochinou, Jean‐Emmanuel, Asandei, Alexandru D., Kumbar, Sangamesh G., Weber, Eckhard, Laurencin, Cato T.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.11.2021
Wiley Subscription Services, Inc
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Summary:Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly‐lactic acid co—epsilon‐caprolactone (PLA‐CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically‐unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. The matrix obtained from the highest polymeric‐film casting concentration showed a controlled release of model biologics payload. The tested matrices rapidly degraded during the initial 4 weeks due to preferential hydrolysis of the lactide‐rich regions within the polymer, and subsequently maintained a stable molecular weight due to the emergence of highly‐crystalline caprolactone‐rich regions. pH evaluation in the interior of the matrix showed minimal change signifying lesser accumulation of acidic degradation byproducts than seen in other bulk‐degrading polymers, and maintenance of conformational stability of the model biologic payload. The context‐dependent biocompatibility evaluation in a rodent model of acute rotator cuff repair showed matrix remodeling without eliciting excessive inflammatory reaction and is anticipated to completely degrade within 6 months. The engineered PLA‐CL matrices offer unique advantages in controlled and protected biologic delivery, non‐toxic biodegradation, and biocompatibility overcoming several limitations of commonly‐used biodegradable polyesters.
Bibliography:Funding information
NIH Pioneer Grant, Grant/Award Number: 1DP1OD019349‐01; University of Connecticut Office of the Vice President for Research, Grant/Award Number: 401543; NIH Pioneer, Grant/Award Number: 1DP1OD019349‐01; University of Connecticut Office of the Vice President for Research Fund, Grant/Award Number: 401543; Novartis, Grant/Award Number: G600795
Anupama Prabhath and Varadraj N. Vernekar contributed equally to this study.
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.37200