Prabhath , Anupama , Vernekar , Varadraj N, Vasu , Vignesh , Badon, Mary , Avochinou , Jean-Emmanuel, Asandei , Alexandru D, Kumbar , Sangamesh G, Weber, Eckhard and Laurencin , Cato T (2021) In Vitro Kinetic Degradation and In Vivo Biocompatibility Evaluation of Polycaprolactone-Based Growth Factor Delivery Matrices in the Rotator Cuff. Journal of Biomedical Materials Research Part A. ISSN 1549-32961552-4965

Abstract

The recent years have seen a significant surge in the use of synthetic biodegradable polymers for growth factor delivery in the rotator cuff. While these polymers have been successfully applied in delivery of factors in other tissues, the anatomical complexity, hypovascularity, cellularity, and reduced clearance of degradation by-products in the rotator cuff, creates unique requirements in tailoring the physical dimensions, chemical constituents, drug release and degradation characteristics of biomaterials for implantation. In this study, we investigate poly-lactic acid co-epsilon-caprolactone (30:70 LA:CL ratio) at 35-45kDa range and varying polymeric films casting concentrations (5-20%) as potential growth factor delivery matrices in the rotator cuff. Matrices were fabricated of 300µm thickness and 3x3mm surface area to facilitate model protein encapsulation and controlled release, and smooth translation of the matrix under the bony acromion after implantation in the rotator cuff. The matrix with the highest casting concentration (20wt%) showed unique, highly regular, and controlled release of the protein payload compared to the lower- casting concentrations (15 and 10wt%) and - molecular weights (35kDa) matrices. All films were found to lose molecular weight rapidly during the first 4 weeks due to the preferential hydrolysis of lactide-rich regions within the polymer, and then maintain a relatively stable molecular weight between week 4 and 8 due to the emergence of highly-crystalline caprolactone-rich regions. Nevertheless, the cleaved lactide-chains were not small enough to exit through the polymeric matrix as was evident from the maintenance of bulk matrix weight, form, and polymer dispersity index. This resulted in recrystallization of the cleaved chains in the presence of water molecules increasing the crystallinity of the matrix as was evident from the H-NMR and thermal analysis. Kinetic analysis revealed an inverse-linear relationship between polymer casting concentration and polymer break down. The ‘context-dependent’ biocompatibility evaluation was carried in a clinically-relevant rat model of acute rotator cuff repair model to address the unique features of both the tissue and the biomaterial being investigated. The matrices were found to remodel locally without undergoing catastrophic breakdown or causing excessive inflammatory reaction at the tissue site during the study period and is anticipated to completely degrade within 6 months of implantation. Our study is significant as it provides a systematic assessment of polymer properties that can be modifies to engineer morphogen release, degradation rates and mechanisms for biologic delivery in the rotator cuff. It also provides a pilot assessment of in situ biocompatibility of the polymeric matrix in the complex rotator cuff tissue.

Item Type:	Article
Date Deposited:	26 May 2021 00:45
Last Modified:	26 May 2021 00:45
URI:	https://oak.novartis.com/id/eprint/43467