Development of Peptide-Polymer Conjugates for Enhanced Cartilage Tissue Engineering
Oleg Kolosov 1*, Gordon Hamilton 1, Cheryl Hawkes 1
Biosensors and Nanotheranostics 4(1) 1-8 https://doi.org/10.25163/biosensors.419987
Submitted: 04 December 2025 Revised: 19 February 2025 Published: 20 February 2025
Abstract
Background: Articular cartilage provides a low-friction surface for joint function but has limited self-repair capabilities due to its avascular nature. Hyaluronic acid (HA), a key component of the cartilage extracellular matrix (ECM), plays a crucial role in maintaining tissue structure and function. Electrospun scaffolds incorporating HA-binding peptides have emerged as a promising strategy for cartilage repair. This study aims to develop peptide-polymer conjugates combining HA-binding peptides with polycaprolactone (PCL) to fabricate nanofibrous scaffolds with enhanced bioactivity and mechanical stability. Methods: HA-binding peptides were synthesized via solid-phase peptide synthesis, purified using high-performance liquid chromatography (HPLC), and characterized using mass spectrometry. Peptide-polymer conjugates were synthesized by covalently linking peptides to PCL using maleimide chemistry and verified using nuclear magnetic resonance (NMR) spectroscopy. Functionalized scaffolds were fabricated through electrospinning, and their physical and biological properties were assessed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal microscopy. Chondrocyte attachment, proliferation, and extracellular matrix production were evaluated through in vitro cell culture assays, including DNA quantification, glycosaminoglycan (GAG) content analysis, and metabolic activity assessment. Results: SEM imaging confirmed the uniform nanofibrous structure of the electrospun scaffolds, resembling native cartilage ECM. TEM and confocal microscopy demonstrated successful peptide conjugation and gradient distribution within the scaffolds. Functionalized scaffolds exhibited enhanced HA retention and sustained release over 12 days, as confirmed by fluorescent HA binding assays. Chondrocytes cultured on peptide-functionalized scaffolds showed significantly improved attachment, proliferation, and ECM production compared to control scaffolds. The gradient presentation of bioactive peptides facilitated spatially controlled cell behavior, mimicking the zonal organization of cartilage. Conclusion: Peptide-functionalized PCL scaffolds significantly improved HA retention, chondrocyte adhesion, and ECM synthesis, demonstrating their potential for cartilage tissue engineering. The sustained release of HA and spatial peptide gradients provide a biomimetic environment for tissue regeneration.
Keywords: Articular cartilage regeneration, Hyaluronic acid-binding peptides, Electrospun nanofibrous scaffolds, Peptide-polymer conjugates, Chondrocyte proliferation
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