Poster AA4 - Catechol-modified multifunctional hydrogel for improved durability of the skin/implant interface for osseontigrated prosthetic devices

Introduction: Failure to support formation of an impervious seal at the skin-percutaneous implant interface results in implant loosening (13-29%) and/or soft-tissue infection (29-77%) resulting in implant failure. Different surface modification strategies for improving the attachment of skin to the metal abutment have been employed with limited success. However, one strategy that has been overlooked is designing an interface that closely resembles the extracellular matrix (ECM) in terms of its chemistry and biomolecular content of percutaneous organs/tissues like tooth and nails. In this study we propose utilization of an ECM mimicking gelatin methacryloyl (GelMA) hydrogel as an intermediate interface between the skin and titanium. To improve interfacial adhesivity and bioactive functionality, GelMA was further functionalized with mussel-inspired catechol group ‘dopamine’ – GelMA-DOPA and incorporated with bioactive peptide sequences Net1 (cell adhesive peptide; CAP) and D-GL13K (antimicrobial peptide; AMP). Net1 is derived from large biomolecules present in basement membrane known to support keratinocyte attachment and hemidesmosome formation. D-GL13K is derived from human salivary parotid secretory protein and is effective against both Gram-positive and Gram-negative bacteria. Here, we aimed to assess the ability of unmodified and modified hydrogel to support growth and proliferation of keratinocytes and fibroblasts seeded on different hydrogel platforms while combating infection against methicillin resistant Staphylococcus aureus (MRSA).

Materials and

Methods: We generated a library of ECM-mimicking highly adhesive hydrogels with or without Net1 and/or D-GL13K which were then tested for their physico-mechanical and adhesive properties. To do so, GelMA was first synthesized which was then modified with dopamine using carbodiimide chemistry where the carboxyl group in the gelatin was reacted with amine group of dopamine. NMR was used to confirm the conjugation of methacryloyl and dopamine group in the synthesized macromer. Different hydrogels with and without CAP and AMP were fabricated using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and light at λ=400nm along with sodium periodate and their physico-mechanical and adhesive properties of the hydrogel were tested. Additionally, the ability of adhesive hydrogels to support growth and proliferation of keratinocytes (HaCaTs) and fibroblasts (HDFs) and their antibacterial efficacy against methicillin resistant Staphylococcus aureus (MRSA) was assessed. Statistical significances (p < 0.05) were assessed by one-way ANOVA with Tukey post hoc tests.

Results, Conclusions, and Discussions: The physico-mechanical properties confirmed that incorporation of dopamine didn’t impact the cross-linking capability of the matrix but improved its metal and skin adhesivity. Additionally, incorporation of Net1 and D-GL13K improved proliferation and expression of Igβ4 of HaCaTs and collagen I expression for HDFs while significantly inhibiting growth of MRSA. The study supports the use of Net1 and D-GL13K in combination with GelMA-DOPA as a transient interface between the epithelial tissue and the titanium abutment.
The current study proposes the utilization of a material-based approach whereby carefully designing the composition of the adhesive surgical glue improved soft tissue attachment via cell-matrix interaction can be achieved. This bioactive surgical glue will not only facilitate the attachment between metal and skin but will provide the necessary cues that are integral for soft tissue attachment and re-epithelialization and thus, it can aid in preventing the fragile tissue-implant interface from eventual infection.

Acknowledgements (Optional): This work was supported by the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Orthopaedic Research Program (PRORP) under Applied Research Award No W81XWH-20-1-0563. The U.S. Army Medical Research Acquisition Activity, 839 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office