OXIDIZED HYALURONIC ACID/ADIPIC ACID DIHYDRAZIDE HYDROGEL AS DRUG-CARRIER FOR CYTOPROTECTIVE MEDICATIONS — PRELIMINARY RESULTS

摘要

The oxidised hyaluronic acid/adipic acid dihydrazide hydrogel (oxi-HA/ADH) is a biocompatible and biodegradable hydrogel that has been applied in tissue engineering in musculoskeletal medicine. The present study investigated the feasibility of using oxi-HA/ADH as a drug carrier to incorporate cytoprotective medications for possible tendinopathy treatment. The cytocompatibility of oxi-HA/ADH, epigallocatechin gallate (EGCG) and piracetam were tested. Medications were incorporated in oxi-HA/ADH in the cross-linking process and the drug release profile was tested in vitro. Sprague-Dawley rats Achilles tendon-derived cells (TDCs) were isolated and cultured in a self-designed bioreactor exerting 8% cyclic strain at 0.5Hz for 8h. TDCs were treated with EGCG, piracetam, or no medication during mechanical loading. Gene expression of type I and type III collagen, Pparg, Sox9, and Runx2 (representing adipogenic, chondrogenic, and osteogenic lineages respectively) were analyzed by quantitative polymerase chain reaction. EGCG and piracetam showed no cytotoxicity at therapeutic range. The cumulative release profile of the drug-loaded oxi-HA/ADH showed a two-phase release of medication, a burst of 50–60% during the first 24h, followed by a steady release over 1–7 days. The decreased type I collagen expression and increased non-tenocyte lineage genes expression of TDCs upon 8% cyclic strain is reversed in the EGCG and piracetam treated groups, compared with non-treated group. Oxi-HA/ADH serves as a potential drug carrier that shows sustained-release characteristics. Anti-oxidative and cytoprotective medications, EGCG and piracetam, were able to suppress the aberrant non-tenocyte lineage genes expression of the TDCs upon excessive mechanical loading.