Encapsula of periosteal stem cells in injectable photopolymerized hydrogel enhances tendon graft osteointegration

Photopolymerized hydrogel based on poly(ethylene glycol) diacrylate (PEGDA) was applied to periosteum-derived periosteal stem cell (PSC) encapsulation and orthopedic tissue engineering. To provide support for cell adhesion, hyaluronic acid (HA) was incorporated into the PEGDA solution prior to photopolymerization. HA can be utilized to mimic the extracellular matrix composition as well as control cell growth and differentiation. In vitro studies have demonstrated its ability to encapsulate PSCs to form bone-like tissue in a photopolymerized hydrogel. Osteointegration of a tendon graft within the bone tunnel is a primary concern when employing tendon grafts for ligament reconstruction. This study presents a novel technique for fabricating injectable hydrogel-photoencapsulated PSCs in a bone tunnel to enhance tendon-bone healing. A total of 21 adult New Zealand white rabbits were used. The long extensor digitorum tendon was transplanted into a bone tunnel of the proximal tibia. The tendon was pulled through a drill hole in the proximal tibia and attached to the medial aspect of the tibia. Hydrogel suspension containing PSCs at a concentration of 20 million/mL was injected into the bone tunnel. Histological examination of the tendon-bone interface and biomechanical testing for maximal pull-out load were evaluated at postoperative weeks 3 and 6. Histological analysis of the tendon-bone interface showed an interface fibrous layer formed by the photoencapsulation of PSCs between the tendon and the bone. This layer became progressive integrated with the tendon-bone surface during the healing process. Biomechanical testing revealed higher maximal pull-out strength in experimental groups with a statistically significant difference at 3 and 6 weeks. These results suggest that photopolymerizable PEGDA and HA hydrogels are promising for tissue-engineered stem cell therapy to enhance tendon-bone healing.