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Photoencapsulation of Bone Morphogenetic Protein-2 and Periosteal Progenitor Cells Improve Tendon Graft Healing in a Bone Tunnel

Chih-Hwa Chen, MD^*, Hsia-Wei Liu, PhD^*,, Ching-Lin Tsai, MD, PhD, Chung-Ming Yu, MD^*, I-Hsuan Lin, MS^* and Ging-Ho Hsiue, PhD^,

From the ^* Department of Orthopaedic Surgery, College of Medicine, Chang Gung Memorial Hospital—Keelung, Chang Gung University, Keelung, Taiwan, Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, and Department of Orthopaedic Surgery, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan

Address correspondence to Ging-Ho Hsiue, PhD, Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan (e-mail: ghhsiue{at}mx.nthu.edu.tw).

Background: Tissue-engineered solutions for promoting the tendon graft incorporation within the bone tunnel appear to be promising.

Hypothesis: To determine the feasibility that conjugation of hyaluronic acid–tethered bone morphogenetic protein-2 can be used to stimulate periosteal progenitor cells direct fibrocartilagenous attachment and new bone formation in an extra-articular tendon-bone healing model.

Study Design: Controlled laboratory study.

Methods: A total of 42 mature New Zealand White rabbits were used. The long digitorum extensor 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. Photopolymerizable hydrogel based on poly (ethylene glycol) diacrylate with hyaluronic acid–tethered bone morphogenetic protein-2 was injected and photogelated in a bone tunnel. Histological and biomechanical examination of the tendon-bone interface was evaluated at postoperative weeks 3 and 6.

Results: Histological analysis showed an interface fibrocartilage and new bone formed by photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells at 6 weeks. Biomechanical testing revealed higher maximum pullout strength and stiffness in experimental groups with a statistically significant difference at 3 and 6 weeks after tendon transplantation.

Conclusion: The healing tendon-bone interface undergoes a gradual remodeling process; it appears that photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells possesses a powerful inductive ability between the tendon and the bone to incorporate the healing in a rabbit model.

Clinical Relevance: Novel technologies, such as those described in this study, including photopolymerization and tissue engineering, may provide minimally invasive therapeutic procedures via arthroscopy to enhance biological healing after reconstruction of the anterior cruciate ligament.

Key Words: bone morphogenetic protein • hydrogel • periosteal progenitor cell • photoencapsulation • tendon-bone healing