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Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

Rotator cuff tears result in shoulder pain, stiffness, weakness and loss of motion. After surgical repair, high failure rates have been reported based on objective imaging and it is recognized that current surgical treatments need improvement. The aim of the study was to assess whether implants composed of freeze-dried chitosan (CS) solubilized in autologous platelet-rich plasma (PRP) can improve rotator cuff repair in a rabbit model. Complete tears were created bilaterally in the supraspinatus tendon of New Zealand White rabbits (n ¼ 4 in a pilot feasibility study followed by n ¼ 13 in a larger efficacy study), which were repaired using transosseous suturing. On the treated side, CS-PRP implants were injected into the transosseous tunnels and the tendon itself, and healing was assessed histologically at time points ranging from one day to two months post-surgery. CS-PRP implants were resident within transosseous tunnels and adhered to tendon surfaces at one day post-surgery and induced recruitment of polymorphonuclear cells from 1 to 14 days. CS-PRP implants improved attachment of the supraspinatus tendon to the humeral head through increased bone remodelling at the greater tuberosity and also inhibited heterotopic ossification of the supraspinatus tendon at two months. In addition, the implants did not induce any detectable deleterious effects. This preliminary study provides the first evidence that CS-PRP implants could be effective in improving rotator cuff tendon attachment in a small animal model.

Rotator cuff tears are a very common shoulder pathology. Different suturing techniques have been used for surgical cuff repair, but failure of healing remains a significant clinical challenge. The objective of this study was to establish and compare chronic and acute ovine rotator cuff tear models in our laboratory and investigate the feasibility of using chitosan (CS)-platelet-rich plasma (PRP) implants in conjunction with suture anchors to treat rotator cuff tears in large animal models. Repair with suture anchors only was used as control. In two preliminary pilot studies, unilateral full-thickness tears were created in the infraspinatus (ISP) tendon of mature female Texel-cross sheep. In the chronic model (n = 4 sheep), the tendons were capped with silicon and allowed to retract for 6 weeks, leading to degenerative changes, whereas the tendons were immediately repaired in the acute model (n = 4 sheep). Transected ISP tendons were reattached with suture anchors and, in the case of treated shoulders, implants composed of freezedried CS solubilized in autologous PRP were additionally applied to the tendon−bone interface and on top of the repaired site. The chronic defect model induced significant tendon degeneration and retraction, which made repair more challenging than in the acute defect model. Half the tendons in the chronic repair model were found to be irrepairable at 6 weeks. In the other half, the tendons could not be reattached to the footprint due to significant retraction, which made this a model of tissue formation in a gap. In contrast, the acute tendon repair model was executed easily. Extensive bone remodeling and tissue ingrowth at the tendon-bone interface were observed in the case of treatment with anchors + CS-PRP in both models, suggesting that CS-PRP implants could potentially modulate rotator cuff healing processes in large animal models.

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