Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics.

Poly[2-(Dimethylamino) ethyl acrylate] (PDMAEA) based polymers have been studied as potential gene delivery system. However, few reports emerging in literature suggesting that star-shaped PDMAEA based polymers are performing better in polyplexation with DNA, cytotoxicity and transfection, as compared to linear counterparts. Nonetheless, little evidences exist on direct comparison between the linear and star-shaped polymer structures. To address this, a series of new star-shaped PDMAEA polymers with linear counterparts were synthesised and directly compared their polyplexation with DNA and cytotoxicity in culture cell lines. The star-shaped PDMAEA polymers were synthesised using pentaerythritol tetrakis [2-(dodecylthiocarbonothioylthio)-2-methylpropionate] (4-arm DDMAT) RAFT agent in a “core-first” approach, whereas 2-(dodecylthiocarbonothioylthio)-2-methylpropionate was used to synthesise linear PDMAEA polymers. In order to investigate the effect of molar mass, both star-shaped and linear PDMAEA were synthesised in low (10kDa) and high (20kDa) molar mass. It must be noted here that the overall molar mass of the star-shaped polymer was equal to that of the linear counterparts. Interestingly, we found that the star-shaped polymer has slightly smaller hydrodynamic diameter (more compact) relative to linear counterparts, and importantly, star-shaped PDMAEA binds to DNA at much lower nitrogen to phosphate ratio (N/P ratio). However, the cytotoxicity studies in cultured 3T3 murine cell lines demonstrated that both star-shaped and linear counterparts have no toxicity at low 10kDa, but significantly toxic at higher 20kDa molar mass, this finding confirmed that the molar mass of PDMAEA play a key role in cytotoxicity effect, not variable polymer structures. Taken together, star-shaped PDMAEA binds more effectively to DNA than linear counterparts and showed no toxicity at 10kDa molar mass at variable polymer concentrations

The natural healing process for tendon repair is associated with high upregulation of collagen type III, leading to scar tissue and tendon adhesions with functionally deficient tendons. Gene delivery systems are widely reported as potential nanotherapeutics to treat diseases, providing a promising approach to modulate collagen type III synthesis. This work investigates a proof-of-concept four-arm cationic polymer-siRNA polyplex to mediate a transient downregulation of collagen type III expression in a tendon cell culture system. The tendon culture system was first supplemented with TGF-β1 to stimulate the upregulation of collagen type III prior to silencing experiments. The four-arm poly [2-(dimethylamino) ethyl acrylate] (PDMAEA) polymer was successfully synthesized via RAFT polymerization and then mixed with siRNA to formulate the PDMAEA-siRNA polyplexes. The formation of the polyplex was optimized for the N:P ratio (10:1) and confirmed by agarose gel electrophoresis. The size and solution behavior of the polyplex were analyzed by dynamic light scattering and zeta potential, showing a hydrodynamic diameter of 155 ± 21 nm and overall positive charge of +30 mV at physiological pH. All the polyplex concentrations used had a minimal effect on the metabolic activity of cultured cells, indicating good biocompatibility. The dose and time effects of the TGF-β1 on collagen type III gene expressions were analyzed by qPCR, showing an optimal dose of 10 ng mL −1 TGF-β1 and 3-fold increase of COL3α1 expression at 48 h in cultured tenocytes. The PDMAEA-siRNA polyplex concept observed a limited yet successful and promising efficiency in silencing collagen type III at 48 h compared to PEI-siRNA. Therefore, this concept is a promising approach to reduce tissue scarring and adhesion following injuries.

The rapid surface immobilization of protein on monodispersed polyester microcarriers is reported. A model protein, functionalized with a dibenzocyclooctyne core, immobilizes on the surface of azide-terminal polycaprolactone microcarriers within 10 min compared to 12 h for other conjugation techniques, and it is conducted in physiological conditions and in the absence of coupling reagents.