Endodontic Tissue Regeneration: A Review for Tissue Engineers and Dentists.

The paradigm shift in the endodontic field from replacement toward regenerative therapies has witnessed the ever-growing research in tissue engineering and regenerative medicine targeting pulp-dentin complex in the past few years. Abundant literature on the subject that has been produced, however, is scattered over diverse areas of knowledge. Moreover, the terminology and concepts are not always consensual, reflecting the range of research fields addressing this subject, from endodontics to biology, genetics, and engineering, among others. This fact triggered some misinterpretations, mainly when the denominations of different approaches were used as synonyms. The evaluation of results is not precise, leading to biased conjectures. Therefore, this literature review aims to conceptualize the commonly used terminology, summarize the main research areas on pulp regeneration, identify future trends, and ultimately clarify whether we are really on the edge of a paradigm shift in contemporary endodontics toward pulp regeneration.

Evaluation of Feline Permanent Canine Tooth Mineral Density Using Micro-Computed Tomography.

The tooth is made up of three mineralized tissues, enamel, dentin, and cementum, which surround a non-mineralized tissue called the dental pulp. Micro-computed tomography (mCT) is an imaging technology based on X-rays that allows non-invasive visualization of objects at a microscopic scale, according to their radiopacity and in three dimensions (3D). Likewise, it allows the subsequent execution of morphological and quantitative analysis of the objects, such as, for example, the determination of the relative mineral density (MD). The present work aimed to describe the MD of feline teeth using mCT. The studied sample consisted of four European Shorthair cats, from which nine canine teeth were extracted per medical indication. These teeth were evaluated through dental radiography before and after their extraction. Using mCT and the CTAn software, the values of the relative mineral density of the root of each tooth and of specific segments corresponding to the coronal, middle, and apical thirds of the root were determined. Mean MD of root tissues was 1.374 ± 0040 g·cm-3, and of hard root, tissues was 1.402 ± 0.035 g·cm-3. Through mCT, it was possible to determine the mean MD values of feline canine teeth. The study of MD could become an ancillary method for the diagnosis and characterization of dental pathology.

Highly elastic and bioactive bone biomimetic scaffolds based on platelet lysate and biomineralized cellulose nanocrystals.

Bone is a vascularized organic-inorganic composite tissue that shows a heavily-mineralized extracellular matrix (ECM) on the nanoscale. Herein, the nucleation of calcium phosphates during the biomineralization process was mimicked using negatively-charged cellulose nanocrystals (CNCs). These mineralized-CNCs were combined with platelet lysate to produce nanocomposite scaffolds through cryogelation to mimic bone ECM protein-mineral composite nature and take advantage of the bioactivity steaming from platelet-derived biomolecules. The nanocomposite scaffolds showed high microporosity (94-95%), high elasticity (recover from 75% strain cycles), injectability, and modulated platelet-derived growth factors sequestration and release. Furthermore, they increased alkaline phosphatase activity (up to 10-fold) and up-regulated the expression of bone-related markers (up to 2-fold), without osteogenic supplementation, demonstrating their osteoinductive properties. Also, the scaffolds promoted the chemotaxis of endothelial cells and enhanced the expression of endothelial markers, showing proangiogenic potential. These results suggest that the mineralized nanocomposite scaffolds can enhance bone regeneration by simultaneously promoting osteogenesis and angiogenesis.

Evaluation of Injectable Hyaluronic Acid-Based Hydrogels for Endodontic Tissue Regeneration.

Dental pulp tissue engineering (TE) endeavors to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface's proper colonization with progenitor cells capable of restoring the dentin/pulp complex. Herein was investigated an injectable self-setting hyaluronic acid-based (HA) hydrogel system, formed by aldehyde-modified (a-HA) with hydrazide-modified (ADH), enriched with platelet lysate (PL), for endodontic regeneration. The hydrogels' working (wT) and setting (sT) times, the adhesion to the dentine walls, the hydrogel's microstructure, and the delivery of human dental pulp cells (DPCs) were studied in vitro. Hydrogels incorporating PL showed a suitable wT and sT and a porous microstructure. The tensile tests showed that the breaking point occurs after 4.3106 ± 1.8677 mm deformation, while in the indentation test after 1.4056 ± 0.3065 mm deformation. Both breaking points occur in the hydrogel extension. The HA/PL hydrogels exhibited supportive properties and promoted cell migration toward dentin surfaces in vitro. Overall, these results support using PL-laden HA injectable hydrogels (HA/PL) as a biomaterial for DPCs encapsulation, thereby displaying great clinical potential towards endodontic regenerative therapies.

Standardized Platelet-Rich Fibrin (PRF) from canine and feline origin: An analysis on its secretome pattern and architectural structure.

Platelet-rich fibrin (PRF) has been incorporated in surgical procedures to promote tissue and bone healing, particularly in human medicine. The rationale for the use of platelet-based products stems from the fact that platelets, after being activated, release growth factors (GFs) and other active molecules such as cytokines, that modulate inflammation and tissue repair. Although PRF has been advanced as a therapeutic treatment for veterinary use, namely in canine and feline patients (following human medicine developments), to our knowledge a full characterization of PRF therapeutic effectors has never been performed. Herein, we studied the biological properties and release profile of GFs and other cytokines throughout ten days in in vitro culture conditions, in order to investigate the potential therapeutic ability of PRF for canine and feline practice. A protocol for obtaining PRF from whole blood without anti-coagulant from both species was optimized, originating large and homogenous PRF clots. Then, PRF clots obtained from four dogs and four cats were incubated in culture medium to assess the temporal release of platelet-derived growth factor-BB (PDGF-BB), vascular endothelial factor-A (VEGF-A), transforming growth factor ß-1 (TGF-ß1), and interleukin-8 (IL-8). Furthermore, morphological characterization of PRF clots, fresh and after 10 days of incubation, was performed by histology and high-resolution field emission electron scanning microscopy. In standard culture conditions, PRF clots from both species released PDGF-BB, TGF- ß1 and VEGF-A, in a sustained manner, up to day 10. Moreover, PRF presents an initial burst release of IL-8, a mediator of inflammatory response which plays a key role in neutrophil recruitment and degranulation. Overall, our findings show that PRF clots may be an efficient therapeutic strategy in canine and feline clinical practice, accelerating the local healing mechanism, through the sustained delivery of signalling molecules involved in the healing cascade.

Supplementary solvent irrigation efficacy on filling remnants removal comparing XP-endo Finisher R vs IrriSafe.

This study aimed to compare the efficacy of XP-endo Finisher R and IrriSafe, with a solvent mixture of Methyl ethyl ketone/Tetrachloroethylene (MEK/TCE), in the removal of root filling residues. Twenty-four human mandibular incisors were pair-matched by micro-computed tomography according to volume and aspect ratio. After retreatment, specimens were allocated to two experimental groups (n = 12), according to the supplementary instrument used. The volume of residual filling material after each irrigating step and the time for retreatment was calculated. Statistical analyses were carried out using Mann-Whitney test, with a significance level of 5%. The volume of initial root canal filling material between the groups was similar (p > 0.05). With the final irrigation protocol (NaOCl and EDTA) the volume of the filling remnants decreased significantly (p < 0.05) with no differences between IrriSafe or XP-endo Finisher R (p > 0.05). The additional solvent mixture MEK/TCE increased the efficiency of filling materials reduction, regardless of the agitating instruments employed, IrriSafe or XP-endo Finisher R (p < 0.05). There was no difference between the two groups regarding the time (p = 0.149). Both supplementary instruments were effective in the reduction of filling remnants. The additional step with a solvent mixture of MEK/TCE enabled a total recovery of patency and the achievement of cleaner canals, independently of the agitation instrument.

Platelet-Derived Products in Veterinary Medicine: A New Trend or an Effective Therapy?

Platelet-derived products (PDPs) have gained popularity, mainly due to their high concentrations of bioactive molecules such as growth factors and cytokines, which play important roles in tissue healing and regeneration. PDPs are obtained through minimally invasive procedures and their therapeutic effect has been widely recognized. In veterinary medicine, however, the lack of standard protocols to generate PDPs is a major hurdle for assessing the clinical relevance of PDP-based therapies and for their widespread usage. The aim of this review is to analyze the technical and scientific specificities of PDPs in terms of preparation methodologies, classification categorization, nomenclature, and biological proprieties to advance their future biotechnological potential in veterinary contexts.

Hyaluronic Acid Oligomer Immobilization as an Angiogenic Trigger for the Neovascularization of TE Constructs.

Tissue engineered (TE) substitutes of clinically relevant sizes need an adequate vascular system to ensure function and proper tissue integration after implantation. However, the predictable vascularization of TE substitutes is yet to be achieved. Molecular weight variations in hyaluronic acid (HA) have been pointed to trigger angiogenesis. Thus, this study investigates HA oligomer immobilization as a promoter for TE construct vascularization. As a proof-of-concept, the surface of methacrylated gelatin (GelMA) hydrogels were functionalized with high molecular weight (HMW; 1.5 to 1.8 MDa) and low molecular weight (LMW; < 10 kDa) HA, previously modified with aldehyde groups to enable the immobilization through Schiff's base formation. The ability of A-HA to bind amine-presenting surfaces was confirmed by Surface Plasmon Resonance (SPR). Human Umbilical Vein Endothelial Cells (HUVECs) seeded over hydrogels functionalized with LMW HA showed higher proliferation and expression of angiogenic markers (KDR and CD31), than those grown in HMW HA conjugated- or plain surfaces, in line with the activation of HA ERK1/2 mediated downstream signaling. Moreover, when cocultured with human dental pulp cells (hDPCs) encapsulated into the GelMA, an increase in endothelial cell migration was observed for the LMW HA functionalized formulations. Overall LMW HA functionalization enhanced endothelial cell response showing potential as an angiogenesis inducer for TE applications.

Natural-Based Hydrogels for Tissue Engineering Applications.

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.

Evaluation of hematology, general serum biochemistry, bone turnover markers and bone marrow cytology in a glucocorticoid treated ovariectomized sheep model for osteoporosis research.

Osteoporosis is a metabolic disorder characterized by a loss of bone mass and structure and increasing the risk of fragility fractures, mostly among postmenopausal women. Sheep is a recognized large animal model for osteoporosis research. An experimental group of ewes (3-4 years old) was subjected to ovariectomy (OVX) and weekly glucocorticoid (GC) application for 24 weeks and compared with a sham control group. Blood and bone marrow parameters were analyzed before and 24 weeks after OVX and GC administration. Osteopenia was confirmed through micro-computed tomography and histomorphometric analysis of L4 vertebra in the study end. A statistically significant increase was observed in mean corpuscular volume, mean cell hemoglobin and monocytes and a decrease in red blood count and eosinophils (p<0.05). Alkaline phosphatase (ALP), gamma-glutamyl transpeptidase, magnesium and α1-globulin increased, and creatinine, albumin, sodium and estradiol decreased (p<0.05). A slight decrease of bone formation markers (bone ALP and osteocalcin) and an increase of bone resorption markers (C-terminal telopeptides of collagen type 1 and tartrate-resistant acid phosphatase) were observed, but without statistical significance. This study aims to contribute to better knowledge of sheep as a model for osteoporosis research and the consequences that a performed induction protocol may impose on organic metabolism.

Intrinsically Bioactive Cryogels Based on Platelet Lysate Nanocomposites for Hemostasis Applications.

The currently used hemostatic agents are highly effective in stopping hemorrhages but have a limited role in the modulation of the wound-healing environment. Herein, we propose an intrinsically bioactive hemostatic cryogel based on platelet lysate (PL) and aldehyde-functionalized cellulose nanocrystals (a-CNCs). PL has attracted great attention as an inexpensive milieu of therapeutically relevant proteins; however, its application as a hemostatic agent exhibits serious constraints (e.g., structural integrity and short shelf-life). The incorporation of a-CNCs reinforced the low-strength PL matrix by covalent cross-linking its amine groups that exhibit an elastic interconnected porous network after full cryogelation. Upon blood immersion, the PL-CNC cryogels absorbed higher volumes of blood at a faster rate than commercial hemostatic porcine gelatin sponges. Simultaneously, the cryogels released biomolecules that increased stem cell proliferation, metabolic activity, and migration as well as downregulated the expression of markers of the fibrinolytic process. In an in vivo liver defect model, PL-CNC cryogels showed similar hemostatic performance in comparison with gelatin sponges and normal material-induced tissue response upon subcutaneous implantation. Overall, owing to their structure and bioactive composition, the proposed PL-CNC cryogels provide an alternative off-the-shelf hemostatic and antibacterial biomaterial with the potential to deliver therapeutically relevant proteins in situ.

Effect of Sonic Agitation of a Binary Mixture of Solvents on Filling Remnants Removal as an Alternative to Apical Enlargement-A Micro-CT Study.

BACKGROUND: This work aimed to evaluate the efficacy of sonic agitation of a binary mixture of solvents (methyl ethyl ketone/tetrachloroethylene) on filling remnants removal and compare the effects of solvent agitation with the enlargement to the next instrument size. METHODS: Twenty-four mandibular incisors were prepared with ProTaper Next (X1, X2) and obturated with the single-cone technique and AH Plus sealer. The teeth were retreated with ProTaper Universal Retreatment and ProTaper Next and divided into two groups (n = 12) according to the final instrument (X3 or X4). All canals were submitted to a supplementary procedure consisting of a mixture of solvents-methyl ethyl ketone/tetrachloroethylene, agitated with EndoActivator. The volume of filling remnants was assessed through micro-computed tomography in the apical 5 mm. Statistical analysis was performed with a significance level of 5%. RESULTS: The supplementary procedure of agitation of the solvent mixture was beneficial in both groups (p < 0.05). There were no statistically significant differences between canals re-prepared until X4 and canals re-prepared until X3 plus solvent (p > 0.05). CONCLUSIONS: An additional step with a two-solvent solution potentiated by EndoActivator showed to be very effective for the removal of gutta-percha and resinous sealer remnants from apical root canals of mandibular incisors, avoiding further enlargement.

Platelet-rich Blood Derivatives for Tendon Regeneration.

Tendon injuries constitute a significant healthcare problem with variable clinical outcomes. The complex interplay of tissue homeostasis, degeneration, repair, and regeneration makes the development of successful delivery therapeutic strategies challenging. Platelet-rich hemoderivatives, a source of supra-physiologic concentrations of human therapeutic factors, are a promising application to treat tendon injuries from the perspective of tendon tissue engineering, although the outcomes remain controversial.

Injectable and Magnetic Responsive Hydrogels with Bioinspired Ordered Structures.

Injectable hydrogels are particularly interesting for applications in minimally invasive tissue engineering and regenerative medicine strategies. However, the typical isotropic microstructure of these biomaterials limits their potential for the regeneration of ordered tissues. In the present work, we decorated rod-shaped cellulose nanocrystals with magnetic nanoparticles and coated these with polydopamine and polyethylene glycol polymer brushes to obtain chemical and colloidal stable nanoparticles. Then, these nanoparticles (0.1-0.5 wt %) were incorporated within gelatin hydrogels, creating injectable and magnetically responsive materials with potential for various biomedical applications. Nanoparticle alignment within the hydrogel matrix was achieved under exposure to uniform low magnetic fields (108 mT), resulting in biomaterials with directional microstructure and anisotropic mechanical properties. The biological performance of these nanocomposite hydrogels was studied using adipose tissue derived human stem cells. Cells encapsulated in the nanocomposite hydrogels showed high rates of viability demonstrating that the nanocomposite biomaterials are not cytotoxic. Remarkably, the microstructural patterns stemming from nanoparticle alignment induced the directional growth of seeded and, to a lower extent, encapsulated cells in the hydrogels, suggesting that this injectable system might find application in both cellular and acellular strategies targeting the regeneration of anisotropic tissues.

Bioengineered surgical repair of a chronic oronasal fistula in a cat using autologous platelet-rich fibrin and bone marrow with a tailored 3D printed implant.

Clinical summary: A tissue engineering approach was used to aid the surgical repair of a chronic oronasal fistula (ONF) in a 13-year-old cat. A three-dimensional (3D) printed mesh, tailored to the size and shape of the ONF, was created to support a soft tissue flap used to close the defect; and also to provide a matrix for mesenchymal stromal cells present in bone marrow aspirate and bioactive cytokines and growth factors present in platelet-rich fibrin harvested from the patient. A CT scan at day 75 after surgery revealed the formation of new tissue in the defect and the healing process was complete at follow-up 6 months after surgery. Relevance and novel information: Complications are frequently reported following surgical repair of ONFs and include dehiscence of the palatal suture line, flap necrosis due to damage to the greater palatine artery and maxillary osteomyelitis, mainly due to chronic infection and bone lysis. The case described here demonstrates how input from a multidisciplinary team and the use of a biomaterial, processed by sophisticated technologies, can create a precision regenerative medicine strategy adapted to the patient's clinical needs; this provided a novel therapeutic solution for an otherwise hard to treat clinical problem.

Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration.

Bioengineered soft tissues on any meaningful scale or complexity must incorporate aspects of the functional tissue, namely a vasculature, providing cells oxygen and nutrients critical for their survival. However, the ability of tissue engineering strategies to promote a fast revascularization is critically limited. Particularly in endodontic regenerative therapies, the complicated anatomy of the root canal system, and the narrow apical access limit the supply of new blood vessels and pulp tissue ingrowth. Here we characterize the viscoelastic and microstructural properties of a class of injectable hyaluronic acid (HA) hydrogels formed in situ, reinforced with cellulose nanocrystals (CNCs) and enriched with platelet lysate (PL), and test its ability to promote cells recruitment and proangiogenic activity in vitro. The incorporation of CNCs enhanced the stability of the materials against hydrolytic and enzymatic degradation. Moreover, the release of the chemotactic and pro-angiogenic growth factors (GFs) (PDGF and VEGF) from the PL-laden hydrogels showed an improved sustained profile proportional to the amount of incorporated CNCs. The PL-laden hydrogels exhibited preferential supportive properties of encapsulated human dental pulp cells (hDPCs) in in vitro culture conditions. Finally, PL-laden hydrogels stimulated chemotactic and pro-angiogenic activity by promoting hDPCs recruitment and cell sprouting in hDPCs/human umbilical vein endothelial cell co-cultures in vitro, and in an ex vivo model. These results support the use of the combined system as a scaffold for GFs delivery and cells recruitment, thereby exhibiting great clinical potential in treating injuries in vascularized tissues. STATEMENT OF SIGNIFICANCE: Innovative strategies for improved chemotactic and pro-angiogenic features of TE constructs are needed. In this study, we developed an injectable HA/CNC/PL hydrogel with improved structural and biologic properties, that not only provide a sustained release of chemotactic and proangiogenic GFs from PL but also enhance the cells' viability and angiogenic activity. As a result of their unique traits, the developed hydrogels are ideally suited to simultaneously act as a GFs controlled delivery system and as a supportive matrix for cell culture, recruitment, and revascularization induction, holding great potential for the regeneration of vascularized soft tissues, such as the dentin-pulp complex.

Hyaluronic acid hydrogels incorporating platelet lysate enhance human pulp cell proliferation and differentiation.

The restoration of dentine-pulp complex remains a challenge for dentists; nonetheless, it has been poorly addressed. An ideal system should modulate the host response, as well as enable the recruitment, proliferation and differentiation of relevant progenitor cells. Herein was proposed a photocrosslinkable hydrogel system based on hyaluronic acid (HA) and platelet lysate (PL). PL is a cocktail of growth factors (GFs) and cytokines involved in wound healing orchestration, obtained by the cryogenic processing of platelet concentrates, and was expected to provide the HA hydrogels specific biochemical cues to enhance pulp cells' recruitment, proliferation and differentiation. Stable HA hydrogels incorporating PL (HAPL) were prepared after photocrosslinking of methacrylated HA (Met-HA) previously dissolved in PL, triggered by the Ultra Violet activated photoinitiator Irgacure 2959. Both the HAPL and plain HA hydrogels were shown to be able to recruit cells from a cell monolayer of human dental pulp stem cells (hDPSCs) isolated from permanent teeth. The hDPCs were also seeded directly over the hydrogels (5 × 104 cells/hydrogel) and cultured in osteogenic conditions. Cell metabolism and DNA quantification were higher, in all time-points, for PL supplemented hydrogels (p < 0,05). Alkaline phosphatase (ALPL) activity and calcium quantification peaks were observed for the HAPL group at 21 days (p < 0,05). The gene expression for ALPL and COLIA1 was up-regulated at 21 days to HAPL, compared with HA group (p < 0,05). Within the same time point, the gene expression for RUNX2 did not differ between the groups. Overall, data demonstrated that the HA hydrogels incorporating PL increased the cellular metabolism and stimulate the mineralized matrix deposition by hDPSCs, providing clear evidence of the potential of the proposed system for the repair of damaged pulp/dentin tissue and endodontics regeneration.

Preclinical and Translational Studies in Small Ruminants (Sheep and Goat) as Models for Osteoporosis Research.

PURPOSE OF THE REVIEW: This review summarizes research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies. RECENT FINDINGS: The most frequent osteoporotic sheep model used is the ovariectomized sheep with 12 months post-operatively or more and the combined treatment of ovariectomized sheep associated to calcium/vitamin D-deficient diet and glucocorticoid applications for 6 months, but other methods are also described, like pinealectomy or hypothalamic-pituitary disconnection in ovariectomized sheep. The goat model for osteoporosis research has been used in a very limited number of studies in osteoporosis research relative to sheep. These osteoporotic small ruminant models are applied for biomaterial research, bone augmentation, efficacy of implant fixation, fragility fracture-healing process improvement, or bone-defect repair studies in the osteopenic or osteoporotic bone. Sheep are a recognized large animal model for preclinical and translational studies in osteoporosis research and the goat to a lesser extent. Recently, the pathophysiological mechanism underlying induction of osteoporosis in glucocorticoid-treated ovariectomized aged sheep was clarified, being similar to what occurs in postmenopausal women with glucocorticoid-induced osteoporosis. It was also concluded that the receptor activator of NF-κB ligand was stimulated in the late progressive phase of the osteoporosis induced by steroids in sheep. The knowledge of the pathophysiological mechanisms at the cellular and molecular levels of the induction of osteoporosis in small ruminants, if identical to humans, will allow in the future, the use of these animal models with greater confidence in the preclinical and translational studies for osteoporosis research.

The effects of platelet lysate patches on the activity of tendon-derived cells.

Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an antibacterial effect by preventing the adhesion, proliferation and biofilm formation by S. aureus, a common pathogen in orthopaedic surgical site infections. Furthermore, these patches supported the activity of human tendon-derived cells (hTDCs). Cells were able to proliferate over time and an up-regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon-related extracellular matrix proteins, namely collagen type I and tenascin C. In summary, PL patches can act as a reservoir of biomolecules derived from PL and support the activity of native tendon cells, being proposed as bioinstructive patches for tendon regeneration. STATEMENT OF SIGNIFICANCE: Platelet-derived biomaterials hold great interest for the delivery of therapeutic factors for applications in endogenous regenerative medicine. In the particular case of tendon repair, patch augmentation strategies aiming at shifting the injury environment are explored to improve tendon regeneration. In this study, PL patches were developed with remarkable features, including the controlled release of growth factors and antibacterial efficacy. Remarkably, PL patches supported the activity of native tendon cells by up-regulating tenogenic genes and enabling the deposition of ECM proteins. This patch holds great potential towards simultaneously reducing post-implantation surgical site infections and promoting tendon regeneration for prospective in vivo applications.