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Tendon Biology and Healing

68 citationsUpdated Sep 2026
Illustration: Tendon Biology and Healing

Overview

Tendons and ligaments heal through a similar process consisting of inflammatory, proliferative, and remodeling phases [46]. Native fibroblasts serve as the active cells during this healing, while inflammatory cells and their mediators play an important role in both tendinopathy and tendon healing [46]. Direct insertions, such as the ACL and rotator cuff, consist of a fibrocartilage transition between bone and tendon [46]. These direct insertions do not regenerate when injured [46]. Consequently, healing following repair or reconstruction of direct insertions produces a fibrovascular scar tissue bridge [46]. The healing process at the tendon-bone insertion site results in a reactive scar rather than a histologically normal tendon-bone insertion site [4]. Primary repair remains the standard of care for tendon injuries [20]. However, repaired tendon tissue rarely achieves functionality equal to that of the preinjured state [20].

Biologic augmentation of surgical repair includes techniques such as BMAC, PRP, and growth factors [46]. Stem cells can have a positive effect on tendon healing, likely due to regeneration potential producing tissue similar to the preinjury state, although results regarding their use can be variable [9]. PRP confers several effects on tendon healing compared with a control in basic science studies [1]. Growth factors may be useful in tendon healing, possibly introduced using gene therapy [2]. Understanding the role that growth factors play in tendon repair should enable a more targeted approach to improve the results of flexor tendon repair [5]. Currently, no strategies for manipulating growth factors are routinely used in clinical practice for flexor tendon repair [5]. The clinical relevance of identified growth factors for the practicing hand surgeon remains unclear [7].

A greater understanding of the molecular mechanisms involved in tendon and ligament development and natural healing should lead to regenerative procedures that more closely recapitulate morphogenesis [12]. Understanding the biology and organization of the native tendon and the process of morphogenesis of tendon tissue is necessary to improve current treatment modalities [13]. The application of biochemical and molecular techniques to the study of tendinopathy has led to a greater understanding of these conditions [67]. The continuum model of tendon pathology has been cited extensively, but its clinical utility has yet to be fully elucidated [66]. Significant long-term harms to tendon tissue and cells are associated with glucocorticoid injections [17]. The vascularisation of the healthy Achilles tendon affects tensile strength and rupture vulnerability, though vascularisation is unlikely to be the sole or most significant contributor to Achilles tendon rupture vulnerability [62]. The only clinically justified intervention for adhesion prevention in flexor tendon surgery is early post-operative mobilization of digits, although the best method of mobilization remains controversial [65]. The term 'tendon' may mislead understanding of pathology and management for intramuscular tendon pathologies [30].

How It Works

Molecular and Cellular Mechanisms

Basic science studies indicate that platelet-rich plasma (PRP) confers several effects on tendon healing compared with a control [1]. The molecular basis of flexor tendon wound healing involves growth factors, although their clinical relevance for the practicing hand surgeon remains unclear [7]. Understanding the role of growth factors in tendon repair should enable a more targeted approach to improve the results of flexor tendon repair, although currently no strategies are routinely used in clinical practice [5]. Biochemical pathways activated during repair and parallels between tendon healing and tendon development are emphasized in the healing process [11]. Chemokines may exhibit vital targets for biological modulation of tendon repair [40]. Apoptosis in adhesions and at the adhesion-tendon interface is a prominent event in the tendon-healing process [38]. In ruptured human Achilles tendons, the tissue in the ruptured area undergoes marked rearrangement at molecular levels which involves MMP-2 activity [41]. All investigated MMPs and TIMP-1 contribute to the early human tendon healing process, while TIMP-2, -3, and -4 play a minor role [35]. Diabetes adversely affects properties of native extracellular matrix proteins and delays tendon healing after injury by affecting a variety of factors [42]. Anabolic steroids did not induce ultrastructural collagen changes that might predispose to tendon rupture in humans [37].

Healing Dynamics and Tissue Response

The healing process of the tendon-bone insertion site results in a reactive scar rather than a histologically normal tendon-bone insertion site [4]. A better understanding of the balance between intrinsic and extrinsic healing processes may allow surgeons to tailor their surgical procedures to best reestablish tendon continuity and function [14]. Early controlled motion after flexor tendon repair has a favorable effect on the healing and remodeling response, resulting in stronger repairs and enabling greater excursion of the repaired tendon [28]. Differences in healing mechanisms reveal that extrasynovial tendons heal more effectively than intrasynovial tendons [36]. Recent research has focused on using pharmacologic agents to modify the healing environment to increase the healing response within the tendon while decreasing adhesion formation between the tendon and its sheath [23]. The review emphasizes the challenges in tenocyte characterisation and the need for improved strategies to enhance tendon repair and regeneration [3].

Biologic Augmentation and Regeneration

Stem cells can have a positive effect on tendon healing, likely due to regeneration potential producing tissue similar to the preinjury state, though results can be variable [9]. A phase I/II randomized clinical trial protocol was designed to test the hypothesis that mesenchymal stem cells (MSC) and LP-PRP will restore function, with tendon regeneration expected only in the MSC group [6]. Biological therapies facilitate the regeneration of the correct microarchitecture of the tendon attachment to the bone and reduce failures after surgical rotator cuff repair [25]. The development and applications of compatible biomaterials are highlighted to better recapitulate the tendon-bone interface and improve delivery of biological factors for enhanced integrative repair [15]. Octacalcium phosphate might be beneficial for the healing of rotator cuff tendon to bone [24]. No novel biologic healing approach has been successful in enhancing healing of the injured enthesis [16]. Tissue engineering approaches involve making new combinations of materials, designs, cells, and bioactive molecules to achieve personalized regeneration of a functional tendon [21]. PRP manipulates tendon healing through specific molecular and cellular mechanisms, which are reviewed to understand its effects on tendinopathy and differences in clinical trial outcomes [10].

What the Evidence Shows

Basic Biology and Healing Mechanisms

Tendon repair results in a reactive scar rather than a histologically normal tendon-bone insertion site [4]. Research emphasizes biochemical pathways activated during repair, experimental injury models, and parallels between tendon healing and development [11]. A greater understanding of molecular mechanisms in tendon and ligament development, coupled with the capability to produce complex biomaterials, should lead to regenerative procedures that more closely recapitulate morphogenesis [12]. Understanding the role of growth factors in tendon repair should enable a more targeted approach to improve flexor tendon repair results [5]. However, while basic science reports have identified various growth factors involved in flexor tendon wound healing, their clinical relevance for the practicing hand surgeon remains unclear [7]. A better understanding of the balance between intrinsic and extrinsic healing processes may allow surgeons to eventually tailor their surgical procedures to best reestablish tendon continuity and function [14]. The immunobiological responses following rotator cuff lesions and the inherent repair mechanisms elicited by the body are critically reviewed in the literature [70]. Early controlled passive motion stimulates an intrinsic healing response, restores the gliding surface at an early stage, and results in a repair that is mechanically stronger and structurally more similar to the normal tendon-sheath interface compared to immobilization [50]. Further investigation is needed to determine the most suitable methods of incorporating mechanical loading findings toward improving tendon repair, including optimal timing, parameters, and application in rehabilitation and tissue engineering [34].

Biologics and Regenerative Strategies

The development and applications of compatible biomaterials to better recapitulate the tendon-bone interface and improve delivery of biological factors for enhanced integrative repair are highlighted [15]. Although many biologic therapies have achieved some degree of success in improving structural, histological, and clinical outcomes after surgical tendon-bone enthesis repair, none have reliably and consistently led to clinical improvement [29]. Few clinical trials have examined the effect of scaffolds on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups [26]. Recent research has focused on using pharmacologic agents to modify the healing environment to increase the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath [23]. Recent incremental improvements in clinical outcomes suggest that new biologic strategies, such as cell-based strategies and tissue engineering, may be useful adjuncts to further improve current clinical outcomes in flexor tendon surgery [31]. Biologic adjuvants have great potential to improve rotator cuff healing and reduce rates of reinjury, but current surgical treatments remain inadequate with high failure rates for large and massive tears [32]. The primary use of glucocorticoids did not exert any obvious deleterious side effects on the treated tendon but instead enhanced the regenerative effects of platelet-rich plasma in early inflammatory tendinopathy [33]. Research in biologic modulators to promote scarless healing continues to show promise [63]. The combination of stem cells and growth factors resulted in enhanced repair that emulated uninjured tissue, but the literature search reflected a paucity of research in this field [69]. The potential role of exosomes in tendon regeneration and the novel use of exosomes alone or seeded onto biomaterial matrices to stimulate secretion of favorable cellular factors in accelerating the healing response following rotator cuff repair are proposed [71]. The treatment efficacy of Growth Differentiation Factor 8 (Myostatin) in early tendon repair remains to be defined [27].

Platelet-Rich Plasma (PRP) Specifics

A review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes [10]. A phase I/II randomized clinical trial protocol was designed to test the hypothesis that mesenchymal stem cells (MSC) and leukocyte-poor platelet-rich plasma (LP-PRP) will restore function, but tendon regeneration will only be observed in the MSC group [6]. Compared with leukocyte-rich PRP (Lr-PRP), leukocyte-poor PRP (Lp-PRP) improves tendon healing and is a preferable option for the clinical treatment of tendinopathy [54]. The immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at the early phase of tendon healing [55]. Current data does not show consistent improvement in healing or clinical outcomes with bone marrow stimulation or leukocyte-rich PRP [57].

Tissue Engineering and Biomaterials

Primary repair remains the standard of care, but repaired tendon tissue rarely achieves functionality equal to that of the preinjured state [20]. A demineralized bone matrix (DBM) enhanced with mesenchymal stem cells (MSCs) can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels [51]. Co-administration of atelocollagen and hyaluronic acid improves healing of the rotator cuff and increases the integrity of the rotator cuff repair site [52]. Different in vivo animal studies have shown good results in achieving restoration of the native enthesis using stem cell therapy [53]. The control group demonstrated a similar outcome to augmented repairs in a chronic rotator cuff tear model using demineralized cortical bone matrix [47].

Clinical Management and Outcomes

The review summarizes the basic biology of tendon tissues and provides an update on the latest repair proposals for tendon tears [8]. The review synthesizes literature to address historical controversies and evolving research in primary flexor tendon repair [22]. This review supports the emerging clinical evidence that shows significant long-term harms to tendon tissue and cells associated with glucocorticoid injections [17]. The paper reviews challenges and opportunities for developing effective treatment strategies for enthesis repair, highlighting the need for better understanding of disease pathoetiology, improved outcome measures, and well-designed clinical trials to test repair augmentation strategies [18]. There is a large body of evidence addressing treatment of acute and chronic Achilles tendon ruptures; however, controversy remains [19]. Numerous randomized controlled trials have shown no difference in healing rates between early mobilization and delayed rehabilitation protocols after rotator cuff repair [44]. Current treatments with the highest evidence entail non-surgical methods to promote tendon healing with focused eccentric exercises and biophysical procedures [48]. Revision endoscopic proximal hamstring repair with suture staples provides broad tendon compression, preserves the intact footprint, and includes augmentation to improve healing [56].

Practical Considerations

Biologic Augmentation and Regeneration

The ultimate goal of biologic interventions in rotator cuff surgery is to stimulate a regenerative healing pathway, as the standard healing process results in a reactive scar rather than a histologically normal tendon-bone insertion site [4]. While basic science reports have identified various growth factors involved in flexor tendon wound healing, their clinical relevance for the practicing hand surgeon remains unclear [7]. Understanding the role of growth factors in tendon repair should enable a more targeted approach to improve flexor tendon repair results, although no such strategies are currently used routinely in clinical practice [5]. Current evidence shows that stem cells can have a positive effect on tendon healing, likely due to regeneration potential producing tissue similar to the preinjury state, though results can be variable [9]. The development and application of compatible biomaterials are highlighted to better recapitulate the tendon-bone interface and improve delivery of biological factors for enhanced integrative repair [15]. Autologous tenocyte injection (ATI) might represent a safe and valuable option in the management of chronic tendinopathies as a second line treatment in the case of resistant tendinopathies, with a minimal risk of side effects [59]. While the independent use of developmental biology, tissue engineering, and surgical strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ [60].

Mechanical Loading and Rehabilitation

No specific evidence regarding mechanical loading and rehabilitation protocols is provided in the current evidence base for this section.

Pharmacologic Considerations

Emerging clinical evidence shows significant long-term harms to tendon tissue and cells associated with glucocorticoid injections [17].

Surgical Technique and Tissue Engineering

A surgical technique using lateral-row anchors to repair musculotendinous junction tears of the supraspinatus preserves tendon length, avoids excess tension, and preserves the enthesis, resulting in tendon-to-tendon healing and avoiding cut-through [58]. Generating tissue engineered tendon constructs can be of considerable clinical benefit given the lack of adequate intrasynovial tendon graft sources, donor site morbidity, and the propensity for current methods of repair to cause adhesion formation, though this requires careful consideration of key aspects of developing a functional, durable, and biocompatible scaffold [49]. There is considerable variability in published protocols for in vitro testing of flexor tendon repairs, with no standardized method currently in place [61].

General Clinical Context

Perhaps the most appropriate term for the pathology should not include ‘tendon’ as it misleads our understanding of both the pathology and its management [30]. The repair of tendon injuries still presents a major clinical challenge to orthopedic medicine [43]. Rotator cuff repair is cost-effective for all populations [45].

Key Evidence

  • [L1] In the basic science studies evaluated, it appears that PRP confers several effects on tendon healing compared with a control. [1] (10.1016/j.arthro.2013.07.117)
  • [L5] Growth factors may be useful in tendon healing, possibly introduced using gene therapy. [2] (10.1136/bjsm.36.5.315)
  • [L5] The review emphasizes the challenges in tenocyte characterisation and the need for improved strategies to enhance tendon repair and regeneration. [3] (10.1089/ten.teb.2016.0181)
  • [Paper] The review evaluates the use of biologics to improve healing of the tendon-bone insertion site after repair, noting that while the healing process results in a reactive scar rather than a histologically normal tendon-bone insertion site, the ultimate goal is to stimulate a regenerative healing pathway. [4] (10.1016/j.csm.2012.07.003)
  • [L5] Understanding the role that growth factors play in tendon repair should enable a more targeted approach to be developed to improve the results of flexor tendon repair, although currently no strategies are routinely used in clinical practice. [5] (10.1177/1753193413509231)
  • [L2] This document describes the protocol for a phase I/II randomized clinical trial designed to test the hypothesis that MSC and LP-PRP will restore function, but tendon regeneration will only be observed in the MSC group. [6] (10.1186/s13018-019-1477-2)
  • [L5] The article reviews the molecular basis of flexor tendon wound healing and the role of growth factors, noting that while basic science reports have identified various factors, their clinical relevance for the practicing hand surgeon remains unclear. [7] (10.1016/j.jhsa.2004.04.020)
  • [L4] The review summarizes the basic biology of tendon tissues and provides an update on the latest repair proposals for tendon tears. [8] (10.1302/2058-5241.2.160075)
  • [L4] The current evidence shows that stem cells can have a positive effect on tendon healing, likely due to regeneration potential producing tissue similar to the preinjury state, though results can be variable. [9] (10.1016/j.arthro.2011.12.009)
  • [L4] This review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes. [10] (10.3389/fbioe.2023.1187974)
  • [L5] Biochemical pathways activated during repair, experimental injury models, and parallels between tendon healing and tendon development are emphasized. [11] (10.1146/annurev-bioeng-071811-150122)
  • [L5] A greater understanding of the molecular mechanisms involved in tendon and ligament development and natural healing, coupled with the capability of producing complex biomaterials, should lead to regenerative procedures that more closely recapitulate morphogenesis. [12] (10.1002/bdrc.21041)
  • [L5] Understanding the biology and organization of the native tendon and the process of morphogenesis of tendon tissue is necessary to improve current treatment modalities. [13] (10.1016/j.jhsa.2007.09.007)
  • [L4] A better understanding of the balance between intrinsic and extrinsic healing processes may allow surgeons to eventually tailor their surgical procedures to best reestablish tendon continuity and function. [14] (10.1016/j.jbiomech.2003.11.005)
  • [L4] Finally, the development and applications of compatible biomaterials to both better recapitulate the tendon-bone interface and improve delivery of biological factors for enhanced integrative repair are highlighted. [15] (10.1111/nyas.13267)
  • [L5] No novel biologic healing approach has been successful in enhancing healing of the injured enthesis. [16] (10.1016/j.jse.2017.10.030)
  • [L4] This review supports the emerging clinical evidence that shows significant long-term harms to tendon tissue and cells associated with glucocorticoid injections. [17] (10.1016/j.semarthrit.2013.08.006)
  • [L5] The paper reviews challenges and opportunities for developing effective treatment strategies for enthesis repair, highlighting the need for better understanding of disease pathoetiology, improved outcome measures, and well-designed clinical trials to test repair augmentation strategies. [18] (10.2106/jbjs.18.00200)
  • [L5] There is a large body of evidence addressing treatment of acute and chronic Achilles tendon ruptures; however, controversy remains. [19] (10.2106/jbjs.o.00002)
  • [L5] Primary repair remains the standard of care, but repaired tendon tissue rarely achieves functionality equal to that of the preinjured state. [20] (10.5435/00124635-201103000-00002)
  • [L5] These approaches involve making new combinations of materials, designs, cells, and bioactive molecules to achieve personalized regeneration of a functional tendon. [21] (10.1016/j.jconrel.2021.03.040)
  • [L4] The review synthesizes literature to address historical controversies and evolving research in primary flexor tendon repair. [22] (10.4081/or.2015.6125)
  • [L5] Recent research has been focused on using pharmacologic agents to modify the healing environment to increase the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath. [23] (10.1016/j.ocl.2015.08.019)
  • [L5] It might be beneficial for the healing of rotator cuff tendon to bone. [24] (10.1016/j.jse.2015.01.011)
  • [L2] Biological therapies facilitate the regeneration of the correct microarchitecture of the tendon attachment to the bone and reduce failures after surgical rotator cuff repair. [25] (10.1530/eor-24-0012)
  • [L4] Few clinical trials have examined the effect of scaffolds on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. [26] (10.1177/2325967115587495)
  • [L5] GDF-8's treatment efficacy of the early tendon repair remains to be defined. [27] (10.1177/1558944718792708)
  • [L5] Early controlled motion after flexor tendon repair has a favorable effect on the healing and remodeling response, resulting in stronger repairs and enabling greater excursion of the repaired tendon. [28] (10.1016/s0749-0712(21)00284-5)
  • [L4] Although many biologic therapies have achieved some degree of success in improving structural, histological, and clinical outcomes after surgical tendon-bone enthesis repair, none have reliably and consistently led to clinical improvement. [29] (10.5435/jaaos-d-20-01011)
  • [L5] Perhaps the most appropriate term for the pathology should not include ‘tendon’ as it misleads our understanding of both the pathology and its management. [30] (10.1136/bjsports-2017-098834)
  • [L5] Recent incremental improvements in clinical outcomes suggest that new biologic strategies, such as cell-based strategies and tissue engineering, may be useful adjuncts to further improve current clinical outcomes in flexor tendon surgery. [31] (10.1016/j.hcl.2005.01.001)
  • [L5] Biologic adjuvants have great potential to improve rotator cuff healing and reduce rates of reinjury, but current surgical treatments remain inadequate with high failure rates for large and massive tears. [32] (10.1177/2325967116636586)
  • [L5] The primary use of glucocorticoids did not exert any obvious deleterious side effects on the treated tendon but instead enhanced the regenerative effects of platelet-rich plasma in early inflammatory tendinopathy. [33] (10.1177/03635465211037354)
  • [L5] Further investigation with a focus on improving clinical outcomes is needed to determine the most suitable methods of incorporating mechanical loading findings toward improving tendon repair, including optimal timing, parameters, and application in rehabilitation and tissue engineering. [34] (10.2106/jbjs.l.01004)
  • [L4] The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process. [35] (10.3390/ijms18102199)
  • [L5] These differences reveal mechanisms through which extrasynovial tendons heal more effectively than do intrasynovial tendons. [36] (10.2106/jbjs.20.01253)
  • [L4] The authors conclude that anabolic steroids did not induce ultrastructural collagen changes that might predispose to tendon rupture in humans. [37] (10.1016/s0020-1383(98)00183-1)
  • [L5] Apoptosis in adhesions and at the adhesion-tendon interface is a prominent event in the tendon-healing process. [38] (10.1016/j.jhsa.2013.03.012)
  • [L3] Chemokines may thus exhibit vital targets for biological modulation of tendon repair. [40] (10.1007/s00167-014-3010-9)
  • [L4] Our data support the hypothesis that in ruptured human Achilles tendons the tissue in the ruptured area undergoes marked rearrangement at molecular levels which involves MMP-2 activity and support the critical role of MMPs in tendon physiology. [41] (10.1007/s11999-008-0255-y)
  • [L5] Diabetes adversely affects properties of native ECM proteins and delays tendon healing after injury by affecting a variety of factors. [42] (10.1007/978-3-319-33943-6_16)
  • [L5] The repair of tendon injuries still presents a major clinical challenge to orthopedic medicine. [43] (10.1159/000347059)
  • [L2] Numerous randomized controlled trials have shown no difference in healing rates between early mobilization and delayed rehabilitation protocols. [44] (10.1016/j.ocl.2015.08.017)
  • [L4] Rotator cuff repair is cost-effective for all populations. [45] (10.2106/jbjs.l.01495)
  • [L5] The control group demonstrated a similar outcome to augmented repairs. [47] (10.1016/j.jse.2017.01.003)
  • [L5] Current treatments with the highest evidence entail non-surgical methods to promote tendon healing with focused eccentric exercises and biophysical procedures. [48] (10.1136/jisakos-2018-000202)
  • [L5] Generating tissue engineered tendon constructs can be of considerable clinical benefit given the lack of adequate intrasynovial tendon graft sources, donor site morbidity, and the propensity for current methods of repair to cause adhesion formation, though this requires careful consideration of key aspects of developing a functional, durable, and biocompatible scaffold. [49] (10.1177/1753193413512432)
  • [L5] Early controlled passive motion stimulates an intrinsic healing response, restores the gliding surface at an early stage, and results in a repair that is mechanically stronger and structurally more similar to the normal tendon-sheath interface compared to immobilization. [50] (10.2106/00004623-198365010-00010)
  • [L5] A DBM enhanced with MSCs can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels. [51] (10.1177/0363546517727512)
  • [L1] Co-administration of atelocollagen and HA improves healing of the rotator cuff and increases the integrity of the rotator cuff repair site. [52] (10.5397/cise.2021.00234)
  • [L4] Different in vivo animal studies have shown good results in achieving restoration of the native enthesis. [53] (10.4252/wjsc.v7.i4.691)
  • [L5] Compared with Lr-PRP, Lp-PRP improves tendon healing and is a preferable option for the clinical treatment of tendinopathy. [54] (10.1177/0363546517694357)
  • [L5] At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. [55] (10.1002/jcp.21368)
  • [L5] It provides broad tendon compression, preserves the intact footprint, and includes augmentation to improve healing. [56] (10.1016/j.eats.2025.103928)
  • [L5] Current data does not show consistent improvement in healing or clinical outcomes with bone marrow stimulation or leukocyte-rich PRP. [57] (10.5435/jaaos-d-25-00069)
  • [Paper] The described technique preserves the tendon length, avoids excess tension, and preserves the enthesis, resulting in tendon-to-tendon healing and avoiding cut-through. [58] (10.1016/j.eats.2016.09.001)
  • [L4] Autologous tenocyte injection (ATI) might represent a safe and valuable option in the management of chronic tendinopathies as a second line treatment in the case of resistant tendinopathies, with a minimal risk of side effects. [59] (10.3390/jfmk10010095)
  • [Paper] While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. [60] (10.1089/ten.teb.2016.0446)
  • [L4] There is considerable variability in published protocols for in vitro testing of flexor tendon repairs, with no standardized method currently in place. [61] (10.1177/17531934221139068)
  • [L5] Whilst no definitive conclusion was reached, it was concluded that the vascularisation does affect the tensile strength and so rupture vulnerability of the healthy Achilles tendon, although it is unlikely to be either the sole, or most significant, contributor. [62] (10.1016/j.injury.2005.02.012)
  • [L5] Research in biologic modulators to promote scarless healing continues to show promise. [63] (10.1016/j.hcl.2014.12.004)
  • [L4] The only thing that appears clinically justified in adhesion prevention is the need for early post-operative mobilization of digits after tendon injury or repair but the best method of mobilization remains controversial. [65] (10.1093/bmb/ldp013)
  • [L5] The continuum model of tendon pathology has been cited extensively, but its clinical utility has yet to be fully elucidated. [66] (10.1136/bjsports-2015-095422)
  • [L5] The application of biochemical and molecular techniques to the study of both animal and human tendinopathy has led to a greater understanding of these common and disabling conditions. [67] (10.1093/rheumatology/keg448)
  • [L4] The combination of stem cells and growth factors resulted in enhanced repair that emulated uninjured tissue, but the literature search reflected paucity of research in this field. [69] (10.1016/j.jse.2011.10.004)
  • [L5] The article critically reviews the immunobiological responses following rotator cuff lesions and the inherent repair mechanisms elicited by the body. [70] (10.1007/s11010-016-2710-5)
  • [L4] This article critically reviews the potential role of exosomes in tendon regeneration and proposes the novel use of exosomes alone or seeded onto biomaterial matrices to stimulate secretion of favorable cellular factors in accelerating the healing response following rotator cuff repair. [71] (10.1007/s00774-019-01013-z)

References

[1] Paper #113: Pain and Activity Levels Before and After L‐PRP Treatment of Patellar Tendinopathy: A Prospective Cohort Study and the Influence of Previous Treatments. Arthroscopy. 2013. DOI: 10.1016/j.arthro.2013.07.117

[2] Tendon healing: can it be optimised?. British Journal of Sports Medicine. 2002. DOI: 10.1136/bjsm.36.5.315

[3] A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration. Tissue Engineering Part B: Reviews. 2016. DOI: 10.1089/ten.teb.2016.0181

[4] Biologics in the Management of Rotator Cuff Surgery. Clinics in Sports Medicine. 2012. DOI: 10.1016/j.csm.2012.07.003

[5] The growth factors involved in flexor tendon repair and adhesion formation. Journal of Hand Surgery (European Volume). 2013. DOI: 10.1177/1753193413509231

[6] Autologous bone marrow expanded mesenchymal stem cells in patellar tendinopathy: protocol for a phase I/II, single-centre, randomized with active control PRP, double-blinded clinical trial. Journal of Orthopaedic Surgery and Research. 2019. DOI: 10.1186/s13018-019-1477-2

[7] Clinical implications of growth factors in flexor tendon wound healing. The Journal of Hand Surgery. 2004. DOI: 10.1016/j.jhsa.2004.04.020

[8] Tendon injuries. EFORT Open Reviews. 2017. DOI: 10.1302/2058-5241.2.160075

[9] Exploring the Application of Stem Cells in Tendon Repair and Regeneration. Arthroscopy. 2012. DOI: 10.1016/j.arthro.2011.12.009

[10] Platelet-rich plasma in the pathologic processes of tendinopathy: a review of basic science studies. Frontiers in Bioengineering and Biotechnology. 2023. DOI: 10.3389/fbioe.2023.1187974

[11] Tendon Healing: Repair and Regeneration. Annual Review of Biomedical Engineering. 2012. DOI: 10.1146/annurev-bioeng-071811-150122

[12] Tendon and ligament regeneration and repair: Clinical relevance and developmental paradigm. Birth Defects Research Part C: Embryo Today: Reviews. 2013. DOI: 10.1002/bdrc.21041

[13] Tendon: Biology, Biomechanics, Repair, Growth Factors, and Evolving Treatment Options. The Journal of Hand Surgery. 2008. DOI: 10.1016/j.jhsa.2007.09.007

[14] Biomechanics of tendon injury and repair. Journal of Biomechanics. 2004. DOI: 10.1016/j.jbiomech.2003.11.005

[15] Advances in biologic augmentation for rotator cuff repair. Annals of the New York Academy of Sciences. 2016. DOI: 10.1111/nyas.13267

[16] Assembly, maturation, and degradation of the supraspinatus enthesis. Journal of Shoulder and Elbow Surgery. 2018. DOI: 10.1016/j.jse.2017.10.030

[17] The risks and benefits of glucocorticoid treatment for tendinopathy: A systematic review of the effects of local glucocorticoid on tendon. Seminars in Arthritis and Rheumatism. 2014. DOI: 10.1016/j.semarthrit.2013.08.006

[18] Enthesis Repair. Journal of Bone and Joint Surgery. 2018. DOI: 10.2106/jbjs.18.00200

[19] Everything Achilles: Knowledge Update and Current Concepts in Management. The Journal of Bone and Joint Surgery-American Volume. 2015. DOI: 10.2106/jbjs.o.00002

[20] Tissue Engineering Solutions for Tendon Repair. American Academy of Orthopaedic Surgeon. 2011. DOI: 10.5435/00124635-201103000-00002

[21] Tendon tissue engineering: Cells, growth factors, scaffolds and production techniques. Journal of Controlled Release. 2021. DOI: 10.1016/j.jconrel.2021.03.040

[22] A review of current concepts in flexor tendon repair: physiology, biomechanics, surgical technique and rehabilitation.. Orthopedic Review. 2015. DOI: 10.4081/or.2015.6125

[23] Flexor Tendon Repair. Orthopedic Clinics of North America. 2016. DOI: 10.1016/j.ocl.2015.08.019

[24] The role of an octacalcium phosphate in the re-formation of infraspinatus tendon insertion. Journal of Shoulder and Elbow Surgery. 2015. DOI: 10.1016/j.jse.2015.01.011

[25] Biological strategies in rotator cuff repair: a clinical application and molecular background. EFORT Open Reviews. 2024. DOI: 10.1530/eor-24-0012

[26] Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds. Orthopaedic Journal of Sports Medicine. 2015. DOI: 10.1177/2325967115587495

[27] The Effect of Growth Differentiation Factor 8 (Myostatin) on Bone Marrow–Derived Stem Cell–Coated Bioactive Sutures in a Rabbit Tendon Repair Model. HAND. 2018. DOI: 10.1177/1558944718792708

[28] EARLY MOTION AFTER FLEXOR TENDON SURGERY. Hand Clinics. 1996. DOI: 10.1016/s0749-0712(21)00284-5

[29] Augmentation of Rotator Cuff Healing With Orthobiologics. Journal of the American Academy of Orthopaedic Surgeons. 2021. DOI: 10.5435/jaaos-d-20-01011

[30] Does the intramuscular tendon act like a free tendon?. British Journal of Sports Medicine. 2018. DOI: 10.1136/bjsports-2017-098834

[31] The Future of Flexor Tendon Surgery. Hand Clinics. 2005. DOI: 10.1016/j.hcl.2005.01.001

[32] Biologic Treatments for Sports Injuries II Think Tank—Current Concepts, Future Research, and Barriers to Advancement, Part 2. Orthopaedic Journal of Sports Medicine. 2016. DOI: 10.1177/2325967116636586

[33] Early-Stage Primary Anti-inflammatory Therapy Enhances the Regenerative Efficacy of Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211037354

[34] The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair. Journal of Bone and Joint Surgery. 2013. DOI: 10.2106/jbjs.l.01004

[35] Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture. International Journal of Molecular Sciences. 2017. DOI: 10.3390/ijms18102199

[36] Flexor Tendon Injury and Repair. Journal of Bone and Joint Surgery. 2021. DOI: 10.2106/jbjs.20.01253

[37] Ultrastructural analysis of ruptured tendon from anabolic steroid users. Injury. 1998. DOI: 10.1016/s0020-1383(98)00183-1

[38] Apoptosis in Adhesions and the Adhesion-Tendon Gliding Interface: Relationship to Adhesion-Tendon Gliding Mechanics. The Journal of Hand Surgery. 2013. DOI: 10.1016/j.jhsa.2013.03.012

[40] Chemokine expression of CCL2, CCL3, CCL5 and CXCL10 during early inflammatory tendon healing precedes nerve regeneration: an immunohistochemical study in the rat. Knee Surgery, Sports Traumatology, Arthroscopy. 2014. DOI: 10.1007/s00167-014-3010-9

[41] Collagens, Proteoglycans, MMP-2, MMP-9 and TIMPs in Human Achilles Tendon Rupture. Clinical Orthopaedics & Related Research. 2008. DOI: 10.1007/s11999-008-0255-y

[42] Does Diabetes Mellitus Affect Tendon Healing?. Advances in Experimental Medicine and Biology. 2016. DOI: 10.1007/978-3-319-33943-6_16

[43] Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells. Pathobiology. 2013. DOI: 10.1159/000347059

[44] Immobilization After Rotator Cuff Repair. Orthopedic Clinics of North America. 2016. DOI: 10.1016/j.ocl.2015.08.017

[45] The Societal and Economic Value of Rotator Cuff Repair. Journal of Bone and Joint Surgery. 2013. DOI: 10.2106/jbjs.l.01495

[46] Orthopaedic Basic Science Fifth Edition Print Ebook. Lumbar Spondylosis, Degenerative Disk Disease, and Radiculopathy > Summary.

[47] The effectiveness of demineralized cortical bone matrix in a chronic rotator cuff tear model. Journal of Shoulder and Elbow Surgery. 2017. DOI: 10.1016/j.jse.2017.01.003

[48] Treatment of Achilles tendinopathy: state of the art. Journal of ISAKOS. 2018. DOI: 10.1136/jisakos-2018-000202

[49] Tissue engineering in flexor tendon surgery: current state and future advances. Journal of Hand Surgery (European Volume). 2013. DOI: 10.1177/1753193413512432

[50] Flexor tendon healing and restoration of the gliding surface. An ultrastructural study in dogs.. The Journal of Bone & Joint Surgery. 1983. DOI: 10.2106/00004623-198365010-00010

[51] Application of a Demineralized Cortical Bone Matrix and Bone Marrow–Derived Mesenchymal Stem Cells in a Model of Chronic Rotator Cuff Degeneration. The American Journal of Sports Medicine. 2017. DOI: 10.1177/0363546517727512

[52] Effect of co-administration of atelocollagen and hyaluronic acid on rotator cuff healing. Clinics in Shoulder and Elbow. 2021. DOI: 10.5397/cise.2021.00234

[53] Stem cell therapy in the management of shoulder rotator cuff disorders. World Journal of Stem Cells. 2015. DOI: 10.4252/wjsc.v7.i4.691

[54] Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model. The American Journal of Sports Medicine. 2017. DOI: 10.1177/0363546517694357

[55] Platelet‐rich plasma enhances the initial mobilization of circulation‐derived cells for tendon healing. Journal of Cellular Physiology. 2008. DOI: 10.1002/jcp.21368

[56] Revision Endoscopic Proximal Hamstring Repair with Suture Staples. Arthroscopy Techniques. 2025. DOI: 10.1016/j.eats.2025.103928

[57] Orthobiologic Augmentation to Improve Rotator Cuff Repair Outcomes: Current and Future Strategies. Journal of the American Academy of Orthopaedic Surgeons. 2025. DOI: 10.5435/jaaos-d-25-00069

[58] Surgical Technique to Repair Musculotendinous Junction Tear of Supraspinatus Using Lateral‐Row Anchors to Avoid Cut‐Through. Arthroscopy Techniques. 2017. DOI: 10.1016/j.eats.2016.09.001

[59] Effects of Autologous Tenocyte Injection for Overuse and Degenerative Tendinopathies: A Systematic Review. Journal of Functional Morphology and Kinesiology. 2025. DOI: 10.3390/jfmk10010095

[60] The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears. Tissue Engineering Part B: Reviews. 2017. DOI: 10.1089/ten.teb.2016.0446

[61] In vitro testing of flexor tendon repair models: variability in the current literature. Journal of Hand Surgery (European Volume). 2022. DOI: 10.1177/17531934221139068

[62] Review of the vascularisation of the human Achilles tendon. Injury. 2005. DOI: 10.1016/j.injury.2005.02.012

[63] Management of Complications of Flexor Tendon Injuries. Hand Clinics. 2015. DOI: 10.1016/j.hcl.2014.12.004

[65] Prevention of adhesions in surgery of the flexor tendons of the hand: what is the evidence?. British Medical Bulletin. 2009. DOI: 10.1093/bmb/ldp013

[66] Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research?. British Journal of Sports Medicine. 2016. DOI: 10.1136/bjsports-2015-095422

[67] The pathogenesis of tendinopathy. A molecular perspective. Rheumatology. 2003. DOI: 10.1093/rheumatology/keg448

[69] Biologic approaches to enhance rotator cuff healing after injury. Journal of Shoulder and Elbow Surgery. 2012. DOI: 10.1016/j.jse.2011.10.004

[70] Immunobiological factors aggravating the fatty infiltration on tendons and muscles in rotator cuff lesions. Molecular and Cellular Biochemistry. 2016. DOI: 10.1007/s11010-016-2710-5

[71] Therapeutic potential of exosomes in rotator cuff tendon healing. Journal of Bone and Mineral Metabolism. 2019. DOI: 10.1007/s00774-019-01013-z

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