European Journal of Cardiovascular Medicine

The rotator cuff is the principal dynamic stabiliser of the glenohumeral joint, and disorders of the supraspinatus tendon constitute the most frequent cause of atraumatic shoulder pain encountered in orthopaedic outpatient practice. Partial-thickness rotator cuff tears account for a substantial proportion of surgically and radiologically confirmed cuff pathology, and bursal-sided partial tears, though less common than articular-sided lesions, are recognised to be biomechanically more significant because they propagate more rapidly toward full-thickness tears when left untreated.

Epidemiological data from the Indian subcontinent, though historically limited compared with Western literature, have progressively clarified the burden of rotator cuff disease in this population. Park et al. [1], reporting from an Indian tertiary centre, highlighted that outcomes following treatment of shoulder impingement and associated cuff pathology are influenced significantly by concomitant stiffness and duration of symptoms, underscoring the importance of early, targeted intervention rather than prolonged empirical treatment. Later Indian series have similarly emphasised that a considerable fraction of the working-age population presenting with chronic shoulder pain harbours partial-thickness supraspinatus lesions that are frequently under-recognised on plain clinical examination alone and require dedicated sonographic or magnetic resonance evaluation for accurate grading.

The classical management pathway for partial-thickness supraspinatus tears begins with activity modification, oral anti-inflammatory medication, and structured physiotherapy directed at scapular stabilisation and rotator cuff strengthening. When these measures fail, subacromial corticosteroid injection has traditionally been used to control pain, but there is increasing concern regarding the deleterious effect of repeated corticosteroid exposure on tendon collagen architecture and the theoretical risk of accelerating tear progression. This concern has driven interest in biologically active alternatives that aim not merely to suppress inflammation but to actively promote tendon matrix repair.

Growth factor concentrate, most commonly prepared as autologous platelet-rich plasma (PRP), is obtained by differential centrifugation of a patient's own peripheral blood to yield a plasma fraction with a platelet concentration several-fold above baseline. Activated platelets degranulate to release a cocktail of growth factors, including platelet-derived growth factor, transforming growth factor-beta, vascular endothelial growth factor, and insulin-like growth factor-1, which collectively promote angiogenesis, fibroblast proliferation, and collagen synthesis at the site of tendon injury. Dhillon et al. [2], in a widely cited review from a leading Indian orthopaedic institution, comprehensively summarised the biological rationale and evolving clinical applications of orthobiologics, including PRP, in musculoskeletal healing and cautioned that clinical benefit is critically dependent on preparation protocol, platelet yield, and the precise anatomical site of delivery.

The application of growth factor concentrate specifically to partial-thickness rotator cuff tears is biologically attractive because the bursal and tendon-bursal interface is relatively avascular, and the intrinsic healing response of the tendon substance is known to be limited. Sambandam et al. [3], in a comprehensive evidence-based review of rotator cuff pathology, noted that the natural history of partial-thickness tears is heterogeneous, with a meaningful subset progressing in size over time, and argued that interventions capable of favourably altering the local biological environment merit systematic clinical evaluation before tears progress to a stage requiring surgical repair.

Despite this rationale, the published evidence on growth factor concentrate injection for partial bursal-sided supraspinatus tears remains heterogeneous, with considerable variation in PRP preparation methods, injection technique (image-guided versus landmark-guided), leukocyte content, activation protocols, and outcome measures used across studies. Patel et al. [4], in a randomised trial from an Indian institution evaluating platelet-rich plasma in a different musculoskeletal context, demonstrated statistically significant symptomatic benefit of PRP over placebo, lending broader support to the biological premise of platelet-derived growth factor therapy, though direct extrapolation to bursal-sided supraspinatus tears requires caution given differences in the target tissue.

Given this background, the present study was designed to prospectively evaluate the clinical, functional, and sonographic outcomes of a single ultrasound-guided growth factor concentrate injection administered specifically for partial bursal-sided tears of the supraspinatus tendon, with structured follow-up extending to 24 months. The primary objective was to determine whether GFC injection produces sustained improvement in pain and shoulder function, while secondary objectives included assessment of sonographic tear healing, complication rates, and the proportion of patients ultimately requiring surgical intervention.

Study Design and Setting

This was a prospective, single-arm, observational cohort study conducted in the Department of Orthopaedics, in collaboration with the Department of Radiodiagnosis, at a tertiary care teaching hospital with clinical and sonographic follow-up to complete the 2-year observation period for all enrolled patients. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants prior to enrolment. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Sample Size

Sample size was calculated on the basis of an anticipated mean reduction in VAS score of 3.5 points with a standard deviation of 1.8, derived from pilot data and comparable published series, using a two-sided alpha of 0.05 and power of 90%. This yielded a minimum requirement of 54 patients; accounting for an anticipated 15% loss to follow-up, 64 patients were planned for enrolment.

Inclusion Criteria

Patients aged 30-65 years with clinically suspected rotator cuff pathology, radiologically confirmed partial bursal-sided supraspinatus tendon tear on high-resolution ultrasonography and corroborated by MRI (Ellman classification grade I or II, tear involving less than 50% of tendon thickness), symptom duration of more than 8 weeks, and failure of a structured 8-week trial of oral analgesics/NSAIDs and supervised physiotherapy were included.

Exclusion Criteria

Patients with full-thickness rotator cuff tears, articular-sided or intrasubstance tears, associated glenohumeral instability, adhesive capsulitis, significant glenohumeral or acromioclavicular joint osteoarthritis, prior ipsilateral shoulder surgery, calcific tendinitis requiring separate intervention, uncontrolled diabetes mellitus, active local or systemic infection, bleeding diathesis or anticoagulant therapy, and pregnancy were excluded. Patients who had received a corticosteroid injection into the affected shoulder within the preceding 3 months were also excluded to avoid confounding.

Preparation of Growth Factor Concentrate

Growth factor concentrate was prepared from autologous peripheral venous blood using a closed double-spin centrifugation technique. Eighteen millilitres of venous blood was drawn into acid-citrate-dextrose anticoagulant tubes and subjected to a first ('soft') spin at 1500 rpm for 10 minutes to separate red blood cells from the plasma fraction. The supernatant plasma, containing platelets and leukocytes, was transferred to a sterile tube and subjected to a second ('hard') spin at 3500 rpm for 10 minutes to concentrate platelets in the lower third of the plasma column. The platelet-poor plasma in the upper two-thirds was discarded, yielding approximately 3-4 mL of growth factor concentrate with a platelet concentration of approximately 4-6 times the peripheral blood baseline, confirmed by automated cell counting in a representative subset of samples. The concentrate was used fresh, without exogenous activation, within 30 minutes of preparation.

Injection Technique

All injections were performed by a single experienced musculoskeletal radiologist using a high-frequency linear array transducer (7-12 MHz) under strict aseptic precautions. With the patient seated and the arm in modified Crass position, the subacromial-subdeltoid bursa and the bursal surface of the supraspinatus tendon were identified in the long-axis plane. Using an in-plane, lateral-to-medial needle approach, a 21-gauge spinal needle was advanced under continuous real-time visualisation to the tendon-bursal interface at the site of the tear, and 3-4 mL of growth factor concentrate was deposited in a fanning technique across the bursal surface and peritendinous region. Correct needle-tip position and distribution of the injectate were confirmed sonographically before needle withdrawal.

Post-Injection Protocol and Rehabilitation

Patients were advised relative rest and arm-sling support for 48 hours, with avoidance of NSAIDs for 2 weeks to prevent blunting of the platelet-mediated inflammatory response. A structured, supervised physiotherapy programme was initiated from day 3, progressing through phases of pain control and passive range-of-motion exercises (weeks 1-2), active-assisted and active range-of-motion exercises (weeks 2-6), and progressive rotator cuff and scapular stabiliser strengthening (from week 6 onward), continued for a minimum of 12 weeks under supervision and thereafter as a home-based maintenance programme.

Outcome Measures

Clinical outcomes were assessed at baseline and at 6 weeks, 3 months, 6 months, 1 year, and 2 years using: (i) Visual Analogue Scale (VAS, 0-10) for pain; (ii) American Shoulder and Elbow Surgeons (ASES) score; (iii) Constant-Murley score; and (iv) Shoulder Pain and Disability Index (SPADI). Sonographic assessment of tear dimensions (anteroposterior length and mediolateral width) was performed at baseline, 6 months, 1 year, and 2 years by a radiologist blinded to clinical scores. Complete sonographic healing was defined as absence of a demonstrable hypoechoic defect at the tendon-bursal interface. Adverse events and any subsequent requirement for arthroscopic repair were recorded throughout follow-up.

Statistical Analysis

Data were analysed using SPSS version 26.0 (IBM Corp.). Continuous variables are expressed as mean ± standard deviation and were compared across time points using repeated-measures analysis of variance (ANOVA) with Bonferroni post-hoc correction; categorical variables are expressed as frequencies and percentages and were compared using the chi-square test or Fisher's exact test as appropriate. A p-value of less than 0.05 was considered statistically significant.

Of 78 patients screened, 62 fulfilled the inclusion criteria and were enrolled. Fifty-six patients (90.3%) completed clinical and sonographic follow-up to 24 months; six patients (9.7%) were lost to follow-up after the 1-year assessment and were excluded from the 2-year analysis. Baseline demographic and clinical characteristics of the cohort are summarised in Table 1.

Table 1. Baseline demographic and clinical characteristics (n = 62)

AP: anteroposterior; ML: mediolateral; SD: standard deviation.

A statistically significant, progressive improvement in pain and shoulder function was observed at every follow-up interval compared with baseline (repeated-measures ANOVA, p < 0.001 for VAS, ASES, and Constant-Murley scores). The greatest rate of improvement occurred between baseline and 3 months, with a more gradual but sustained improvement thereafter through 2 years. Table 2 summarises the trend in VAS, ASES, and Constant-Murley scores across the study period.

Table 2. Trend in VAS, ASES, and Constant-Murley scores over 2-year follow-up

VAS: Visual Analogue Scale (0-10); ASES: American Shoulder and Elbow Surgeons score (0-100); Constant-Murley score (0-100). p < 0.001 for all comparisons across time points (repeated-measures ANOVA with Bonferroni correction).

The Shoulder Pain and Disability Index (SPADI) showed a corresponding decline, with a 78.5% reduction from baseline at the 2-year assessment (Table 3), reflecting a clinically meaningful improvement in composite pain and disability scoring that exceeded the commonly cited minimal clinically important difference for this instrument.

Table 3. Shoulder Pain and Disability Index (SPADI) trend

SPADI: Shoulder Pain and Disability Index (0-100, higher score indicates greater disability).

Sonographic follow-up demonstrated a progressive reduction in both anteroposterior tear length and mediolateral tear width, with complete resolution of the sonographically demonstrable tendon-bursal defect in an increasing proportion of patients over time, reaching 37.5% at 2 years (Table 4; n = 56 (patients completing 2-year follow-up)). No patient demonstrated sonographic worsening of tear dimensions between the 1-year and 2-year assessments among those who did not proceed to surgery.

Table 4. Sonographic tear dimensions and rate of complete healing

Values expressed as mean ± SD unless otherwise indicated.

On subgroup analysis by baseline tear severity, patients with Ellman Grade I tears achieved significantly better functional scores and higher rates of complete sonographic healing at 2 years compared with those with Grade II tears, although the difference in subsequent surgical conversion rate did not reach statistical significance (Table 5).

Table 5. Outcome comparison by baseline Ellman grade

Values expressed as mean ± SD unless otherwise indicated. p-values by independent samples t-test (continuous variables) or chi-square/Fisher's exact test (categorical variables).

The procedure was well tolerated overall. No patient developed a deep infection, neurovascular injury, or major systemic adverse effect. Minor, self-limiting adverse events are detailed in Table 6. Four patients (6.5%) ultimately required arthroscopic rotator cuff repair for persistent or progressive symptoms despite GFC injection and structured rehabilitation, three of whom belonged to the Ellman Grade II subgroup.

Table 6. Adverse events and complications

Percentages calculated out of 62 enrolled patients unless otherwise specified.

This prospective study demonstrates that a single ultrasound-guided growth factor concentrate injection, combined with a structured rehabilitation programme, produces statistically significant and clinically meaningful improvement in pain, shoulder function, and sonographic tendon morphology in patients with partial bursal-sided supraspinatus tendon tears, with benefits sustained through 2 years of follow-up. These findings are consistent with the broader premise, articulated in Indian and international literature, that biologically active injectates capable of favourably modulating the local healing environment offer an attractive alternative to purely symptomatic measures such as corticosteroid injection.

The magnitude of clinical improvement observed in the present cohort - a mean VAS reduction of 5.2 points and ASES improvement of over 44 points at 2 years - compares favourably with outcomes reported for corticosteroid injection in partial-thickness cuff tears, which typically provide more rapid but less durable symptomatic relief and do not address the underlying tendon defect. Dhillon et al. [2] had earlier cautioned that the clinical benefit of orthobiologic preparations is highly dependent on precise technique and adequate platelet concentration at the delivery site; the double-spin centrifugation protocol and strict ultrasound-guided delivery to the tendon-bursal interface employed in the present study were specifically designed to address this concern, and may partly explain the relatively high rate of sustained functional improvement observed.

The observed reduction in sonographic tear dimensions, with complete healing demonstrated in over a third of patients at 2 years, provides objective structural corroboration of the clinical improvement and argues against the possibility that symptomatic benefit was purely a placebo or natural-history effect. Nonetheless, it must be acknowledged that partial-thickness tears, particularly low-grade bursal-sided lesions, are known to have a variable natural history, and a proportion of patients may improve with rehabilitation alone irrespective of any injectate administered. The absence of a comparator arm receiving corticosteroid, saline, or physiotherapy alone in the present study is therefore an important limitation that precludes definitive attribution of the observed benefit to the growth factor concentrate itself.

The subgroup analysis demonstrating superior outcomes in Ellman Grade I compared with Grade II tears is biologically plausible and clinically relevant, suggesting that growth factor concentrate injection may be most beneficial when used earlier in the disease course, before the tendon defect becomes large enough to compromise the biomechanical integrity of the remaining intact fibres. This observation aligns with the broader evidence-based perspective offered by Sambandam et al. [3], who emphasised that tear size and chronicity are key determinants of the biological potential for spontaneous or augmented healing, and that intervention strategies should ideally be stratified by tear severity rather than applied uniformly across the spectrum of partial-thickness pathology.

The relatively low rate of subsequent arthroscopic conversion (6.5%) in this cohort is encouraging and suggests that growth factor concentrate injection may, in a meaningful proportion of patients, obviate or at least defer the need for surgical repair, with its attendant costs, rehabilitation burden, and procedural risk. This is of particular relevance in resource-limited settings and in patients with occupational or comorbid factors that increase perioperative risk or limit access to surgical care.

The safety profile observed in this study, with no major complications and only transient, self-limiting minor adverse events, is consistent with the favourable safety record generally reported for autologous blood-derived orthobiologic preparations, reflecting the absence of any foreign or allogeneic material and the autologous, non-immunogenic nature of the injectate. This is an important practical advantage over corticosteroid injection, which carries recognised risks of tendon weakening, skin atrophy, and, with repeated use, acceleration of tear progression - concerns that have driven the search for regenerative alternatives such as the growth factor concentrate evaluated in this study.

Several limitations of the present study warrant emphasis. First, the absence of a control or comparator arm limits causal inference regarding the specific contribution of growth factor concentrate relative to the structured physiotherapy programme that all patients received concurrently. Second, the single-centre, single-arm design and moderate sample size limit generalisability, and selection bias inherent to a tertiary referral population cannot be excluded. Third, platelet and growth factor concentration in the injectate was not quantified for every patient, introducing potential preparation-related variability that could not be fully controlled. Fourth, blinding of clinical outcome assessors was not feasible given the nature of the intervention, which may have introduced a degree of observer or patient expectation bias, although the objective sonographic outcomes assessed by a blinded radiologist partially mitigate this concern. Finally, the 9.7% loss to follow-up by 2 years, while comparable to similar longitudinal orthopaedic cohorts, may have introduced attrition bias if patients with poorer outcomes were disproportionately lost to follow-up.

Future research should prioritise adequately powered, randomised, sham- or comparator-controlled trials directly comparing growth factor concentrate against corticosteroid injection, hyaluronic acid, and physiotherapy alone, with standardised PRP preparation protocols, quantified platelet yield, and blinded outcome assessment, to more definitively establish the incremental benefit and cost-effectiveness of this biological therapy in the management of partial bursal-sided supraspinatus tendon tears, particularly within Indian healthcare settings where such comparative data remain scarce.

Ultrasound-guided growth factor concentrate injection, when combined with a structured post-injection rehabilitation programme, is associated with significant and sustained improvement in pain, shoulder function, and sonographic tendon morphology in patients with partial bursal-sided supraspinatus tendon tears at 2-year follow-up, with a favourable safety profile and a relatively low rate of subsequent surgical conversion. These findings support the consideration of growth factor concentrate injection as a viable non-operative treatment option in appropriately selected patients, particularly those with lower-grade tears, before proceeding to arthroscopic repair. However, the absence of a control arm in this study necessitates cautious interpretation, and well-designed randomised controlled trials are required before growth factor concentrate injection can be firmly established as superior to existing conservative modalities in the management of this common condition.

Declarations

Ethical Approval

This study was approved by the Institutional Ethics Committee, Venkateshwara Institute of Medical Sciences, Gajraula, was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Written informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author Contributions

All authors contributed to study conception, design, data acquisition, analysis, manuscript drafting, and critical revision, and approved the final version submitted.

Data Availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.,

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